Efficacy of Topical Heparin Spray on Donor Site Wound Healing Time Compared to Conventional Dressing Among Patients Undergoing Split Thickness Skin Grafting

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This single-center prospective randomized controlled preprint studied split-thickness skin graft donor-site wound healing in 60 patients with healthy granulating wounds (Sep 2020–Jul 2021), comparing daily heparin spray/irrigation from the next day post-op versus conventional dressings, with outcomes assessed via questionnaires and photographic review through postoperative day 7. The authors report lower dressing soakage and reduced itching at the intervention site primarily among males, a greater proportion of participants showing improved edema with heparin versus no change with conventional therapy, and no participant scoring worst pain at the heparin-treated area. The main caveat is that the paper is presented as a preprint (not peer reviewed) and includes a limited follow-up window confined to 7 days, alongside subgroup patterns (e.g., females reporting no difference) that complicate overall interpretation. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Efficacy of Topical Heparin Spray on Donor Site Wound Healing Time Compared to Conventional Dressing Among Patients Undergoing Split Thickness Skin Grafting | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Efficacy of Topical Heparin Spray on Donor Site Wound Healing Time Compared to Conventional Dressing Among Patients Undergoing Split Thickness Skin Grafting Faraz Adil, Mahak Ali Memon, Faisal Akhlaq, Farhan Zahid Piprani, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4535856/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted 12 You are reading this latest preprint version Abstract Background All wounds that cannot be closed primarily needs skin coverage earliest to prevent form infections. Skin graft provides earliest and easiest wound coverage, but produces another wound, i.e. donor site wound. This study is conducted to see healing time efficacy of topical heparin spray versus conventional dressing in healing donor site wounds. METHODOLOGY The study was designed as a single center, prospective, randomized control trial study. It was conducted in the Department of Plastic and Reconstructive Surgery at Civil Hospital Karachi. The study was carried out for 10 months of the period from Sep 2020 to July 2021. The sample was calculated by using OpenEpi version 3.01.The minimum sample size was calculated to be 8 at 95% confidence level and 80% power, though the study included 60 patients who underwent split thickness skin grafting for healthy granulating wounds. From the next day of surgery heparin dressing and conventional dressings groups were made and dressing was done daily till seventh postoperative day. Data in form of questionnaire and photographic assessment was recorded filled at every change of dressing. This study was a self-controlled trial, therefore every trial participant served as his/her own control. Data was analyzed by using Statistical Package for Social Sciences (SPSS version 24). RESULT The results of the analysis showed the mean age of the participants was (35.30 ± 8.87). Male gender predominated with a frequency of 82% while females were 18%. A decrease in soakage of dressing was recorded in 48 (98.0%) male participants at interventional half; however, all females experienced no difference at both dressing sites. Similarly 48 (98.0%) male participants a reduction in itching at intervention site and all females had experienced no difference in itching at both dressing sites. In regard to wound size, 40% of participants showed a reduction in wound size and only 20% showed no improvement at interventional half. During 7days, 81.67% of participants showed improvement in edema at intervention half and 96.7% of participants reported no change in edema with conventional therapy. None of the participants scored worst pain at the intervention area. CONCLUSION The study showed heparin irrigation result in better wound healing and significantly reduces pain, edema, enhances faster healing and reduces soakage of dressings. Trial registration: The study was approved by Institutional Review Board of Dow University of Health Sciences and was registered at Clinical Trials.gov (ID: NCT04613336). Biological sciences/Drug discovery Health sciences/Medical research Heparin Wounds Donor site wound Dressings Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Background The Skin composes the largest organ of the human body. Uninjured skin performs a wide variety of vital functions for human body, that constitutes as a protective barrier against solar radiations( 2 ), preventing water loss from the body, entry of injurious elements and organisms from the environment. It also serves in sensations of touch, temperature, and pain; and regularity of functions such as thermal, hydration and excretions( 3 , 4 ). Skin performs these roles by the integrations of epidermis and dermis( 5 ). During surgery after excising the abnormal skin or closing the post-operative wounds it is not always possible to directly oppose the wound edges, in these circumstances’ skin grafting is the easiest, least traumatic and most reliable method of wound coverage( 6 ). The fundamental goal for skin closure is restoration of the normal anatomy and physiology of the uninjured skin after healing of the wound. Currently only full thickness skin grafts and flaps can restore structures and functions of uninjured skin( 7 , 8 ). Table 1 compares the functional qualities of normal skin with skin-grafted skin. Table 1 Comparsion of Cell Types in Native and Grafted skin Tissue Type Cell Type Uninjuired Skin Split thickness autograft Healed Skin after grafting Epidermis Keratinocytes Hair follicle Sebaceous Gland Sweat Gland Melanocytes Nerve + + + + + + + - - - +/- + + - - - +/- + Dermis Fibroblasts Endothelial Cells Smooth cells Nerve + + + + + + + + + + +/- +/- Any open wound resulting from any injury like large traumatic wounds( 9 ), burn wounds( 10 ), oncological excision or in burns needs to be covered at earliest to prevent from wound infections. Studies in burns shows early excisions and coverage by skin grafts by 1–2 days minimizes the risks of infection and decreases mortality( 5 , 11 ). Following the step ladder pattern skin grafting remains the first choice of in many cases ( 12 ). Although the extracellular matrix is essential for the functional restoration of the skin, closure of full thickness wounds demands for the transplantation of epithelial cells. Skin grafting is an easy and effective surgical technique that can be employed in operation theatre either in local or general anesthesia. However, in skin grafting morbidity also occurs at skin graft donor site along with the primary wound( 13 ). Broadly there are two types of skin grafting, split thickness skin graft (Thiersch) and full thickness skin graft (Wolfe-krause)( 14 ) In split thickness skin graft, epidermis and part of dermis is harvested from the donor side, using grafting knife (Figure no. 1.0) creating a self-created wound i.e. Donor Side Wound (DSW), although this wound is created in sterile conditions, they can get infected too and cause physical burden to the patients along with the presence of primary wound. Since prior to the surgery the emphasis of treatment relies upon the primary wound, this new DSW is often neglected after the surgery to such an extent that it may get infected or leads to delayed healing with pain and discomfort ( 15 – 17 ) to the patient at the previous normal site thus adding to the misery of the patient. In early postoperative period, DSW pain is the most distressing symptom complained about and affects mobilization, sleep and demands for early analgesics( 18 ). With appropriate dressings and wound care DSW should heal by two- three weeks( 18 , 19 ). There are a number of knife designs to harvest Split thickness skin graft. Figure 1 shows Graham Humhy Knife. In general donor site is left dressed for weeks to heal and epithelialization occurs in around 10–21 days( 20 ). If proper wound care is not provided to DSW it cause itching, pain, infection dyschromia, hyperpigmentation, and hypertrophic scarring ( 5 , 9 , 21 ). The goal of donor site wound dressings include patients comfort with minimal pain, minimum to nil soakage, quick epithelialization, least odor, and affordable costs( 5 , 22 ). Current dressings’ choices includes moist gauzes, cholorohexidine impregnated wax gauzes and calcium alginate dressings. In literature films and hydrocolloids serve most effectively for patient pain relief and comfort ( 15 , 23 , 24 ). Although a number of dressings has been suggested for DSW, their usage varies from surgeon choice ( 21 , 25 – 27 ). Despite of the presence of both moist and wet dressings, no literature shows any significance of one dressing over another for donor site wound healing( 10 , 28 ). There is no specific principle to guide for donor site wound management. As mentioned earlier for the restoration of tissue integrity, extracellular matrix (ECM) needs interaction with inflammatory cells and epithelial cells through integrin receptors and adhesion molecules ( 29 – 31 ). ECM molecules includes glycosaminoglycan (GAGs) have a vital role in all phases of wound healing. GAG includes sulfated glycosaminoglycans, heparan sulfate/heparin (HS/Hp), keratin sulfate (KS), and hyaluronic acid (HA). In wound healing heparin is essential for signal transduction by binding and regulating growth factors, protease inhibitors and proteolytic enzymes( 32 , 33 ). As an anti-inflammatory agent it inhibits enzymes and cytotoxic mediators, discharged from pro-inflammatory cells, accounting for increase in inflammation( 34 , 35 ). Moreover, heparin appearing in wound after 24-72hrs binds to heparin binding growth factors (Hb-EGF) and serves as in mitogenic activity for fibroblasts, smooth muscle cells and epithelial cells( 36 ). Heparin influence hepatocyte growth factor and stimulates endothelial and epithelial repair( 37 ) In human body heparin is produced by basophils and mast cells of liver, lungs and intestines and it helps in antioxidant, anti-inflammatory and vasodilation( 38 ). In a study effect of wound healing time on quality of scar tissue was assessed on skin graft donor site wound. Comparing two different types of dressings, healing was evaluated using scar height, surface appearance and color mismatch as parameters. Study concluded that treatment strategies that accelerates healing also improves scar outcome( 39 ). In an another study comparing two techniques to heal STSG DSW; non-contact low frequency ultrasound (NLFU) and standard care (SC) with standard care alone, healing time was measured in terms of absence of drainage, pain and itching scores, presence of epithelialization. The study demonstrated significant accelerated healing time with complete epithelialization in 4weeks and reduced pain and itching in NLFU group( 40 ). It is proven in superficial burns that heparin irrigation showed better wound healing parameters like necrotic tissue score and granulations tissue score as compared to saline irrigation ( 41 ). Furthermore a study investigated the effects of heparin and growth factors alone and combination of heparin along with growth factors in wound healing potential. The combination group showed the highest potential in cell line proliferation with 65–98% increase in endothelial cells( 42 ) . Studies on the effect of heparin on burn wounds and other wounds have shown promising results, however, there is extreme scarcity of literature on the effect of heparin on donor site healing especially from low and middle income countries. Therefore this study was conducted to study the effect of heparin as a topical wound dressing to improve healing time at donor site. METHODOLOGY Study Design and settings The study was designed as a single center, prospective, randomized control trial study. It was conducted in the Department of Plastic and Reconstructive Surgery at Dr. Ruth K.M. Pfau, Civil Hospital Karachi. Sampling and Participants The sample size was calculated using the healing time differences reported by Manzoor S et al in heparin and conventional dressing groups of burns patients as 14 ± 1 days 20 ± 4 days( 43 ). The minimum required sample size was calculated to be 8 at 95% confidence level and 80% power. However study included 60 patients who underwent split thickness skin grafting for healthy granulation tissue as primary wound. Exclusion criteria included patients under the age of 15 years and over 55 years, those who were pregnant, hypertensive or with bleeding disorders and finally immune-compromised i.e. diabetic patients and steroids users. SURGICAL METHOD The surgery was performed under both general and local anesthesia. Graft donor sites i.e. thigh and recipient sites were prepared using antiseptic agents. Pyodine scrub or Petroleum jelly was applied to lubricate the skin graft donor site. Split thickness skin graft was harvested with Humby knife from the inner side of thigh in two long strips of about 10*6cm with some centimeter break in among them by a surgeon other than the primary investigator, Humby knife was manually calibrated on a randomized setting to harvest a fixed depth of split thickness skin graft. After harvesting the donor site was washed with normal saline and dressed initially with chlorohexidine impregnated wax gauze and then rolled with burn gauze i.e sterilized cotton covered in roll gauze and finally thigh was bandaged. Humby knife was used as other calibrated knives’ blades were expensive and were not always available. Intervention and Data Collection On the first postoperative day, grouping was done among heparin and conventional groups. Allocation was done through randomization in order to prevent any confounding factors such as baseline differences in depth of wound. Before opening the dressings patients were given with paper chits to choose from, with A or B marked on it. Then the proximal strip of donor site wound (DSW) was dressed according to the chit chosen. Patients picking up A chit were considered as ‘control half (conventional dressing)’, whereas patients picking up B chit were considered as ‘intervention half’. In patients in whom bilateral thigh were used to harvest skin graft, one thigh was taken as interventional half and the other as control half. Here right thigh was dressed according to chit chosen. On opening the dressings, the ‘control half’ was redressed in same manner as earlier with chlorohexidine impregnated wax gauze and burn gauze i.e. sterilized cotton covered in roll gauze whereas ‘intervention half’ of wound was sprayed; on wound after removing the chlorohexidine impregnated wax gauze, with 5000 I.U/ml concentration of the heparin placed in a 5 cc syringe and finally was redressed with chlorohexidine impregnated wax gauze and sterilized cotton covered in roll gauze. This procedure was repeated on DSW wound on daily basis for seven days from operation. Analgesics were stopped from the second postoperative day to see the effects of heparin as analgesic to the wound. Since primary wound was a healthy granulation tissue, there was nil to no pain at that site postoperatively. Data in form of questionnaire and photographic assessment was done at every change of dressing. Statistical Analysis Strict exclusion criteria were followed to control confounders and bias in study results. Data were analyzed by using Statistical Package for Social Sciences (SPSS version 21). Descriptive statistics were reported using mean and standard deviation for all continuous variables and frequencies and percentages for all categorical variables. Mean wound healing time (recorded in days) between two intervention groups were compared using Repeated measures ANOVA. p-value < 0.05 was considered as level of significance. Evaluation The pain severity was evaluated using Visual Analogue Scale (VAS), scored from 0—no pain to 10—unbearable pain, demonstrated in Fig. 2 . The pain severity was measured from the first postoperative day until the last day of dressing. The dressing soakage and the signs of healing were recorded on all assessment days. Wound healing was assessed by noting the decrease in size of wound and reduction of surrounding skin edema by an independent investigator who was not aware of the site of treatment given. This study was a self-controlled trial, therefore every trial participant served as his/her own control. The benefit of self-control trial was that factors like age, gender and co-morbid conditions and underlying background changes were completely controlled. RESULTS Data Analysis: Data analysis had done on SPSS version 24. Descriptive statistics were computed for numeric and categorical variables along with Mean and SD for continuous variables. The Pearson chi-square test was applied, to identify the relationship between therapy groups and selected wound healing parameters. Fisher exact test was applied where the assumption of Pearson chi-square test did not achieve. Moreover, gender-based comparison had done with soakage of dressing and itching at both control and interventional donor skin graft area. Demographics of the participants In the demographics, the majority of participants were middle-aged adults as shown (Table-2). The means age of the participants was (35.30 ± 8.87). Male gender predominated in this study with a frequency of (n = 49) while females were only 18% (n = 11) as shown in (Figure-3). Table no. 2 Mean age distribution of participants : Variable N Mean SD Minimum Maximum Age 60 35.30 8.87 20 52 Figure no. 3 Gender distribution of participants Subjective and Objective wound healing signs among participants In the current study, wound healing signs were assessed through a pain scale and the presence of edema or redness at both (n = 60) conventional and (n = 60) intervention (heparin spray) therapy sites of donor site wound. Change in soaking of dressing and itching were also witnessed. Furthermore, wound healing assessment was also recorded by the reduction of the edema and wound size at both sites wound. Pain and edema signs were reported by all the participants in both the control (conventional) group and intervention (heparin) group. However, in the subjective status of wound healing manifestation, the pain scale was categorized from (not hurt) to (hurts worse). 30% of the participant scored pain as (hurts little more) and (hurts even more) respectively while none of the participants scored worst pain at the dressing area. Change in soakage and itching at the dressing area of donor skin graft was reported 40% less at (site-B) where heparin spray had done, while no remarkable change in soaking and itching was observed at a conventional dressing area of donor skin graft, as shown in (Table-3). Regarding the objective status of wound healing, a 40% reduction of wound size was reported at site-B (heparin dressing area) of the participants. However, wound size was reduced by only 8% in the conventional therapy area of participants during 7days follow-up. Similarly, 40.8% edema reduction was recorded at the heparin therapy area of the donor skin graft. On the other hand, only a 1.7% decrease in edema was recorded at the conventional dressing area of the donor skin graft during a 7days follow-up (Table-3). Table no 3 Wound healing status among participants. Variables n (%) Pain Scale No hurt 0 (0) Hurts little bit 24 ( 20 ) Hurts little more 36 ( 30 ) Hurts even more 36 ( 30 ) Hurts whole a lot 24 ( 20 ) Hurts worst 0 (0) Change in soakage at dressing area No change in soakage 72 ( 60 ) Less soakage at site A (conventional therapy) 0 (0) Less soakage at site B (heparin spray therapy) 48 ( 40 ) Change in itching at dressing area No change in itching 72 ( 60 ) Less itching at site A (conventional therapy) 0 (0) Less itching at site B (heparin spray therapy) 48 ( 40 ) Change in wound size No change in wound size 71( 59 ) Decrease wound size at site A (conventional therapy) 1 ( 8 ) Decrease wound size at site B (heparin spray therapy) 48 ( 40 ) Change in edema No change in edema 69 (57.5) Decrease edema at site A (conventional therapy) 2 (1.7) Decrease edema at site B (heparin spray therapy) 49 (40.8) Comparison of pain status of the participants and the types of dressing. Comparison of the types of dressing groups with the pain scale of the participants as shown in (Table- 4), when scoring was recorded with no pain to worst pain from (score 0–10). All the (n = 60) participants had reported pain in both conventional and heparin dressing areas of the donor skin graft but none of the participants had experienced the worst pain. The Pearson chi-square test had shown a significant relationship of pain score with the heparin dressing group. In the conventional dressing group, 40% of the individuals reported higher levels of pain. However, in the heparin dressing group, 40% of the patients reported little pain. Table 4 Comparison of dressing types and pain scale Types of dressing P-value Pain scale Conventional therapy n (%) Heparin spray n (%) Hurts little bit 0 (0) 24 ( 40 ) < 0.0001* Hurts little more 24 ( 40 ) 12 ( 20 ) Hurts even more 12 ( 20 ) 24 ( 40 ) Hurts whole lot 24 ( 40 ) 0 (0) Hurts worst 0 (0) 0 (0) *significant p-value < 0.05, Gender based distribution of change in soakage of both dressing areas of skin graft. The significant relationship between gender and change in soakage of dressings among the two donor sites of skin graft was reported, as the p-value was less than (p = 0.05) in (Table-5). A remarkable decrease in soakage of dressing was recorded (98.0%) at site-B area (heparin spray dressing) of males. However, all females experienced no difference in soakage at both dressing sites. Table 5. Gender based comparison of soakage of both dressing areas. Gender Site A Site B P-value Overall n=60 Less soakage n=0 Overall n=60 Less soakage n=48 < 0.0001 β Male (Total=98sites) 49 0 (0) 49 48 (98.0) Female (Total=22 sites) 11 0 (0) 11 0 (0) Site-A (Conventional dressing), Site-B (heparin spray dressing). β Fisher’s exact test applied Comparison of gender group with change in itching at both dressing areas of donor skin graft The gender-based comparison had done with reduction in itching at dressings areas among the two donor sites of skin graft. Similar to the soakage of the dressing groups, a significant relationship was present with a p-value (< 0.05). Remarkable reduction in itching at 48 (98.0%) sites of heparin spray dressing (site-B) was reported in male donor skin graft. However, all females had experienced no difference in itching at both dressing sites (Table.6). Table 6 . Comparison of gender and change in itching of both dressing areas Gender Site A Site B P-value Overall n=60% Less itching n=0(%) Overall n=60% Less itching n=48(%) < 0.0001 β Male (Total=98sites) 49 0 (0) 49 48 (98.0) Female (Total=22 sites) 11 0 (0) 11 0 (0) Site-A (Conventional dressing), Site-B (heparin spray dressing). β Fisher’s exact test applied Comparison of the dressing types and reduction of wound size. The comparison had done between two types of dressing and wound size reduction. In a 1week follow-up, no absolute variation was reported in the early two days among both dressing groups shown in figure no 4. Later within 4days, 40% of participants had shown a reduction in wound size at size-B (heparin spray dressing). Moreover, 98.3% of the participants had shown no reduction of wound size with conventional dressing at the donor skin graft area. However, only 20% of the participant showed no improvement in wound size with heparin spray dressing. Hence, the Pearson chi-square test had shown a significant relationship between types of dressing and changes in wound size as shown in (Table no. 7). Table 7 Comparison of the two dressing types and reduction of wound size Therapy groups P-value Wound size Conventional n(%) Heparin n(%) <0.0001* Day 3 0(0) 12(20) Day 4 0(0) 24(40) Day 5 0(0) 12(20) Day 7 1(1.7) 0(0) No improvement 59(98.3) 12(20) *significant p-value <0.05 Comparison of types of the dressing groups and reduction of edema. Edema reduction at both conventional and heparin dressing areas was recorded during 7days follow-up, as shown in figure-5. In the early days of follow-up, a dramatic decrease in edema was recorded at the heparin dressing area of the donor skin graft. However, only 3.3% of participants had reported a decrease in edema with conventional dressing on day7. After the specific follow-up, 96.7% of participants had reported no change in edema with conventional therapy. Although, 18.3% of participants did not show improvement in edema with heparin dressing. This relationship between dressing types and reduction in edema was significant (p < 0.05), as shown in (Table 8 ). Table 8 Comparison of types of dressing with reduction of edema Types of dressing P-value Reduction of edema Conventional n (%) Heparin n (%) <0.0001* Day 2 0(0) 1(1.7) Day 3 0(0) 12(20) Day 4 0(0) 24(40) Day 5 0(0) 12(20) Day 7 2(3.3) 0(0) No improvement 58(96.7) 11(18.3) *significant p-value <0.05 Some cases with pictures are presented below showing initial presentation at Day 1, Heparin spray and final day picture. Figure 6 – 14 DISCUSSION The clinical trial supports the hypothesis that Heparin has an effective role in the treatment of burns to reduce pain and faster wound healing process. However, previous literature has already explained the physiology of heparin but still, scientists are experimenting with its usage in a variety of treatment application methods for the benefit of humanity ( 44 ). The current randomized control trial was a single-blind study in which conventional and Heparin group’s allocation was done on the same participant to control bias. Overall 60 patients were recruited for the study, the majority of them were middle-aged adults with average an age of 35.30 ± 8.87. The male gender is more likely to be dominated with the frequency of 82% as compared to the female. As heparin exhibits, multi-functional properties such as anti-inflammation, anti-thrombosis, enhanced blood circulation in ischemic parts, pain reduction, revascularization, the process of healing makes faster and decrease in wound size, etc. Likewise, It also increases the blood circulation at the site of the burn, and studies had demonstrated well the effectiveness of heparin in burns management( 45 , 46 ). Pain is the dominant variable in terms of burns which inhibits the mobility of patients and ought to extend the period of hospital stay ( 47 ). According to our study pain status was evaluated by visual analog scale (VAS) during the seven days of the clinical trial period. At present, we found that patients treated with heparin spray (40%) complaint a little bit of pain in contrast to those who received conventional treatment (40%) who reported more pain (p-value = < 0.001). However, Venakatachalapathy T.S. et.al. reported severity of pain with the requirement of analgesic supplements, and apparently, there was a dramatic decrease in analgesic supplement demand in the heparin group in contrast, to the control group ( 48 ) consequently, this would be beneficial in terms of cost-effectiveness along with the reduction of medication requirement. Similarly, Chellappa Vijayakumar claimed the significance of heparin in pain relief as compared to those who were managed by conventional therapy groups ( 49 ). Moreover, In connection with significant pain reduction, few studies also reported that heparin makes re-epithelialization, preventing the formation of tissue hypertrophy, scars, and contractures establishment ( 50 , 51 ). On the other hand along with countable benefits, Teles et.al had reported that heparin should be applicable cautiously in the management of second-degree facial and neck burns but there is controversy regarding its beneficial effects ( 52 ). One of the major findings of healing is less soakage in dressing. It comprises shielding the inner area of the wound to stave off the pathogenic environment; this might be served only when dressing keeps dry persistently. To prolong the dryness there are several dressing types have been designed. Apparently in our study evidence of significant association was based on gender and soakage of both heparin and conventional dressing. 100% male patients reported less soakage where heparin spray dressing was applied in contrast to females (p-value = < 0.001). Heparin’s anti-inflammatory effects were reported in some researches, Apart from its anticoagulant properties. Heparin possesses immunomodulatory characteristics and mechanisms of anti-inflammatory actions( 53 ). Tissue injury caused the formation of liquid exudate that plays an important role specifically associated chronic wounds( 54 ) In connection with our research Srikanth Reddy Challaoalli et al, explained the positive effects of topical heparin as compared to the nebulized heparin in burn patients regarding pain management, dressings of the wound, scar formation and wound infection rate, additionally, there was less soakage in dressing. The findings from this research resemble our study results( 55 ). However, Rakesh Rai et al, reported in contrast to the heparin, collagen dressing was significantly more helpful in the wound healing process and required less time. It was found to be effective in decreasing pain associated with burn injuries. According to their findings, the additional benefit of collagen dressing was a short hospital stay ( 56 ). Moreover, this study has shown a significant association between gender and change in itching of both dressing areas treated with heparin and conventional. 48 patients out of total experienced less itching after heparin spray dressing while the decreased number of female patients did not experience any reduction in itching at both sides of dressing (p-value = < 0.001). Dry skin is one of the explanations that exacerbate itching and may increase the probability of scar formation. Although in burned patients fibrotic hypertrophic scar is likely to form in the process of wound healing. It represents as hoisted, red, intransigent, and possess more capability to cause significant functional and cosmetic issues. Regarding the complaint of itching in burns patients, Marcos Guilherme Praxedes Barretto reported the significant effect of topical heparin in pain management and itching ( 57 ). A similar study conducted by Young Hee et.al supported our findings in respect to the formation of post-burn hypertrophic scars caused severe itching and pain. Besides this pain, this scar formation is the process of healing, however, in this regard heparin administration was found effective in reducing the itching and pain ( 58 ). Hypertrophic scar formation appears to involve a wide range of subsequent processes including impaired haemostasis, excessive inflammation, and protracted re-epithelialization, overabundant production of extracellular matrix, formation of new capillaries, remodeling of extracellular matrix, and diminished necroptosis. Ahmed Muhammad Salah EI-Din EI-Badawi et al evaluated in their study that there was a significantly remarkable reduction in tissue scarring with shorter healing time at the heparin group area in contrast to the control group area. However, symptoms of pain, itching, and infection at the heparin group area were also less but the results were insignificant ( 59 ). Some more studies evidenced that burn wounds exhibit the properties of the long-term inflammation process and neutrophil stagnancy. The plausibility of wound healing process inhibition is due to the destruction of extracellular matrix and growth factors, this affected by the secretory products of neutrophils ( 46 , 60 ). Zayas G.J. et al said that heparin was more effective in altering morbidity, mortality, and decreasing sepsis in severely burn children. It increased the survival rate from 11–60% in 1999 when compared to 1998 in which burns patients were treated without heparin. They claimed that whether heparin was applied topically or infused intravascular, patients experienced relief in pain, reduction in edema, decrease in burn size, and improvement in blood circulation to the ischemic tissues, as this study found with the help of a few procedures and better cosmetic results( 61 ). Furthermore, in the current study, it was well-identified that the wound size reduction was fairly dependent on the type of dressing. On the 4th day, the wound size had been reduced 40% in patients who received heparin spray while 98.3% of patients did not experience any sort of reduction in wound size with conventional dressing (p-value = < 0.001). In favor of the heparin used in the healing process Ravikumar T et al, reported the favorable anti-inflammatory effect of heparin that prompted healing process at the wound site and frequently relief pain ( 62 ) In addition to the above findings LMWH proposed various beneficial effects in the progression of wound healing ( 63 ) Indeed use of heparin in faster wound healing and tissue repair in burns patients is a promising solution ( 64 ). An evidence-based report of Peplow and Wang et.al reported the characteristics of atrocious wounds with prolonged inflammatory processes and deposition of substantial numbers of neutrophils. Heparin and its attributed molecules are associated with the inhibitory action of secretory products through electrostatic interaction ( 65 , 66 ). In the current study with 7days of follow-up, it was observed that there was a reduction in edema on the 4th day in 40% of patients treated with heparin spray dressing in contrast to their other counterparts. However, a minimal decrease in edema was observed in only 3.3% of patients. This dramatic change in the reduction of oedematous fluid and redness is the beneficial characteristic of heparin. Michael J. Saliba. Jr et.al reported large doses of heparin in the treatment of severe burns resulted in reduced edema, required less pain medication, inhibit the progression of infection and wound size and additionally induced blood flow to the burned tissues and initiated angiogenesis at affected area ( 67 ). However, in the study of Joakim Johansson a discrepancy regarding the effects of neutrophil derived heparin binding protein that increased vascular permeability in burn patients. On the other hand, it is the crucial marker that was clinically involved in reducing the frequency of infection and edema in burns patients ( 68 ). Furthermore, there is a controversy about the effectiveness of heparin reported by Pobert H. Demling, M.D et.al according to them therapeutically, heparin was ineffectual in reducing edema and it has no major effects to escalate the process of absorption ( 69 ). Similar to our study results, this study evaluated the efficiency of heparin for the therapeutic purpose of facial burn. They reported significant improvement in blood circulation, ameliorating pain, subside inflammation, rejuvenation of ischemic tissues, limiting scarring, and enhancing collagen. Similar to our study, this research also found substantial declination in pain and edema following tropical use of heparin ( 70 ). Although wound shapes can vary, it is not known if wound form affects the dynamics of wound healing ( 17 ). Thus, it is in line with clinical practice to use a straightforward wound volume measurement (length x breadth x depth). Additionally, the raw volume measurements of various wounds are not compared since volume is utilised to compute healing rate in terms of percent healed. However, it is possible to compare patient groups by averaging the percent healed (decrease from baseline) among all patients. As a facility, one objective may be to think about wound care procedures that might promote quicker healing. CONCLUSION This study showed that in comparison to conventional dressing the use of topical heparin significantly reduces pain, edema, and promotes healing. As dressing with topical heparin can be done easily, patients can be advised to get their wounds dressing at home providing psychological comfort to patient and family as well. This can also be beneficial for early rehabilitation as well. Abbreviations CHK Civil Hospital Karachi DSW Donor Site Wound FGF Fibroblast growth factor GAG Glycosaminoglycan HS/Hp Heparan sulfate/Heparin HA Hyaluronic acid Hb-EGF Heparin binding Growth Factors I.U International Unit KS Keratin sulfate NLFU Non-contact Low Frequency Ultrasound SNOSE Sequentially Numbered, Opaque, Sealed Envelopes SPSS Statistical Package for Social Sciences STSG Split Thickness Skin Graft TOPOX Topical Oxygen Therapy VAS Visual Analogue Scale Declarations Ethics approval and consent to participate This research was approved by Institutional Review Board of Dow University of Health Sciences (IRB-1837/DUHS/Approval/2020/162). The trial was registered at Clinical Trials.gov (ID: NCT04613336). The study protocol, potential benefits and discomforts of the study were explained in detail to the potential study participants before obtaining informed written consent to participate in the study. Special permission was obtained to take photographs of the wound which were anonymized and coded. Physical data (proformas) was stored in a locked facility while digital data (including photographs) was stored in a separate desktop computer not connected to internet, in an encrypted folder. Informed consent was obtained from the participants. Accordance: We confirmed that all experiments in this study were performed in accordance with the relevant guidelines and regulations. Informed consent: All the participants are informed about the study, and they have all signed the informed consent form. Consent for publication The consent for publication was taken from all participants. Data availability The data that supports findings of this study are available from the corresponding author, FA upon reasonable request. Competing interests The authors declare that there is potentially no conflict of interest related to the article. Funding The study was self-funded. This study was not funded by any agency in public, commercial or not-for-profit sectors. Author contributions Dr.Faraz Adil (FA), the principal investigator, made a substantial contribution to the conception, design of the work, sample processing, data analysis and interpretation and led the writing. Dr. Mahak Ali Memon (MAM), contributed to the sample collection, data analysis, processing and drafting designed figures and tables. Dr. Faisal Akhlaq Ali Khan (FAAK), supervised and proofread the project. Dr. Saad uddin Siddiqui (SS), aided in data analysis, revised the manuscript Dr. Asadullah Awan (AA), edited the final manuscript. Dr. Farhan Zahid Piprani (FZP), conceived the idea of study Acknowledgements The authors would like to thank the participants who took part in this study. References Barber S. A clinically relevant wound assessment method to monitor healing progression. Ostomy Wound Management. 2008;54(3):42. Brandner J, Jensen J. The skin: an indispensable barrier. 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Supplementary Files Appendi1.docx Cite Share Download PDF Status: Published Journal Publication published 30 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 14 Nov, 2024 Reviews received at journal 13 Nov, 2024 Reviewers agreed at journal 26 Oct, 2024 Reviewers agreed at journal 30 Aug, 2024 Reviews received at journal 22 Jul, 2024 Reviewers agreed at journal 22 Jul, 2024 Reviewers agreed at journal 22 Jul, 2024 Reviewers invited by journal 22 Jul, 2024 Editor assigned by journal 22 Jul, 2024 Editor invited by journal 22 Jul, 2024 Submission checks completed at journal 17 Jul, 2024 First submitted to journal 05 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4535856","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":336924335,"identity":"42cfac8f-9519-4575-9f39-298ab094b851","order_by":0,"name":"Faraz 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follow-up\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Picture8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4535856/v1/ea9acdcf3fc4e89fb01bc0e0.jpg"},{"id":62653556,"identity":"80e245fe-22ea-40e0-9aac-b61d12d0f664","added_by":"auto","created_at":"2024-08-17 01:13:42","extension":"jpg","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":334774,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFirst day of Donor Site wound during 7 day of follow-up\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Picture9.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4535856/v1/31174c4b79d6cab1cad3762c.jpg"},{"id":62652115,"identity":"22d69d83-e974-495f-b715-48569b3aafd6","added_by":"auto","created_at":"2024-08-17 00:57:42","extension":"jpg","order_by":10,"title":"Figure 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follow-up\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Picture11.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4535856/v1/5b2bb53e1b1c2fbe83d86c80.jpg"},{"id":62653007,"identity":"9e5ba2e7-1b54-43a4-96c2-45bd82c632e2","added_by":"auto","created_at":"2024-08-17 01:05:42","extension":"jpg","order_by":12,"title":"Figure 12","display":"","copyAsset":false,"role":"figure","size":339067,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFirst day of Donor site wound during 7 day follow-up\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Picture12.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4535856/v1/40be6c1d8ed6f2a47a213771.jpg"},{"id":62652121,"identity":"69a06703-23c4-4f83-9710-28c0b4b7cd20","added_by":"auto","created_at":"2024-08-17 00:57:42","extension":"jpg","order_by":13,"title":"Figure 13","display":"","copyAsset":false,"role":"figure","size":236739,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eInterventional half sprayed with Heparin during 7 day follow up\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Picture13.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4535856/v1/55d07b2fb159c0d0998e71c6.jpg"},{"id":62653010,"identity":"615f25f4-d5ca-490c-8196-04f0096bdc39","added_by":"auto","created_at":"2024-08-17 01:05:42","extension":"jpg","order_by":14,"title":"Figure 14","display":"","copyAsset":false,"role":"figure","size":151832,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of Control and interventional half at 7 day of follow-up\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Picture14.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4535856/v1/04e87101e467088d08bdfbeb.jpg"},{"id":88268444,"identity":"0a6443d4-9d71-46e6-bb63-8474364dd3ee","added_by":"auto","created_at":"2025-08-04 16:51:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4602204,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4535856/v1/2beec292-5eba-48b9-9b16-5b6bd885438b.pdf"},{"id":62652107,"identity":"71532875-6742-4e65-ae4c-c8dc2c152f9b","added_by":"auto","created_at":"2024-08-17 00:57:41","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":25360,"visible":true,"origin":"","legend":"","description":"","filename":"Appendi1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4535856/v1/24bbb425fcac53fecf89fb4e.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eEfficacy of Topical Heparin Spray on Donor Site Wound Healing Time Compared to Conventional Dressing Among Patients Undergoing Split Thickness Skin Grafting\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eThe Skin composes the largest organ of the human body. Uninjured skin performs a wide variety of vital functions for human body, that constitutes as a protective barrier against solar radiations(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), preventing water loss from the body, entry of injurious elements and organisms from the environment. It also serves in sensations of touch, temperature, and pain; and regularity of functions such as thermal, hydration and excretions(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Skin performs these roles by the integrations of epidermis and dermis(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDuring surgery after excising the abnormal skin or closing the post-operative wounds it is not always possible to directly oppose the wound edges, in these circumstances\u0026rsquo; skin grafting is the easiest, least traumatic and most reliable method of wound coverage(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The fundamental goal for skin closure is restoration of the normal anatomy and physiology of the uninjured skin after healing of the wound. Currently only full thickness skin grafts and flaps can restore structures and functions of uninjured skin(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e compares the functional qualities of normal skin with skin-grafted skin.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eComparsion of Cell Types in Native and Grafted skin\u003c/span\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTissue Type\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCell Type\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUninjuired Skin\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSplit thickness autograft\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHealed Skin after grafting\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpidermis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKeratinocytes\u003c/p\u003e \u003cp\u003eHair follicle\u003c/p\u003e \u003cp\u003eSebaceous Gland\u003c/p\u003e \u003cp\u003eSweat Gland\u003c/p\u003e \u003cp\u003eMelanocytes\u003c/p\u003e \u003cp\u003eNerve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003cp\u003e+\u003c/p\u003e \u003cp\u003e+\u003c/p\u003e \u003cp\u003e+\u003c/p\u003e \u003cp\u003e+\u003c/p\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003cp\u003e+/-\u003c/p\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003cp\u003e+/-\u003c/p\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDermis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFibroblasts\u003c/p\u003e \u003cp\u003eEndothelial Cells\u003c/p\u003e \u003cp\u003eSmooth cells\u003c/p\u003e \u003cp\u003eNerve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003cp\u003e+\u003c/p\u003e \u003cp\u003e+\u003c/p\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003cp\u003e+\u003c/p\u003e \u003cp\u003e+\u003c/p\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003cp\u003e+\u003c/p\u003e \u003cp\u003e+/-\u003c/p\u003e \u003cp\u003e+/-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAny open wound resulting from any injury like large traumatic wounds(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), burn wounds(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), oncological excision or in burns needs to be covered at earliest to prevent from wound infections. Studies in burns shows early excisions and coverage by skin grafts by 1\u0026ndash;2 days minimizes the risks of infection and decreases mortality(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Following the step ladder pattern skin grafting remains the first choice of in many cases (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough the extracellular matrix is essential for the functional restoration of the skin, closure of full thickness wounds demands for the transplantation of epithelial cells.\u003c/p\u003e \u003cp\u003eSkin grafting is an easy and effective surgical technique that can be employed in operation theatre either in local or general anesthesia. However, in skin grafting morbidity also occurs at skin graft donor site along with the primary wound(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Broadly there are two types of skin grafting, split thickness skin graft (Thiersch) and full thickness skin graft (Wolfe-krause)(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn split thickness skin graft, epidermis and part of dermis is harvested from the donor side, using grafting knife (Figure no. 1.0) creating a self-created wound i.e. Donor Side Wound (DSW), although this wound is created in sterile conditions, they can get infected too and cause physical burden to the patients along with the presence of primary wound. Since prior to the surgery the emphasis of treatment relies upon the primary wound, this new DSW is often neglected after the surgery to such an extent that it may get infected or leads to delayed healing with pain and discomfort (\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) to the patient at the previous normal site thus adding to the misery of the patient. In early postoperative period, DSW pain is the most distressing symptom complained about and affects mobilization, sleep and demands for early analgesics(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). With appropriate dressings and wound care DSW should heal by two- three weeks(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). There are a number of knife designs to harvest Split thickness skin graft. Figure\u0026nbsp;\u003cspan refid=\"Fig14\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows Graham Humhy Knife.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn general donor site is left dressed for weeks to heal and epithelialization occurs in around 10\u0026ndash;21 days(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). If proper wound care is not provided to DSW it cause itching, pain, infection dyschromia, hyperpigmentation, and hypertrophic scarring (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). The goal of donor site wound dressings include patients comfort with minimal pain, minimum to nil soakage, quick epithelialization, least odor, and affordable costs(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCurrent dressings\u0026rsquo; choices includes moist gauzes, cholorohexidine impregnated wax gauzes and calcium alginate dressings. In literature films and hydrocolloids serve most effectively for patient pain relief and comfort (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Although a number of dressings has been suggested for DSW, their usage varies from surgeon choice (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite of the presence of both moist and wet dressings, no literature shows any significance of one dressing over another for donor site wound healing(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). There is no specific principle to guide for donor site wound management.\u003c/p\u003e \u003cp\u003eAs mentioned earlier for the restoration of tissue integrity, extracellular matrix (ECM) needs interaction with inflammatory cells and epithelial cells through integrin receptors and adhesion molecules (\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). ECM molecules includes glycosaminoglycan (GAGs) have a vital role in all phases of wound healing. GAG includes sulfated glycosaminoglycans, heparan sulfate/heparin (HS/Hp), keratin sulfate (KS), and hyaluronic acid (HA).\u003c/p\u003e \u003cp\u003eIn wound healing heparin is essential for signal transduction by binding and regulating growth factors, protease inhibitors and proteolytic enzymes(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). As an anti-inflammatory agent it inhibits enzymes and cytotoxic mediators, discharged from pro-inflammatory cells, accounting for increase in inflammation(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). Moreover, heparin appearing in wound after 24-72hrs binds to heparin binding growth factors (Hb-EGF) and serves as in mitogenic activity for fibroblasts, smooth muscle cells and epithelial cells(\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHeparin influence hepatocyte growth factor and stimulates endothelial and epithelial repair(\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e) In human body heparin is produced by basophils and mast cells of liver, lungs and intestines and it helps in antioxidant, anti-inflammatory and vasodilation(\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn a study effect of wound healing time on quality of scar tissue was assessed on skin graft donor site wound. Comparing two different types of dressings, healing was evaluated using scar height, surface appearance and color mismatch as parameters. Study concluded that treatment strategies that accelerates healing also improves scar outcome(\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn an another study comparing two techniques to heal STSG DSW; non-contact low frequency ultrasound (NLFU) and standard care (SC) with standard care alone, healing time was measured in terms of absence of drainage, pain and itching scores, presence of epithelialization. The study demonstrated significant accelerated healing time with complete epithelialization in 4weeks and reduced pain and itching in NLFU group(\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIt is proven in superficial burns that heparin irrigation showed better wound healing parameters like necrotic tissue score and granulations tissue score as compared to saline irrigation (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurthermore a study investigated the effects of heparin and growth factors alone and combination of heparin along with growth factors in wound healing potential. The combination group showed the highest potential in cell line proliferation with 65\u0026ndash;98% increase in endothelial cells(\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e) .\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eStudies on the effect of heparin on burn wounds and other wounds have shown promising results, however, there is extreme scarcity of literature on the effect of heparin on donor site healing especially from low and middle income countries. Therefore this study was conducted to study the effect of heparin as a topical wound dressing to improve healing time at donor site.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"METHODOLOGY","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and settings\u003c/h2\u003e \u003cp\u003eThe study was designed as a single center, prospective, randomized control trial study. It was conducted in the Department of Plastic and Reconstructive Surgery at Dr. Ruth K.M. Pfau, Civil Hospital Karachi.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eSampling and Participants\u003c/h2\u003e \u003cp\u003eThe sample size was calculated using the healing time differences reported by Manzoor S et al in heparin and conventional dressing groups of burns patients as 14\u0026thinsp;\u0026plusmn;\u0026thinsp;1 days 20\u0026thinsp;\u0026plusmn;\u0026thinsp;4 days(\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e). The minimum required sample size was calculated to be 8 at 95% confidence level and 80% power. However study included 60 patients who underwent split thickness skin grafting for healthy granulation tissue as primary wound. Exclusion criteria included patients under the age of 15 years and over 55 years, those who were pregnant, hypertensive or with bleeding disorders and finally immune-compromised i.e. diabetic patients and steroids users.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSURGICAL METHOD\u003c/h2\u003e \u003cp\u003eThe surgery was performed under both general and local anesthesia. Graft donor sites i.e. thigh and recipient sites were prepared using antiseptic agents. Pyodine scrub or Petroleum jelly was applied to lubricate the skin graft donor site. Split thickness skin graft was harvested with Humby knife from the inner side of thigh in two long strips of about 10*6cm with some centimeter break in among them by a surgeon other than the primary investigator, Humby knife was manually calibrated on a randomized setting to harvest a fixed depth of split thickness skin graft. After harvesting the donor site was washed with normal saline and dressed initially with chlorohexidine impregnated wax gauze and then rolled with burn gauze i.e sterilized cotton covered in roll gauze and finally thigh was bandaged. Humby knife was used as other calibrated knives\u0026rsquo; blades were expensive and were not always available.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eIntervention and Data Collection\u003c/h2\u003e \u003cp\u003eOn the first postoperative day, grouping was done among heparin and conventional groups. Allocation was done through randomization in order to prevent any confounding factors such as baseline differences in depth of wound. Before opening the dressings patients were given with paper chits to choose from, with A or B marked on it. Then the proximal strip of donor site wound (DSW) was dressed according to the chit chosen. Patients picking up A chit were considered as \u0026lsquo;control half (conventional dressing)\u0026rsquo;, whereas patients picking up B chit were considered as \u0026lsquo;intervention half\u0026rsquo;. In patients in whom bilateral thigh were used to harvest skin graft, one thigh was taken as interventional half and the other as control half. Here right thigh was dressed according to chit chosen.\u003c/p\u003e \u003cp\u003eOn opening the dressings, the \u0026lsquo;control half\u0026rsquo; was redressed in same manner as earlier with chlorohexidine impregnated wax gauze and burn gauze i.e. sterilized cotton covered in roll gauze whereas \u0026lsquo;intervention half\u0026rsquo; of wound was sprayed; on wound after removing the chlorohexidine impregnated wax gauze, with 5000 I.U/ml concentration of the heparin placed in a 5 cc syringe and finally was redressed with chlorohexidine impregnated wax gauze and sterilized cotton covered in roll gauze. This procedure was repeated on DSW wound on daily basis for seven days from operation. Analgesics were stopped from the second postoperative day to see the effects of heparin as analgesic to the wound. Since primary wound was a healthy granulation tissue, there was nil to no pain at that site postoperatively. Data in form of questionnaire and photographic assessment was done at every change of dressing.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStrict exclusion criteria were followed to control confounders and bias in study results. Data were analyzed by using Statistical Package for Social Sciences (SPSS version 21). Descriptive statistics were reported using mean and standard deviation for all continuous variables and frequencies and percentages for all categorical variables. Mean wound healing time (recorded in days) between two intervention groups were compared using Repeated measures ANOVA. p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered as level of significance.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eEvaluation\u003c/h2\u003e \u003cp\u003eThe pain severity was evaluated using Visual Analogue Scale (VAS), scored from 0\u0026mdash;no pain to 10\u0026mdash;unbearable pain, demonstrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig16\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe pain severity was measured from the first postoperative day until the last day of dressing. The dressing soakage and the signs of healing were recorded on all assessment days. Wound healing was assessed by noting the decrease in size of wound and reduction of surrounding skin edema by an independent investigator who was not aware of the site of treatment given. This study was a self-controlled trial, therefore every trial participant served as his/her own control. The benefit of self-control trial was that factors like age, gender and co-morbid conditions and underlying background changes were completely controlled.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003eData Analysis:\u003c/h2\u003e\n \u003cp\u003eData analysis had done on SPSS version 24. Descriptive statistics were computed for numeric and categorical variables along with Mean and SD for continuous variables. The Pearson chi-square test was applied, to identify the relationship between therapy groups and selected wound healing parameters. Fisher exact test was applied where the assumption of Pearson chi-square test did not achieve. Moreover, gender-based comparison had done with soakage of dressing and itching at both control and interventional donor skin graft area.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eDemographics of the participants\u003c/h2\u003e\n \u003cp\u003eIn the demographics, the majority of participants were middle-aged adults as shown (Table-2). The means age of the participants was (35.30\u0026thinsp;\u0026plusmn;\u0026thinsp;8.87). Male gender predominated in this study with a frequency of (n\u0026thinsp;=\u0026thinsp;49) while females were only 18% (n\u0026thinsp;=\u0026thinsp;11) as shown in (Figure-3).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable no. 2 Mean age distribution of participants\u003c/strong\u003e:\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Taba\" border=\"1\"\u003e\n \u003ccolgroup cols=\"6\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMinimum\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMaximum\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eFigure no. 3 Gender distribution of participants\u003c/span\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003eSubjective and Objective wound healing signs among participants\u003c/h2\u003e\n \u003cp\u003eIn the current study, wound healing signs were assessed through a pain scale and the presence of edema or redness at both (n\u0026thinsp;=\u0026thinsp;60) conventional and (n\u0026thinsp;=\u0026thinsp;60) intervention (heparin spray) therapy sites of donor site wound. Change in soaking of dressing and itching were also witnessed. Furthermore, wound healing assessment was also recorded by the reduction of the edema and wound size at both sites wound. Pain and edema signs were reported by all the participants in both the control (conventional) group and intervention (heparin) group. However, in the subjective status of wound healing manifestation, the pain scale was categorized from (not hurt) to (hurts worse). 30% of the participant scored pain as (hurts little more) and (hurts even more) respectively while none of the participants scored worst pain at the dressing area. Change in soakage and itching at the dressing area of donor skin graft was reported 40% less at (site-B) where heparin spray had done, while no remarkable change in soaking and itching was observed at a conventional dressing area of donor skin graft, as shown in (Table-3).\u003c/p\u003e\n \u003cp\u003eRegarding the objective status of wound healing, a 40% reduction of wound size was reported at site-B (heparin dressing area) of the participants. However, wound size was reduced by only 8% in the conventional therapy area of participants during 7days follow-up. Similarly, 40.8% edema reduction was recorded at the heparin therapy area of the donor skin graft. On the other hand, only a 1.7% decrease in edema was recorded at the conventional dressing area of the donor skin graft during a 7days follow-up (Table-3).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable no 3 Wound healing status among participants.\u003c/strong\u003e\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tabb\" border=\"1\"\u003e\n \u003ccolgroup cols=\"2\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePain Scale\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo hurt\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHurts little bit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24 (\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHurts little more\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36 (\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHurts even more\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36 (\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHurts whole a lot\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24 (\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHurts worst\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eChange in soakage at dressing area\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo change in soakage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72 (\u003cspan class=\"CitationRef\"\u003e60\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLess soakage at site A (conventional therapy)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLess soakage at site B (heparin spray therapy)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48 (\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eChange in itching at dressing area\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo change in itching\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72 (\u003cspan class=\"CitationRef\"\u003e60\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLess itching at site A (conventional therapy)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLess itching at site B (heparin spray therapy)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48 (\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eChange in wound size\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo change in wound size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71(\u003cspan class=\"CitationRef\"\u003e59\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDecrease wound size at site A (conventional therapy)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDecrease wound size at site B (heparin spray therapy)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48 (\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eChange in edema\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo change in edema\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69 (57.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDecrease edema at site A (conventional therapy)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDecrease edema at site B (heparin spray therapy)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49 (40.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cstrong\u003eComparison of pain status of the participants and the types of dressing.\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eComparison of the types of dressing groups with the pain scale of the participants as shown in (Table- 4), when scoring was recorded with no pain to worst pain from (score 0\u0026ndash;10). All the (n\u0026thinsp;=\u0026thinsp;60) participants had reported pain in both conventional and heparin dressing areas of the donor skin graft but none of the participants had experienced the worst pain. The Pearson chi-square test had shown a significant relationship of pain score with the heparin dressing group. In the conventional dressing group, 40% of the individuals reported higher levels of pain. However, in the heparin dressing group, 40% of the patients reported little pain.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eComparison of dressing types and pain scale\u003c/span\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eTypes of dressing\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePain scale\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eConventional therapy\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHeparin spray\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHurts little bit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24 (\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"5\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHurts little more\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24 (\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHurts even more\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24 (\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHurts whole lot\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24 (\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHurts worst\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e*significant p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05,\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cstrong\u003eGender based distribution of change in soakage of both dressing areas of skin graft.\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe significant relationship between gender and change in soakage of dressings among the two donor sites of skin graft was reported, as the p-value was less than (p\u0026thinsp;=\u0026thinsp;0.05) in (Table-5). A remarkable decrease in soakage of dressing was recorded (98.0%) at site-B area (heparin spray dressing) of males. However, all females experienced no difference in soakage at both dressing sites.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003eTable 5. \u0026nbsp; Gender based comparison of soakage of both dressing areas.\u003c/div\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.604068857589983%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.169014084507044%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite A\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.604068857589983%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite B\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.62284820031299%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.604068857589983%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.302034428794991%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=60\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.710485133020343%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLess soakage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.89358372456964%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=60\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.86697965571205%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLess soakage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=48\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.62284820031299%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u003c/strong\u003e0.0001\u003csup\u003e\u0026beta;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.69230769230769%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Male (Total=98sites)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.346153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.076923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.615384615384615%\" valign=\"top\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.26923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e48 (98.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.69230769230769%\" valign=\"top\"\u003e\n \u003cp\u003eFemale (Total=22 sites)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.346153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.076923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.615384615384615%\" valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.26923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003eSite-A (Conventional dressing), Site-B (heparin spray dressing).\u003c/p\u003e\n \u003cp\u003e\u003csup\u003e\u0026beta;\u0026nbsp;\u003c/sup\u003eFisher\u0026rsquo;s exact test applied\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cstrong\u003eComparison of gender group with change in itching at both dressing areas of donor skin graft\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe gender-based comparison had done with reduction in itching at dressings areas among the two donor sites of skin graft. Similar to the soakage of the dressing groups, a significant relationship was present with a p-value (\u0026lt;\u0026thinsp;0.05). Remarkable reduction in itching at 48 (98.0%) sites of heparin spray dressing (site-B) was reported in male donor skin graft. However, all females had experienced no difference in itching at both dressing sites (Table.6).\u003c/p\u003e\n \u003cp\u003eTable 6\u003cstrong\u003e. \u0026nbsp;Comparison of gender and change in itching of both dressing areas\u003c/strong\u003e\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.666151468315302%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.820710973724886%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite A\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.57496136012365%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite B\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.938176197836167%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.666151468315302%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.746522411128284%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=60%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.0741885625966%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLess itching\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=0(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.891808346213292%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=60%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.683153013910356%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLess itching\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=48(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.938176197836167%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u003c/strong\u003e0.0001\u003csup\u003e\u0026beta;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.55598455598456%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Male (Total=98sites)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.671814671814673%\" valign=\"top\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.077220077220076%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.355212355212355%\" valign=\"top\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33976833976834%\" valign=\"top\"\u003e\n \u003cp\u003e48 (98.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.55598455598456%\" valign=\"top\"\u003e\n \u003cp\u003eFemale (Total=22 sites)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.671814671814673%\" valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.077220077220076%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.355212355212355%\" valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33976833976834%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003eSite-A (Conventional dressing), Site-B (heparin spray dressing).\u003c/p\u003e\n \u003cp\u003e\u003csup\u003e\u0026beta;\u0026nbsp;\u003c/sup\u003eFisher\u0026rsquo;s exact test applied\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cstrong\u003eComparison of the dressing types and reduction of wound size.\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe comparison had done between two types of dressing and wound size reduction. In a 1week follow-up, no absolute variation was reported in the early two days among both dressing groups shown in figure no 4. Later within 4days, 40% of participants had shown a reduction in wound size at size-B (heparin spray dressing). Moreover, 98.3% of the participants had shown no reduction of wound size with conventional dressing at the donor skin graft area. However, only 20% of the participant showed no improvement in wound size with heparin spray dressing. Hence, the Pearson chi-square test had shown a significant relationship between types of dressing and changes in wound size as shown in (Table no. 7).\u003c/p\u003e\n \u003cp\u003eTable 7 Comparison of the two dressing types and reduction of wound size\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.69565217391305%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.78260869565217%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTherapy groups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.52173913043478%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.69565217391305%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWound size\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.869565217391305%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eConventional\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91304347826087%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHeparin\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.52173913043478%\" rowspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.0001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.137855579868706%\" valign=\"top\"\u003e\n \u003cp\u003eDay 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.291028446389497%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.571115973741794%\" valign=\"top\"\u003e\n \u003cp\u003e12(20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.137855579868706%\" valign=\"top\"\u003e\n \u003cp\u003eDay 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.291028446389497%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.571115973741794%\" valign=\"top\"\u003e\n \u003cp\u003e24(40)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.137855579868706%\" valign=\"top\"\u003e\n \u003cp\u003eDay 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.291028446389497%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.571115973741794%\" valign=\"top\"\u003e\n \u003cp\u003e12(20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.137855579868706%\" valign=\"top\"\u003e\n \u003cp\u003eDay 7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.291028446389497%\" valign=\"top\"\u003e\n \u003cp\u003e1(1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.571115973741794%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.137855579868706%\" valign=\"top\"\u003e\n \u003cp\u003eNo improvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.291028446389497%\" valign=\"top\"\u003e\n \u003cp\u003e59(98.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.571115973741794%\" valign=\"top\"\u003e\n \u003cp\u003e12(20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e*significant p-value \u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cstrong\u003eComparison of types of the dressing groups and reduction of edema.\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eEdema reduction at both conventional and heparin dressing areas was recorded during 7days follow-up, as shown in figure-5. In the early days of follow-up, a dramatic decrease in edema was recorded at the heparin dressing area of the donor skin graft. However, only 3.3% of participants had reported a decrease in edema with conventional dressing on day7. After the specific follow-up, 96.7% of participants had reported no change in edema with conventional therapy. Although, 18.3% of participants did not show improvement in edema with heparin dressing. This relationship between dressing types and reduction in edema was significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), as shown in (Table \u003cspan class=\"InternalRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eTable 8 Comparison of types of dressing with reduction of edema\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.69565217391305%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.78260869565217%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTypes of dressing\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.52173913043478%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.69565217391305%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eReduction of edema\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.869565217391305%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eConventional\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.91304347826087%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHeparin\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.52173913043478%\" rowspan=\"7\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.0001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.137855579868706%\" valign=\"top\"\u003e\n \u003cp\u003eDay 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.291028446389497%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.571115973741794%\" valign=\"top\"\u003e\n \u003cp\u003e1(1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.137855579868706%\" valign=\"top\"\u003e\n \u003cp\u003eDay 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.291028446389497%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.571115973741794%\" valign=\"top\"\u003e\n \u003cp\u003e12(20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.137855579868706%\" valign=\"top\"\u003e\n \u003cp\u003eDay 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.291028446389497%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.571115973741794%\" valign=\"top\"\u003e\n \u003cp\u003e24(40)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.137855579868706%\" valign=\"top\"\u003e\n \u003cp\u003eDay 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.291028446389497%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.571115973741794%\" valign=\"top\"\u003e\n \u003cp\u003e12(20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.137855579868706%\" valign=\"top\"\u003e\n \u003cp\u003eDay 7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.291028446389497%\" valign=\"top\"\u003e\n \u003cp\u003e2(3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.571115973741794%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.137855579868706%\" valign=\"top\"\u003e\n \u003cp\u003eNo improvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.291028446389497%\" valign=\"top\"\u003e\n \u003cp\u003e58(96.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.571115973741794%\" valign=\"top\"\u003e\n \u003cp\u003e11(18.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e*significant p-value \u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eSome cases with pictures are presented below showing initial presentation at Day 1, Heparin spray and final day picture. Figure \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan class=\"InternalRef\"\u003e14\u003c/span\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003cbr\u003e\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe clinical trial supports the hypothesis that Heparin has an effective role in the treatment of burns to reduce pain and faster wound healing process. However, previous literature has already explained the physiology of heparin but still, scientists are experimenting with its usage in a variety of treatment application methods for the benefit of humanity (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). The current randomized control trial was a \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003esingle-blind study\u003c/span\u003e in which conventional and Heparin group\u0026rsquo;s allocation was done on the same participant to control bias. Overall 60 patients were recruited for the study, the majority of them were middle-aged adults with average an age of 35.30\u0026thinsp;\u0026plusmn;\u0026thinsp;8.87. The male gender is more likely to be dominated with the frequency of 82% as compared to the female.\u003c/p\u003e \u003cp\u003eAs heparin exhibits, multi-functional properties such as anti-inflammation, anti-thrombosis, enhanced blood circulation in ischemic parts, pain reduction, revascularization, the process of healing makes faster and decrease in wound size, etc. Likewise, It also increases the blood circulation at the site of the burn, and studies had demonstrated well the effectiveness of heparin in burns management(\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e). Pain is the dominant variable in terms of burns which inhibits the mobility of patients and ought to extend the period of hospital stay (\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e). According to our study pain status was evaluated by visual analog scale (VAS) during the seven days of the clinical trial period. At present, we found that patients treated with heparin spray (40%) complaint a little bit of pain in contrast to those who received conventional treatment (40%) who reported more pain (p-value\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, Venakatachalapathy T.S. et.al. reported severity of pain with the requirement of analgesic supplements, and apparently, there was a dramatic decrease in analgesic supplement demand in the heparin group in contrast, to the control group (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e) consequently, this would be beneficial in terms of cost-effectiveness along with the reduction of medication requirement. Similarly, Chellappa Vijayakumar claimed the significance of heparin in pain relief as compared to those who were managed by conventional therapy groups (\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMoreover, In connection with significant pain reduction, few studies also reported that heparin makes re-epithelialization, preventing the formation of tissue hypertrophy, scars, and contractures establishment (\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e). On the other hand along with countable benefits, Teles et.al had reported that heparin should be applicable cautiously in the management of second-degree facial and neck burns but there is controversy regarding its beneficial effects (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOne of the major findings of healing is less soakage in dressing. It comprises shielding the inner area of the wound to stave off the pathogenic environment; this might be served only when dressing keeps dry persistently. To prolong the dryness there are several dressing types have been designed. Apparently in our study evidence of significant association was based on gender and soakage of both heparin and conventional dressing. 100% male patients reported less soakage where heparin spray dressing was applied in contrast to females (p-value\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Heparin\u0026rsquo;s anti-inflammatory effects were reported in some researches, Apart from its anticoagulant properties. Heparin possesses immunomodulatory characteristics and mechanisms of anti-inflammatory actions(\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e). Tissue injury caused the formation of liquid exudate that plays an important role specifically associated chronic wounds(\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e) In connection with our research Srikanth Reddy Challaoalli et al, explained the positive effects of topical heparin as compared to the nebulized heparin in burn patients regarding pain management, dressings of the wound, scar formation and wound infection rate, additionally, there was less soakage in dressing. The findings from this research resemble our study results(\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e). However, Rakesh Rai et al, reported in contrast to the heparin, collagen dressing was significantly more helpful in the wound healing process and required less time. It was found to be effective in decreasing pain associated with burn injuries. According to their findings, the additional benefit of collagen dressing was a short hospital stay (\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMoreover, this study has shown a significant association between gender and change in itching of both dressing areas treated with heparin and conventional. 48 patients out of total experienced less itching after heparin spray dressing while the decreased number of female patients did not experience any reduction in itching at both sides of dressing (p-value\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Dry skin is one of the explanations that exacerbate itching and may increase the probability of scar formation. Although in burned patients fibrotic hypertrophic scar is likely to form in the process of wound healing. It represents as hoisted, red, intransigent, and possess more capability to cause significant functional and cosmetic issues. Regarding the complaint of itching in burns patients, Marcos Guilherme Praxedes Barretto reported the significant effect of topical heparin in pain management and itching (\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e). A similar study conducted by Young Hee et.al supported our findings in respect to the formation of post-burn hypertrophic scars caused severe itching and pain. Besides this pain, this scar formation is the process of healing, however, in this regard heparin administration was found effective in reducing the itching and pain (\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHypertrophic scar formation appears to involve a wide range of subsequent processes including impaired haemostasis, excessive inflammation, and protracted re-epithelialization, overabundant production of extracellular matrix, formation of new capillaries, remodeling of extracellular matrix, and diminished necroptosis. Ahmed Muhammad Salah EI-Din EI-Badawi et al evaluated in their study that there was a significantly remarkable reduction in tissue scarring with shorter healing time at the heparin group area in contrast to the control group area. However, symptoms of pain, itching, and infection at the heparin group area were also less but the results were insignificant (\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSome more studies evidenced that burn wounds exhibit the properties of the long-term inflammation process and neutrophil stagnancy. The plausibility of wound healing process inhibition is due to the destruction of extracellular matrix and growth factors, this affected by the secretory products of neutrophils (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e). Zayas G.J. et al said that heparin was more effective in altering morbidity, mortality, and decreasing sepsis in severely burn children. It increased the survival rate from 11\u0026ndash;60% in 1999 when compared to 1998 in which burns patients were treated without heparin. They claimed that whether heparin was applied topically or infused intravascular, patients experienced relief in pain, reduction in edema, decrease in burn size, and improvement in blood circulation to the ischemic tissues, as this study found with the help of a few procedures and better cosmetic results(\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurthermore, in the current study, it was well-identified that the wound size reduction was fairly dependent on the type of dressing. On the 4th day, the wound size had been reduced 40% in patients who received heparin spray while 98.3% of patients did not experience any sort of reduction in wound size with conventional dressing (p-value\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In favor of the heparin used in the healing process Ravikumar T et al, reported the favorable anti-inflammatory effect of heparin that prompted healing process at the wound site and frequently relief pain (\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e) In addition to the above findings LMWH proposed various beneficial effects in the progression of wound healing (\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e) Indeed use of heparin in faster wound healing and tissue repair in burns patients is a promising solution (\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAn evidence-based report of Peplow and Wang et.al reported the characteristics of atrocious wounds with prolonged inflammatory processes and deposition of substantial numbers of neutrophils. Heparin and its attributed molecules are associated with the inhibitory action of secretory products through electrostatic interaction (\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e, \u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn the current study with 7days of follow-up, it was observed that there was a reduction in edema on the 4th day in 40% of patients treated with heparin spray dressing in contrast to their other counterparts. However, a minimal decrease in edema was observed in only 3.3% of patients. This dramatic change in the reduction of oedematous fluid and redness is the beneficial characteristic of heparin. Michael J. Saliba. Jr et.al reported large doses of heparin in the treatment of severe burns resulted in reduced edema, required less pain medication, inhibit the progression of infection and wound size and additionally induced blood flow to the burned tissues and initiated angiogenesis at affected area (\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e). However, in the study of Joakim Johansson a discrepancy regarding the effects of neutrophil derived heparin binding protein that increased vascular permeability in burn patients. On the other hand, it is the crucial marker that was clinically involved in reducing the frequency of infection and edema in burns patients (\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e). Furthermore, there is a controversy about the effectiveness of heparin reported by Pobert H. Demling, M.D et.al according to them therapeutically, heparin was ineffectual in reducing edema and it has no major effects to escalate the process of absorption (\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSimilar to our study results, this study evaluated the efficiency of heparin for the therapeutic purpose of facial burn. They reported significant improvement in blood circulation, ameliorating pain, subside inflammation, rejuvenation of ischemic tissues, limiting scarring, and enhancing collagen. Similar to our study, this research also found substantial declination in pain and edema following tropical use of heparin (\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough wound shapes can vary, it is not known if wound form affects the dynamics of wound healing (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Thus, it is in line with clinical practice to use a straightforward wound volume measurement (length x breadth x depth). Additionally, the raw volume measurements of various wounds are not compared since volume is utilised to compute healing rate in terms of percent healed. However, it is possible to compare patient groups by averaging the percent healed (decrease from baseline) among all patients. As a facility, one objective may be to think about wound care procedures that might promote quicker healing.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis study showed that in comparison to conventional dressing the use of topical heparin significantly reduces pain, edema, and promotes healing.\u003c/p\u003e \u003cp\u003eAs dressing with topical heparin can be done easily, patients can be advised to get their wounds dressing at home providing psychological comfort to patient and family as well. This can also be beneficial for early rehabilitation as well.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCHK \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Civil Hospital Karachi\u003c/p\u003e\n\u003cp\u003eDSW \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Donor Site Wound \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFGF \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Fibroblast growth factor\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGAG \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Glycosaminoglycan\u003c/p\u003e\n\u003cp\u003eHS/Hp \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Heparan sulfate/Heparin\u003c/p\u003e\n\u003cp\u003eHA \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Hyaluronic acid\u003c/p\u003e\n\u003cp\u003eHb-EGF \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Heparin binding Growth Factors\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eI.U \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;International Unit\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eKS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Keratin sulfate\u003c/p\u003e\n\u003cp\u003eNLFU \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Non-contact Low Frequency Ultrasound\u003c/p\u003e\n\u003cp\u003eSNOSE \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Sequentially Numbered, Opaque, Sealed Envelopes SPSS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Statistical Package for Social Sciences\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSTSG \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Split Thickness Skin Graft\u003c/p\u003e\n\u003cp\u003eTOPOX \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Topical Oxygen Therapy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eVAS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Visual Analogue Scale\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was approved by Institutional Review Board of Dow University of Health Sciences (IRB-1837/DUHS/Approval/2020/162).\u0026nbsp;The trial was registered at Clinical Trials.gov (ID: NCT04613336). The study protocol, potential benefits and discomforts of the study were explained in detail to the potential study participants before obtaining informed written consent to participate in the study. Special permission was obtained to take photographs of the wound which were anonymized and coded. Physical data (proformas) was stored in a locked facility while digital data (including photographs) was stored in a separate desktop computer not connected to internet, in an encrypted folder.\u0026nbsp;Informed consent was obtained from the participants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAccordance: We confirmed that all experiments in this study were performed in accordance with the relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003eInformed consent: \u0026nbsp;All the participants are informed about the study, and they have all signed the informed consent form.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe consent for publication was taken from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that supports findings of this study are available from the corresponding author, FA upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there is potentially no conflict of interest related to the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was self-funded. This study was not funded by any agency in public, commercial or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr.Faraz Adil (FA),\u003c/strong\u003e the principal investigator, made a substantial contribution to the conception, design of the work, sample processing, data analysis and interpretation and led the writing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Mahak Ali Memon\u003c/strong\u003e \u003cstrong\u003e(MAM),\u003c/strong\u003e contributed to the sample collection, data analysis, processing and drafting\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003edesigned figures and tables.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Faisal Akhlaq Ali Khan\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;(FAAK),\u0026nbsp;\u003c/strong\u003esupervised and proofread the project.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Saad uddin Siddiqui (SS),\u0026nbsp;\u003c/strong\u003eaided in data analysis,\u0026nbsp;revised the manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Asadullah Awan\u003c/strong\u003e (AA), edited the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Farhan Zahid Piprani\u003c/strong\u003e (FZP), conceived the idea of study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the participants who took part in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBarber S. A clinically relevant wound assessment method to monitor healing progression. Ostomy Wound Management. 2008;54(3):42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrandner J, Jensen J. The skin: an indispensable barrier. Exp Dermatol. 2008;17:1063\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElias PM. Epidermal lipids, barrier function, and desquamation. Journal of Investigative Dermatology. 1983;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElias PM. Stratum corneum architecture, metabolic activity and interactivity with subjacent cell layers. Experimental dermatology. 1996;5(4):191\u0026ndash;201.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuogienė I, Kievišas M, Varkalys K, Braziulis K, Rimdeika R. Split-thickness skin grafting using grafts of different thickness. 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Journal of wound care. 2017;26(6):281\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalemark KP, Lars. How to dress donor sites of split thickness skin grafts: a prospective, randomised study of four dressings. Scandinavian journal of plastic and reconstructive surgery and hand surgery. 2000;34(1):55\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEskes A, Gerbens L, Ubbink D, Vermeulen H. Current treatment policies of donor site wounds after split-skin grafting: a national survey. Ned Tijdschr Heelkd. 2011;20(2):66\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHermans MH. Results of an internet survey on the treatment of partial thickness burns, full thickness burns, and donor sites. Journal of burn care \u0026amp; research. 2007;28(6):835\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLyall PW, Sinclair SW. Australasian survey of split skin graft donor site dressings. Australian and New Zealand Journal of Surgery. 2000;70(2):114\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVoineskos SH, Ayeni OA, McKnight L, Thoma A. Systematic review of skin graft donor-site dressings. Plastic and reconstructive surgery. 2009;124(1):298\u0026ndash;306.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMidwood KS, Orend G. The role of tenascin-C in tissue injury and tumorigenesis. Journal of cell communication and signaling. 2009;3(3\u0026ndash;4):287\u0026ndash;310.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKlingberg F, Hinz B, White ES. The myofibroblast matrix: implications for tissue repair and fibrosis. The Journal of pathology. 2013;229(2):298\u0026ndash;309.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchultz GS, Wysocki A. Interactions between extracellular matrix and growth factors in wound healing. Wound repair and regeneration. 2009;17(2):153\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlczyk P, Komosińska-Vassev K, Winsz-Szczotka K, Koźma EM, Wisowski G, Stojko J, et al. Propolis modulates vitronectin, laminin, and heparan sulfate/heparin expression during experimental burn healing. Journal of Zhejiang University Science B. 2012;13(11):932\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTong M, Zbinden MM, Hekking IJ, Vermeij M, Barritault D, Van Neck JW. RGTA OTR 4120, a heparan sulfate proteoglycan mimetic, increases wound breaking strength and vasodilatory capability in healing rat full-thickness excisional wounds. Wound repair and regeneration. 2008;16(2):294\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNelson SM, Greer IA. The potential role of heparin in assisted conception. 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Thrombosis and Haemostasis. 2005;94(07):4\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWerdin F, Tenenhaus M, Becker M, Rennekampff H-O. Healing time correlates with the quality of scaring: results from a prospective randomized control donor site trial. Dermatologic Surgery. 2018;44(4):521\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrather JL, Tummel EK, Patel AB, Smith DJ, Gould LJ. Prospective Randomized Controlled Trial Comparing the Effects of Noncontact Low-Frequency Ultrasound with Standard Care in Healing Split-Thickness Donor Sites. Journal of the American College of Surgeons. 2015;221(2):309\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVijayakumar C, Prabhu R, Velan MS, Krishnan VM, Kalaiarasi R. Role of Heparin Irrigation in the Management of Superficial Burns with Special Reference to Pain Relief and Wound Healing: A Pilot Study. Cureus. 2018;10(8).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKlein-Soyer C, Beretz A, Cazenave J-P, Driot F, Maffrand J-P. Behavior of confluent endothelial cells after irradiation. Modulation of wound repair by heparin and acidic fibroblast growth factor. Biology of the Cell. 1990;68(1\u0026ndash;3):231\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eManzoor S, Khan FA, Muhammad S, Qayyum R, Muhammad I, Nazir U, et al. Comparative study of conventional and topical heparin treatment in second degree burn patients for burn analgesia and wound healing. Burns. 2019;45(2):379\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaliba Jr MJJB. Heparin in the treatment of burns: a review. 2001;27(4):349\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmith GS, Barss PJEr. 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Heparin and related drugs: beyond anticoagulant activity. 2013;2013.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeplow PVJT, Haemostasis. Glycosaminoglycan: a candidate to stimulate the repair of chronic wounds. 2005;94(07):4\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang J, Zheng H, Qiu X, Kulkarni A, Fink LM, Hauer-Jensen MJT, et al. Modulation of the intestinal response to ionizing radiation by anticoagulant and non-anticoagulant heparins. 2005;94(11):1054\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaliba MJ, Dempsey WC, Kruggel JLJJ. Large burns in humans: Treatment with heparin. 1973;225(3):261\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohansson J, Lindbom L, Herwald H, Sj\u0026ouml;berg FJB. Neutrophil-derived heparin binding protein\u0026mdash;A mediator of increased vascular permeability after burns? 2009;35(8):1185\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDemling RH, Mazess R, Hanson J, Wolberg WJJoSR. Effect of heparin on edema after second-and third-degree burns. 1979;26(1):27\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHamza FA, Salim AA-E, Rizk HNJA-AIMJ. Evaluation of the Effect of Topical Heparin on the Treatment of Facial Burn. 2020;1(1):198\u0026ndash;202.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Heparin, Wounds, Donor site wound, Dressings","lastPublishedDoi":"10.21203/rs.3.rs-4535856/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4535856/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAll wounds that cannot be closed primarily needs skin coverage earliest to prevent form infections. Skin graft provides earliest and easiest wound coverage, but produces another wound, i.e. donor site wound. This study is conducted to see healing time efficacy of topical heparin spray versus conventional dressing in healing donor site wounds.\u003c/p\u003e\u003ch2\u003eMETHODOLOGY\u003c/h2\u003e \u003cp\u003eThe study was designed as a single center, prospective, randomized control trial study. It was conducted in the Department of Plastic and Reconstructive Surgery at Civil Hospital Karachi. The study was carried out for 10 months of the period from Sep 2020 to July 2021. The sample was calculated by using OpenEpi version 3.01.The minimum sample size was calculated to be 8 at 95% confidence level and 80% power, though the study included 60 patients who underwent split thickness skin grafting for healthy granulating wounds. From the next day of surgery heparin dressing and conventional dressings groups were made and dressing was done daily till seventh postoperative day. Data in form of questionnaire and photographic assessment was recorded filled at every change of dressing. This study was a self-controlled trial, therefore every trial participant served as his/her own control. Data was analyzed by using Statistical Package for Social Sciences (SPSS version 24).\u003c/p\u003e\u003ch2\u003eRESULT\u003c/h2\u003e \u003cp\u003eThe results of the analysis showed the mean age of the participants was (35.30\u0026thinsp;\u0026plusmn;\u0026thinsp;8.87). Male gender predominated with a frequency of 82% while females were 18%. A decrease in soakage of dressing was recorded in 48 (98.0%) male participants at interventional half; however, all females experienced no difference at both dressing sites. Similarly 48 (98.0%) male participants a reduction in itching at intervention site and all females had experienced no difference in itching at both dressing sites. In regard to wound size, 40% of participants showed a reduction in wound size and only 20% showed no improvement at interventional half. During 7days, 81.67% of participants showed improvement in edema at intervention half and 96.7% of participants reported no change in edema with conventional therapy. None of the participants scored worst pain at the intervention area.\u003c/p\u003e\u003ch2\u003eCONCLUSION\u003c/h2\u003e \u003cp\u003eThe study showed heparin irrigation result in better wound healing and significantly reduces pain, edema, enhances faster healing and reduces soakage of dressings.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e \u003cp\u003e The study was approved by Institutional Review Board of Dow University of Health Sciences and was registered at Clinical Trials.gov (ID: NCT04613336).\u003c/p\u003e","manuscriptTitle":"Efficacy of Topical Heparin Spray on Donor Site Wound Healing Time Compared to Conventional Dressing Among Patients Undergoing Split Thickness Skin Grafting","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-17 00:57:36","doi":"10.21203/rs.3.rs-4535856/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-14T05:54:08+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-13T13:40:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"246040025777450573737412610324555211339","date":"2024-10-26T11:28:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"163282128117754727573431252684998587828","date":"2024-08-30T05:38:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-23T02:54:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"252455821612162006661074256083286746758","date":"2024-07-23T02:46:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"102209710190741473293905336804084461516","date":"2024-07-23T01:04:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-22T20:29:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-22T20:24:32+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-07-22T18:52:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-17T07:29:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-06-05T18:40:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a9a7f717-7ecd-4c4a-a7f3-b74e5b72079f","owner":[],"postedDate":"August 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":35919680,"name":"Biological sciences/Drug discovery"},{"id":35919681,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-08-04T16:46:54+00:00","versionOfRecord":{"articleIdentity":"rs-4535856","link":"https://doi.org/10.1038/s41598-025-95437-5","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-07-30 16:38:15","publishedOnDateReadable":"July 30th, 2025"},"versionCreatedAt":"2024-08-17 00:57:36","video":"","vorDoi":"10.1038/s41598-025-95437-5","vorDoiUrl":"https://doi.org/10.1038/s41598-025-95437-5","workflowStages":[]},"version":"v1","identity":"rs-4535856","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4535856","identity":"rs-4535856","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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