A Preliminary Study on Wound Healing and Scar Reduction Using Platelet-rich Fibrin Matrix

A Preliminary Study on Wound Healing and Scar Reduction Using Platelet-rich Fibrin Matrix | 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 A Preliminary Study on Wound Healing and Scar Reduction Using Platelet-rich Fibrin Matrix Samuel Kwadwo Peprah Bempah, Chrissie Stansie Abaidoo, Samuel Bimpong, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7245060/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract Wound healing is a natural response to tissue injury. Many factors come into play during the process leading to the body making compromises to ensure healing which leads to the formation of scars. Over the years, several approaches have been made to aid in the healing of wounds. Platelet-rich plasma is believed to have various important capabilities such as being a source of growth and clotting factors as well as possessing both chemotactic and mitogenic properties which would aid in wound closure and healing as well as reduce the formation of scars as much as possible. This experimental animal study aimed to increase the rate of wound healing by using platelet-rich fibrin matrix, a derivative of platelet-rich plasma to improve healing rates and quality with particular focus on reepithelialisation and scar tissue reduction. Platelet-rich fibrin matrix treated wounds proved superior in time of closure, rate of closure, rate of reepithelialisation and scar resolution. The test group recorded 73.18% reduction in wound diameter for the first week and 100% closure by day 14. The control group recorded 65.32% reduction in wound diameter by the end of the first week, 92.09% at the end of the second week and 100% closure by day 18. Wound closure was accompanied by reepithelialisation. The test group showed higher rates of scar resolution with statistically significant differences compared to what was observed in the control group. This can be attributed to the abundance of growth factors and other important chemicals provided by the platelets. Based on the results recorded by the test group, it could be speculated that that of platelet-rich fibrin matrix is effective. This study provides preliminary baseline data for wound healing and could be useful in the treatment and management of wounds in the clinical setting. Health sciences/Diseases Health sciences/Medical research Wound healing Platelet-rich fibrin matrix Reepithelialisation Scar reduction 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 Figure 15 INTRODUCTION 1.1 Background Wound healing and repair happen to be one of the most complex biological processes that occur during human life. After an injury, several biological pathways come into play with many overlapping mechanisms, including haemostasis, inflammation, proliferation, and tissue remodelling (Eming et al., 2007 ; Gurtner et al., 2008 ). As a natural process, wound healing is accompanied by scar formation, which is a mass of non-functioning fibrotic tissue. It is formed as a means of preventing infection of the wounded tissue (Bayat et al., 2003 ). The formation of scars in mammals proves inevitable, and there is considerable evidence to suggest that inflammation is the precursor for scar formation. Normal scar tissue restores the skin barrier. It however, is inferior in aspects such as strength, structure, function and aesthetics (Baumann et al., 2021 ). To prevent infection, rapid inflammatory responses and scar tissue form. It could be said that scars are a price to pay if wounds are to be covered quickly to prevent infections (Eming et al., 2007 ). Over the years, several approaches have been made to aid in the healing of wounds. Several topical treatments, including the application of imiquimod, mitomycin C and plant extracts such as onion extract, green tea, Aloe vera , vitamin D and E, to heal wounds (Sidgwick et al., 2015 ). Other natural agents, such as whey proteins (Belokrylov et al., 1992 ), (honey) bee venom and propolis have also been used in some studies (De Vecchi and Drago, 2007 ; Fitzmaurice et al., 2011 ). Another approach which has contributed to wound healing is the use of internally generated factors, with the chief being platelets (Garraud et al., 2017 ; Garraud and Cognasse, 2015 ). In such studies, platelet-rich plasma (PRP) was used as a topical treatment to facilitate the healing of wounds. At least seven locally acting growth factors from alpha granules are present in platelets. Vascular endothelial growth factor, epidermal growth factor, two transforming growth factor-βs, and three platelet-derived growth factors (Greer et al., 2013 ). These growth factors are beneficial in chronic wounds like diabetic ulcers, which typically lack cytokines and growth factors, and platelet treatment effectively fills this gap (Martí-Carvajal et al., 2015 ). This compensates for diminished cellular activity in wounds that are challenging to heal. Therefore, as governed by cytokines and growth factors, diabetic wounds that prove to be particularly problematic have increased cell proliferation, angiogenesis, extracellular matrix synthesis, and other inflammatory processes (Middleton, 2011 ). Numerous clinical advantages and different platelet therapies have been created over time. Different production methods, technicalities, and other issues are still up for debate (do Amaral et al., 2015 ). Several studies have been conducted specifically on diabetic wounds in comparison to other chronic wounds. More and more often, platelet-rich plasma is utilised to speed up the healing of wounds. The platelet-rich fibrin matrix (PRFM) is one of the most recent advancements in the use of platelet-rich plasma. This has a denser and more malleable structure than usual. The fibrin matrix retains the platelets and aids in ensuring the highest possible platelet number for use. Platelet-rich fibrin matrix (PRFM), which is one of the newest generations of platelet concentrates, is prepared simply without the need for biochemicals like bovine thrombin. In PRP, fibrin is slowly polymerised to form PRFM, which has a structure similar to natural fibrin (Choukroun et al., 2006 ). To increase cell migration, cell proliferation, and cyclic peptide creation, this particular structure is crucial. All of the platelets in PRP will be deposited between the PRFM fibrin fibres as a result of this polymerisation process. By that reasoning, levels of platelets (and therefore growth factors) in PRFM should be comparable to those in PRP. An increase in levels of platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor beta (TGF-β) have been observed on the first day following the use of PRFM in particular media, then a gradual decrease on the next day, according to laboratory studies (Lucarelli et al., 2010 ; Sclafani, 2011 ). Additionally, PRFM exhibits fibrin features, including a denser and more flexible macroscopic structure that resembles the body's response to injury and a more natural platelet distribution (Gole et al., 2019 ; Kobayashi et al., 2016 ). Theoretically, PRFM is better for use in wound healing because of these features. By evaluating a modified method proposed by Reksodiputro et al. ( 2021 ) to produce PRFM to be used as dressings for wounds to aid in their closure and healing, as well as reduce the formation of scars as much as possible, this study seeks to address the issues raised above and strengthen the weaknesses of the existing invention. MATERIALS AND METHODS 3.1 Study Design and Location The study was carried out at the Anatomy Department, SMD, KNUST. Ethical approval was obtained from the Committee on Human Research, Publications and Ethics (CHRPE) (CHRPE/ RC/ 205/ 17). The study was conducted in accordance with the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines (du Sert et al., 2020 ; NC3Rs, 2022 ). Ten mature New Zealand rabbits (5 males and 5 females) were used in the study. After a week of observation and adaptation, the healthy and fit New Zealand rabbits were shaved and prepared for incision. The fleshy backs of the rabbits served as the site of incision. New Zealand rabbits share certain physiological traits with humans, especially in skin structure and wound healing processes. This makes them suitable for researching skin treatments, and they generally heal faster than humans, allowing researchers to observe treatment effects over a shorter period. This is particularly useful for studying wound healing and repair mechanisms. 3.2 Wound Creation and Treatment Before surgery, the animals were anaesthetised intramuscularly and sedated during the procedure using Pentone (50 mg/ml). Each animal was weighed, and the anaesthesia was administered at a rate of 1 ml per kilogram. The hair on the back of the rabbits was shaved, and the skin was disinfected. Two different rows of five 15 mm circular full-thickness wounds not extending past the panniculus carnosus muscle were created on the backs of the rabbits with a scalpel. Platelet-rich fibrin matrix was used as the dressing for the various wounds of one row (Lacci and Dardik, 2010 ). The control row was treated with Drez solution and ointment (Iodinated-Povidone BP 5.0% w/v, Metronidazole BP 1.0% w/v) to serve as a control (Fig. 1 ). The wounds were all sealed with Vaseline® triple refined petroleum jelly to maintain moisture. Occlusive dressing was used to cover the dressings, and they were secured with surgical tapes to prevent the animals from tampering with the dressed wounds. 3.3 Platelet-rich Fibrin Matrix Preparation 20 ml of blood was collected from each animal from the Central Auricular Artery or the Marginal Ear Vein into a citrated dextrose tube (Fig. 2 ). The tubes were then centrifuged (Thermo Scientific Heraeus Biofuge Primo Centrifuge (Fig. 3 )) at 3000 RPM (1207 × g) for six minutes at room temperature (Fig. 4 ) (O’Connell et al., 2008 ). The supernatant plasma was transferred from the first tube into a test tube containing calcium chloride (0.1 M) (0.2 ml per 1 ml of platelet-rich plasma). It was then placed back into the centrifuge and spun at a higher g-force 5,500 RPM (4058 × g) for 25 minutes. A circular membrane of platelet-rich fibrin matrix was formed at the bottom of the container as it was spun using radial centrifugation (Fig. 5 ). The Platelet-rich plasma fibrin matrix was then used as dressing for the test wounds (Fig. 6 ). Eighteen millilitres of blood produced 7–8mL of PRP, which in turn yielded a 35mm membrane of 0.03 cm thickness; 36mL of blood produces a 50mm membrane of 0.03 cm thickness (Reksodiputro et al., 2021 ). In order to guarantee the production of ideal PRFM, the modified method used ensured that platelet-poor plasma (PPP), a by-product in PRFM production, has a platelet content of 0/µl, representing the fact that all platelets are attached to the PRFM fibrin matrix at the bottom of the tube. 3.4 Sample Taking and Tissue Processing Tissue samples were taken from each wound to be observed under the microscope to determine the extent of damage after incision and the rate of healing at regular intervals (days 7, 14, 21, 28, 35). In this study, all assessors were blinded to the identity of the test and control wounds during the evaluation. This blinding was implemented to prevent any potential bias that could arise from prior knowledge of the treatment conditions. The histopathologic grading was conducted using standardised criteria, which were uniformly applied across all samples. This method enhances the reliability of the findings, as it ensures that any observed differences in healing are attributed solely to the treatments rather than to assessor preconceptions. The samples were fixed in 10% neutral buffered formaldehyde. The samples were then dehydrated by immersion in serial ethanol (alcohol) solutions of increasing concentration until pure, water-free alcohol was reached. The samples were subsequently cleared using xylene as a clearing agent before being infiltrated with paraffin wax. The specimens were then embedded in paraffin, sectioned and stained with eosin and haematoxylin. Light microscopy was done using Leica DM 500 and 750. (Rolls et al., 2020 ). After three to six weeks, the final observation of the healed wounds was done. The fit animals were released, while the weak animals were euthanised using sodium pentobarbital via intravenous injection, based on the rabbit's weight (100 mg/kg of body weight) (National Research Council (US) Committee on Pain and Distress in Laboratory Animals, 1992). This was followed by confirmation of death and appropriate disposal of the body according to the American Veterinary Medical Association regulatory guidelines, and discarded via deep burial (American Veterinary Medical Association, 2020 ). 3.5 Computerized Planimetry and Data Analyses Pictures of the wounds were taken digitally using a 12MP camera (Samsung Galaxy Note 9) and computerized planimetry using Adobe Photoshop 23.0.0. Data analyses was done using IBM SPSS Version 26 (SPSS® Inc, Chicago, USA). Percentage of closure for the wounds (± standard error of the mean) was determined by calculating the decrease in the wound area as measured by digital photography and computerized planimetry using Adobe Photoshop 23.0.0 normalized to the initial wound area. A descriptive analysis was made for each variable. The associations between the different qualitative variables were studied using Pearson’s chi squared test at 99% confidence interval. Statistical significance was accepted for P value ≤ 0·01. RESULTS 4.1 Wound healing progression During the first 7 days after the wound creation, both the test and control groups recorded a very rapid rate of contraction illustrated in Figure 7. From day 0 to day 8 (Figure 8) the wound diameters reduced by 60-70%. The test group wound diameters reduced by 77.24 ± 0.91% and the control by 69.28 ± 1.16% on the 11 th day. The test wounds had reduced by 96.92 ± 0.22% and the control by 87.31 ± 0.91% on the 12 th day as shown in Figure 9. By day 14, the test group showed more progress with 100% closure in all cases (Figure 10). Healing continued through the subsequent days as seen in Figure 11 for the control group till complete closure was recorded by day 18 shown in Figure 13. No records beyond day 18 were statistically significant as both the test and control groups had achieved 100% closure. The healed wounds were monitored till the 5 th week. 4.2 Efficacy of Platelet-rich fibrin matrix Parameters involving complete wound closure and time required for complete closure were measured to determine the clinical efficacy of platelet-rich fibrin matrix. 4.2.1 Complete Closure According to the Food and drug administration, a fully healed wound must demonstrate complete reepithelialisation of the wound surface without any discernible exudate, drainage, or dressing requirements (Food and Drug Administration Wound Healing Clinical Focus Group, 2001). The test group showed complete closure by day 14 (Figure 12). The control group on the other hand achieved complete closure by day 18 (Figure 13). 4.2.2 Time of Closure The test group recorded a mean of 73.18 ± 1.40% by the 8 th day. The control group on the other hand recorded a mean of 65.32 ± 0.59% (Figure 14). By day 14, the test group showed more progress with 100% closure in all cases. The control group recorded a mean of 92.09 ± 0.62% for closure. No records beyond day 18 were statistically significant as both the test and control groups had achieved 100% closure. 4.3 Histopathological changes across week 1 to week 5 By day 7, reepithelization was observed for both the test and control groups. This is shown in Figure 15 (A-D). This layer of epithelium was formed under the eschar of the wound marked W. The epithelial layer was more prominent in the test group than the control. Acute inflammation was recorded for both the test group and the control group. The epithelial layer (W) for the control group became very prominent at day 14 and begun to increase in thickness. Chronic inflammation begun to show. The test group on the other hand showed signs of chronic inflammation as granulation tissue exhibited connective tissue hyperplasia labelled as Y. The epithelial layer labelled X thickened as well. Chronic inflammation for the test group showed signs of resolution as they thinned out and adnexal skin structures like hair follicles (Z) begun to appear at day 21. The epithelial layer also begun to even out and reduce in thickness. The control group showed signs of chronic inflammation and a relatively thicker epithelial layer. The rate of connective tissue hyperplasia was not as prominent as what was seen in the test group at day 14. The number of adnexal skin structures had greatly increased for the test group and had begun to appear in the control group as well at day 28. Chronic inflammation continued to reduce in both cases. The test group recorded almost complete resolution of chronic inflammation and the population of adnexal skin structures were almost normalised at day 35. The layer of hyperplasia in the control group was also reduced although not up to that seen in the test group. Adnexal skin structures were abundant. 4.4 Reepithelialisation By day 7, the test group showed higher rates of epithelialisation with statistically significant differences compared to what was seen in the control group ( P = 0.006). At day 14, the trend continued with the test group showing higher rates of epithelialisation with statistically significant differences compared to what was seen in the control group ( P = 0.013). Days 21 to 35, however did not have the differences between the test and the control being statistically significant ( P = 0.133 and 0.035 respectively). This was because the entire wound surface had been covered between weeks 2 and 3 (Table 1 and Table 2 ). Table 1 : A Table showing Histopathologic Grading Scale to Evaluate Reepithelialisation Histopathologic Grading Scale to Evaluate Reepithelialization 1 Reepithelialisation at the edge of the wound 2 Reepithelialisation covering less than half of the wound 3 Reepithelialisation covering more than half of the wound 4 Reepithelialisation covering the entire wound, irregular thickness 5 Reepithelialisation covering the entire wound, normal thickness (Sinha and Gallagher, 2003) Table 2 : A Table showing Grades of wound reepithelialisation from 7 to 35 days (total values) (Pearson’s chi squared test) using the histopathologic evaluation scale for grading wound reepithelialisation ∗ Day Group Skin Total Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 P value 7 Test Group 10 0 0 2 1 7 0.006 Control 10 0 0 2 5 3 14 Test Group 10 0 0 0 2 8 0.013 Control 10 0 0 1 3 6 21 Test Group 10 0 0 0 1 9 0.133 Control 10 0 0 0 3 7 28 Test Group 10 0 0 0 1 9 0.035 Control 10 0 0 0 2 8 35 Test Group 10 0 0 0 0 10 b Control 10 0 0 0 1 9 PRFM: Platelet-rich fibrin matrix. ∗ Grade 1: reepithelialisation at the edge of the wound; grade 2: reepithelialisation covering less than half of the wound; grade 3: reepithelialisation covering more than half of the wound; grade 4: reepithelialisation covering the entire wound, with irregular thickness; grade 5: reepithelialisation covering the entire wound, normal thickness. b – Value could not be computed because at least one of the variables was constant. (P value - Correlation is significant at the 0.01 level) . 4.5 Scar Resolution By day 7, the test group showed higher rates of scar resolution with statistically significant differences compared to what was seen in the control group ( P = 0.000). Similar values were recorded at day 14 with the test group showing higher rates of scar resolution with statistically significant differences compared to what was seen in the control group ( P = 0.005). At day 21, 60% of the test group showed signs of scar resolution compared to 50% seen for the control group. This was also statistically significant ( P = 0.008). Days 28 to 35, however did not have the differences between the test and the control being statistically significant ( P = 0.020 and 0.133 respectively). This was because all the wounds had shown signs of recovery at this point with the only difference being the test group barely having any connective tissue hyperplasia and having more hair follicles and dermal appendages than the control group (Table 3 and Table 4 ). Table 3 : A Table showing Histopathologic Grading Scale to Evaluate scar resolution Histopathologic Grading Scale to Evaluate scar resolution 1 Acute inflammation (pyogenic membrane formation) 2 Predominance of diffuse acute inflammation (predominance of granulation tissue) 3 Predominance of chronic inflammation (fibroblasts beginning to proliferate) 4 Resolution and healing (reduction or disappearance of chronic inflammation, although occasional round cells may persist) 5 Proliferation of hair follicles and dermal appendages (Molina-Miñano et al ., 2009; Turksen, 2018) Table 4 : A Table showing the Grades of Scar Resolution from 7 to 35 days (total values) (Pearson’s chi squared test) using the histopathologic evaluation scale for grading scar resolution ∗ Day Group Skin Total Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 P value 7 Test Group 10 0 2 4 4 0 0.000 Control 10 0 2 5 3 0 14 Test Group 10 0 1 4 5 0 0.005 Control 10 0 1 6 3 0 21 Test Group 10 0 0 4 5 1 0.008 Control 10 0 0 5 5 0 28 Test Group 10 0 0 2 6 2 0.020 Control 10 0 0 5 4 1 35 Test Group 10 0 0 0 1 9 0.133 Control 10 0 0 0 3 7 PRFM: Platelet-rich fibrin matrix. ∗ Grade 1: acute inflammation (pyogenic membrane is formed); grade 2: predominance of diffuse acute inflammation (predominance of granulation tissue); grade 3: predominance of chronic inflammation (fibroblasts beginning to proliferate); grade 4: resolution and healing (reduction or disappearance of chronic inflammation); grade 5: proliferation of hair follicles and dermal appendages. (P value - Correlation is significant at the 0.01 level). DISCUSSION 5.1 Wound healing progression From Fig. 8 , a rapid rate of contraction was seen, especially during the first 7 days. This is most likely due to the cascade of events that occur during the first few hours to the first few days. The wound diameter had reduced by 60–70% which is consistent with literature (DiPietro and Burns, 2003 ). According to Clark, ( 1988 ) contraction starts after granulation tissue has been well established usually 3–5 days after injury. Strickland ( 2005 ) reported that contraction usually begins after a latency period of 2 to 3 days. By 2 to 3 weeks, wounds are usually less than 20% of the original wound area. By day 14, the test group showed more progress with 100% closure in all cases (Fig. 10 ). This was a good sign that platelet-rich fibrin matrix proved effective. Studies have shown that complete reepithelialisation before day 14 greatly reduces the risk of persistent and hypertrophic scar formation (Chen et al., 2016 ; Deitch et al., 1983 ; Holmes et al., 1983 ; Machesney et al., 1998 ). The control group recorded complete closure by day 18. This was within acceptable range for normal wound healing. In a study conducted by Svensjo et al. ( 2000 ), 0% of dry, 20% of moist, and 86% of saline-treated wounds were completely reepithelialised by day 12. Garraud et al. ( 2017 ) estimates complete wound closure to happen between the second week and the third month. Hom et al. ( 2007 ), in a study using autologous platelet gel observed complete closure between days 28 and 35. No records beyond day 18 were statistically significant as both the test and control groups had achieved 100% closure. Compared to other studies, wound healing rates for the test group were on the high side while the control group showed normal trends consistent with literature (Kordestani, 2019 ). 5.2 Efficacy of Platelet-rich fibrin matrix 5.2.1 Complete Closure The test group showed complete closure by day 14 (Fig. 12 ). The control group on the other hand achieved complete closure by day 18 (Fig. 13 ). The wounds were assessed according to a protocol by the Food and drug administration, (Food and Drug Administration Wound Healing Clinical Focus Group, 2001 ). Garraud et al. ( 2017 ) estimates complete wound closure to happen between the second week and the third month. Hom et al. ( 2007 ), in a study using autologous platelet gel, complete closure occurred between days 28 and 35. Thus the test group showing complete closure by day 14 attests to the efficacy of platelet-rich fibrin matrix. Platelets are a rich source of growth factors and have been increasingly used effectively in the treatment of chronic wounds (Bhanot and Alex, 2002 ). The alpha granules of platelets have at least seven growth factors (Greer et al., 2013 ). As such chronic and difficult to heal wounds like diabetic wounds have responded quite well to treatment with platelet-rich plasma. 5.2.2 Time of Closure The first 7 days showed the fastest rate of wound contraction. The test group recorded a mean of 73.18 ± 1.40% by the 8th day. The control group on the other hand recorded a mean of 65.32 ± 0.59% (Fig. 14 ). By day 14, the test group showed more progress with 100% closure in all cases. The control group recorded a mean of 92.09 ± 0.62% for closure. No records beyond day 18 were statistically significant as both the test and control groups had achieved 100% closure. As seen from above, the test group had better result overall. This is also consistent with literature. Huang et al. ( 2021 ) conducted a meta-analysis of 8 randomized controlled trials with a total of 539 patients. It was observed that platelet-rich plasma could improve the healing rates of burn wound and had shorter healing time. Several clinical benefits and various platelet therapies have been documented. Issues such as differing production processes, technicalities and others are still under debate (do Amaral et al., 2015 ). 5.3 Histopathological changes across week 1 to week 5 From Fig. 15 (A to L), the test group showed a much better healing profile compared to what was observed for the control group. The consistent positive results especially seen in the test group could be due to the use of PRFM. This method may allow a gradual release of growth factors which improved the wound healing process. O’Connell et al. ( 2006 ) reported that PRFM exhibited a gradual and consistent release of growth factors even up to the 7th day. Reepithelialisation was witnessed after day 7. This restoration probably contributed to the wound healing process. As stated above, the quality and speed at which healing takes place during the first 14 days is important. Reepithelialisation restores haemostatic balance and this in turn reduces the time of inflammation ensuring minimal scar formation (Chen et al., 2016 ; Deitch et al., 1983 ; Holmes et al., 1983 ; Machesney et al., 1998 ). By day 14, chronic inflammation was observed for both test and control groups. Both the epithelial lining and the underlying connective tissue showed signs of hyperplasia. The resulting scar tissue due to collagen deposition was expected to regress according to Karrer ( 2007 ). This regression was observed at day 21 for the test group while the control group merely showed signs of regression. Adnexal skin structures like hair follicles and sebaceous glands begun to appear in the test group at this stage. These may sprout from deep epithelial cells from hair shafts. The wounds created in the study were all full thickness wounds, thus those remnant epidermal cells wound be absent. There would however be contributions from adjacent healthy skin appendages evidenced by how adnexal skin structures seem to creep in from the periphery towards the centre of the scar tissue. This was consistent with a study conducted amongst burn victims by Mani et al. ( 2013 ). Day 28 saw adnexal skin structure proliferation for the control group as well. Chronic inflammation continued to regress in both cases and by day 35, the test group recorded almost complete resolution of chronic inflammation and the population of adnexal skin structures were almost normalised. The layer of hyperplasia in the control group was also reduced although not up to that observed in the test group. The result was consistent with O’Connell and Cockbill for the PRFM treated wounds and the control respectively (Cockbill, 2002 ; O’Connell et al., 2008 ). 5.4 Reepithelialisation By day 7, the test group showed higher rates of epithelialisation with statistically significant differences compared to what was observed in the control group ( P = 0.006). At day 14, the trend continued with the test group showing higher rates of epithelialisation with statistically significant differences compared with the control group ( P = 0.013). Days 21 to 35, however did not have the differences between the test and the control being statistically significant ( P = 0.133 and 0.035 respectively). This was because the entire wound surface had been covered between weeks 2 and 3. The quality and speed at which healing takes place during the first 14 days is important. Reepithelialisation restores haemostatic balance and this in turn reduces the time of inflammation ensuring minimal scar formation (Chen et al., 2016 ). The reepithelialised layer was likely to be contributed from adjacent healthy skin epithelial cells and dermal appendages 5.5 Scar Resolution By day 7, the test group showed higher rates of scar resolution with statistically significant differences compared to what was seen in the control group ( P = 0.000). Similar values were recorded at day 14 with the test group showed higher rates of scar resolution with statistically significant differences compared to what was seen in the control group ( P = 0.005). The first two weeks generally present with the infiltration of a lot of inflammatory cells. There is however considerable evidence to suggest that inflammation is an essential prerequisite for scarring (Eming et al., 2007 ). Thus, wounds with relatively shorter inflammation time generally scar less compared to others that experience longer inflammatory periods. It is therefore not surprising that the test group recorded better scar resolution in the first two weeks. This can be attributed to the abundance of growth factors and other necessary chemicals provided by the platelets. The resulting scar tissue due to collagen deposition was expected to regress according to Karrer ( 2007 ). The trend continued over the subsequent weeks and at day 21, 60% of the test group showed signs of scar resolution compared to 50% seen for the control group. This was also statistically significant ( P = 0.008). Days 28 to 35, however did not have the differences between the test and the control being statistically significant ( P = 0.020 and 0.133 respectively). This was because all the wounds had shown signs of recovery at this point with the only difference being the test group barely having any connective tissue hyperplasia and having more hair follicles and dermal appendages than the control group. CONCLUSION Platelet-rich fibrin matrix treated wounds had better results for all parameters checked in this study. It proved superior in time of closure, rate of closure, rate of reepithelialisation and scar resolution. The test group recorded 73.18% reduction in wound diameter for the first week and 100% closure by day 14. The control group recorded 65.32% reduction in wound diameter by the end of the first week, 92.09% at the end of the second week and 100% closure by day 18. Wound closure was accompanied by reepithelialisation. The test group showed higher rates of scar resolution with statistically significant differences compared to what was observed in the control group. This can be attributed to the abundance of growth factors and other necessary chemicals provided by the platelets. Based on the results recorded by the test group, it could be speculated that platelet-rich fibrin matrix may be effective for wound treatment. The significance of this study is the provision of preliminary baseline data for wound healing and will prove useful in the treatment and management of wounds in the clinical setting. Declarations Data Availability Statement Data used to support the findings of this study would be made available by the corresponding author (Samuel Kwadwo Peprah Bempah) upon request. Conflicts of Interest The authors declare no conflicts of interest. Author Contributions Samuel Kwadwo Peprah Bempah, Daniel Kobina Okwan, Juliet Robertson, and Chrissie Stansie Abaidoo conceived and designed the experiments, acquired data, analysed and interpreted the data, prepared figures and tables, authored the first draft and reviewed subsequent drafts of the paper, and approved the final draft. Clement Nsobire Atobiga, Samuel Bimpong, Thomas Kouakou Diby, Atta Kusi Appiah, Francis Kofi Sarkodie, and James Nketsiah reviewed subsequent drafts of the paper, provided critical revision of the manuscript, and approved the final manuscript. Priscilla Obeng, Sarah Afriyie Owusu, Ethel Akua Achiaa Domfeh, and Michael Osei Ampofo aided with the data acquisition and subsequent laboratory work. All authors reviewed the manuscript. Funding The authors received no specific funding for this work. References American Veterinary Medical Association . (2020) . AVMA Guidelines for the Euthanasia of Animals: 2020 Edition (pp. 1–121). 1–121. 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Accelerated healing of full-thickness skin wounds in a wet environment. Plastic and Reconstructive Surgery , 106 :(3). Turksen, K. (2018) . Wound Healing: Stem Cells Repair and Restorations, Basic and Clinical Aspects. Wound Healing: Stem Cells Repair and Restorations, Basic and Clinical Aspects . Additional Declarations No competing interests reported. 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(×0.3).\u003c/p\u003e","description":"","filename":"131.png","url":"https://assets-eu.researchsquare.com/files/rs-7245060/v1/47825d3000088e0803d31055.png"},{"id":89002901,"identity":"184fa895-9059-43b1-8606-b2fec2dfe54c","added_by":"auto","created_at":"2025-08-13 15:42:06","extension":"png","order_by":14,"title":"Figure 14","display":"","copyAsset":false,"role":"figure","size":80645,"visible":true,"origin":"","legend":"\u003cp\u003eA bar chart showing the percentage of wound closure\u003c/p\u003e","description":"","filename":"14.png","url":"https://assets-eu.researchsquare.com/files/rs-7245060/v1/b93d474fca74debe4509995d.png"},{"id":89001988,"identity":"09cdc6cd-d84f-4b28-ab9b-5d692869af8a","added_by":"auto","created_at":"2025-08-13 15:34:06","extension":"png","order_by":15,"title":"Figure 15","display":"","copyAsset":false,"role":"figure","size":3539009,"visible":true,"origin":"","legend":"\u003cp\u003eLight photomicrographs of weeks 1 to 5 of wound healing progress\u003c/p\u003e\n\u003cp\u003e(A-B) – Wound healing progression at week 1. (W). Epithelial layer under eschar (Staining: haematoxylin and eosin; magnification × 100); (\u003cem\u003eC\u003c/em\u003e-\u003cem\u003eD\u003c/em\u003e) – Wound healing progression at week 1. (W). Epithelial layer under the eschar (Staining: haematoxylin and eosin; magnification × 400)\u003cem\u003e; \u003c/em\u003e(\u003cem\u003eE\u003c/em\u003e-\u003cem\u003eF\u003c/em\u003e) –Wound healing progression at week 2. Epithelial layer (X), connective tissue hyperplasia (Y). Epithelial layer with increased thickness (W) (Staining: haematoxylin and eosin; magnification × 100)\u003cem\u003e; \u003c/em\u003e(\u003cem\u003eG\u003c/em\u003e-\u003cem\u003eH\u003c/em\u003e) – Wound healing at week 3. Thickened epithelial layer (X), connective tissue hyperplasia (Y) and adnexal structures (hair follicles) (Z) (Staining: haematoxylin and eosin; magnification × 100)\u003cem\u003e, \u003c/em\u003e(\u003cem\u003eI\u003c/em\u003e-\u003cem\u003eJ\u003c/em\u003e) – Wound healing at week 4. Adnexal structures (hair follicles) (Z) (Staining: haematoxylin and eosin; magnification × 100)\u003cem\u003e; \u003c/em\u003e(\u003cem\u003eK\u003c/em\u003e-\u003cem\u003eL\u003c/em\u003e) – Wound healing at week 5 (Staining: haematoxylin and eosin; magnification × 100)\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"15.png","url":"https://assets-eu.researchsquare.com/files/rs-7245060/v1/4b619c009d1cdcc5d8e7efe5.png"},{"id":89063827,"identity":"ee52ef40-9942-4d85-badd-fdb81c76a847","added_by":"auto","created_at":"2025-08-14 10:08:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":14501459,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7245060/v1/e21238b4-b49c-433e-aa52-23f536d52ab1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eA Preliminary Study on Wound Healing and Scar Reduction Using Platelet-rich Fibrin Matrix\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e\u003ch2\u003e1.1 Background\u003c/h2\u003e\u003cp\u003eWound healing and repair happen to be one of the most complex biological processes that occur during human life. After an injury, several biological pathways come into play with many overlapping mechanisms, including haemostasis, inflammation, proliferation, and tissue remodelling (Eming et al., \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; Gurtner et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2008\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAs a natural process, wound healing is accompanied by scar formation, which is a mass of non-functioning fibrotic tissue. It is formed as a means of preventing infection of the wounded tissue (Bayat et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2003\u003c/span\u003e). The formation of scars in mammals proves inevitable, and there is considerable evidence to suggest that inflammation is the precursor for scar formation. Normal scar tissue restores the skin barrier. It however, is inferior in aspects such as strength, structure, function and aesthetics (Baumann et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). To prevent infection, rapid inflammatory responses and scar tissue form. It could be said that scars are a price to pay if wounds are to be covered quickly to prevent infections (Eming et al., \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2007\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eOver the years, several approaches have been made to aid in the healing of wounds. Several topical treatments, including the application of imiquimod, mitomycin C and plant extracts such as onion extract, green tea, \u003cem\u003eAloe vera\u003c/em\u003e, vitamin D and E, to heal wounds (Sidgwick et al., \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). Other natural agents, such as whey proteins (Belokrylov et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e1992\u003c/span\u003e), (honey) bee venom and propolis have also been used in some studies (De Vecchi and Drago, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; Fitzmaurice et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2011\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAnother approach which has contributed to wound healing is the use of internally generated factors, with the chief being platelets (Garraud et al., \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Garraud and Cognasse, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). In such studies, platelet-rich plasma (PRP) was used as a topical treatment to facilitate the healing of wounds. At least seven locally acting growth factors from alpha granules are present in platelets. Vascular endothelial growth factor, epidermal growth factor, two transforming growth factor-βs, and three platelet-derived growth factors (Greer et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). These growth factors are beneficial in chronic wounds like diabetic ulcers, which typically lack cytokines and growth factors, and platelet treatment effectively fills this gap (Mart\u0026iacute;-Carvajal et al., \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). This compensates for diminished cellular activity in wounds that are challenging to heal. Therefore, as governed by cytokines and growth factors, diabetic wounds that prove to be particularly problematic have increased cell proliferation, angiogenesis, extracellular matrix synthesis, and other inflammatory processes (Middleton, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). Numerous clinical advantages and different platelet therapies have been created over time. Different production methods, technicalities, and other issues are still up for debate (do Amaral et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). Several studies have been conducted specifically on diabetic wounds in comparison to other chronic wounds. More and more often, platelet-rich plasma is utilised to speed up the healing of wounds. The platelet-rich fibrin matrix (PRFM) is one of the most recent advancements in the use of platelet-rich plasma. This has a denser and more malleable structure than usual. The fibrin matrix retains the platelets and aids in ensuring the highest possible platelet number for use.\u003c/p\u003e\u003cp\u003ePlatelet-rich fibrin matrix (PRFM), which is one of the newest generations of platelet concentrates, is prepared simply without the need for biochemicals like bovine thrombin. In PRP, fibrin is slowly polymerised to form PRFM, which has a structure similar to natural fibrin (Choukroun et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). To increase cell migration, cell proliferation, and cyclic peptide creation, this particular structure is crucial. All of the platelets in PRP will be deposited between the PRFM fibrin fibres as a result of this polymerisation process. By that reasoning, levels of platelets (and therefore growth factors) in PRFM should be comparable to those in PRP.\u003c/p\u003e\u003cp\u003eAn increase in levels of platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor beta (TGF-β) have been observed on the first day following the use of PRFM in particular media, then a gradual decrease on the next day, according to laboratory studies (Lucarelli et al., \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2010\u003c/span\u003e; Sclafani, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). Additionally, PRFM exhibits fibrin features, including a denser and more flexible macroscopic structure that resembles the body's response to injury and a more natural platelet distribution (Gole et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Kobayashi et al., \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Theoretically, PRFM is better for use in wound healing because of these features. By evaluating a modified method proposed by Reksodiputro et al. (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) to produce PRFM to be used as dressings for wounds to aid in their closure and healing, as well as reduce the formation of scars as much as possible, this study seeks to address the issues raised above and strengthen the weaknesses of the existing invention.\u003c/p\u003e\u003c/div\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003e3.1 Study Design and Location\u003c/h2\u003e\n \u003cp\u003eThe study was carried out at the Anatomy Department, SMD, KNUST. Ethical approval was obtained from the Committee on Human Research, Publications and Ethics (CHRPE) (CHRPE/ RC/ 205/ 17). The study was conducted in accordance with the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines (du Sert et al., \u003cspan class=\"CitationRef\"\u003e2020\u003c/span\u003e; NC3Rs, \u003cspan class=\"CitationRef\"\u003e2022\u003c/span\u003e). Ten mature New Zealand rabbits (5 males and 5 females) were used in the study. After a week of observation and adaptation, the healthy and fit New Zealand rabbits were shaved and prepared for incision. The fleshy backs of the rabbits served as the site of incision. New Zealand rabbits share certain physiological traits with humans, especially in skin structure and wound healing processes. This makes them suitable for researching skin treatments, and they generally heal faster than humans, allowing researchers to observe treatment effects over a shorter period. This is particularly useful for studying wound healing and repair mechanisms.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2 Wound Creation and Treatment\u003c/h2\u003e\n \u003cp\u003eBefore surgery, the animals were anaesthetised intramuscularly and sedated during the procedure using Pentone (50 mg/ml). Each animal was weighed, and the anaesthesia was administered at a rate of 1 ml per kilogram. The hair on the back of the rabbits was shaved, and the skin was disinfected. Two different rows of five 15 mm circular full-thickness wounds not extending past the panniculus carnosus muscle were created on the backs of the rabbits with a scalpel. Platelet-rich fibrin matrix was used as the dressing for the various wounds of one row (Lacci and Dardik, \u003cspan class=\"CitationRef\"\u003e2010\u003c/span\u003e). The control row was treated with Drez solution and ointment (Iodinated-Povidone BP 5.0% w/v, Metronidazole BP 1.0% w/v) to serve as a control (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The wounds were all sealed with Vaseline\u0026reg; triple refined petroleum jelly to maintain moisture. Occlusive dressing was used to cover the dressings, and they were secured with surgical tapes to prevent the animals from tampering with the dressed wounds.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003e3.3 Platelet-rich Fibrin Matrix Preparation\u003c/h2\u003e\n \u003cp\u003e20 ml of blood was collected from each animal from the Central Auricular Artery or the Marginal Ear Vein into a citrated dextrose tube (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThe tubes were then centrifuged (Thermo Scientific Heraeus Biofuge Primo Centrifuge (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e)) at 3000 RPM (1207 \u0026times; g) for six minutes at room temperature (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e) (O\u0026rsquo;Connell et al., \u003cspan class=\"CitationRef\"\u003e2008\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThe supernatant plasma was transferred from the first tube into a test tube containing calcium chloride (0.1 M) (0.2 ml per 1 ml of platelet-rich plasma). It was then placed back into the centrifuge and spun at a higher g-force 5,500 RPM (4058 \u0026times; g) for 25 minutes. A circular membrane of platelet-rich fibrin matrix was formed at the bottom of the container as it was spun using radial centrifugation (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThe Platelet-rich plasma fibrin matrix was then used as dressing for the test wounds (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eEighteen millilitres of blood produced 7\u0026ndash;8mL of PRP, which in turn yielded a 35mm membrane of 0.03 cm thickness; 36mL of blood produces a 50mm membrane of 0.03 cm thickness (Reksodiputro et al., \u003cspan class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eIn order to guarantee the production of ideal PRFM, the modified method used ensured that platelet-poor plasma (PPP), a by-product in PRFM production, has a platelet content of 0/\u0026micro;l, representing the fact that all platelets are attached to the PRFM fibrin matrix at the bottom of the tube.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003e3.4 Sample Taking and Tissue Processing\u003c/h2\u003e\n \u003cp\u003eTissue samples were taken from each wound to be observed under the microscope to determine the extent of damage after incision and the rate of healing at regular intervals (days 7, 14, 21, 28, 35). In this study, all assessors were blinded to the identity of the test and control wounds during the evaluation. This blinding was implemented to prevent any potential bias that could arise from prior knowledge of the treatment conditions.\u003c/p\u003e\n \u003cp\u003eThe histopathologic grading was conducted using standardised criteria, which were uniformly applied across all samples. This method enhances the reliability of the findings, as it ensures that any observed differences in healing are attributed solely to the treatments rather than to assessor preconceptions.\u003c/p\u003e\n \u003cp\u003eThe samples were fixed in 10% neutral buffered formaldehyde. The samples were then dehydrated by immersion in serial ethanol (alcohol) solutions of increasing concentration until pure, water-free alcohol was reached. The samples were subsequently cleared using xylene as a clearing agent before being infiltrated with paraffin wax. The specimens were then embedded in paraffin, sectioned and stained with eosin and haematoxylin. Light microscopy was done using Leica DM 500 and 750. (Rolls et al., \u003cspan class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eAfter three to six weeks, the final observation of the healed wounds was done. The fit animals were released, while the weak animals were euthanised using sodium pentobarbital via intravenous injection, based on the rabbit\u0026apos;s weight (100 mg/kg of body weight) (National Research Council (US) Committee on Pain and Distress in Laboratory Animals, 1992). This was followed by confirmation of death and appropriate disposal of the body according to the American Veterinary Medical Association regulatory guidelines, and discarded via deep burial (American Veterinary Medical Association, \u003cspan class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003e3.5 Computerized Planimetry and Data Analyses\u003c/h2\u003e\n \u003cp\u003ePictures of the wounds were taken digitally using a 12MP camera (Samsung Galaxy Note 9) and computerized planimetry using Adobe Photoshop 23.0.0. Data analyses was done using IBM SPSS Version 26 (SPSS\u0026reg; Inc, Chicago, USA). Percentage of closure for the wounds (\u0026plusmn;\u0026thinsp;standard error of the mean) was determined by calculating the decrease in the wound area as measured by digital photography and computerized planimetry using Adobe Photoshop 23.0.0 normalized to the initial wound area. A descriptive analysis was made for each variable. The associations between the different qualitative variables were studied using Pearson\u0026rsquo;s chi squared test at 99% confidence interval. Statistical significance was accepted for \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026le;\u0026thinsp;0\u0026middot;01.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"RESULTS","content":"\u003ch2\u003e4.1 Wound healing progression\u003c/h2\u003e\n\u003cp\u003eDuring the first 7 days after the wound creation, both the test and control groups recorded a very rapid rate of contraction illustrated in\u0026nbsp;Figure 7. From day 0 to day 8 (Figure 8) the wound diameters reduced by 60-70%. The test group wound diameters reduced by 77.24 \u0026plusmn; 0.91% and the control by 69.28 \u0026plusmn; 1.16% on the 11\u003csup\u003eth\u003c/sup\u003e day. The test wounds had reduced by 96.92 \u0026plusmn; 0.22% and the control by 87.31 \u0026plusmn; 0.91% on the 12\u003csup\u003eth\u003c/sup\u003e day as shown in Figure 9. By day 14, the test group showed more progress with 100% closure in all cases (Figure 10). Healing continued through the subsequent days as seen in Figure 11 for the control group till complete closure was recorded by day 18 shown in Figure 13. No records beyond day 18 were statistically significant as both the test and control groups had achieved 100% closure. The healed wounds were monitored till the 5\u003csup\u003eth\u003c/sup\u003e week.\u003c/p\u003e\n\u003ch2 id=\"_Toc141376579\"\u003e4.2 Efficacy of Platelet-rich fibrin matrix\u003c/h2\u003e\n\u003cp\u003eParameters involving complete wound closure and time required for complete closure were measured to determine the clinical efficacy of platelet-rich fibrin matrix.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cspan id=\"_Toc146130406\"\u003e4.2.1 Complete Closure\u0026nbsp;\u003c/span\u003e\u003c/h2\u003e\n\u003cp\u003eAccording to the Food and drug administration, a fully healed wound must demonstrate complete reepithelialisation of the wound surface without any discernible exudate, drainage, or dressing requirements (Food and Drug Administration Wound Healing Clinical Focus Group, 2001). The test group showed complete closure by day 14 (Figure 12). The control group on the other hand achieved complete closure by day 18 (Figure 13).\u0026nbsp;\u003c/p\u003e\n\u003ch2 id=\"_Toc146130407\"\u003e4.2.2 Time of Closure\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe test group recorded a mean of 73.18 \u0026plusmn; 1.40% by the 8\u003csup\u003eth\u003c/sup\u003e day. The control group on the other hand recorded a mean of 65.32 \u0026plusmn; 0.59% (Figure 14).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBy day 14, the test group showed more progress with 100% closure in all cases. The control group recorded a mean of 92.09 \u0026plusmn; 0.62% for closure. No records beyond day 18 were statistically significant as both the test and control groups had achieved 100% closure.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e4.3 Histopathological changes across week 1 to week 5\u003c/h2\u003e\n\u003cp\u003eBy day 7, reepithelization was observed for both the test and control groups. This is shown in\u0026nbsp;Figure\u0026nbsp;15 (A-D). This layer of epithelium was formed under the eschar of the wound marked W. The epithelial layer was more prominent in the test group than the control. Acute inflammation was recorded for both the test group and the control group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe epithelial layer (W) for the control group became very prominent at day 14 and begun to increase in thickness. Chronic inflammation begun to show. The test group on the other hand showed signs of chronic inflammation as granulation tissue exhibited connective tissue hyperplasia labelled as Y. The epithelial layer labelled X thickened as well.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eChronic inflammation for the test group showed signs of resolution as they thinned out and adnexal skin structures like hair follicles (Z) begun to appear at day 21. The epithelial layer also begun to even out and reduce in thickness. The control group showed signs of chronic inflammation and a relatively thicker epithelial layer. The rate of connective tissue hyperplasia was not as prominent as what was seen in the test group at day 14.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe number of adnexal skin structures had greatly increased for the test group and had begun to appear in the control group as well at day 28. Chronic inflammation continued to reduce in both cases.\u003c/p\u003e\n\u003cp\u003eThe test group recorded almost complete resolution of chronic inflammation and the population of adnexal skin structures were almost normalised at day 35. The layer of hyperplasia in the control group was also reduced although not up to that seen in the test group. Adnexal skin structures were abundant.\u003c/p\u003e\n\u003ch2\u003e4.4 Reepithelialisation\u003c/h2\u003e\n\u003cp\u003eBy day 7, the test group showed higher rates of epithelialisation with statistically significant differences compared to what was seen in the control group (\u003cem\u003eP\u003c/em\u003e = 0.006). At day 14, the trend continued with the test group showing higher rates of epithelialisation with statistically significant differences compared to what was seen in the control group (\u003cem\u003eP\u003c/em\u003e = 0.013). Days 21 to 35, however did not have the differences between the test and the control being statistically significant (\u003cem\u003eP\u003c/em\u003e = 0.133 and 0.035 respectively). This was because the entire wound surface had been covered between weeks 2 and 3 (Table 1 and Table \u003cstrong\u003e2\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e: A Table showing Histopathologic Grading Scale to Evaluate Reepithelialisation\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"643\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 643px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistopathologic Grading Scale to Evaluate Reepithelialization\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 599px;\"\u003e\n \u003cp\u003eReepithelialisation at the edge of the wound\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 599px;\"\u003e\n \u003cp\u003eReepithelialisation covering less than half of the wound\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 599px;\"\u003e\n \u003cp\u003eReepithelialisation covering more than half of the wound\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 599px;\"\u003e\n \u003cp\u003eReepithelialisation covering the entire wound, irregular thickness\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 599px;\"\u003e\n \u003cp\u003eReepithelialisation covering the entire wound, normal thickness\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e(Sinha and Gallagher, 2003)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e: A Table showing Grades of wound reepithelialisation from 7 to 35 days (total values) (Pearson\u0026rsquo;s chi squared test) using the histopathologic evaluation scale for grading wound reepithelialisation\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 195px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 365px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003csup\u003e\u0026lowast;\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDay\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003eSkin Total\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003eGrade 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003eGrade 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003eGrade 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003eGrade 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eTest Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e14\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eTest Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e21\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eTest Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.133\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e28\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eTest Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e35\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eTest Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eb\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003ePRFM: Platelet-rich fibrin matrix.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026lowast;\u003c/em\u003e\u003cem\u003eGrade 1: reepithelialisation at the edge of the wound; grade 2: reepithelialisation covering less than half of the wound; grade 3: reepithelialisation covering more than half of the wound; grade 4: reepithelialisation covering the entire wound, with irregular thickness; grade 5: reepithelialisation covering the entire wound, normal thickness. b \u0026ndash; Value could not be computed because at least one of the variables was constant. (P value - Correlation is significant at the 0.01 level)\u003c/em\u003e.\u0026nbsp;\u003c/p\u003e\n\u003ch2 id=\"_Toc146130411\"\u003e4.5 Scar Resolution\u003c/h2\u003e\n\u003cp\u003eBy day 7, the test group showed higher rates of scar resolution with statistically significant differences compared to what was seen in the control group (\u003cem\u003eP\u003c/em\u003e = 0.000). Similar values were recorded at day 14 with the test group showing higher rates of scar resolution with statistically significant differences compared to what was seen in the control group (\u003cem\u003eP\u003c/em\u003e = 0.005). At day 21, 60% of the test group showed signs of scar resolution compared to 50% seen for the control group. This was also statistically significant (\u003cem\u003eP\u003c/em\u003e = 0.008). Days 28 to 35, however did not have the differences between the test and the control being statistically significant (\u003cem\u003eP\u003c/em\u003e = 0.020 and 0.133 respectively). This was because all the wounds had shown signs of recovery at this point with the only difference being the test group barely having any connective tissue hyperplasia and having more hair follicles and dermal appendages than the control group (Table 3 and Table \u003cstrong\u003e4\u003c/strong\u003e).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3\u003c/strong\u003e: A Table showing Histopathologic Grading Scale to Evaluate scar resolution\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 553px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistopathologic Grading Scale to Evaluate scar resolution\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 515px;\"\u003e\n \u003cp\u003eAcute inflammation (pyogenic membrane formation)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 515px;\"\u003e\n \u003cp\u003ePredominance of diffuse acute inflammation (predominance of granulation tissue)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 515px;\"\u003e\n \u003cp\u003ePredominance of chronic inflammation (fibroblasts beginning to proliferate)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 515px;\"\u003e\n \u003cp\u003eResolution and healing (reduction or disappearance of chronic inflammation, although occasional round cells may persist)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 515px;\"\u003e\n \u003cp\u003eProliferation of hair follicles and dermal appendages\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e(Molina-Mi\u0026ntilde;ano \u003cem\u003eet al\u003c/em\u003e., 2009; Turksen, 2018)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e4\u003c/strong\u003e: A Table showing the Grades of Scar Resolution from 7 to 35 days (total values) (Pearson\u0026rsquo;s chi squared test) using the histopathologic evaluation scale for grading scar resolution\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 195px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 365px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003csup\u003e\u0026lowast;\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDay\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003eSkin Total\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003eGrade 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003eGrade 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003eGrade 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003eGrade 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eTest Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e14\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eTest Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e21\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eTest Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e28\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eTest Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e35\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eTest Group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.133\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 44px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003ePRFM: Platelet-rich fibrin matrix.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026lowast;\u003c/em\u003e\u003cem\u003eGrade 1: acute inflammation (pyogenic membrane is formed); grade 2: predominance of diffuse acute inflammation (predominance of granulation tissue); grade 3: predominance of chronic inflammation (fibroblasts beginning to proliferate); grade 4: resolution and healing (reduction or disappearance of chronic inflammation); grade 5: proliferation of hair follicles and dermal appendages. (P value - Correlation is significant at the 0.01 level).\u003c/em\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003e5.1 Wound healing progression\u003c/h2\u003e\u003cp\u003eFrom Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e, a rapid rate of contraction was seen, especially during the first 7 days. This is most likely due to the cascade of events that occur during the first few hours to the first few days. The wound diameter had reduced by 60\u0026ndash;70% which is consistent with literature (DiPietro and Burns, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2003\u003c/span\u003e). According to Clark, (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e1988\u003c/span\u003e) contraction starts after granulation tissue has been well established usually 3\u0026ndash;5 days after injury.\u003c/p\u003e\u003cp\u003eStrickland (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2005\u003c/span\u003e) reported that contraction usually begins after a latency period of 2 to 3 days. By 2 to 3 weeks, wounds are usually less than 20% of the original wound area. By day 14, the test group showed more progress with 100% closure in all cases (Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e10\u003c/span\u003e). This was a good sign that platelet-rich fibrin matrix proved effective.\u003c/p\u003e\u003cp\u003eStudies have shown that complete reepithelialisation before day 14 greatly reduces the risk of persistent and hypertrophic scar formation (Chen et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Deitch et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e1983\u003c/span\u003e; Holmes et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e1983\u003c/span\u003e; Machesney et al., \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e1998\u003c/span\u003e). The control group recorded complete closure by day 18. This was within acceptable range for normal wound healing.\u003c/p\u003e\u003cp\u003eIn a study conducted by Svensjo et al. (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e2000\u003c/span\u003e), 0% of dry, 20% of moist, and 86% of saline-treated wounds were completely reepithelialised by day 12. Garraud et al. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2017\u003c/span\u003e) estimates complete wound closure to happen between the second week and the third month. Hom et al. (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2007\u003c/span\u003e), in a study using autologous platelet gel observed complete closure between days 28 and 35. No records beyond day 18 were statistically significant as both the test and control groups had achieved 100% closure. Compared to other studies, wound healing rates for the test group were on the high side while the control group showed normal trends consistent with literature (Kordestani, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003e5.2 Efficacy of Platelet-rich fibrin matrix\u003c/h2\u003e\u003cdiv id=\"Sec20\" class=\"Section3\"\u003e\u003ch2\u003e5.2.1 Complete Closure\u003c/h2\u003e\u003cp\u003eThe test group showed complete closure by day 14 (Fig.\u0026nbsp;\u003cspan refid=\"Fig12\" class=\"InternalRef\"\u003e12\u003c/span\u003e). The control group on the other hand achieved complete closure by day 18 (Fig.\u0026nbsp;\u003cspan refid=\"Fig13\" class=\"InternalRef\"\u003e13\u003c/span\u003e). The wounds were assessed according to a protocol by the Food and drug administration, (Food and Drug Administration Wound Healing Clinical Focus Group, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2001\u003c/span\u003e). Garraud et al. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2017\u003c/span\u003e) estimates complete wound closure to happen between the second week and the third month. Hom et al. (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2007\u003c/span\u003e), in a study using autologous platelet gel, complete closure occurred between days 28 and 35. Thus the test group showing complete closure by day 14 attests to the efficacy of platelet-rich fibrin matrix. Platelets are a rich source of growth factors and have been increasingly used effectively in the treatment of chronic wounds (Bhanot and Alex, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2002\u003c/span\u003e). The alpha granules of platelets have at least seven growth factors (Greer et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). As such chronic and difficult to heal wounds like diabetic wounds have responded quite well to treatment with platelet-rich plasma.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec21\" class=\"Section3\"\u003e\u003ch2\u003e5.2.2 Time of Closure\u003c/h2\u003e\u003cp\u003eThe first 7 days showed the fastest rate of wound contraction. The test group recorded a mean of 73.18\u0026thinsp;\u0026plusmn;\u0026thinsp;1.40% by the 8th day. The control group on the other hand recorded a mean of 65.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59% (Fig.\u0026nbsp;\u003cspan refid=\"Fig14\" class=\"InternalRef\"\u003e14\u003c/span\u003e). By day 14, the test group showed more progress with 100% closure in all cases. The control group recorded a mean of 92.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.62% for closure. No records beyond day 18 were statistically significant as both the test and control groups had achieved 100% closure. As seen from above, the test group had better result overall. This is also consistent with literature. Huang et al. (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) conducted a meta-analysis of 8 randomized controlled trials with a total of 539 patients. It was observed that platelet-rich plasma could improve the healing rates of burn wound and had shorter healing time. Several clinical benefits and various platelet therapies have been documented. Issues such as differing production processes, technicalities and others are still under debate (do Amaral et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2015\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec22\" class=\"Section2\"\u003e\u003ch2\u003e5.3 Histopathological changes across week 1 to week 5\u003c/h2\u003e\u003cp\u003eFrom Fig.\u0026nbsp;15 (A to L), the test group showed a much better healing profile compared to what was observed for the control group. The consistent positive results especially seen in the test group could be due to the use of PRFM. This method may allow a gradual release of growth factors which improved the wound healing process. O\u0026rsquo;Connell et al. (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2006\u003c/span\u003e) reported that PRFM exhibited a gradual and consistent release of growth factors even up to the 7th day. Reepithelialisation was witnessed after day 7. This restoration probably contributed to the wound healing process. As stated above, the quality and speed at which healing takes place during the first 14 days is important. Reepithelialisation restores haemostatic balance and this in turn reduces the time of inflammation ensuring minimal scar formation (Chen et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Deitch et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e1983\u003c/span\u003e; Holmes et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e1983\u003c/span\u003e; Machesney et al., \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e1998\u003c/span\u003e). By day 14, chronic inflammation was observed for both test and control groups. Both the epithelial lining and the underlying connective tissue showed signs of hyperplasia. The resulting scar tissue due to collagen deposition was expected to regress according to Karrer (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2007\u003c/span\u003e). This regression was observed at day 21 for the test group while the control group merely showed signs of regression. Adnexal skin structures like hair follicles and sebaceous glands begun to appear in the test group at this stage. These may sprout from deep epithelial cells from hair shafts. The wounds created in the study were all full thickness wounds, thus those remnant epidermal cells wound be absent. There would however be contributions from adjacent healthy skin appendages evidenced by how adnexal skin structures seem to creep in from the periphery towards the centre of the scar tissue. This was consistent with a study conducted amongst burn victims by Mani et al. (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Day 28 saw adnexal skin structure proliferation for the control group as well. Chronic inflammation continued to regress in both cases and by day 35, the test group recorded almost complete resolution of chronic inflammation and the population of adnexal skin structures were almost normalised. The layer of hyperplasia in the control group was also reduced although not up to that observed in the test group. The result was consistent with O\u0026rsquo;Connell and Cockbill for the PRFM treated wounds and the control respectively (Cockbill, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2002\u003c/span\u003e; O\u0026rsquo;Connell et al., \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2008\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec23\" class=\"Section2\"\u003e\u003ch2\u003e5.4 Reepithelialisation\u003c/h2\u003e\u003cp\u003eBy day 7, the test group showed higher rates of epithelialisation with statistically significant differences compared to what was observed in the control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006). At day 14, the trend continued with the test group showing higher rates of epithelialisation with statistically significant differences compared with the control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013). Days 21 to 35, however did not have the differences between the test and the control being statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.133 and 0.035 respectively). This was because the entire wound surface had been covered between weeks 2 and 3. The quality and speed at which healing takes place during the first 14 days is important. Reepithelialisation restores haemostatic balance and this in turn reduces the time of inflammation ensuring minimal scar formation (Chen et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). The reepithelialised layer was likely to be contributed from adjacent healthy skin epithelial cells and dermal appendages\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec24\" class=\"Section2\"\u003e\u003ch2\u003e5.5 Scar Resolution\u003c/h2\u003e\u003cp\u003eBy day 7, the test group showed higher rates of scar resolution with statistically significant differences compared to what was seen in the control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.000). Similar values were recorded at day 14 with the test group showed higher rates of scar resolution with statistically significant differences compared to what was seen in the control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005). The first two weeks generally present with the infiltration of a lot of inflammatory cells. There is however considerable evidence to suggest that inflammation is an essential prerequisite for scarring (Eming et al., \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2007\u003c/span\u003e). Thus, wounds with relatively shorter inflammation time generally scar less compared to others that experience longer inflammatory periods. It is therefore not surprising that the test group recorded better scar resolution in the first two weeks. This can be attributed to the abundance of growth factors and other necessary chemicals provided by the platelets. The resulting scar tissue due to collagen deposition was expected to regress according to Karrer (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2007\u003c/span\u003e). The trend continued over the subsequent weeks and at day 21, 60% of the test group showed signs of scar resolution compared to 50% seen for the control group. This was also statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008). Days 28 to 35, however did not have the differences between the test and the control being statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020 and 0.133 respectively). This was because all the wounds had shown signs of recovery at this point with the only difference being the test group barely having any connective tissue hyperplasia and having more hair follicles and dermal appendages than the control group.\u003c/p\u003e\u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003ePlatelet-rich fibrin matrix treated wounds had better results for all parameters checked in this study. It proved superior in time of closure, rate of closure, rate of reepithelialisation and scar resolution. The test group recorded 73.18% reduction in wound diameter for the first week and 100% closure by day 14. The control group recorded 65.32% reduction in wound diameter by the end of the first week, 92.09% at the end of the second week and 100% closure by day 18. Wound closure was accompanied by reepithelialisation. The test group showed higher rates of scar resolution with statistically significant differences compared to what was observed in the control group. This can be attributed to the abundance of growth factors and other necessary chemicals provided by the platelets. Based on the results recorded by the test group, it could be speculated that platelet-rich fibrin matrix may be effective for wound treatment. The significance of this study is the provision of preliminary baseline data for wound healing and will prove useful in the treatment and management of wounds in the clinical setting.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData used to support the findings of this study would be made available by the corresponding author (Samuel Kwadwo Peprah Bempah) upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSamuel Kwadwo Peprah Bempah, Daniel Kobina Okwan, Juliet Robertson, and Chrissie Stansie Abaidoo conceived and designed the experiments, acquired data, analysed and interpreted the data, prepared figures and tables, authored the first draft and reviewed subsequent drafts of the paper, and approved the final draft. Clement Nsobire Atobiga, Samuel Bimpong, Thomas Kouakou Diby, Atta Kusi Appiah, Francis Kofi Sarkodie, and James Nketsiah reviewed subsequent drafts of the paper, provided critical revision of the manuscript, and approved the final manuscript. Priscilla Obeng, Sarah Afriyie Owusu, Ethel Akua Achiaa Domfeh, and Michael Osei Ampofo aided with the data acquisition and subsequent laboratory work. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no specific funding for this work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cstrong\u003eAmerican Veterinary Medical Association\u003c/strong\u003e. \u003cstrong\u003e(2020)\u003c/strong\u003e. \u003cem\u003eAVMA Guidelines for the Euthanasia of Animals: 2020 Edition\u003c/em\u003e (pp. 1\u0026ndash;121). 1\u0026ndash;121. 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Wound healing: Process, phases and promoting. \u003cem\u003eWound Healing: Process, Phases and Promoting\u003c/em\u003e.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eMolina-Mi\u0026ntilde;ano, F., L\u0026oacute;pez-Jornet, P., Camacho-Alonso, F., and Vicente-Ortega, V.\u003c/strong\u003e \u003cstrong\u003e(2009)\u003c/strong\u003e. Effects of plasma rich in growth factors on wound healing of the tongue. Experimental study in rabbits. \u003cem\u003eMedicina Oral, Patologia Oral y Cirugia Bucal\u003c/em\u003e, \u003cstrong\u003e\u003cem\u003e14\u003c/em\u003e\u003c/strong\u003e:(9), 145\u0026ndash;148.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eNational Research Council (US) Committee on Pain and Distress in Laboratory Animals\u003c/strong\u003e. \u003cstrong\u003e(1992)\u003c/strong\u003e. \u003cem\u003eEuthanasia\u003c/em\u003e. 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Wound Healing: Stem Cells Repair and Restorations, Basic and Clinical Aspects. \u003cem\u003eWound Healing: Stem Cells Repair and Restorations, Basic and Clinical Aspects\u003c/em\u003e.\u003c/li\u003e\n\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":"Wound healing, Platelet-rich fibrin matrix, Reepithelialisation, Scar reduction","lastPublishedDoi":"10.21203/rs.3.rs-7245060/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7245060/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWound healing is a natural response to tissue injury. Many factors come into play during the process leading to the body making compromises to ensure healing which leads to the formation of scars. Over the years, several approaches have been made to aid in the healing of wounds. Platelet-rich plasma is believed to have various important capabilities such as being a source of growth and clotting factors as well as possessing both chemotactic and mitogenic properties which would aid in wound closure and healing as well as reduce the formation of scars as much as possible. This experimental animal study aimed to increase the rate of wound healing by using platelet-rich fibrin matrix, a derivative of platelet-rich plasma to improve healing rates and quality with particular focus on reepithelialisation and scar tissue reduction. Platelet-rich fibrin matrix treated wounds proved superior in time of closure, rate of closure, rate of reepithelialisation and scar resolution. The test group recorded 73.18% reduction in wound diameter for the first week and 100% closure by day 14. The control group recorded 65.32% reduction in wound diameter by the end of the first week, 92.09% at the end of the second week and 100% closure by day 18. Wound closure was accompanied by reepithelialisation. The test group showed higher rates of scar resolution with statistically significant differences compared to what was observed in the control group. This can be attributed to the abundance of growth factors and other important chemicals provided by the platelets. Based on the results recorded by the test group, it could be speculated that that of platelet-rich fibrin matrix is effective. This study provides preliminary baseline data for wound healing and could be useful in the treatment and management of wounds in the clinical setting.\u003c/p\u003e","manuscriptTitle":"A Preliminary Study on Wound Healing and Scar Reduction Using Platelet-rich Fibrin Matrix","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-13 15:34:00","doi":"10.21203/rs.3.rs-7245060/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-30T12:11:23+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-30T02:19:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-27T06:36:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"162654557685714745013184638352477096276","date":"2025-10-22T16:04:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"280800516370279172822716173608338939519","date":"2025-10-22T15:42:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-11T15:29:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"247644442392634002672041823169483216929","date":"2025-08-11T04:00:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-10T05:04:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"97865853774540168594922234292669025222","date":"2025-08-10T04:52:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-08T01:29:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-08T01:23:54+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-05T22:27:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-01T16:21:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-08-01T16:19:08+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":"31e609fc-7aef-4f25-87a7-0b1002687d21","owner":[],"postedDate":"August 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":53118605,"name":"Health sciences/Diseases"},{"id":53118606,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2026-01-02T05:39:01+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-13 15:34:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7245060","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7245060","identity":"rs-7245060","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}