Investıgatıon of the Effects of Treatment with Enoxaparın Sodıum and Hyperbarıc Oxygen Therapy on the Recovery of Rats Wıth Achılles Tendon Rupture

Investıgatıon of the Effects of Treatment with Enoxaparın Sodıum and Hyperbarıc Oxygen Therapy on the Recovery of Rats Wıth Achılles Tendon Rupture | 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 Research Article Investıgatıon of the Effects of Treatment with Enoxaparın Sodıum and Hyperbarıc Oxygen Therapy on the Recovery of Rats Wıth Achılles Tendon Rupture Cafer Erman Aytekin, Yalçın Turhan, Zekeriya Okan Karaduman, Mehmet Arican, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4143967/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Jul, 2024 Read the published version in BMC Musculoskeletal Disorders → Version 1 posted 14 You are reading this latest preprint version Abstract Purpose In this study, we aimed to investigate the effects of hyperbaric oxygen therapy and enoxaparin sodium, which are known to accelerate bone tissue healing as well as tendon and soft tissue healing, on the healing of Achilles tendon rupture. Methods Thirty-six rats were used in the present study. All rats were divided into groups of nine. The groups were the enoxaparin sodium group, enoxaparin sodium and hyperbaric oxygen group, hyperbaric oxygen group and control group. After 21 days, the process was completed, and the rats were sacrificed. Achilles tendon samples were evaluated histopathologically. Results The groups were compared according to the results of statistical analysis based on the histopathological data. There was no significant difference between the groups in terms of acute inflammation (p = 0.785) or chronic inflammation (p = 0.827) scores, but there were significant differences in neovascularization (p = 0.009), proliferation (p < 0.001) and fibrosis (p = 0.006) scores. Conclusion Our study showed that the use of enoxaparin sodium and hyperbaric oxygen had a positive effect on the healing of the Achilles tendon. Based on these results, we believe that the use of enoxaparin sodium and hyperbaric oxygen therapy after Achilles tendon rupture will be beneficial for healing and preventing complications. Achilles tendon rupture hyperbaric oxygen therapy enoxaparin sodium rat Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Although the Achilles tendon is one of the strongest tendons in the human body, rupture rates have increased significantly in recent years with increasing physical activity in middle-aged and older people. There have been many studies on the treatment and healing of Achilles tendon rupture, and research on tendon healing is still ongoing to accelerate the return to social life after rupture and to reduce rerupture rates. The treatment of tendon pathologies, which are becoming increasingly common as a result of prolonged life expectancy and the increasing involvement of sporting activities for hobbies or health purposes, is maintaining importance in orthopedic surgery.[ 1 ] Although significant gains have been achieved with numerous studies and many surgical methods developed in this field, the difficulties and complications encountered continue to play an important role in the treatment process.[ 2 – 4 ]Tendons are the most important parts of the musculoskeletal system and transfer the energy produced by the muscles to the bone. Because of the functions of these devices, tendon pathologies cause significant morbidity. Tendon injuries may occur due to acute trauma, chronic inflammatory conditions or overuse.[ 5 ] Tendon healing is a slow, progressive process.[ 6 ] Because of these problems, new studies are constantly being conducted to improve treatment. HBO therapy is a treatment method applied for many diseases; patients intermittently inhale 100% oxygen via various methods (mask, endotracheal tube, etc.) under pressure greater than one atmosphere in a closed pressure chamber.[ 7 ] The efficacy of HBO therapy, which has been shown to have many positive effects on tissues, is due to hyperoxygenation, neovascularization, antimicrobial activity, pressure effects, vasoconstriction and a reduction in reperfusion damage.[ 8 ] There are studies with successful results in many pathological conditions, such as necrotizing soft tissue infections, acute traumatic ischemia, crush injury, compartment syndrome, problematic wounds, problematic skin grafts and flaps, refractory osteomyelitis, osteonecrosis, sports injuries, fracture healing, nerve healing, carbon monoxide poisoning, and decompression sickness; additionally, there are cases where HBO therapy is added to treatment modalities. Antithrombotic agents are now routinely used for thromboembolism prophylaxis in thromboembolism-prone patients before and after surgery in patients with major orthopedic injuries. Several studies have reported that low-molecular-weight heparin (LMWH) positively affects wound healing, increases macrophage stimulation, increases new vessel formation and decreases fibrous tissue formation.[ 9 , 10 ] LMWH were developed to overcome the disadvantages of intravenous standard heparin. These patients do not require monitoring due to their predictable activity and do not require heparin. Moreover, the risk of thrombocytopenia is lower. Physiologically, LMWH shows high anti-Factor Xa activation[ 11 ] but relatively low anti-Factor IIa activity. This has made it an inevitable pharmacological agent for reducing deep vein thrombosis (DVT) risk, especially after orthopedic surgeries. [ 12 ] The American Academy of Orthopaedic Surgeons (ACCP) recommends LMWHs as the main drug for VTE prophylaxis. (13) While such effects of LMWH are known, it is not known whether they affect tendon healing. In this study, we aimed to histopathologically compare the effects of LMWH, enoxaparin sodium treatment and HBO treatment, which are used to reduce the incidence of embolism prophylaxis due to immobilization after orthopedic surgeries, on Achilles tendon healing and to determine whether these treatments have positive or negative effects on healing. Methods Study Design In this study, a total of 36 male Wistar albino rats (age: three months [range, 2.5–3.5 months], weighing 200 grams [range, 180–220 grams]) (Duzce University Duzce Medical Faculty Experimental Animals Application and Research Center, Turkey) were used. Before the study, the necessary permission was obtained from the Ethics Committee (2021/02/03). The study was conducted in the Laboratory of the Experimental Animal Practice and Research Center of Duzce University. The principles of laboratory animal care were followed in this study. Our study was reported in accordance with ARRIVE guidelines and experimental animal ethics committee. Animals were randomly divided into 4 groups with 9 rats in each cage and monitored in the laboratory for 1 week preoperatively. During the study period, the rats were given unlimited tap water (ad libitum) and standard rodent feed. The animals were caged in a room with a controlled temperature (23–25°C) and a 12/12-hour light/dark cycle with 50–60% humidity. After the animals used in the study were brought to the laboratory center, they were followed in their cages for approximately 1 week without any treatment. On the day of the study, the rats were brought to the research laboratory and weighed. The HBO cabinet designed for animals is shown in Fig. 1 . Surgical Procedure The rats were anesthetized intramuscularly with ketamine (90 mg/kg) and xylazine (6 mg/kg), and the posterior regions of the left hindfoot were shaved, following the rules of asepsis and antisepsis. For the exposure of the Achilles tendon, a 2.5 cm long longitudinal midline incision was made over the tendon. The Achilles tendon was then cut horizontally 0.5 cm proximal to its attachment to the calcaneus with a No. 15 scalpel. No external fixation agent was applied to the rats, and they were allowed to move freely in the cage after surgery. Fentanyl citrate (0.02 mg/kg) was administered subcutaneously for analgesia for 3 days after surgery. Exposing the Achilles tendon and cutting it horizontally is shown in Fig. 2 . Study groups Prophylactic antibiotics were administered to all groups after surgery. No rats died in any group after the operation. No wound site infection was observed in any of the rats during follow-up. The control group (n = 9) was named Group 1, and the enoxaparin sodium group (n = 9) was named Group 2. The HBO group (n = 9) was used as Group 3, and the enoxaparin sodium and HBO groups (n = 9) were used as Group 4. The distribution of the experimental animals used in the study according to group is given in Table 1 . Table 1 Distribution of experimental animals used in the study according to group. Groups Time of sacrification (histopathologic examination) Group1 Control (n = 9) 21st day Group2 Enoxaparin sodium group (n = 9) 21st day Group3 HBO therapy group (n = 9) 21st day Group4 HBO and Enoxaparin sodium group (n = 9) 21st day Treatment was started on the first postoperative day. A total of 21 sessions of HBO treatment were administered to 9 rats in Group 3 and Group 4 once a day. The treatment was performed in a 100x55 cm hyperbaric oxygen chamber specially built for experimental animals, where 18 rats could fit together with their cages at the same time. After 21 sessions, the treatment was terminated. The treatments were performed at 2.5 ATA pressure, and each session lasted 60 minutes in total. Before the treatment, the chamber was flushed with 100% oxygen for 5 minutes, after which the pressure in the chamber was gradually increased, and the desired treatment depth was reached within 5 minutes. Treatment was performed at 2.5 ATA pressure for 60 minutes, decompression was achieved in 10 minutes, and the treatment was terminated in a total of 80 minutes. Eighteen rats were in Group 2, and 18 rats were in Group 4. Clexane (clexane with the active ingredient enoxaparin sodium) was administered subcutaneously at a single dose of 1 mg/kg/day in a standard manner. No complications were encountered. Histopathological examination In each group, the experimental animals underwent resection at least 1 cm from the distal and proximal ends of the wound site. A 1 cm portion of the wound site was excised 0.5 cm proximal and 0.5 cm distal. After the animals were sacrificed, the sections taken from the Achilles tendons were incubated in xylol twice for 10 minutes each in the Department of Pathology, Duzce University Faculty of Medicine. In this study, we used the modified Curtis method described by Kobayashi et al. for histopathological examination.[ 13 ] From 15 different areas, inflammatory cells, vessels, and fusiform fibroblastic cells were counted and averaged. Inflammatory cells were graded according to fibroblastic profiling and fibrosis status: (0) no fibroblastic profiling and fibrosis, (1) mild, (2) moderate, and (3) significant. Neovascularization was recorded as (1) mild or capillary vessel number between 0 and 5. (2) Moderate: capillary vessel number between 5 and 10. (3) A capillary vessel number greater than 10 was considered to be significant. Statistical analysis The Kruskal‒Wallis test was used for group comparisons. For multiple comparisons, groups were compared with post hoc Bonferroni correction. The data are presented as medians, interquartile ranges and minimum-maximum values. Categorical variables were compared with the Fisher–Freeman–Halton test and are presented as numbers and percentages. All the statistical analyses were performed with the SPSS v.22 package, and a level of statistical significance was set at 0.05. Results Histopathologic scoring between the groups is given in Table 2 . Table 2 Histopathological score distributions between groups Control Enoxaparin sodium group HBO therapy group HBO and Enoxaparin sodium group p Acute inflammation 0 1 7 (87.5%) 1 (12.5%) 7 (87.5%) 1 (12.5%) 7 (87.5%) 1 (12.5%) 8 (100%) 0 (0.0%) 1.000 Chronic inflammation 0 1 2 4 (50.0%) 3 (37.5%) 1 (12.5%) 4 (50.0%) 3 (37.5%) 1 (12.5%) 5 (62.5%) 3 (37.5%) 0 (0.0%) 5 (62.5%) 3 (37.5%) 0 (0.0%) 1.000 Neovascularization 0 1 2 3 0 (0.0%) 5 (62.5%) 3 (37.5%) 0 (0.0%) 0 (0.0%) 3 (37.5%) 4 (50.0%) 1 (12.5%) 2 (25.0%) 5 (62.5%) 1 (12.5%) 0 (0.0%) 0 (0.0%) 2 (25.0%) 1 (12.5%) 5 (62.5%) 0.004 * Proliferation 1 2 3 0 (0.0%) 7 (87.5%) 1 (12.5%) 3 (37.5%) 5 (62.5%) 0 (0.0%) 2 (25.0%) 4 (50.0%) 2 (25.0%) 0 (0.0%) 0 (0.0%) 8 (100%) <0.001 * Fibrosis 1 2 3 4 (50.0%) 4 (50.0%) 0 (0.0%) 0 (0.0%) 5 (62.5%) 3 (37.5%) 1 (12.5%) 6 (75.0%) 1 (12.5%) 5 (62.5%) 3 (37.5%) 0 (0.0%) 0.025 * Foreign object - + 2 (25.0%) 6 (75.0%) 5 (62.5%) 3 (37.5%) 6 (75.0%) 2 (25.0%) 3 (37.5%) 5 (62.5%) 0.233 *p<0.05 HBO therapy: hyperbaric oxygen therapy The groups were compared according to the results of statistical analysis based on the histopathological data. The weights of the rats were recorded before the surgical procedure and at regular intervals, and the weights were equal between the groups; no statistically significant difference was observed (p = 0.956) (Table 3 ). Table 3 Comparison of the groups in terms of weight Control Enoxaparin sodium group HBO therapy group HBO and Enoxaparin sodium group p Weight 250.5 ± 14.8 247.7 ± 14.5 247.9 ± 11.8 247.4 ± 14.4 0.956 HBO therapy: hyperbaric oxygen therapy There was no significant difference between the groups in terms of acute inflammation (p = 0.785) or chronic inflammation (p = 0.827) scores, but there were significant differences in neovascularization (p = 0.009), proliferation (p < 0.001) and fibrosis (p = 0.006) scores. A statistical comparison of the histopathological findings between the groups is given in Table 4 . Table 4 Statistical comparison of histopathological findings between groups. Control Enoxaparin sodium group HBO therapy group HBO and Enoxaparin sodium group p Acute inflammation 0 (0) [0–1] 0 (0) [0–1] 0 (0) [0–1] 0 (0) [0–0] 0.785 Chronic inflammation 0.5 (1) [0–2] 0.5 (1) [0–2] 0 (1) [0–1] 0 (1) [0–1] 0.827 Neovascularization 1 (1) [ 1 – 2 ] 2 (1) [ 1 – 3 ] 1 (0.75) [0–2] 3 (1.75) [ 1 – 3 ] 0.009 * Proliferation 2 (0) [ 2 – 3 ] 2 (1) [ 1 – 2 ] 2 (1.5) [ 1 – 3 ] 3 (0) [ 3 – 3 ] < 0.001 * Fibrosis 1.5 (1) [ 1 – 2 ] 2 (1) [ 2 – 3 ] 2 (0) [ 1 – 3 ] 1 (1) [ 1 – 2 ] 0.006 * *p < 0.05 for HBO therapy: Hyperbarıc Oxygen Therapy. Data are presented as the median (interquartile range) and [minimum-maximum] values. A significant difference in terms of neovascularization was observed only between the hyperbaric oxygen and enoxaparin sodium + HBO groups (p = 0.006); the other groups were similar according to pairwise comparisons. Boxplots for neovascularization scores in the groups and mean rank plots for multiple comparisons are given in Fig. 3 . A significant difference in proliferation was observed in the enoxaparin sodium + HBO group compared with the other groups. The other groups were found to be similar when pairwise compared with the enoxaparin sodium and enoxaparin sodium + HBO (p < 0.001), hyperbaric oxygen and enoxaparin sodium + HBO (p = 0.017) and control and enoxaparin sodium + HBO (p = 0.034) groups. Boxplots for fibroblastic proliferation scores in the groups and mean rank plots for multiple comparisons are given in Fig. 4 . A significant difference in fibrosis was observed between the enoxaparin sodium group and the enoxaparin sodium + HBO group (p = 0.012) and between the control and enoxaparin sodium (p = 0.046) groups; the other groups were similar according to pairwise comparisons. Boxplots for fibrosis scores in the groups and mean rank plots for multiple comparisons are given in Fig. 5 . Discussion In this study, we determined the effect of enoxaparin sodium, which is frequently used after orthopedic surgery, and HBO therapy, which has been used for musculoskeletal problems in the last year, on Achilles tendon healing in rats. Tendon healing is a complex process in which cell proliferation, angiogenesis, extracellular matrix production, remodeling and maturation follow each other, and some growth factors affect healing.[ 14 ] Fibrin formation is mediated by thrombin. In clinical practice, antithrombotic agents are usually given as a single daily dose to prevent continuous thrombin and fibrin formation.[ 15 , 16 ] In some studies, antithrombotic agents were shown to positively affect healing by affecting the steps of the tendon healing process. However, it should be noted that these studies are very limited in number, and there are no studies in the literature investigating the effects of enoxaparin sodium on Achilles tendon healing.[ 17 , 18 ] In some studies, acute postrupture findings, such as hemorrhage and inflammation, have been shown to be prominent in Achilles tendon specimens. The reflex system, which is normally activated when the muscle-tendon junction is overloaded and prevents stretching, is impaired, so muscle strength exceeds tendon strength and rupture occurs.[ 19 ] There is still no consensus about the treatment applied after Achilles tendon rupture.[ 20 ] However, whichever treatment method is chosen, the aim should be for the patient to return to social life quickly and to reach his/her former sportive level. According to studies performed in athletes, while the rupture rate is 10–30% with conservative treatment, this rate remains at 2–3% with appropriate surgical techniques. It has been reported that the risk of rupture, muscle atrophy, and stiffness in the related joints are lower and that the return to sports is faster with surgical treatment.[ 21 ] With conservative treatment, the risk of adhesions, deep vein thrombosis, muscle trophism and joint stiffness due to long-term immobilization is greater.[ 22 ] There are various studies on Achilles tendon healing in the literature. Some applications showing positive effects on Achilles tendon healing include laser, ultrasound, and direct current electrical applications.[ 23 ] Again, some studies have reported that injecting platelets into the rat Achilles tendon accelerates healing.[ 24 ] HBO has a positive effect on wound healing by increasing oxygen in tissues. Therefore, it increases the formation of new vessels in tissue with reduced vascularization.[ 25 ] In different studies, the effects of hyperbaric oxygen therapy on early tendon healing in the treatment of Achilles tendon ruptures have been investigated, and while conflicting results have emerged, additional studies are needed on this subject.[ 26 ] In some studies, similar to our study, HBO therapy had a positive histological and biomechanical effect on tendon healing after Achilles tendon repair.[ 27 ] In the literature, the effect of LMWH on Achilles tendon healing has been investigated in studies on rats, and similar positive effects were found in our study; however, compared with all the other groups, the HBO treatment significantly contributed to the tendon healing process.[ 28 – 30 ] Although positive effects of these HBO treatment methods on healing have been shown, a definite treatment protocol has not yet been established. According to the results of our study, we found histopathologically that HBO therapy accelerates healing after Achilles tendon repair. In addition, the pharmacologic agent enoxaparin sodium, which is mostly used for reducing DVT risk, has a positive effect on healing after Achilles tendon surgery. For this reason, orthopedic surgeons in particular may need to use the clexane group recommendation longer. However, studies in larger series are needed on this subject. Since our study was an experimental study, no comparison could be made in terms of clinical or functional outcomes. Therefore, evaluating the results obtained in a manner similar to that used for Achilles tendon ruptures in humans may be misleading. Some of the important points that should not be overlooked when evaluating the results are the Achilles tendon incision we made, the age of the subject and the subject's ability to heal. In humans, such injuries are usually seen as ruptures in middle-aged individuals, where degenerative changes occur and there is less vascularity. Our injury model was created by making a straight incision with a scalpel, and the rats were young. Although these conditions seem to constitute limitations of our study, because the same type of injury was created in the tissues of the damaged area, the subjects were the same age, the feeding and living conditions were the same, and the metabolism and healing potential of the animals were equal, thus allowing the effectiveness of the treatments to be reliably investigated. Care was taken to ensure that the number of subjects in the study was the minimum number of subjects that would be statistically significant within the framework of ethical rules by performing power analysis by examining previous studies. The limitation of our study is that biomechanical evaluation could not be performed in our study. One of the limiting factors in our study was histologic evaluation. The lack of difference between the groups on histologic examination may be due to giant cell reactions caused by the suture material passing through the tendon and the resulting separations. As a result, the artifacts that were frequently observed may have negatively affected our histologic evaluation. Another limiting factor is that the duration of tendon healing in rats is not known.[ 31 ]According to the findings of our study, the use of enoxaparin sodium and hyperbaric oxygen had positive effects on the healing of Achilles tendon tears. Based on these results and considering the complications that may occur after Achilles tendon rupture, we believe that treatment with enoxaparin sodium and hyperbaric oxygen will be beneficial because it contributes to healing and prevents complications. Declarations Ethics approval: This study was approved by the Duzce University of Medical Sciences Ethics Committee for animal experiments and adhered to the institutional guidelines for the care and treatment of laboratory animals. (2021/02/03). Consent for publication: Not applicable. Availability of data and materials: The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request. Competing interests: The authors declare no competing interests. Funding: Not applicable. Authors contributions: Concept: C.E.A.,Y.T.,Z.O.K. ; Design: C.E.A.,Y.T.,M.A. ; Supervision – Y.T., Z.O.K., M.A.,S.S. ; Funding – None; Data Collection – C.E.A., S.K.C., V.U. ; Materials – C.E.A.,Y.T.,Z.O.K. ; Analysis – C.E.A., Y.T., Z.O.K., M.A. ; Literature Review – C.E.A., V.U., Z.O.K. S.S. ; Writing, M.A., Z.O.K., Y.T., S.K.C., S.S. and V.U. ; Critical Review – M.A., Z.O.K., V.U. Acknowledgements: Not applicable. References Suchak AA, Bostick G, Reid D, Blitz S, Jomha N (2005) The incidence of Achilles tendon ruptures in Edmonton, Canada. Foot Ankle Int 26:932-936. DOI 10.1177/107110070502601106 Park SH, Lee HS, Young KW, Seo SG (2020) Treatment of Acute Achilles Tendon Rupture. Clin Orthop Surg 12:1-8. DOI 10.4055/cios.2020.12.1.1 Holm C, Kjaer M, Eliasson P (2015) Achilles tendon rupture--treatment and complications: a systematic review. Scand J Med Sci Sports 25:e1-10. DOI 10.1111/sms.12209 Gould HP, Bano JM, Akman JL, Fillar AL (2021) Postoperative Rehabilitation Following Achilles Tendon Repair: A Systematic Review. Sports Med Arthrosc Rev 29:130-145. DOI 10.1097/jsa.0000000000000309 Maffulli N, Via AG, Oliva F (2015) Chronic Achilles Tendon Disorders: Tendinopathy and Chronic Rupture. Clin Sports Med 34:607-624. DOI 10.1016/j.csm.2015.06.010 Andarawis-Puri N, Flatow EL, Soslowsky LJ (2015) Tendon basic science: Development, repair, regeneration, and healing. J Orthop Res 33:780-784. DOI 10.1002/jor.22869 Sen S, Sen S (2021) Therapeutic effects of hyperbaric oxygen: integrated review. Med Gas Res 11:30-33. DOI 10.4103/2045-9912.310057 Shah J (2010) Hyperbaric oxygen therapy. J Am Col Certif Wound Spec 2:9-13. DOI 10.1016/j.jcws.2010.04.001 Onishi A, St Ange K, Dordick JS, Linhardt RJ (2016) Heparin and anticoagulation. Front Biosci (Landmark Ed) 21:1372-1392. DOI 10.2741/4462 Wong CC, Yeh YY, Yang TL, Tsuang YH, Chen CH (2020) Augmentation of Tendon Graft-Bone Tunnel Interface Healing by Use of Bioactive Platelet-Rich Fibrin Scaffolds. Am J Sports Med 48:1379-1388. DOI 10.1177/0363546520908849 Warkentin TE, Chong BH, Greinacher A (1998) Heparin-induced thrombocytopenia: towards consensus. Thromb Haemost 79:1-7 Sandset PM, Bendz B, Hansen JB (2000) Physiological function of tissue factor pathway inhibitor and interaction with heparins. Haemostasis 30 Suppl 2:48-56. DOI 10.1159/000054163 Kobayashi Y, Takeuchi H, Kitade M, Kikuchi I, Sato Y, Kinoshita K (2006) Pathological study of Fitz-Hugh-Curtis syndrome evaluated from fallopian tube damage. J Obstet Gynaecol Res 32:280-285. DOI 10.1111/j.1447-0756.2006.00399.x Voleti PB, Buckley MR, Soslowsky LJ (2012) Tendon healing: repair and regeneration. Annu Rev Biomed Eng 14:47-71. DOI 10.1146/annurev-bioeng-071811-150122 Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, Ortel TL, Pauker SG, Colwell CW, Jr. (2012) Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141:e278S-e325S. DOI 10.1378/chest.11-2404 Yang G, Rothrauff BB, Tuan RS (2013) Tendon and ligament regeneration and repair: clinical relevance and developmental paradigm. Birth Defects Res C Embryo Today 99:203-222. DOI 10.1002/bdrc.21041 Santana DC, Emara AK, Orr MN, Klika AK, Higuera CA, Krebs VE, Molloy RM, Piuzzi NS (2020) An Update on Venous Thromboembolism Rates and Prophylaxis in Hip and Knee Arthroplasty in 2020. Medicina (Kaunas) 56. DOI 10.3390/medicina56090416 Haac BE, O'Hara NN, Manson TT, Slobogean GP, Castillo RC, O'Toole RV, Stein DM (2020) Aspirin versus low-molecular-weight heparin for venous thromboembolism prophylaxis in orthopaedic trauma patients: A patient-centered randomized controlled trial. PLoS One 15:e0235628. DOI 10.1371/journal.pone.0235628 Dakin SG, Newton J, Martinez FO, Hedley R, Gwilym S, Jones N, Reid HAB, Wood S, Wells G, Appleton L, Wheway K, Watkins B, Carr AJ (2018) Chronic inflammation is a feature of Achilles tendinopathy and rupture. Br J Sports Med 52:359-367. DOI 10.1136/bjsports-2017-098161 Barfod KW (2014) Achilles tendon rupture; assessment of nonoperative treatment. Dan Med J 61:B4837 Caldwell JE, Vosseller JT (2019) Maximizing Return to Sports After Achilles Tendon Rupture in Athletes. Foot Ankle Clin 24:439-445. DOI 10.1016/j.fcl.2019.04.003 Brumann M, Baumbach SF, Mutschler W, Polzer H (2014) Accelerated rehabilitation following Achilles tendon repair after acute rupture - Development of an evidence-based treatment protocol. Injury 45:1782-1790. DOI 10.1016/j.injury.2014.06.022 Demir H, Menku P, Kirnap M, Calis M, Ikizceli I (2004) Comparison of the effects of laser, ultrasound, and combined laser + ultrasound treatments in experimental tendon healing. Lasers Surg Med 35:84-89. DOI 10.1002/lsm.20046 Aspenberg P, Virchenko O (2004) Platelet concentrate injection improves Achilles tendon repair in rats. Acta Orthop Scand 75:93-99. DOI 10.1080/00016470410001708190 Hyldegaard O, Hedetoft M (2020) [Hyperbaric oxygen therapy]. Ugeskr Laeger 182 Kirby JP, Snyder J, Schuerer DJE, Peters JS, Bochicchio GV (2019) Essentials of Hyperbaric Oxygen Therapy: 2019 Review. Mo Med 116:176-179 Sieg R, Garcia EJ, Schoenfeld AJ, Collins T, Owens BD (2011) Effects of supplemental oxygen and hyperbaric oxygen on tendon healing in a rat model. J Surg Orthop Adv 20:225-229 Moghadam N, Hieda M, Ramey L, Levine BD, Guilliod R (2020) Hyperbaric Oxygen Therapy in Sports Musculoskeletal Injuries. Med Sci Sports Exerc 52:1420-1426. DOI 10.1249/mss.0000000000002257 Kubo K, Ikebukuro T (2012) Acute and chronic effects of hyperbaric oxygen therapy on blood circulation of human muscle and tendon in vivo. J Strength Cond Res 26:2765-2770. DOI 10.1519/JSC.0b013e31826791da Leite CBG, Tavares LP, Leite MS, Demange MK (2023) Revisiting the role of hyperbaric oxygen therapy in knee injuries: Potential benefits and mechanisms. J Cell Physiol 238:498-512. DOI 10.1002/jcp.30947 Palabıyık MT, Akalın Y, Yalçın Ö, Şahin İ G, Çevik N, Öztürk A (2019) The Effect of Pentoxifylline and Hyperbaric Oxygen on Achilles Osteotendinous Junction İnjury: An experimental animal model study. Ortop Traumatol Rehabil 21:437-446. DOI 10.5604/01.3001.0013.7401 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 18 Jul, 2024 Read the published version in BMC Musculoskeletal Disorders → Version 1 posted Editorial decision: Revision requested 21 Jun, 2024 Reviews received at journal 07 Jun, 2024 Reviewers agreed at journal 29 May, 2024 Reviews received at journal 22 May, 2024 Reviewers agreed at journal 22 May, 2024 Reviews received at journal 05 May, 2024 Reviews received at journal 13 Apr, 2024 Reviewers agreed at journal 11 Apr, 2024 Reviewers agreed at journal 10 Apr, 2024 Reviewers invited by journal 09 Apr, 2024 Editor assigned by journal 04 Apr, 2024 Editor invited by journal 01 Apr, 2024 Submission checks completed at journal 28 Mar, 2024 First submitted to journal 21 Mar, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4143967","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":286201959,"identity":"3c64be2f-5e1b-41f1-8230-3b287b660a6f","order_by":0,"name":"Cafer Erman Aytekin","email":"","orcid":"","institution":"Duzce University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Cafer","middleName":"Erman","lastName":"Aytekin","suffix":""},{"id":286201960,"identity":"99f54dc4-412c-474b-82bf-782a4f2df04a","order_by":1,"name":"Yalçın Turhan","email":"","orcid":"","institution":"Duzce University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yalçın","middleName":"","lastName":"Turhan","suffix":""},{"id":286201961,"identity":"fb81086e-135e-452b-9f23-75081d79147a","order_by":2,"name":"Zekeriya Okan Karaduman","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIiWNgGAWjYBACCRDBA2YyHwNTbOzEa2FLY2BIAFLMxGvhMQNrYSCkRbL97MMPb9u2yZuz93x78PHHNnk+ZgbGDx9zcGuR5kk3lpzbdttwZ8/Z7YYzEm4btjEzMEvO3IZbixxDGoM0b9ttxg03crdJ8yTcZgRqYWPmxaeF/xnzb6AW+w03cp6BtNgT1CItkcYGsiURqIUNpCWRoBbJGc/YLOecu5284cwxM8kZabeT25gZm/H6ReJ8GvONN2W3bTccb34m8cHmtu389uaDHz7i0YINMDaQpn4UjIJRMApGAQYAAH3UTbVahxFCAAAAAElFTkSuQmCC","orcid":"","institution":"Duzce University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Zekeriya","middleName":"Okan","lastName":"Karaduman","suffix":""},{"id":286201963,"identity":"a8fc83dd-315d-468f-844f-0ce94c142283","order_by":3,"name":"Mehmet Arican","email":"","orcid":"","institution":"Duzce University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mehmet","middleName":"","lastName":"Arican","suffix":""},{"id":286201965,"identity":"0f5bc008-eafd-4e66-9317-84f19e8a42e2","order_by":4,"name":"Sönmez Sağlam","email":"","orcid":"","institution":"Duzce University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sönmez","middleName":"","lastName":"Sağlam","suffix":""},{"id":286201967,"identity":"8704a737-84f3-44db-8c1b-1c94896357c7","order_by":5,"name":"Sinem Kantarcıoğlu Coşkun","email":"","orcid":"","institution":"Duzce University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sinem","middleName":"Kantarcıoğlu","lastName":"Coşkun","suffix":""},{"id":286201969,"identity":"75e366c4-d1ef-4799-b44a-2b9ab5a69d5c","order_by":6,"name":"Veysel Uludağ","email":"","orcid":"","institution":"Duzce University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Veysel","middleName":"","lastName":"Uludağ","suffix":""}],"badges":[],"createdAt":"2024-03-21 13:44:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4143967/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4143967/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12891-024-07694-6","type":"published","date":"2024-07-18T16:13:13+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":53947767,"identity":"bf9d3e59-1a66-493f-b27a-a34514b38b97","added_by":"auto","created_at":"2024-04-02 15:01:40","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":71130,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHBO cabinet designed for animals\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"figure1300.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4143967/v1/8d87dc011ef4031fba99949d.jpg"},{"id":53947768,"identity":"dc1e5d70-d670-4bdf-8166-3fcb3ea0ce7b","added_by":"auto","created_at":"2024-04-02 15:01:40","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":603696,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eExposing and horizontally cutting the achilles tendon\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"figure2300.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4143967/v1/e79c3ff7f18787aa5777db68.jpg"},{"id":53947766,"identity":"6543b942-66db-4f7a-a052-cbad270315f3","added_by":"auto","created_at":"2024-04-02 15:01:40","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":234735,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e[A] Independent samplesKruskal‒Wallis test for neovascularization in the groups. [B] Boxplot for neovascularization scores in groups and mean rank plot for multiple comparisons\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4143967/v1/0b93b4973220c9bebe26edd1.jpg"},{"id":53947770,"identity":"77ca1cf7-b1ae-49f0-bddf-89e11f586f8a","added_by":"auto","created_at":"2024-04-02 15:01:41","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":231187,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e[A] Independent samplesKruskal‒Wallis test for fibroblastic proliferation in the groups. [B] Boxplot and mean rank plot for multiple comparisons of fibroblastic proliferation scores\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4143967/v1/6b846061e7fe1caece5e1eb3.jpg"},{"id":53947769,"identity":"3a2e442e-e59a-4dde-8993-b2b0aaaecc42","added_by":"auto","created_at":"2024-04-02 15:01:40","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":246700,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e[A] Independent samplesKruskal‒Wallis test for fibrosis incidence in the groups. [B] Boxplot with mean rank plot for fibrosis scores in groups and multiple comparisons\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4143967/v1/bb762a341f1e1c122a6d2f14.jpg"},{"id":61596715,"identity":"322f448a-ba18-498b-85cb-ce7c283822ed","added_by":"auto","created_at":"2024-08-01 17:29:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2070648,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4143967/v1/15bb94d1-140e-45ab-b8dd-da44d1c544f8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Investıgatıon of the Effects of Treatment with Enoxaparın Sodıum and Hyperbarıc Oxygen Therapy on the Recovery of Rats Wıth Achılles Tendon Rupture","fulltext":[{"header":"Background","content":"\u003cp\u003eAlthough the Achilles tendon is one of the strongest tendons in the human body, rupture rates have increased significantly in recent years with increasing physical activity in middle-aged and older people. There have been many studies on the treatment and healing of Achilles tendon rupture, and research on tendon healing is still ongoing to accelerate the return to social life after rupture and to reduce rerupture rates.\u003c/p\u003e \u003cp\u003eThe treatment of tendon pathologies, which are becoming increasingly common as a result of prolonged life expectancy and the increasing involvement of sporting activities for hobbies or health purposes, is maintaining importance in orthopedic surgery.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Although significant gains have been achieved with numerous studies and many surgical methods developed in this field, the difficulties and complications encountered continue to play an important role in the treatment process.[\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]Tendons are the most important parts of the musculoskeletal system and transfer the energy produced by the muscles to the bone. Because of the functions of these devices, tendon pathologies cause significant morbidity. Tendon injuries may occur due to acute trauma, chronic inflammatory conditions or overuse.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Tendon healing is a slow, progressive process.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] Because of these problems, new studies are constantly being conducted to improve treatment.\u003c/p\u003e \u003cp\u003eHBO therapy is a treatment method applied for many diseases; patients intermittently inhale 100% oxygen via various methods (mask, endotracheal tube, etc.) under pressure greater than one atmosphere in a closed pressure chamber.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] The efficacy of HBO therapy, which has been shown to have many positive effects on tissues, is due to hyperoxygenation, neovascularization, antimicrobial activity, pressure effects, vasoconstriction and a reduction in reperfusion damage.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] There are studies with successful results in many pathological conditions, such as necrotizing soft tissue infections, acute traumatic ischemia, crush injury, compartment syndrome, problematic wounds, problematic skin grafts and flaps, refractory osteomyelitis, osteonecrosis, sports injuries, fracture healing, nerve healing, carbon monoxide poisoning, and decompression sickness; additionally, there are cases where HBO therapy is added to treatment modalities.\u003c/p\u003e \u003cp\u003eAntithrombotic agents are now routinely used for thromboembolism prophylaxis in thromboembolism-prone patients before and after surgery in patients with major orthopedic injuries. Several studies have reported that low-molecular-weight heparin (LMWH) positively affects wound healing, increases macrophage stimulation, increases new vessel formation and decreases fibrous tissue formation.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] LMWH were developed to overcome the disadvantages of intravenous standard heparin. These patients do not require monitoring due to their predictable activity and do not require heparin. Moreover, the risk of thrombocytopenia is lower. Physiologically, LMWH shows high anti-Factor Xa activation[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] but relatively low anti-Factor IIa activity. This has made it an inevitable pharmacological agent for reducing deep vein thrombosis (DVT) risk, especially after orthopedic surgeries. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] The American Academy of Orthopaedic Surgeons (ACCP) recommends LMWHs as the main drug for VTE prophylaxis. (13) While such effects of LMWH are known, it is not known whether they affect tendon healing.\u003c/p\u003e \u003cp\u003eIn this study, we aimed to histopathologically compare the effects of LMWH, enoxaparin sodium treatment and HBO treatment, which are used to reduce the incidence of embolism prophylaxis due to immobilization after orthopedic surgeries, on Achilles tendon healing and to determine whether these treatments have positive or negative effects on healing.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eIn this study, a total of 36 male Wistar albino rats (age: three months [range, 2.5\u0026ndash;3.5 months], weighing 200 grams [range, 180\u0026ndash;220 grams]) (Duzce University Duzce Medical Faculty Experimental Animals Application and Research Center, Turkey) were used. Before the study, the necessary permission was obtained from the Ethics Committee (2021/02/03). The study was conducted in the Laboratory of the Experimental Animal Practice and Research Center of Duzce University. The principles of laboratory animal care were followed in this study. Our study was reported in accordance with ARRIVE guidelines and experimental animal ethics committee.\u003c/p\u003e \u003cp\u003eAnimals were randomly divided into 4 groups with 9 rats in each cage and monitored in the laboratory for 1 week preoperatively. During the study period, the rats were given unlimited tap water (ad libitum) and standard rodent feed. The animals were caged in a room with a controlled temperature (23\u0026ndash;25\u0026deg;C) and a 12/12-hour light/dark cycle with 50\u0026ndash;60% humidity. After the animals used in the study were brought to the laboratory center, they were followed in their cages for approximately 1 week without any treatment. On the day of the study, the rats were brought to the research laboratory and weighed. The HBO cabinet designed for animals is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eSurgical Procedure\u003c/h2\u003e \u003cp\u003eThe rats were anesthetized intramuscularly with ketamine (90 mg/kg) and xylazine (6 mg/kg), and the posterior regions of the left hindfoot were shaved, following the rules of asepsis and antisepsis. For the exposure of the Achilles tendon, a 2.5 cm long longitudinal midline incision was made over the tendon. The Achilles tendon was then cut horizontally 0.5 cm proximal to its attachment to the calcaneus with a No. 15 scalpel. No external fixation agent was applied to the rats, and they were allowed to move freely in the cage after surgery. Fentanyl citrate (0.02 mg/kg) was administered subcutaneously for analgesia for 3 days after surgery. Exposing the Achilles tendon and cutting it horizontally is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStudy groups\u003c/h2\u003e \u003cp\u003eProphylactic antibiotics were administered to all groups after surgery. No rats died in any group after the operation. No wound site infection was observed in any of the rats during follow-up. The control group (n\u0026thinsp;=\u0026thinsp;9) was named Group 1, and the enoxaparin sodium group (n\u0026thinsp;=\u0026thinsp;9) was named Group 2. The HBO group (n\u0026thinsp;=\u0026thinsp;9) was used as Group 3, and the enoxaparin sodium and HBO groups (n\u0026thinsp;=\u0026thinsp;9) were used as Group 4.\u003c/p\u003e \u003cp\u003eThe distribution of the experimental animals used in the study according to group is given in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of experimental animals used in the study according to group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTime of sacrification (histopathologic examination)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21st day\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEnoxaparin sodium group (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21st day\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHBO therapy group (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21st day\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHBO and Enoxaparin sodium group (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21st day\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTreatment was started on the first postoperative day. A total of 21 sessions of HBO treatment were administered to 9 rats in Group 3 and Group 4 once a day. The treatment was performed in a 100x55 cm hyperbaric oxygen chamber specially built for experimental animals, where 18 rats could fit together with their cages at the same time. After 21 sessions, the treatment was terminated. The treatments were performed at 2.5 ATA pressure, and each session lasted 60 minutes in total. Before the treatment, the chamber was flushed with 100% oxygen for 5 minutes, after which the pressure in the chamber was gradually increased, and the desired treatment depth was reached within 5 minutes. Treatment was performed at 2.5 ATA pressure for 60 minutes, decompression was achieved in 10 minutes, and the treatment was terminated in a total of 80 minutes.\u003c/p\u003e \u003cp\u003eEighteen rats were in Group 2, and 18 rats were in Group 4. Clexane (clexane with the active ingredient enoxaparin sodium) was administered subcutaneously at a single dose of 1 mg/kg/day in a standard manner. No complications were encountered.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eHistopathological examination\u003c/h2\u003e \u003cp\u003eIn each group, the experimental animals underwent resection at least 1 cm from the distal and proximal ends of the wound site. A 1 cm portion of the wound site was excised 0.5 cm proximal and 0.5 cm distal. After the animals were sacrificed, the sections taken from the Achilles tendons were incubated in xylol twice for 10 minutes each in the Department of Pathology, Duzce University Faculty of Medicine. In this study, we used the modified Curtis method described by Kobayashi et al. for histopathological examination.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] From 15 different areas, inflammatory cells, vessels, and fusiform fibroblastic cells were counted and averaged. Inflammatory cells were graded according to fibroblastic profiling and fibrosis status: (0) no fibroblastic profiling and fibrosis, (1) mild, (2) moderate, and (3) significant. Neovascularization was recorded as (1) mild or capillary vessel number between 0 and 5. (2) Moderate: capillary vessel number between 5 and 10. (3) A capillary vessel number greater than 10 was considered to be significant.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe Kruskal‒Wallis test was used for group comparisons. For multiple comparisons, groups were compared with post hoc Bonferroni correction. The data are presented as medians, interquartile ranges and minimum-maximum values. Categorical variables were compared with the Fisher\u0026ndash;Freeman\u0026ndash;Halton test and are presented as numbers and percentages. All the statistical analyses were performed with the SPSS v.22 package, and a level of statistical significance was set at 0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eHistopathologic scoring between the groups is given in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003ctable style=\"width: 870px;\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cp\u003eTable 2\u003c/p\u003e\n\u003cp\u003eHistopathological score distributions between groups\u003c/p\u003e\n\u003c/caption\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 152.469px;\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 100.531px;\"\u003e\n\u003cp\u003e\u003cstrong\u003eControl\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 118px;\"\u003e\n\u003cp\u003e\u003cstrong\u003eEnoxaparin sodium group\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\"\u003e\n\u003cp\u003e\u003cstrong\u003eHBO therapy group\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156px;\"\u003e\n\u003cp\u003e\u003cstrong\u003eHBO and Enoxaparin sodium group\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 167px;\"\u003e\n\u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 152.469px;\"\u003e\n\u003cp\u003eAcute inflammation\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 0\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 100.531px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e7 (87.5%)\u003c/p\u003e\n\u003cp\u003e1 (12.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 118px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e7 (87.5%)\u003c/p\u003e\n\u003cp\u003e1 (12.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e7 (87.5%)\u003c/p\u003e\n\u003cp\u003e1 (12.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e8 (100%)\u003c/p\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 167px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 152.469px;\"\u003e\n\u003cp\u003eChronic inflammation\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 0\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 1\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 100.531px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e4 (50.0%)\u003c/p\u003e\n\u003cp\u003e3 (37.5%)\u003c/p\u003e\n\u003cp\u003e1 (12.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 118px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e4 (50.0%)\u003c/p\u003e\n\u003cp\u003e3 (37.5%)\u003c/p\u003e\n\u003cp\u003e1 (12.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e5 (62.5%)\u003c/p\u003e\n\u003cp\u003e3 (37.5%)\u003c/p\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e5 (62.5%)\u003c/p\u003e\n\u003cp\u003e3 (37.5%)\u003c/p\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 167px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 152.469px;\"\u003e\n\u003cp\u003eNeovascularization\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 0\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 1\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 2\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 100.531px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003cp\u003e5 (62.5%)\u003c/p\u003e\n\u003cp\u003e3 (37.5%)\u003c/p\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 118px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003cp\u003e3 (37.5%)\u003c/p\u003e\n\u003cp\u003e4 (50.0%)\u003c/p\u003e\n\u003cp\u003e1 (12.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2 (25.0%)\u003c/p\u003e\n\u003cp\u003e5 (62.5%)\u003c/p\u003e\n\u003cp\u003e1 (12.5%)\u003c/p\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003cp\u003e2 (25.0%)\u003c/p\u003e\n\u003cp\u003e1 (12.5%)\u003c/p\u003e\n\u003cp\u003e5 (62.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 167px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.004\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 152.469px;\"\u003e\n\u003cp\u003eProliferation\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 1\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 2\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 100.531px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003cp\u003e7 (87.5%)\u003c/p\u003e\n\u003cp\u003e1 (12.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 118px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3 (37.5%)\u003c/p\u003e\n\u003cp\u003e5 (62.5%)\u003c/p\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2 (25.0%)\u003c/p\u003e\n\u003cp\u003e4 (50.0%)\u003c/p\u003e\n\u003cp\u003e2 (25.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003cp\u003e8 (100%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 167px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026lt;0.001\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 152.469px;\"\u003e\n\u003cp\u003eFibrosis\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 1\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 2\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 100.531px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e4 (50.0%)\u003c/p\u003e\n\u003cp\u003e4 (50.0%)\u003c/p\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 118px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003cp\u003e5 (62.5%)\u003c/p\u003e\n\u003cp\u003e3 (37.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1 (12.5%)\u003c/p\u003e\n\u003cp\u003e6 (75.0%)\u003c/p\u003e\n\u003cp\u003e1 (12.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e5 (62.5%)\u003c/p\u003e\n\u003cp\u003e3 (37.5%)\u003c/p\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 167px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.025\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 152.469px;\"\u003e\n\u003cp\u003eForeign object\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; -\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; +\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 100.531px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2 (25.0%)\u003c/p\u003e\n\u003cp\u003e6 (75.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 118px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e5 (62.5%)\u003c/p\u003e\n\u003cp\u003e3 (37.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e6 (75.0%)\u003c/p\u003e\n\u003cp\u003e2 (25.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 156px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3 (37.5%)\u003c/p\u003e\n\u003cp\u003e5 (62.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 167px;\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.233\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*p\u0026lt;0.05 HBO therapy: hyperbaric oxygen therapy\u003c/p\u003e\n\u003cp\u003eThe groups were compared according to the results of statistical analysis based on the histopathological data. The weights of the rats were recorded before the surgical procedure and at regular intervals, and the weights were equal between the groups; no statistically significant difference was observed (p\u0026thinsp;=\u0026thinsp;0.956) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eComparison of the groups in terms of weight\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eControl\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eEnoxaparin sodium group\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eHBO therapy group\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eHBO and Enoxaparin sodium group\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWeight\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e250.5\u0026thinsp;\u0026plusmn;\u0026thinsp;14.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e247.7\u0026thinsp;\u0026plusmn;\u0026thinsp;14.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e247.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e247.4\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.956\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"6\"\u003eHBO therapy: hyperbaric oxygen therapy\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThere was no significant difference between the groups in terms of acute inflammation (p\u0026thinsp;=\u0026thinsp;0.785) or chronic inflammation (p\u0026thinsp;=\u0026thinsp;0.827) scores, but there were significant differences in neovascularization (p\u0026thinsp;=\u0026thinsp;0.009), proliferation (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and fibrosis (p\u0026thinsp;=\u0026thinsp;0.006) scores. A statistical comparison of the histopathological findings between the groups is given in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eStatistical comparison of histopathological findings between groups.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eControl\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eEnoxaparin sodium group\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eHBO therapy group\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eHBO and Enoxaparin sodium group\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAcute inflammation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003cp\u003e[0\u0026ndash;1]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003cp\u003e[0\u0026ndash;1]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003cp\u003e[0\u0026ndash;1]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003cp\u003e[0\u0026ndash;0]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.785\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChronic inflammation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.5 (1)\u003c/p\u003e\n\u003cp\u003e[0\u0026ndash;2]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.5 (1)\u003c/p\u003e\n\u003cp\u003e[0\u0026ndash;2]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (1)\u003c/p\u003e\n\u003cp\u003e[0\u0026ndash;1]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (1)\u003c/p\u003e\n\u003cp\u003e[0\u0026ndash;1]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.827\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNeovascularization\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (1)\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (1)\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (0.75)\u003c/p\u003e\n\u003cp\u003e[0\u0026ndash;2]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (1.75)\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.009\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eProliferation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (0)\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (1)\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (1.5)\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (0)\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFibrosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.5 (1)\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (1)\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (0)\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (1)\u003c/p\u003e\n\u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.006\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"6\"\u003e*p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 for HBO therapy: Hyperbarıc Oxygen Therapy. Data are presented as the median (interquartile range) and [minimum-maximum] values.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eA significant difference in terms of neovascularization was observed only between the hyperbaric oxygen and enoxaparin sodium\u0026thinsp;+\u0026thinsp;HBO groups (p\u0026thinsp;=\u0026thinsp;0.006); the other groups were similar according to pairwise comparisons. Boxplots for neovascularization scores in the groups and mean rank plots for multiple comparisons are given in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003eA significant difference in proliferation was observed in the enoxaparin sodium\u0026thinsp;+\u0026thinsp;HBO group compared with the other groups. The other groups were found to be similar when pairwise compared with the enoxaparin sodium and enoxaparin sodium\u0026thinsp;+\u0026thinsp;HBO (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), hyperbaric oxygen and enoxaparin sodium\u0026thinsp;+\u0026thinsp;HBO (p\u0026thinsp;=\u0026thinsp;0.017) and control and enoxaparin sodium\u0026thinsp;+\u0026thinsp;HBO (p\u0026thinsp;=\u0026thinsp;0.034) groups. Boxplots for fibroblastic proliferation scores in the groups and mean rank plots for multiple comparisons are given in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003eA significant difference in fibrosis was observed between the enoxaparin sodium group and the enoxaparin sodium\u0026thinsp;+\u0026thinsp;HBO group (p\u0026thinsp;=\u0026thinsp;0.012) and between the control and enoxaparin sodium (p\u0026thinsp;=\u0026thinsp;0.046) groups; the other groups were similar according to pairwise comparisons. Boxplots for fibrosis scores in the groups and mean rank plots for multiple comparisons are given in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we determined the effect of enoxaparin sodium, which is frequently used after orthopedic surgery, and HBO therapy, which has been used for musculoskeletal problems in the last year, on Achilles tendon healing in rats. Tendon healing is a complex process in which cell proliferation, angiogenesis, extracellular matrix production, remodeling and maturation follow each other, and some growth factors affect healing.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] Fibrin formation is mediated by thrombin. In clinical practice, antithrombotic agents are usually given as a single daily dose to prevent continuous thrombin and fibrin formation.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] In some studies, antithrombotic agents were shown to positively affect healing by affecting the steps of the tendon healing process. However, it should be noted that these studies are very limited in number, and there are no studies in the literature investigating the effects of enoxaparin sodium on Achilles tendon healing.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn some studies, acute postrupture findings, such as hemorrhage and inflammation, have been shown to be prominent in Achilles tendon specimens. The reflex system, which is normally activated when the muscle-tendon junction is overloaded and prevents stretching, is impaired, so muscle strength exceeds tendon strength and rupture occurs.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] There is still no consensus about the treatment applied after Achilles tendon rupture.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] However, whichever treatment method is chosen, the aim should be for the patient to return to social life quickly and to reach his/her former sportive level. According to studies performed in athletes, while the rupture rate is 10\u0026ndash;30% with conservative treatment, this rate remains at 2\u0026ndash;3% with appropriate surgical techniques. It has been reported that the risk of rupture, muscle atrophy, and stiffness in the related joints are lower and that the return to sports is faster with surgical treatment.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] With conservative treatment, the risk of adhesions, deep vein thrombosis, muscle trophism and joint stiffness due to long-term immobilization is greater.[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThere are various studies on Achilles tendon healing in the literature. Some applications showing positive effects on Achilles tendon healing include laser, ultrasound, and direct current electrical applications.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] Again, some studies have reported that injecting platelets into the rat Achilles tendon accelerates healing.[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] HBO has a positive effect on wound healing by increasing oxygen in tissues. Therefore, it increases the formation of new vessels in tissue with reduced vascularization.[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] In different studies, the effects of hyperbaric oxygen therapy on early tendon healing in the treatment of Achilles tendon ruptures have been investigated, and while conflicting results have emerged, additional studies are needed on this subject.[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] In some studies, similar to our study, HBO therapy had a positive histological and biomechanical effect on tendon healing after Achilles tendon repair.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn the literature, the effect of LMWH on Achilles tendon healing has been investigated in studies on rats, and similar positive effects were found in our study; however, compared with all the other groups, the HBO treatment significantly contributed to the tendon healing process.[\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAlthough positive effects of these HBO treatment methods on healing have been shown, a definite treatment protocol has not yet been established. According to the results of our study, we found histopathologically that HBO therapy accelerates healing after Achilles tendon repair. In addition, the pharmacologic agent enoxaparin sodium, which is mostly used for reducing DVT risk, has a positive effect on healing after Achilles tendon surgery. For this reason, orthopedic surgeons in particular may need to use the clexane group recommendation longer. However, studies in larger series are needed on this subject.\u003c/p\u003e \u003cp\u003eSince our study was an experimental study, no comparison could be made in terms of clinical or functional outcomes. Therefore, evaluating the results obtained in a manner similar to that used for Achilles tendon ruptures in humans may be misleading. Some of the important points that should not be overlooked when evaluating the results are the Achilles tendon incision we made, the age of the subject and the subject's ability to heal. In humans, such injuries are usually seen as ruptures in middle-aged individuals, where degenerative changes occur and there is less vascularity. Our injury model was created by making a straight incision with a scalpel, and the rats were young. Although these conditions seem to constitute limitations of our study, because the same type of injury was created in the tissues of the damaged area, the subjects were the same age, the feeding and living conditions were the same, and the metabolism and healing potential of the animals were equal, thus allowing the effectiveness of the treatments to be reliably investigated. Care was taken to ensure that the number of subjects in the study was the minimum number of subjects that would be statistically significant within the framework of ethical rules by performing power analysis by examining previous studies.\u003c/p\u003e \u003cp\u003eThe limitation of our study is that biomechanical evaluation could not be performed in our study. One of the limiting factors in our study was histologic evaluation. The lack of difference between the groups on histologic examination may be due to giant cell reactions caused by the suture material passing through the tendon and the resulting separations. As a result, the artifacts that were frequently observed may have negatively affected our histologic evaluation. Another limiting factor is that the duration of tendon healing in rats is not known.[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]According to the findings of our study, the use of enoxaparin sodium and hyperbaric oxygen had positive effects on the healing of Achilles tendon tears. Based on these results and considering the complications that may occur after Achilles tendon rupture, we believe that treatment with enoxaparin sodium and hyperbaric oxygen will be beneficial because it contributes to healing and prevents complications.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e This study was approved by the Duzce University of Medical Sciences Ethics Committee for animal experiments and adhered to the institutional guidelines for the care and treatment of laboratory animals. (2021/02/03).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contributions:\u003c/strong\u003e Concept: C.E.A.,Y.T.,Z.O.K. ; Design: C.E.A.,Y.T.,M.A. ; Supervision \u0026ndash; Y.T., Z.O.K., M.A.,S.S. ; Funding \u0026ndash; None; Data Collection \u0026ndash; C.E.A., S.K.C., V.U. ; Materials \u0026ndash; C.E.A.,Y.T.,Z.O.K. ; Analysis \u0026ndash; C.E.A., Y.T., Z.O.K., M.A. ; Literature Review \u0026ndash; C.E.A., V.U., Z.O.K. S.S. ; Writing, M.A., Z.O.K., Y.T., S.K.C., S.S. and V.U. ; Critical Review \u0026ndash; M.A., Z.O.K., V.U.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e Not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSuchak AA, Bostick G, Reid D, Blitz S, Jomha N (2005) The incidence of Achilles tendon ruptures in Edmonton, Canada. Foot Ankle Int 26:932-936. DOI 10.1177/107110070502601106\u003c/li\u003e\n\u003cli\u003ePark SH, Lee HS, Young KW, Seo SG (2020) Treatment of Acute Achilles Tendon Rupture. Clin Orthop Surg 12:1-8. DOI 10.4055/cios.2020.12.1.1\u003c/li\u003e\n\u003cli\u003eHolm C, Kjaer M, Eliasson P (2015) Achilles tendon rupture--treatment and complications: a systematic review. Scand J Med Sci Sports 25:e1-10. DOI 10.1111/sms.12209\u003c/li\u003e\n\u003cli\u003eGould HP, Bano JM, Akman JL, Fillar AL (2021) Postoperative Rehabilitation Following Achilles Tendon Repair: A Systematic Review. Sports Med Arthrosc Rev 29:130-145. DOI 10.1097/jsa.0000000000000309\u003c/li\u003e\n\u003cli\u003eMaffulli N, Via AG, Oliva F (2015) Chronic Achilles Tendon Disorders: Tendinopathy and Chronic Rupture. Clin Sports Med 34:607-624. DOI 10.1016/j.csm.2015.06.010\u003c/li\u003e\n\u003cli\u003eAndarawis-Puri N, Flatow EL, Soslowsky LJ (2015) Tendon basic science: Development, repair, regeneration, and healing. J Orthop Res 33:780-784. DOI 10.1002/jor.22869\u003c/li\u003e\n\u003cli\u003eSen S, Sen S (2021) Therapeutic effects of hyperbaric oxygen: integrated review. Med Gas Res 11:30-33. DOI 10.4103/2045-9912.310057\u003c/li\u003e\n\u003cli\u003eShah J (2010) Hyperbaric oxygen therapy. J Am Col Certif Wound Spec 2:9-13. DOI 10.1016/j.jcws.2010.04.001\u003c/li\u003e\n\u003cli\u003eOnishi A, St Ange K, Dordick JS, Linhardt RJ (2016) Heparin and anticoagulation. Front Biosci (Landmark Ed) 21:1372-1392. DOI 10.2741/4462\u003c/li\u003e\n\u003cli\u003eWong CC, Yeh YY, Yang TL, Tsuang YH, Chen CH (2020) Augmentation of Tendon Graft-Bone Tunnel Interface Healing by Use of Bioactive Platelet-Rich Fibrin Scaffolds. Am J Sports Med 48:1379-1388. DOI 10.1177/0363546520908849\u003c/li\u003e\n\u003cli\u003eWarkentin TE, Chong BH, Greinacher A (1998) Heparin-induced thrombocytopenia: towards consensus. Thromb Haemost 79:1-7\u003c/li\u003e\n\u003cli\u003eSandset PM, Bendz B, Hansen JB (2000) Physiological function of tissue factor pathway inhibitor and interaction with heparins. Haemostasis 30 Suppl 2:48-56. DOI 10.1159/000054163\u003c/li\u003e\n\u003cli\u003eKobayashi Y, Takeuchi H, Kitade M, Kikuchi I, Sato Y, Kinoshita K (2006) Pathological study of Fitz-Hugh-Curtis syndrome evaluated from fallopian tube damage. J Obstet Gynaecol Res 32:280-285. DOI 10.1111/j.1447-0756.2006.00399.x\u003c/li\u003e\n\u003cli\u003eVoleti PB, Buckley MR, Soslowsky LJ (2012) Tendon healing: repair and regeneration. Annu Rev Biomed Eng 14:47-71. DOI 10.1146/annurev-bioeng-071811-150122\u003c/li\u003e\n\u003cli\u003eFalck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, Ortel TL, Pauker SG, Colwell CW, Jr. (2012) Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141:e278S-e325S. DOI 10.1378/chest.11-2404\u003c/li\u003e\n\u003cli\u003eYang G, Rothrauff BB, Tuan RS (2013) Tendon and ligament regeneration and repair: clinical relevance and developmental paradigm. Birth Defects Res C Embryo Today 99:203-222. DOI 10.1002/bdrc.21041\u003c/li\u003e\n\u003cli\u003eSantana DC, Emara AK, Orr MN, Klika AK, Higuera CA, Krebs VE, Molloy RM, Piuzzi NS (2020) An Update on Venous Thromboembolism Rates and Prophylaxis in Hip and Knee Arthroplasty in 2020. Medicina (Kaunas) 56. DOI 10.3390/medicina56090416\u003c/li\u003e\n\u003cli\u003eHaac BE, O\u0026apos;Hara NN, Manson TT, Slobogean GP, Castillo RC, O\u0026apos;Toole RV, Stein DM (2020) Aspirin versus low-molecular-weight heparin for venous thromboembolism prophylaxis in orthopaedic trauma patients: A patient-centered randomized controlled trial. PLoS One 15:e0235628. DOI 10.1371/journal.pone.0235628\u003c/li\u003e\n\u003cli\u003eDakin SG, Newton J, Martinez FO, Hedley R, Gwilym S, Jones N, Reid HAB, Wood S, Wells G, Appleton L, Wheway K, Watkins B, Carr AJ (2018) Chronic inflammation is a feature of Achilles tendinopathy and rupture. Br J Sports Med 52:359-367. DOI 10.1136/bjsports-2017-098161\u003c/li\u003e\n\u003cli\u003eBarfod KW (2014) Achilles tendon rupture; assessment of nonoperative treatment. Dan Med J 61:B4837\u003c/li\u003e\n\u003cli\u003eCaldwell JE, Vosseller JT (2019) Maximizing Return to Sports After Achilles Tendon Rupture in Athletes. Foot Ankle Clin 24:439-445. DOI 10.1016/j.fcl.2019.04.003\u003c/li\u003e\n\u003cli\u003eBrumann M, Baumbach SF, Mutschler W, Polzer H (2014) Accelerated rehabilitation following Achilles tendon repair after acute rupture - Development of an evidence-based treatment protocol. Injury 45:1782-1790. DOI 10.1016/j.injury.2014.06.022\u003c/li\u003e\n\u003cli\u003eDemir H, Menku P, Kirnap M, Calis M, Ikizceli I (2004) Comparison of the effects of laser, ultrasound, and combined laser + ultrasound treatments in experimental tendon healing. Lasers Surg Med 35:84-89. DOI 10.1002/lsm.20046\u003c/li\u003e\n\u003cli\u003eAspenberg P, Virchenko O (2004) Platelet concentrate injection improves Achilles tendon repair in rats. Acta Orthop Scand 75:93-99. DOI 10.1080/00016470410001708190\u003c/li\u003e\n\u003cli\u003eHyldegaard O, Hedetoft M (2020) [Hyperbaric oxygen therapy]. Ugeskr Laeger 182 \u003c/li\u003e\n\u003cli\u003eKirby JP, Snyder J, Schuerer DJE, Peters JS, Bochicchio GV (2019) Essentials of Hyperbaric Oxygen Therapy: 2019 Review. Mo Med 116:176-179\u003c/li\u003e\n\u003cli\u003eSieg R, Garcia EJ, Schoenfeld AJ, Collins T, Owens BD (2011) Effects of supplemental oxygen and hyperbaric oxygen on tendon healing in a rat model. J Surg Orthop Adv 20:225-229\u003c/li\u003e\n\u003cli\u003eMoghadam N, Hieda M, Ramey L, Levine BD, Guilliod R (2020) Hyperbaric Oxygen Therapy in Sports Musculoskeletal Injuries. Med Sci Sports Exerc 52:1420-1426. DOI 10.1249/mss.0000000000002257\u003c/li\u003e\n\u003cli\u003eKubo K, Ikebukuro T (2012) Acute and chronic effects of hyperbaric oxygen therapy on blood circulation of human muscle and tendon in vivo. J Strength Cond Res 26:2765-2770. DOI 10.1519/JSC.0b013e31826791da\u003c/li\u003e\n\u003cli\u003eLeite CBG, Tavares LP, Leite MS, Demange MK (2023) Revisiting the role of hyperbaric oxygen therapy in knee injuries: Potential benefits and mechanisms. J Cell Physiol 238:498-512. DOI 10.1002/jcp.30947\u003c/li\u003e\n\u003cli\u003ePalabıyık MT, Akalın Y, Yal\u0026ccedil;ın \u0026Ouml;, Şahin İ G, \u0026Ccedil;evik N, \u0026Ouml;zt\u0026uuml;rk A (2019) The Effect of Pentoxifylline and Hyperbaric Oxygen on Achilles Osteotendinous Junction İnjury: An experimental animal model study. Ortop Traumatol Rehabil 21:437-446. DOI 10.5604/01.3001.0013.7401\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":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Achilles tendon rupture, hyperbaric oxygen therapy, enoxaparin sodium, rat","lastPublishedDoi":"10.21203/rs.3.rs-4143967/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4143967/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eIn this study, we aimed to investigate the effects of hyperbaric oxygen therapy and enoxaparin sodium, which are known to accelerate bone tissue healing as well as tendon and soft tissue healing, on the healing of Achilles tendon rupture.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThirty-six rats were used in the present study. All rats were divided into groups of nine. The groups were the enoxaparin sodium group, enoxaparin sodium and hyperbaric oxygen group, hyperbaric oxygen group and control group. After 21 days, the process was completed, and the rats were sacrificed. Achilles tendon samples were evaluated histopathologically.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe groups were compared according to the results of statistical analysis based on the histopathological data. There was no significant difference between the groups in terms of acute inflammation (p\u0026thinsp;=\u0026thinsp;0.785) or chronic inflammation (p\u0026thinsp;=\u0026thinsp;0.827) scores, but there were significant differences in neovascularization (p\u0026thinsp;=\u0026thinsp;0.009), proliferation (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and fibrosis (p\u0026thinsp;=\u0026thinsp;0.006) scores.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur study showed that the use of enoxaparin sodium and hyperbaric oxygen had a positive effect on the healing of the Achilles tendon. Based on these results, we believe that the use of enoxaparin sodium and hyperbaric oxygen therapy after Achilles tendon rupture will be beneficial for healing and preventing complications.\u003c/p\u003e","manuscriptTitle":"Investıgatıon of the Effects of Treatment with Enoxaparın Sodıum and Hyperbarıc Oxygen Therapy on the Recovery of Rats Wıth Achılles Tendon Rupture","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-02 15:01:36","doi":"10.21203/rs.3.rs-4143967/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-21T10:44:58+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-07T08:06:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"205139415144971005765351623671805614930","date":"2024-05-29T07:19:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-22T20:21:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"161024486909719673868134774162365894813","date":"2024-05-22T16:57:34+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-05T11:51:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-13T17:13:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"e16eff0a-ac51-4dcb-b24f-45a3449b78f2_SNPRID","date":"2024-04-11T07:41:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"0f8409c9-fa0f-4825-a799-6f230ca0bbc1","date":"2024-04-10T07:40:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-10T01:34:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-05T00:51:05+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-04-01T13:52:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-28T11:39:36+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Musculoskeletal Disorders","date":"2024-03-21T13:42:46+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1ee71456-fe5c-4a99-8c43-168d9542a6f4","owner":[],"postedDate":"April 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-01T17:13:27+00:00","versionOfRecord":{"articleIdentity":"rs-4143967","link":"https://doi.org/10.1186/s12891-024-07694-6","journal":{"identity":"bmc-musculoskeletal-disorders","isVorOnly":false,"title":"BMC Musculoskeletal Disorders"},"publishedOn":"2024-07-18 16:13:13","publishedOnDateReadable":"July 18th, 2024"},"versionCreatedAt":"2024-04-02 15:01:36","video":"","vorDoi":"10.1186/s12891-024-07694-6","vorDoiUrl":"https://doi.org/10.1186/s12891-024-07694-6","workflowStages":[]},"version":"v1","identity":"rs-4143967","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4143967","identity":"rs-4143967","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}