Tendon Healing In Rats Research Articles

The effect of papaverine on tendon healing and adhesion in rats following Achilles tendon repair.

The study aimed to examine the histopathological and biomechanical effects of papaverine administered intraperitoneally and locally on Achilles tendon healing in a rat model. Forty-eight adult male Sprague-Dawley rats (range, 300 to 400 g) were used in this study conducted between October and November 2022. The rats were divided into three groups, with each group further subdivided into two for sacrifice on either the 15th (early period) or 30th (late period) day after surgery. The first (control) group received no treatment following Achilles tendon repair, while papaverine was intraperitoneally administered every other day for 10 days in the second group and locally in the third group after surgery. On the 15th and 30th days, the rats were sacrificed, and their Achilles tendons were subjected to biomechanical testing and histopathological evaluation. Histopathologically, there were no significant differences among the groups on the 15th day. However, on the 30th day, the locally applied papaverine group exhibited superior histopathological outcomes compared to the control group (p<0.05). Concerning the highest tensile strength values before rupture, the biomechanical assessment showed that the group receiving local papaverine treatment in the early period and both the group with systemic papaverine treatment and the one with local papaverine treatment in the late period displayed a statistically significant advantage compared to the control group (p<0.05). Locally administered papaverine has positive biomechanical effects in the early period and exhibits a positive correlation both histopathologically and biomechanically in the late period. Novel therapeutic options may be provided for patients through these findings.

The effects of zinc sulfate mineral supplementation on Achilles tendon healing in rats.

The Achilles tendon is the most commonly injured and ruptured tendon in the body and typically occurs during participation in sports or recreational activities in men between 30 and 50 years of age. Treatment options for Achilles tendon rupture include conservative and surgical approaches. Conservative treatment is associated with a higher risk of rerupture, while surgical treatment carries a risk of wound site complications. Generally, both methods result in a prolonged tendon healing time. Studies are ongoing to identify biomolecules that aid tendon repair. The main objective of our study is to investigate the effects of zinc sulfate (ZnSO4) mineral supplementation on Achilles tendon healing in rats. Forty-eight female Sprague-Dawley rats were divided into four equal groups (C-15, C-30, ZnSO4-15, and ZnSO4-30) after standard Achilles tendon repair surgery. The ZnSO4-15 and ZnSO4-30 groups received an oral zinc sulfate monohydrate solution (50 mg/kg/day) for 15 and 30 days, respectively. The C-15 and C-30 groups were given 1 mL of distilled water per day orally during the experimental periods. Rats were sacrificed on the 15th and 30th day depending on their groups, and the healing of the operated tendons was evaluated using Movin and Bonar histopathologic scoring. For biomechanical analyses, the operated and intact Achilles tendons of all groups were removed, and tensile tests were performed to determine the tensile strength and toughness values for each tendon. Movin and Bonar scores were significantly lower in the ZnSO4-15 group than in the C-15 group and in the ZnSO4-30 group than in the C-30 group (p<0.05). Although we did not find the biomechanical results statistically significant, the intact tendons of the ZnSO4-15 group exhibited higher toughness than those of the C-15 group, and the tensile strength and toughness values of the operated and intact tendons of the ZnSO4-30 group were also higher than those of the C-30 group. Zinc sulfate monohydrate mineral supplementation had histopathologically positive effects on the proliferation and remodeling stages of Achilles tendon healing and may biomechanically benefit both operated and intact tendons.

Histopathological and histomorphometric investigation of the effects of different irrigation solutions on Achilles tendon healing in rats.

This study aimed to examine the effect of irrigation fluids containing povidone-iodine (PVP-I), rifampicin (RF), and chlorhexidine gluconate (CHG) used during surgery on healing on a rat Achilles tendon model. Twenty-eight male Sprague-Dawley rats (range, 300 to 400 g) were used in the experiment carried out between November 2022 and December 2022. The rats were divided into PVP-I, RF, CHG, and control groups, with seven rats in each group. Following the tenotomy and repair of the right Achilles tendon, the surgical site was irrigated using PVP-I, RF, CHG, or normal saline (the control group) for 2 min. All rats were sacrificed on the 21st postoperative day. The samples were evaluated histomorphometrically using the scoring system modified by Svensson, Soslowsky, and Cook and histopathologically using the Bonar and Movin classifications. The RF group gave better results in all three scoring systems compared to the control, PVP-I, and CHG groups (p=0.008, p=0.002, and p=0.006, respectively). Cellularity, rounding, and tenocyte morphology showed a significant difference in favor of the RF group (p=0.004). While the distribution of ground substance glycosaminoglycans showed a significant difference in favor of the RF group, there was no significant difference among the other groups (p=0.22). Irrigation solutions containing PVP-I, RF, or CHG show no negative effect on Achilles tendon healing. Moreover, the findings suggest that RF irrigation can accelerate the healing process.

The effect of caffeic acid on tendon healing in rats with an Achilles tendon injury model.

This study aims to examine the effect of caffeic acid on tendon healing histopathologically and biomechanically in rats with an Achilles tendon injury model. Twenty male Wistar-albino rats were used in this study. The rats were divided into two groups as the experimental group and control group. All rats underwent a bilateral achillotomy injury model and then surgical repair. Postoperatively, for four weeks, the experimental group was given intraperitoneal caffeic acid (100 mg/kg/day suspended in saline), while the control group was given only intraperitoneal saline. At the end of four weeks, after sacrificing each rat, right Achilles tendons were subjected to biomechanical analysis and the Achilles tendons were subjected to histopathological analysis. Bonar and Movin scores were used for histopathological analysis. In biomechanical analysis, tensile test was applied to Achilles tendons until rupture. For each tendon, failure load, displacement, cross-sectional area, maximum energy, total energy, length, stiffness, ultimate stress and strain parameters were recorded. According to Bonar and Movin scoring, the experimental group had lower scoring values than the control group (p=0.002 and p=0.002, respectively). Bonar scoring parameters were analyzed separately. Vascularity, collagen, and ground substance scores were lower in the experimental group compared to the control group (p=0.001, p=0.003, and p=0.047, respectively). No significant difference was found for tenocyte (p=0.064). In biomechanical analysis, failure load, displacement, ultimate stress, strain, and stiffness values were found to be higher in the experimental group compared to the control group (p=0.049, p=0.005, p=0.028, p=0.021, and p=0.049, respectively). The caffeic acid contributed positively to tendon healing histopathologically and biomechanically in rats with an Achilles tendon injury model.

Momordica charantia Enhances Tendon Healing in Rats: An Experimental Study

Momordica charantia (MC) is a traditional plant widely used since ancient times for wound healing. This study evaluated its potential effects on tendon healing. Adult male Wistar albino rats (n = 32, 8 rats in each group) were anesthetized, and their Achilles tendons were prepared for surgical procedures. Group 1 (Cont = control group) was not subjected to any surgery and was used as a control group for baseline values. Group 2 (PR = primary repair group) underwent primary repair (PR) with a monofilament suture after a full-thickness incision of the Achilles tendon. A full-thickness incision was also made to the Achilles tendon of group 3 (CT = collagen tube-administered group), followed by PR and collagen tube insertion. In group 4 (MC = M. charantia-administered group), 1 mL of MC extract was applied locally on the collagen tube in addition to the surgical procedure applied to group 3. The Achilles tendons were excised on the postoperative 40th day and examined stereologically, histologically, and bioinformatically. Data showed that the total volume of the collagen fibers was higher in MC and CT groups than in the PR group. The total volume of the tendon was decreased in MC and CT groups than in the Cont group. The ratios between the volumes of the collagen fibers and total tendon in the MC and CT groups were significantly different from PR, but not different from the Cont group. Additionally, MC improved tenoblastic activity, collagen production, and neovascularization. Bioinformatic interactions showed that the proteases of MC could trigger the signals playing a role on vasculogenesis, reducing inflammation, and contributing to tenoblast activation and collagen remodeling. MC extract ameliorates the healing of injured tendon and can provide satisfactory tendon repair. Further works are recommended to explore the healing capacity of MC.

Can pirfenidone prevent tendon adhesions? An experimental study in rats.

In this experimental study, we aimed to investigate the effectiveness of oral pirfenidone (PFD) treatment on preventing tendon adhesion and tendon healing in rats. A total of 21 rats were assigned into three groups including seven rats in each group. In Group 1 (sham group), no surgical procedure was performed. In Group 2 (control group), tendon repair was performed following right achillotomy. In Group 3 (treatment group), the rats also underwent tendon repair after right achillotomy. Additionally, 30 mg/kg of oral PFD was initiated from the postoperative Day 1 and administered via gavage for 28 days. At the end of the study, tendon healing and fibrosis levels in the tendon repair site were compared macroscopically, histopathologically, and immunohistochemically among the groups. Macroscopically, moderate and severe adhesions were observed in four and three rats, respectively in the control group, while no adhesion was found in four rats and filmy adhesions were observed in three rats in the treatment group (p<0.01). Microscopically, there was moderate adhesions in three rats and severe adhesions in four rats in the control group, while three rats had no adhesions and four rats had slight adhesions in the treatment group (p<0.01). Microscopically, tendon healing was good in six rats and fair in one rat in the control group, while five rats showed excellent tendon healing and two rats showed good tendon healing in the treatment group (p<0.01). Immunohistochemically, expressions of collagen I (p<0.01), collagen III (p<0.001), vascular endothelial growth factor (VEGF) (p<0.001), and proliferating cell nuclear antigen (PCNA) (p<0.001) significantly decreased in the treatment group compared to the control group. Our study results indicated that PFD decreased collagen synthesis and prevented the formation of peritendinous adhesion in rats; however, it did not impair tendon healing.

Effects of L-carnitine on healing of Achilles tendon in rats.

In this experimental study, we aimed to analyze the effects of levocarnitine (L-carnitine) on tendon healing after surgical repair of Achilles tendon rupture in a rat model. The study included 40 Wistar Albino rats divided into four groups: Group 1, neither surgical intervention nor substance applications were performed for the Achilles tendons. In the other groups, the right Achilles tendons were cut using a scalpel and repaired with a modified Kessler-type technique with 3/0 monofilament polydioxanone suture. In Group 2, the rats did not receive any additional treatment, except for surgical repair. In Group 3, the same volume similar to Group 4 of saline solution was administered intraperitoneally for seven days. In Group 4, each rat received 300 mg/kg of L-carnitine intraperitoneally for seven days. At Week 6, all rats were sacrificed. All right Achilles tendons were used for biomechanical tests and histopathological evaluations. Biochemical analysis of the matrix metalloproteinase was also performed using the blood specimens. There were no significant differences among the groups in terms of the histopathological parameters. Although the mean matrix metalloproteinase level was low in the L-carnitine group, it did not reach statistical significance. A significant increase in maximum force, tensile strength, and strength to 2-mm gap was observed in the L-carnitine group. The significant effects of L-carnitine on biomechanical parameters may indicate favorable effects on Achilles tendon healing in rats by reducing matrix metalloproteinase 2 and 9. To improve Achilles tendon healing, further investigation for these markers is needed. Since the effects of L-carnitine on the Achilles tendon cannot be clearly distinguished histopathologically, further studies involving L-carnitine-induced effects are warranted.

Quantitative Analysis of Contrast-Enhanced Ultrasound That Can Be Used to Evaluate Angiogenesis during Patellar Tendon Healing in Rats.

Objective To investigate the efficacy of contrast-enhanced ultrasound (CEUS) in quantitatively evaluating angiogenesis during patellar tendon healing in rats. Methods A total of 40 Sprague–Dawley rats were used in this study. The patellar tendons of 30 rats (60 limbs) that underwent incision and suture were treated as the operation group and monitored after 7, 14, and 28 days. The normal patellar tendons of 10 rats (20 limbs) were treated as the control group and monitored on day 0. The ultrasound examination was used to evaluate the structure and blood perfusion of the patellar tendon. Immunohistochemistry was used to assess angiogenesis, and the biomechanical test was used to verify functional recovery of the patellar tendon. Results The tendons in the operation group were significantly thickened compared with those in the control group (p < 0.01). The peak intensity (PI) in CEUS of the tendons showed a clear difference at each time point after the surgery (p < 0.01). PI increased in the operation group with a maximum on day 7, and then gradually decreased until day 28 when PI was close to the basic intensity (BI) in the control group (p > 0.05). It was consistent with the change of the CD31-positive staining areas representing angiogenesis of the injured patellar tendons. The PI was positively correlated with the CD31-positive staining area fraction (R = 0.849, p < 0.001). The failure load and tensile strength of the repaired patellar tendons in the operation group increased over time. The PI showed negative correlations with the failure load (R = −0.787, p < 0.001) and tensile strength (R = −0.714, p < 0.001). Conclusion The PI in CEUS could quantitatively reflect the time-dependent change in the blood supply of the healing site, and the PI correlated with histologic and biomechanical properties of the healing tendon. Quantitative analysis of contrast-enhanced ultrasound could be a useful method to evaluate angiogenesis in healing tendons.

Effects of Biomaterials for Sustained-Release Growth Factor Biomaterials on Tendon Healing in Rats

To investigate the effect of sustained-release growth factor biomaterials on tendon healing in rats. A total of 45 healthy adult Sprague-Dawley rats were randomly divided into 3 groups viz. blank group, vascular endothelial growth factor group and basic fibroblast growth factor group with 15 rats in each group. The rats in vascular endothelial growth factor group and basic fibroblast growth factor group were injected with 0.2 ml vascular endothelial growth factor (100 ng) and 0.2 ml basic fibroblast growth factor (100 ng) respectively. They were injected again on the 7th d, 14th d and 21st d after operation. At 2, 4 and 6 w after operation, 4 rats in each group were selected for experimental observation. The changes of vascular endothelial growth factor and basic fibroblast growth factor levels in the treated experimental animals and the control rats were compared by the Hematoxylin and Eosin staining and adhesion were observed during the observation period. The expression of both vascular endothelial growth factor and basic fibroblast growth factor in the experimental group was significantly higher than that in the control group. The concentration of the control group at each time phase had no significant change compared with that before operation. Both vascular endothelial growth factor and basic fibroblast growth factor play an important role in the healing process of muscle bonds. Vascular endothelial growth factor is better than basic fibroblast growth factor in promoting micro angiogenesis and cell proliferation in the early stage and basic fibroblast growth factor may be better than vascular endothelial growth factor in promoting collagen synthesis.

The effects of Tendoflex® (polytendon complex) and Hypericum perforatum (St. John's wort oil) on repaired Achilles tendon healing in rats.

Objectives This experimental study aims to examine the effects of Tendoflex® and Hypericum perforatum on tendon healing in rat models undergoing iatrogenic Achilles tendon rupture and similar surgical treatments.Materials and methods Eighty Wistar albino rats weighing 250 to 350 g were randomly divided into four groups. Group A: Tendoflex® was administered orally as 1 capsule/2.5 kg daily by gavage. Group B: Hypericum perforatum was administered orally as 300 mg/kg daily by gavage. Group C: Tendoflex® and Hypericum perforatum were co-administered orally by gavage at the prespecified doses. Group D: No medication was given to the control group. Five rats from each group were sacrificed weekly, and the tissue samples were examined histologically, followed by the biomechanical tests of the Achilles tendon.Results In the mechanical testing, pulling forces were superior in all intervention groups and in all weeks over the control group. In particular, in the early periods (Weeks 1, 2, and 3), the mixed group showed the most favorable results, followed by the Hypericum perforatum group (p=0.010, p=0.591, and p=0.130, respectively). The most favorable collagen type I and type III expression values were found in the mixed and Hypericum perforatum groups at Weeks 2 and 3, respectively (p=0.025 and p=0.018). In the immunohistochemical and Western Blot examinations, extreme collagen type I and type III expression were detected in the mixed and Hypericum perforatum groups at Weeks 2, 3, and 4.Conclusion Tensile strength of the Achilles tendon increased by using Hypericum perforatum and Tendoflex® following rupture and repair of the Achilles tendon in rats. The combined use of these two agents yielded the most favorable mechanical and histological results, particularly in the early period. This result may be related to the higher level of collagen type I and type III immunity in all groups, compared to the control group.

Effect of Liposome Curcumin Combined with PDGF-BB on Tendon Healing in Rats

Objective: To study the effect of liposomal curcumin combined with PDGFBB on tendon healing after tendon injury in rats and explore its mechanism. Methods Thirty-six rats were randomly divided into four groups: healthy control group (group A), liposomal curcumin group (group B), PDGF-BB group (group C) and combined application group (group D). The rats in each group were divided into groups according to the experimental group. At the 4th and 8th weeks after operation, the general morphology, histomorphology, biomechanics and other aspects of rat tendon were detected and statistically analyzed. Results: The degree of tendon adhesion in group B and D was significantly less than that in group A and C, and the difference was statistically significant. The biomechanical test showed that the tendons in group C and D had higher strength and could withstand greater stress than those in group A and B. Conclusion: Liposome curcumin combined with PDGF-BB can significantly reduce the degree of adhesion after tendon injury, increase the strength of tendon healing, and significantly promote tendon healing.

Comparison on effects of platelet-rich plasma versus autologous conditioned serum on Achilles tendon healing in a rat model

The aim of this study was to compare the effects of local administrations of platelet-rich plasma (PRP) with autologous conditioned serum (ACS) on Achilles tendon healing in a rat model. In this study, 40 male Sprague-Dawley rats, aged 12 months and weighing 350 to 400 g were used. The rats were divided into three groups (n=10 in each group): a control group and two treatment groups (PRP vs ACS). A standardized procedure was applied for the complete rupture and repair of the Achilles tendon in each group. The PRP group received one dose of PRP on the operative area, and ACS group received ACS at 24, 48, and 72 hours after the surgery. The control group received no injection. Animals were sacrificed 30 days after the operation, and tendon healing in each group was assessed histopathologically based on Bonar's semi-quantitative score and Movin's semi-quantitative grading scale. For the biomechanical analyses, unoperated Achilles tendons of all rats in the control and ACS groups were also harvested, and pulling tests were applied to the specimen to measure the longitudinal axis strength. The highest force value among the data obtained was defined as the maximum strength value (Fmax). The mean Bonar's score was significantly lower in the PRP group (3.8±0.8) than in the ACS (4.8±0.45) and control groups (5.2±0.837) (p=0.0028). The mean Movin's score was significantly lower in the PRP group (7.80±1.49) than in the ACS (9.8±1) and control groups (11.2±2.4) (p=0.029). The ratio of type I collagen was significantly higher in the PRP group (60±6) than in the ACS (52±4.5) and control groups (42±9) (p=0.005). Biomechanical results obtained from operated sites were comparable in terms of Fmax among groups (PRP, 33.93±2.61; ACS, 35.24±3.26; control, 35.69±3.62) (p=0.674). Similarly, the results obtained from unoperated sites were comparable among groups (PRP, 47.71±1.21; ACS, 48.14±2; control, 49.14.69±1.88) (p=0.395). In terms of histopathological results, PRP seems to be more effective than ACS for Achilles tendon healing in rats.

Relaxin inhibits patellar tendon healing in rats: a histological and biochemical evaluation

BackgroundFemale patients are more likely to have tendon injuries than males, especially those who has a higher concentration of relaxin. Previous studies have demonstrated that relaxin attenuates extracellular matrix (ECM) formation. However, the mechanism of relaxin on tendon repair remains unclear. We hypothesize that relaxin inhibits tendon healing by disrupting collagen synthesis.MethodsA patellar tendon window defect model was established using Sprague-Dawley rats. The center of the patellar tendon was removed from the patella distal apex and inserted to the tibia tuberosity in width of 1 mm. Then, the rats were injected with saline (0.2 μg/kg/day) or relaxin (0.2 μg/kg/day) for two and four weeks, which was followed by biomechanical analysis and histological and histochemical examination.ResultsMechanical results indicated that relaxin induces a significant decrease in tear resistance, stiffness, and Young’s modulus compared to those rats without relaxin treatment. In addition, it was shown that relaxin activates relaxin family peptide receptor 1(RXFP1), disturbs the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs), and reduces the deposition of collagen in injury areas.ConclusionsRelaxin impairs tendon healing in rats. Also, relaxin might lead to tendon injury more commonly for females than males.

Effects of Short Term Oral Administration of Curcumin on Achilles Tendon Healing in Rats

Objective- Tendon healing, in terms of histologic and functional characteristics, is always inferior to its normal level due to the poor vascularity and low metabolic rate. Curcumin possesses anti-inflammatory, anti-oxidant and healing effects. This study aimed to investigate effects of curcumin on Achilles tendon experimental injury using histopathology, biomechanical and functional evaluationsDesign- Experimental studyProcedures- Twenty four adult male rats were divided into control and treatment groups. After aseptic preparation, complete transverse tenotomy through the middle section of right Achilles tendon, followed by modified Kessler suture placement was performed. Normal saline and curcumin (100 mg kg-1) were administered orally for seven days after surgery in control and treatment groups, respectively. Sampling was done six weeks later.Results- Lower peri-tendinous adhesion was found in the treatment group. Histopathology revealed significant increase in density and arrangement of collagen fibers, decrease in fibroblast and inflammatory cells and lower vascularity in treatment group compared to control groups which indicates earlier maturation of granulation tissue by curcumin. Significant increase in maximum load, yield load, stress and absorbed energy in the treatment group were noted by biomechanical analysis. Improved functionality was also found in the treatment group according to hind paw print analysis.Conclusion and Clinical Relevance- The present study indicated that oral administration of curcumin resulted in improved structural, biomechanical properties and functionality of the Achilles tendon in rats.

Role of a combination dietary supplement containing mucopolysaccharides, vitamin C, and collagen on tendon healing in rats

ObjectiveThe aim of this study was to investigate the effect of mucopolysaccharide, vitamin C, and collagen supplementation on the healing of Achilles tendon in rats. MethodsSixteen rats were separated into 2 groups. Both Achilles tendons of all rats were transected 5 mm above the insertion and repaired using a Kessler suture. After the surgical repair, the study group received the daily recommended amount of the supplement by gastric gavage, while the control group received a placebo. At the end of the third week, the animals were sacrificed. The biomechanical properties of the groups were compared with ultimate tensile strength and stiffness tests. The biological properties of the 2 groups were assessed with a histomorphometric comparison to determine the amount of collagen type I (COL1), proliferating cell nuclear antigen (PCNA), and transforming growth factor β1 (TGF-β1) expression in 3 different tissue subgroups (collagen matrix, tenocytes, and endotenon fibroblasts). ResultsAnalysis of histomorphometric results revealed that the rats receiving dietary supplements demonstrated a significant increase in PCNA (mean value of 86 in the control group and 168.85 in the trial group; p < 0.05) and TGF-β1 (mean value of 87.57 in the control group and 161.85 in the trial group; p < 0.05) in the endotenon fibroblasts of the repair site. However, there was no difference between the groups in PCNA or TGF-β1 when the collagen matrix and the tenocytes of the repair site were examined. Furthermore, no significant difference could be found between groups in COL1 in any of the 3 tissue subgroups (collagen matrix, tenocytes, and endotenon fibroblasts). The statistical analysis also indicated that the rats receiving supplements did not demonstrate a significant increase in the ultimate tendon tensile strength or stiffness. ConclusionThe results of this study revealed no advantage to the oral administration of the trial supplement in collagen synthesis or biomechanical properties in rats after 3 weeks using the presented study design. However, the increased expression of PCNA and TGFβ1 seen in the endotenon fibroblasts of the repair site might play a role in the continuum of tendon healing.

Adipose-derived Human Perivascular Stem Cells May Improve Achilles Tendon Healing in Rats.

Achilles tendon rupture is a common injury and the best treatment option remains uncertain between surgical and nonoperative methods. Biologic approaches using multipotent stem cells such as perivascular stem cells pose a possible treatment option, although there is currently a paucity of evidence regarding their clinical therapeutic use. The purpose of this study was to determine whether injected perivascular stem cells (PSCs) would (1) improve histologic signs of tendon healing (such as percent area of collagen); and (2) improve biomechanical properties (peak load or stiffness) in a rat model of Achilles tendon transection. Two subtypes of PSCs were derived from human adipose tissue: pericytes (CD146CD34CD45CD31) and adventitial cells (CD146CD34CD45CD31). Thirty-two athymic rats underwent right Achilles transection and were randomized to receive injection with saline (eight tendons), hydrogel (four tendons), pericytes in hydrogel (four tendons), or adventitial cells in hydrogel (eight tendons) 3 days postoperatively with the left serving as an uninjured control. Additionally, a subset of pericytes was labeled with CM-diI to track cell viability and localization. At 3 weeks, the rats were euthanized, and investigators blinded to treatment group allocation evaluated tendon healing by peak load and stiffness using biomechanical testing and percent area of collagen using histologic analysis with picrosirius red staining. Histologic analysis showed a higher mean percent area collagen for pericytes (30%) and adventitial cells (28%) than hydrogel (21%) or saline (26%). However, a nonparametric statistical analysis yielded no statistical difference. Mechanical testing demonstrated that the pericyte group had a higher peak load than the saline group (41 ± 7 N versus 26 ± 9 N; mean difference 15 N; 95% confidence interval [CI], 4-27 N; p = 0.003) and a higher peak load than the hydrogel group (41 ± 7 N versus 25 ± 3 N; mean difference 16; 95% CI, 8-24 N; p = 0.001). The pericyte group demonstrated higher stiffness than the hydrogel group (36 ± 12 N/mm versus 17 ± 6 N/mm; mean difference 19 N/mm; 95% CI, 5-34 N/mm; p = 0.005). Our results suggest that injection of PSCs improves mechanical but not the histologic properties of early Achilles tendon healing. This is a preliminary study that provides more insight into the use of adipose-derived PSCs as a percutaneous therapy in the setting of Achilles tendon rupture. Further experiments to characterize the function of these cells may serve as a pathway to development of minimally invasive intervention aimed at improving nonoperative management while avoiding the complications associated with surgical treatment down the line.

Histopathological, immunohistochemical, and biomechanical effects of splenectomy on Achilles tendon healing in rats

ABSTRACTPurpose: This study aimed to assess Achilles tendon repair in rats following splenectomy to simulate patients with musculoskeletal system injury who had splenectomy after spleen injury, a situation often seen in orthopedics and traumatology practice.Materials and Methods: The study included 32 male Sprague–Dawley rats (10 months old; average weight, 394.5 ± 28.3 g). The rats were fed with standard rodent food ad libitum at 22°C in a dark environment for 12 h. They were divided into two groups, namely the splenectomy (total splenectomy and Achilles tendon repair) and control groups (only Achilles tendon repair; n = 16). Four weeks after the surgery, the rats were euthanized, and their Achilles tendons were examined histopathologically, immunohistochemically, and biomechanically.Results: In the splenectomy group, proinflammatory cytokines, such as interleukin-1β, tumor necrosis factor-α, and interferon-γ, showed significantly lower values than those in the control group (p ˂0.01); moreover, the levels of anti-inflammatory cytokines like vascular endothelial growth factor, transforming growth factor-β1, interleukin-2, interleukin-10, and hepatocyte growth factor were significantly higher than in the control group (p ˂ 0.001). The average ultimate tensile strengths were 2.58 ± 0.5 in the splenectomy and 2.78 ± 0.3 in the control group (p = 0.043). The average values were 0.33 ± 0.5 in the splenectomy and 0.44 ± 0.1 in the control group (p = 0.021).Conclusion: Splenectomy may positively influence Achilles tendon healing through modification of the proinflammatory/anti-inflammatory ratio in favor of anti-inflammatory cytokines by causing a decrease in spleen-originated inflammatory cells.

Osteopractic total flavone promoting rat extra-articular tendon-bone healing through mTOR pathway

To explore function and related molecular mechanism of osteopractic total flavone (OTF) on tendon healing in rats. Ten male rats aged for 8 weeks were collected and weighted from 180 to 220 g. Tendon stem cells were cultivated, the third tendon stem cells were used for experiment. OTP treated with 0, 0.1, 1, 10 ng/ml were added into tendon stem cells, and expression change of ALP, Runx2, OCN, VEGF, P-S6, P-4E/BP1 were detected after 14 days. Forty male rats aged for 8 weeks (weighted 180 to 220 g) were established extra-articular tendon-bone transplanting healing model, and divided into experimental group and control group. Experimental group were treated with OTF(100 mg·kg⁻¹·d⁻¹), while control group was treated by normal saline with the same volume. Tendon-bone healing degree were detected by biomechanical testing at 3 and 6 weeks after surgery, histological detection were applied to detect tendon-bone healing and number of new vessles. After treated by OTP, ALP staining and active index detection showed there were statistical differences among 0, 0.1, 1, 10 ng/ml group. After 14 days' cultivation, western blotting results showed mTOR downstream marker protein P-S6 protein expression were gradually increased with increase of density of OTP, expression of P-4E/BP1 was reduced, while expression of Runx2, OCN, VEGF were increased. Biological detection results showed that there was no significant difference in mechanical strength between experimental group(0.78±0.05) N/mm and control group (0.51±0.02) N/mm at 3 weeks after surgery, while mechanical strength in experimental group (1.36±0.09) N/mm was higher than control group (1.01±0.08) N/mm at 6 weeks after surgery. Histological results showed maturity of tendon-bone surface cell were higher at 3 and 6 weeks in experimental group, sharpey fiber growth more density, calcification extent of mesenchyme was high, and new bone, vessels were increased. OTF could promote osteogenic differentiation of tendon stem cells through mTOR signaling in vitro, and stimulate tendon-bone healing in bone tunnel and enhance connection quality between tendon and bone.

A high-glucose diet affects Achilles tendon healing in rats

Chronic and acute tendinopathies are difficult to treat and tendon healing is generally a very slow and incomplete process and our general understanding of tendon biology and regeneration lags behind that of muscle or bone. Although still largely unexplored, several studies suggest a positive effect of nutritional interventions on tendon health and repair. With this study, we aim to reveal effects of a high-glucose diet on tendon neoformation in a non-diabetic rat model of Achilles tenotomy. After surgery animals received either a high-glucose diet or a control diet for 2 and 4 weeks, respectively. Compared to the control group, tendon repair tissue thickness and stiffness were increased in the high-glucose group after 2 weeks and gait pattern was altered after 1 and 2 weeks. Cell proliferation was up to 3-fold higher and the expression of the chondrogenic marker genes Sox9, Col2a1, Acan and Comp was significantly increased 2 and 4 weeks post-surgery. Further, a moderate increase in cartilage-like areas within the repair tissue was evident after 4 weeks of a high-glucose diet regimen. In summary, we propose that a high-glucose diet significantly affects tendon healing after injury in non-diabetic rats, potentially driving chondrogenic degeneration.

Histologic and Biomechanical Evaluation of the Effects of Social Stress and the Antidepressant Fluoxetine on Tendon Healing in Rats

Impaired wound healing in humans under psychological stress and the positive effects of antidepressant drugs on wound healing were also shown in the literature. However, there are currently no studies regarding the effects of antidepressant drugs on tendon healing. The aim of this study was to compare tendon healing under normal conditions versus social stress. We also aimed to perform a histological and biomechanical analysis of the effects of the antidepressant drug fluoxetine on tendon healing. Sixty Sprague Dawley rats were divided into six groups. A social stress regimen was used to stress the rats. The use of fluoxetine in the social stress group yielded significantly better biomechanical results and the collagen organizations of the fluoxetine group were more similar to the normal tendon collagen organization. Fluoxetine seems to inhibit the negative effects of stress on tendon healing and seems to improve tendon healing. Level 5.