Achilles Functional Index Research Articles

An Atelocollagen Injection Enhances the Healing of Nonoperatively Treated Achilles Tendon Tears: An Experimental Study in Rats.

There is growing interest in nonoperative treatment for the management of Achilles tendon ruptures (ATRs). However, nonoperative treatment is limited by the risk of tendon reruptures and low satisfaction rates. Recently, atelocollagen injections have been reported to have beneficial effects on tendon healing. To evaluate the beneficial effects of injected atelocollagen on Achilles tendon healing and investigate the mechanism of atelocollagen on tendon healing. Controlled laboratory study. Percutaneous tenotomy of the right Achilles tendon in 66 rats was performed. The animals were equally divided into the noninjection group (NG) and the collagen injection group (CG). At 1, 3, and 6 weeks, the Achilles functional index, cross-sectional area, load to failure, stiffness, stress, and the modified Bonar score were assessed. Transmission electron microscopy, western blotting, and immunohistochemistry were also performed. The Achilles functional index (-6.8 vs -43.0, respectively; P = .040), load to failure (42.1 vs 27.0 N, respectively; P = .049), and stiffness (18.8 vs 10.3 N/mm, respectively; P = .049) were higher in the CG than those in the NG at 3 weeks. There were no significant differences in histological scores between the 2 groups. Transmission electron microscopy analysis showed that the mean diameter of collagen fibrils in the CG was greater than that in the NG at 3 weeks (117.2 vs 72.6 nm, respectively; P < .001) and 6 weeks (202.1 vs 144.0 nm, respectively; P < .001). Western blot analysis showed that the expression of collagen type I in the CG was higher than that in the NG at 1 week (P = .005) and 6 weeks (P = .001). An atelocollagen injection had beneficial effects on the healing of nonoperatively treated Achilles tendon injuries. The Achilles tendon of CG rats exhibited better functional, biomechanical, and morphological outcomes compared with NG rats. The molecular data indicated that the mechanism of atelocollagen injections may be associated with an increased amount of collagen type I. An atelocollagen injection might be a good adjuvant option for the nonoperative treatment of ATRs.

Micro-groove patterned PCL patches with DOPA for rat Achilles tendon regeneration

Achilles tendon regeneration using current tissue engineering techniques requires morphometrically mimetic tendon biomaterials to attain the required microstructural tendon tissue and to achieve the necessary mechanical properties. In this study, we used nano- (400 nm) and micro-groove (5000 nm) patterned polycaprolactone patches (PCL-400, PCL-5000), which offer adequate elastic modulus and biocompatibility. The PCL patches were fabricated via capillary force lithography and were surface modified with 3,4-dihydroxy-l-phenylalanine (DOPA) for increased hydrophilicity. We hypothesized that the resulting biologically surface-modified elastic groove patterned patches would enhance the cell behaviors in vitro and the rat Achilles tendon regeneration in vivo. The micro-groove patterned PCL patches with DOPA coating (DOPA-PCL-5000) exhibited excellent cell elongation, tenogenic differentiation and YAP expression of the mesenchymal stem cells in our in vitro study and these results were further confirmed by application to the rat Achilles tendon rupture model in our in vivo study. DOPA-PCL-5000 induced dramatic regeneration of rat Achilles tendon compared to the other groups, which was further confirmed by the Achilles functional index and histological analysis at 8 weeks. In conclusion, DOPA-PCL-5000 can be used not only for damaged Achilles tendon, but also for various functional tendon regeneration techniques such as rotator cuff, patellar tendon, and flexor tendon.

Comparative analysis of Achilles tendon healing outcomes after open tenotomy versus percutaneous tenotomy: An experimental study in rats.

There is growing interest in conservative treatment of Achilles tendon rupture. However, the majority of experimental studies of Achilles tendon have been performed by open tenotomy. More appropriate model of conservative treatment of Achilles tendon rupture is required. We performed an experimental study to evaluate whether outcomes differ between open tenotomy and percutaneous tenotomy of the Achilles tendon in rats. The Achilles tendons of 48 rats were transected. The animals were divided into two groups according to surgical technique: open tenotomy or microscopy-assisted percutaneous tenotomy. After 1, 2, and 4 weeks, functional, biomechanical, and histological analyses were performed. Western blot was performed for quantitative molecular analysis at 1 week. The Achilles functional index was superior in the percutaneous tenotomy group, compared with the open tenotomy group, at 1 week. The cross-sectional area was significantly larger in the percutaneous tenotomy group than in the open tenotomy group at 4 weeks. Relative to the native tendons, load to failure and stiffness yielded comparable results at 2 weeks in the percutaneous tenotomy group and at 4 weeks in the open tenotomy group. The histological score was significantly better in the percutaneous tenotomy group than in the open tenotomy group at 1 week. At 1 week, interleukin-1β expression in the open tenotomy group was higher than in the percutaneous tenotomy group. In summary, Achilles tendon healing was substantially affected by the tenotomy method. We presume that our percutaneous tenotomy method might constitute a useful experimental animal model for conservative treatment of Achilles tendon rupture.

Effects of low-density pulsed ultrasound treatment on transforming growth factor-beta, collagen level, histology, biomechanics, and function in repaired rat tendons.

Objectives The aim of this study is to compare the effects of low-density pulsed ultrasound (LIPUS) treatment on growth factors/collagen production, histological, biomechanical, and function of rats with Achilles tendon injury. Materials and methods A total of 44 Wistar Albino rats were used in the study between April 2017 and June 2018. The rats were randomized to two treatment groups. Group 1 (n=6) received LIPUS treatment (0.3 Watt/cm2; 1 MHz, 1:5 pulse mode) and Group 2 (n=6)received sham ultrasound (US) treatment following Achilles tendon surgery. Transforming growth factor-beta 1 (TGF-β1) and collagen gene expression levels were evaluated using polymerase chain reaction. The histological evaluation was performed with the Bonar scoring system. The tensile strength was measured by biomechanical testing and the function was evaluated with the Achilles Functional Index (AFI). Results Although TGF-β1 expression and tensile strength evaluation showed a tendency to improve in favor of the LIPUS group, no statistically significant difference was found (p=0.065 and p=0.053, respectively). The COL3 gene expression in the LIPUS group and the COL1 expression in the sham US group were significantly higher. Bonar scores and AFI scores showed a statistically significant improvement in the LIPUS group, compared to the sham US group. Conclusion Our study results show that LIPUS yields positive effects on tendon histology and functional status in repaired Achilles tendon in rats.

Tenogenic effects of silymarin following experimental Achilles tendon transection in rats.

Tendon healing is prolonged due to the small number of cells, poor circulation, and low metabolism. The optimal tendon healing and its complete functional recovery have always been a challenge for researchers. Silymarin possesses anti-inflammatory, anti-oxidant, analgesic, and regenerative properties. The present study aimed to investigate the effects of silymarin on healing the Achilles tendon in rats. Twenty-four male Wistar rats were divided into two groups of control and treatment. After surgical preparation, a complete transverse incision was made in the middle part of the Achilles tendon, and then a modified Kessler suture was placed. The control group received 1.00 mL normal saline for five consecutive days, and the treatment group received 50.00 mg kg-1 of silymarin suspended in 1.00 mL normal saline for five days, orally. During the experimental period, Achilles functional index (AFI) was recorded. Six weeks after surgery, sampling was done. Histopathologically, a significant increase in the density of collagen fibers and reduction in neovascularization and inflammatory cells infiltration were observed in the treatment group. The biomechanical evaluation showed a significant increase in tensile strength of the tendon in the treatment group compared to the control group. The AFI results were concomitant with the results stated above, indicating an improvement in the AFI of rats in the treatment group. The present study results showed that oral administration of silymarin improved tissue healing indices, biomechanical properties, and functional index, leading to optimal healing of experimental Achilles tendon injury in the rat.

Micro-Groove Patterned PCL Patches with DOPA for Rat Achilles Tendon Regeneration

Achilles tendon regeneration using current tissue engineering techniques requires morphometrically mimetic tendon biomaterials to attain the required microstructural tendon tissue and to achieve the necessary mechanical properties. In this study, we used nano- and micro-groove patterned polycaprolactone patches (PCL-400, PCL-5000), which offer adequate elastic modulus and biocompatibility. The PCL patches were fabricated via capillary force lithography and were surface modified with DOPA for increased hydrophilicity. We hypothesized that the resulting biologically surface-modified elastic groove patterned patches would enhance the cell behaviors in vitro and the rat Achilles tendon regeneration in vivo. The micro-groove patterned PCL patches with DOPA coating (DOPA-PCL-5000) exhibited excellent cell elongation, tenogenic differentiation and YAP expression of the mesenchymal stem cells in our in vitro study and these results were further confirmed by application to the rat Achilles tendon rupture model in our in vivo study. DOPA-PCL-5000 induced dramatic regeneration of rat Achilles tendon compared to the other groups, which was further confirmed by the Achilles functional index and histological analysis at 8 weeks. In conclusion, DOPA-PCL-5000 can be used not only for damaged Achilles tendon, but also for various functional tendon regeneration techniques such as rotator cuff, patellar tendon, and flexor tendon.

Construction of Microunits by Adipose-Derived Mesenchymal Stem Cells Laden with Porous Microcryogels for Repairing an Acute Achilles Tendon Rupture in a Rat Model.

ObjectiveTissue engineering approaches seem to be an attractive therapy for tendon rupture. Novel injectable porous gelatin microcryogels (GMs) can promote cell attachment and proliferation, thus facilitating the repair potential for target tissue regeneration. The research objectives of this study were to assess the efficacy of tissue-like microunits constructed by multiple GMs laden with adipose-derived mesenchymal stem cells (ASCs) in accelerated tendon regeneration in a rat model.MethodsThrough a series of experiments, such as isolation and identification of ASCs, scanning electron microscopy, mercury intrusion porosimetry (MIP), laser scanning confocal microscopy and the CCK-8 test, the biocompatibility of GMs was evaluated. In an in vivo study, 64 rat right transected Achilles tendons were randomly divided into four groups: the ASCs+GMs group (microunits aggregated by multiple ASC-laden GMs injected into the gap), the ASCs group (ASCs injected into the gap), the GMs group (GMs injected into the gap) and the blank defect group (non-treated). At 2 and 4 weeks postoperatively, the healing tissue was harvested to evaluate the gross observation and scoring, biomechanical testing, histological staining and quantitative scoring. Gait analysis was performed over time. The 64 rats were randomly assigned into 4 groups: (1) micro-unit group (ASCs+GMs) containing ASC (105)-loaded 120 GMs in 60 μL DMEM; (2) cell control group (ASCs) containing 106 ASCs in 60 μL DMEM; (3) GM control group (GMs) containing 120 blank GMs in 60 μL DMEM; (4) blank defect group (Defect) containing 60 μL DMEM, which were injected into the defect sites. All animals were sacrificed at 2 and 4 weeks postsurgery (Table 1).ResultsIn an in vitro study, GMs (from 126 μm to 348 μm) showed good porosities and a three-dimensional void structure with a good interpore connectivity of the micropores and exhibited excellent biocompatibility with ASCs. As the culture time elapsed, the extracellular matrix (ECM) secreted by ASCs encased the GMs, bound multiple microspheres together, and then formed active tendon tissue-engineering microunits. In animal experiments, the ASCs+GMs group and the ASCs group showed stimulatory effects on Achilles tendon healing. Moreover, the ASCs+GMs group was the best at improving the macroscopic appearance, histological morphology, Achilles functional index (AFI), and biomechanical properties of repair tissue without causing adverse immune reactions.ConclusionPorous GMs were conducive to promoting cell proliferation and facilitating ECM secretion. The ASCs-GMs matrices showed an obvious therapeutic efficiency for Achilles tendon rupture in rats.

Local treatment with ascorbic acid accelerates recovery of post-sutured Achilles tendon in male Wistar rats.

Tendon rupture is a very frequent accident involving average people and high-performance athletes. Clinical studies describe tendon recovery as a painful and slow process involving different biochemical and histological events. Ascorbic acid (AA) is a potent antioxidant as well as an important cofactor for collagen synthesis. In the current study, we evaluated if local treatment with AA is able to promote tendon repair in tenotomized rats. Animals were submitted to Achilles tendon rupture followed by surgical suture. Control and AA groups received in loco injection of saline solution (0.9% NaCl) and 30 mM AA, respectively. Histological and functional recovery of Achilles tendon tissue was evaluated at 7, 14, and 21 days post-surgery. Hematoxylin/eosin staining and collagen fluorescence analysis showed intense disarrangement of tendon tissue in the saline group. Tenotomized animals also showed hypercellularity in tendon tissue compared with non-tenotomized animals. The Achilles functional index (AFI) showed a significant decrease of tendon functionality in tenotomized animals at 7, 14, and 21 days post-surgery. AA accelerated tissue organization and the recovery of function of the Achilles tendons. The beneficial effect of AA treatment was also observed in the organization of the collagen network. Data presented in the current work showed that in loco treatment with AA accelerated the recovery of injured Achilles tendon post-surgery.

Construction of tendon replacement tissue based on collagen sponge and mesenchymal stem cells by coupled mechano-chemical induction and evaluation of its tendon repair abilities

Tissue engineering is an ideal therapeutic strategy for the development of functional tendon replacement tissue for tendon repair in the clinic. Currently, the synergistic roles of mechano-chemical factors and the mechanisms involved in tendon repair and regeneration are not fully understood. In this study, we developed a three-dimensional (3D) culture system based on a silicone chamber and collagen sponge scaffold that can deliver cyclic mechanical stretch and biochemical stimulation to bone marrow-derived mesenchymal stem cells (BMSCs) seeded on the scaffold. We found that the combined stimulation of cyclic stretch and transforming growth factor beta 1 (TGF-β1) treatment not only increased cell viability but also synergistically promoted the differentiation of BMSCs into tenocytes in a 3D culture environment. Meanwhile, the combined stimulation increased the Young’s modulus of the BMSC-collagen sponge constructs by reducing the porosity of the scaffold compared to the non-treated constructs. Furthermore, a rat Achilles tendon in situ repair experiment showed that enhanced tendon regeneration was achieved using the BMSC-collagen sponge construct combined with cyclic stretch and TGF-β1, as confirmed by Achilles functional index (AFI) measurement, morphological observation, histological analysis, and mechanical testing. These results suggest that this approach could offer a practical benefit in tendon healing and future tendon tissue engineering. Statement of SignificanceThis study aims to disclose the crucial roles of the coupled induction by mechano-chemical stimulation in tendon tissue engineering and clarifies their collaborative control mechanisms. We developed a three-dimensional (3D) culture system based on a silicone chamber and collagen sponge scaffold that could deliver cyclic mechanical stretch and biochemical stimulation to bone marrow-derived mesenchymal stem cells (BMSCs). We found that the combined stimulation of cyclic stretch and transforming growth factor beta 1 (TGF-β1) could result in an improvement of tissue-engineered construct for enhancing tendon healing. These results suggest that this approach could offer a practical benefit in tendon healing and future tendon tissue engineering.

Mechano-growth factor E peptide promotes healing of rat injured tendon

To determine the possible beneficial effects of a synthetic mechano-growth factor E peptide (MGF-C25E) on the healing of rat Achilles tendon. A significantly increased Achilles functional index was found in the MGF-C25E-treated tendons relative to the saline-treated tendons. Macroscopic observation showed that the repair of MGF-C25E-treated (1000ng/ml) tendons was superior to that of the saline-treated tendons. The mean value of the stiffness of the repaired tendons was significantly increased in the MGF-C25E-treated (1000ng/ml) tendons relative to the saline-treated tendons. Moreover, histological analysis provided evidence of tissue remodeling and cell alignment. MGF-C25E plays an important role in promoting healing of injured rat tendon and could be used as a potential therapeutic factor for tendon repair.

Local NO synthase inhibition produces histological and functional recovery in Achilles tendon of rats after tenotomy

Repair of injured tendon is a very slow process and involves the release of many molecules, including nitric oxide. We investigate the influence of local nitrergic inhibition in histological and functional recovery of injured Achilles tendon. A standard murine model of tendon injury by rupture was used. The animals were divided into three experimental groups: control, injury + vehicle (normal saline) and injury + Nω-nitro-L-arginine methyl ester (L-NAME). The products were injected into the paratendinous region every 2 days and body weight gain and Achilles functional index (AFI) were evaluated on days 0, 7, 14 and 21 after tendon injury. On day 21 post-injury, the animals were killed to evaluate nitric oxide production and tissue organization. We observed that tendon surgical division led to increased tissue nitrite levels, which were reduced in L-NAME-treated rats. The AFI revealed functional recovery of L-NAME-treated animals on day 21 post-injury, which was not observed in the saline-treated group. Microscopic analysis of hematoxylin-eosin staining and collagen autofluorescence showed that L-NAME-treated rats had more aligned areas of collagen fibers and that the diameter of newly organized collagen in this group was also greater than that in the vehicle-treated one. We demonstrate that local treatment with L-NAME significantly improves the functional parameters and accelerates histomorphological recovery.

The application of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds for tendon repair in the rat model

Tendon injuries and defects present a substantial burden to global healthcare economies. There are no synthetic/biosynthesised implants available which can restore full function or match the mechanical properties of native tendon. Therefore, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) was investigated for its utility as a scaffold in a rat Achilles tendon repair model. Porous PHBHHx tubes and fibres were prepared with particle leaching and extrusion methods, respectively. Collagen gels reinforced by polymer fibres were inserted into the lumen of scaffold tubes to create the operational scaffold unit. Mechanical testing demonstrated that PHBHHx scaffolds had comparable mechanical properties to rat tendon, with maximal loads of 23.73 ± 1.08 N, compared to 17.35 ± 1.76 N in undamaged rat Achilles tendon. Sprague–Dawley (SD) rats were split into four experimental groups: control, PHBHHx scaffold only, PHBHHx scaffold and collagen, PHBHHx scaffold, collagen and tenocyte compositions for implantation to repair an induced Achilles tendon defect. No secondary immune response to PHBHHx was observed over a 40 days period of implantation. Movement was restored in PHBHHx scaffold–collagen–tenocyte recipient rats at an earlier time point than in other experimental groups, with complete load-bearing and function returning 20 days post-surgery as determined by the Achilles Functional Index. In vitro testing of tendon constructs after 40 days demonstrated reductions in PHBHHx molecular weight and polydispersity index accompanied by an increase in mean chain length indicating degradation of smaller polymer chain subunits. Similarly a reduction in PHBHHx tube ultimate tensile strength and elastic modulus was observed. Histological analysis provided evidence of tissue remodelling and cell alignment. In summary, PHBHHx scaffolds have been successfully applied in an in vivo tendon repair model raising promise for future utility in tissue engineering applications.

Video-based Gait Analysis for Functional Evaluation of Healing Achilles Tendon in Rats

Video-based walking track systems have been developed for gait analysis in rat models. However, there is no previous study using video-based tracking systems to address the gait parameters to evaluate the recovery of Achilles tendon rupture models. This study conducted a comprehensive gait analysis using a video-based image processing system. Eighteen Sprague-Dawley rats were randomly assigned to one of three interventional conditions: sham surgery, Achilles tendon repair, and Achilles tendon defect. After surgery, all animals were evaluated using a video-based walking track system. The gait parameters and the Achilles functional index (AFI) were further analyzed. The ankle joint angles of the injury side at mid-stance and pre-swing were highly correlated with the AFI. However, lack of sensitivity was found for the AFI. Increased measurement sensitivity of the Achilles tendon healing condition was found in the ankle joint angle of the involved side at the pre-swing and the level of asymmetry of the hindlimb joint position and stance/swing time. The overall sensitivity of the ankle motion analysis was significantly higher than that of AFI. We conclude that the ankle motion analysis is a reliable, reproducible, and sensitive tool for Achilles tendon analysis in rats.

Modulation of early functional recovery of Achilles tendon to bone unit after transection by BPC 157 and methylprednisolone

In the presented study we compared the effect of stable peptide BPC 157 and methylprednisolone on early functional recovery after Achilles tendon to bone transection in a rat model before collagen healing started. Surgical transection of the right Achilles tendon to bone area was performed in seventy two Wistar Albino male rats. Healing Achilles tendon edges were harvested at days 1-4 following the transection. Using Achilles functional index (AFI), myeloperoxidase activity, histological inflammatory cell influx and vascular index early functional recovery was evaluated. Agents (stable peptide BPC 157 10 microg methylprednisolone 5 mg, normal saline 5 ml) were given alone (/kg b.w., intraperitoneally, once daily, first 30 min after surgery, last 24 h before analysis). Control group received normal saline 5 ml/kg. BPC 157 improved functional recovery (AFI values increased at all time points, p <0.05) by anti-inflammatory (decreased myeloperoxidase (MPO) activity and histological inflammatory cell influx, p <0.05) and increased new blood vessel formation (increased vascular index, p <0.05). Methyprednisolone decreased MPO activity and histological inflammatory cell influx, (p <0.05) but also decreased new blood vessel formation and did not affect early functional recovery. Stable peptide BPC 157 with combined anti-inflammatory action and induction of early new blood vessel formation facilitates early functional recovery in Achilles tendon to bone healing.

Achilles Detachment in Rat and Stable Gastric Pentadecapeptide BPC 157: Promoted Tendon‐to‐Bone Healing and Opposed Corticosteroid Aggravation

Stable gastric pentadecapeptide BPC 157 (BPC 157, as an antiulcer agent in clinical trials for inflammatory bowel disease; PLD-116, PL 14736, Pliva, no toxicity reported) alone (without carrier) ameliorates healing of tendon and bone, respectively, as well as other tissues. Thereby, we focus on Achilles tendon-to-bone healing: tendon to bone could not be healed spontaneously, but it was recovered by this peptide. After the rat's Achilles tendon was sharply transected from calcaneal bone, agents [BPC 157 (10 microg, 10 ng, 10 pg), 6alpha-methylprednisolone (1 mg), 0.9% NaCl (5 mL)] were given alone or in combination [/kg body weight (b.w.) intraperitoneally, once time daily, first 30-min after surgery, last 24 h before analysis]. Tested at days 1, 4, 7, 10, 14, and 21 after Achilles detachment, BPC 157 improves healing functionally [Achilles functional index (AFI) values substantially increased], biomechanically (load to failure, stiffness, and Young elasticity modulus significantly increased), macro/microscopically, immunohistochemistry (better organization of collagen fibers, and advanced vascular appearance, more collagen type I). 6alpha-Methylprednisolone consistently aggravates the healing, while BPC 157 substantially reduces 6alpha-methylprednisolone healing aggravation. Thus, direct tendon-to-bone healing using stabile nontoxic peptide BPC 157 without a carrier might successfully exchange the present reconstructive surgical methods.

Comparison of therapeutic ultrasound and exercises for augmenting tendon healing in rats

We compared therapeutic ultrasound (US) and exercises on Achilles tendon healing in 49 mature male rats. The medial Achilles tendon of the right leg was transected and the rats were divided into five groups: 1. control ( n = 9), 2. 1 W/cm 2 US ( n = 9), 3. 2 W/cm® US ( n = 10), 4. running ( n = 11) and 5. swimming ( n = 10). All animals were treated daily, starting from postsurgical day 5, according to their group assignment, except for group 1 control. Achilles functional index (AFI) was recorded pre- and postoperatively. On day 30, the Achilles tendons were biomechanically tested. Results revealed that groups 3 and 4 had higher tensile strength than the controls ( p = 0.037 and 0.034), but groups 2 and 5 were not different from the controls. No significant difference in stiffness ( p = 0.21) or AFI ( p = 0.22) was found. These findings suggest that therapeutic US treatment at 2 W/cm 2 and running exercise improved the strength of repairing Achilles tendon. (E-mail: rsgng@polyu.edu.hk)

Running exercises improve the strength of a partially ruptured Achilles tendon

Objectives: To examine the effects of running and swimming exercises on the functional performance and mechanical strength of a recovering Achilles tendon. Methods: 30 Sprague-Dawley rats had surgical transection of...

Therapeutic ultrasound improves strength of achilles tendon repair in rats

The purpose of this study was to evaluate the effects of therapeutic ultrasound on structural properties and functional performance of Achilles tendon healing. Thirty Sprague-Dawley rats with surgical hemitransected Achilles tendon were studied. Ten were treated daily with 1 MHz continuous ultrasound at 1.0 W/cm 2 for 4 min, 11 at 2.0 W/cm 2 for 4 min and nine served as control without treatment. Achilles functional index (AFI) was recorded preoperatively and on postoperative days 3, 10 and 30. On day 30, the rats were sacrificed and Achilles tendons were tested for load-relaxation, stiffness and ultimate tensile strength (UTS). Results showed that UTS of both low-dose ( p = 0.023) and high-dose ( p = 0.002) groups was significantly greater than in controls. No significant differences in AFI ( p = 0.179), load-relaxation ( p = 0.205) and stiffness ( p = 0.842) were found among groups. These findings suggested that both low- and high-dose therapeutic ultrasound accelerate the healing process of ruptured tendon. (E-mail: rsgng@polyu.edu.hk)

Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth

In studies intended to improve healing of transected Achilles tendon, effective was a stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419). Currently in clinical trials for inflammatory bowel disease (PLD-116, PL 14736, Pliva), it ameliorates internal and external wound healing. In rats, the right Achilles tendon transected (5 mm proximal to its calcaneal insertion) presents with a large tendon defect between cut ends. Agents (/kg b.w., i.p., once time daily) (BPC 157 (dissolved in saline, with no carrier addition) (10 μg, 10 ng or 10 pg) or saline (5.0 ml)), were firstly applied at 30 min after surgery, the last application at 24 h before autopsy. Achilles functional index (AFI) was assessed once time daily. Biomechanical, microscopical and macroscopical assessment was on day 1, 4, 7, 10 and 14. Controls generally have severely compromised healing. In comparison, pentadecapeptide BPC 157 fully improves recovery: (i) biomechanically, increased load of failure, load of failure per area and Young’s modulus of elasticity; (ii) functionally, significantly higher AFI-values; (iii) microscopically, more mononuclears and less granulocytes, superior formation of fibroblasts, reticulin and collagen; (iv) macroscopically, smaller size and depth of tendon defect, and subsequently the reestablishment of full tendon integrity. Likewise, unlike TGF-β, pentadecapeptide BPC 157, presenting with no effect on the growth of cultured cell of its own, consistently opposed 4-hydroxynonenal (HNE), a negative modulator of the growth. HNE-effect is opposed in both combinations: BPC 157 + HNE (HNE growth inhibiting effect reversed into growth stimulation of cultured tendocytes) and HNE + BPC 157(abolished inhibiting activity of the aldehyde), both in the presence of serum and serum deprived conditions. In conclusion, these findings, particularly, Achilles tendon transection fully recovered in rats, peptide stability suitable delivery, usefully favor gastric pentadecapeptide BPC 157 in future Achilles tendon therapy.

The roles of growth factors in tendon and ligament healing.

Tendon healing is a complex and highly-regulated process that is initiated, sustained and eventually terminated by a large number and variety of molecules. Growth factors represent one of the most important of the molecular families involved in healing, and a considerable number of studies have been undertaken in an effort to elucidate their many functions. This review covers some of the recent investigations into the roles of five growth factors whose activities have been best characterised during tendon healing: insulin-like growth factor-I (IGF-I), transforming growth factor beta (TGFbeta), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF). All five are markedly up-regulated following tendon injury and are active at multiple stages of the healing process. IGF-I has been shown to be highly expressed during the early inflammatory phase in a number of animal tendon healing models, and appears to aid in the proliferation and migration of fibroblasts and to subsequently increase collagen production. TGFbeta is also active during inflammation, and has a variety of effects including the regulation of cellular migration and proliferation, and fibronectin binding interactions. VEGF is produced at its highest levels only after the inflammatory phase, at which time it is a powerful stimulator of angiogenesis. PDGF is produced shortly after tendon damage and helps to stimulate the production of other growth factors, including IGF-I, and has roles in tissue remodelling. In vitro and in vivo studies have shown that bFGF is both a powerful stimulator of angiogenesis and a regulator of cellular migration and proliferation. This review also covers some of the most recent studies into the use of these molecules as therapeutic agents to increase the efficacy and efficiency of tendon and ligament healing. Studies into the effects of the exogenous application of TGFbeta, IGF-I, PDGF and bFGF into the wound site singly and in combination have shown promise, significantly decreasing a number of parameters used to define the functional deficit of a healing tendon. Application of IGF-I has been shown to increase in the Achilles Functional Index and the breaking energy of injured rat tendon. TGFbeta and PDGF have been shown separately to increase the breaking energy of healing tendon. Finally, application of bFGF has been shown to promote cellular proliferation and collagen synthesis in vivo.