Tendon Repair Site Research Articles

Do Postoperative Platelet-Rich Plasma Injections Accelerate Early Tendon Healing and Functional Recovery After Arthroscopic Supraspinatus Repair? A Randomized Controlled Trial

After arthroscopic supraspinatus tendon repair, ultrasound guided PRP injections on two occasions to the tendon repair site do not improve early tendon bone healing or accelerate functional recovery. Establishing early tendon bone healing is critical for subsequent rehabilitation and optimal functional outcome after rotator cuff repair. Biological therapies that elevate local growth-factor concentrations may promote early rotator cuff healing after surgery. The aim of this study was to determine whether postoperative and repeated application of platelet-rich plasma (PRP) to the tendon repair site resulted in improved early tendon healing and enhanced early functional recovery after double-row arthroscopic supraspinatus repair. A total of 60 patients underwent arthroscopic double-row supraspinatus tendon repair. Thirty patients were randomised to receive two ultrasound-guided injections of PRP to the tendon repair site at postoperative days 7 and 14. The control group did not receive placebo injections. Early structural healing of the tendon repair was assessed with MRI at 16 weeks post surgery by a blinded musculoskeletal radiologist, and cuff appearances were graded according to the Sugaya classification. Functional scores were recorded with the Oxford Shoulder Score, quick DASH, and visual analogue scale for pain; and were measured preoperatively and at postoperative weeks 6, 12, and 16. Isokinetic strength and active range of motion were measured in both operated and non-operated shoulders at 16 weeks post surgery. All patients complied with the study protocol and no patients were lost to followup. There were no differences in MRI structural integrity of the supraspinatus repair between the PRP group (0% full-thickness retear; 23% partial tear; 77% intact) and the control group (7% full-thickness retear; 23% partial tear; 70% intact) at 16 weeks postoperatively (p = 0.35). Significant improvements in clinical function and VAS pain scores were observed in both PRP and control groups at 12 weeks and 16 weeks post surgery (p<0.01). However PRP treatment did not result in superior functional scores, range of motion, shoulder strength or pain scores compared to the control group. After arthroscopic supraspinatus tendon repair, image-guided PRP treatment on two occasions does not improve early tendon-bone healing or functional recovery.

A Midterm Evaluation of Postoperative Platelet-Rich Plasma Injections on Arthroscopic Supraspinatus Repair: A Randomized Controlled Trial

Background: Platelet-rich plasma (PRP) has been applied as an adjunct to rotator cuff repair to improve tendon-bone healing and potentially reduce the incidence of subsequent tendon retears. Purpose: To investigate whether the midterm clinical and radiographic outcomes of arthroscopic supraspinatus repair are enhanced after repeated postoperative applications of PRP. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 60 patients (30 control; 30 PRP) were initially randomized to receive 2 ultrasound-guided injections of PRP to the tendon repair site at 7 and 14 days after double-row arthroscopic supraspinatus repair or not. A total of 55 patients (91.7%) underwent a clinical review and magnetic resonance imaging (MRI) at a mean of 3.5 years after surgery (range, 36-51 months). Patient-reported outcome measures (PROMs) included the Constant score, Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire, Oxford Shoulder Score (OSS), and visual analog scale (VAS) for pain. Global rating of change (GRC) scale and patient satisfaction scores were evaluated. Structural integrity of the surgical repair was assessed via MRI using the Sugaya classification system. Results: At the midterm review, there was no difference between the groups for any of the PROMs. No differences between the groups were demonstrated for the subjective and range of motion subscales of the Constant score, although a significantly higher Constant strength subscale score was observed in the PRP group (3.3 points; 95% CI, 1.0-5.7; P = .006). There was no evidence for any group differences in MRI scores or retear rates, with 66.7% of PRP patients and 64.3% of control patients rated as Sugaya grade 1. Two control patients had symptomatic retears (both full thickness) within the first 16 weeks after surgery compared with 2 PRP patients, who suffered symptomatic retears (both partial thickness) between 16 weeks and a mean 3.5-year follow-up. Conclusion: Significant postoperative clinical improvements and high levels of patient satisfaction were observed in patients at the midterm review after supraspinatus repair. While pain-free, maximal abduction strength was greater in the midterm after PRP treatment, repeated applications of PRP delivered at 7 and 14 days after surgery provided no additional benefit to tendon integrity.

The Effect of Myostatin (GDF-8) on Proliferation and Tenocyte Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells.

The future in flexor tendon surgery involves tissue engineering approaches directed toward increasing early repair strength to accelerate tendon healing and to allow for earlier onset of rehabilitation. Previous work has shown that pluripotential mesenchymal stem cells may be successfully delivered to a tendon repair site using a suture carrier. The current work describes the use of Myostatin (GDF-8) to help guide these delivered pluripotential stem cells to differentiate down a tenocyte lineage to potentially maximize the reparative effects of these cells at the tendon repair site. Primary rat bone marrow mesenchymal stem cells isolated from the long bones of male Sprague-Dawley rats were treated with 500 ng/ml myostatin for 24 h, 48 h, and 72 h. Collagen 1 A, scleraxis (Scx), and tenomodulin (Tnmd) expression, indicative of tenogenesis, was analyzed using real time PCR and immunohistochemistry staining. A migration assay was performed to assess the functional activity of BMSCs after they were treated with myostatin. Compared to the control cells (without treatment), the cells treated with 500 ng/ml myostatin for 72 h exhibited higher expression of Col 1A, Scx, and Tnmd. The mRNA expression of Col1A, Scx, Tnmd increased 15.3, 13 and 7 times respectively. Immunohistochemistry staining showed Scx and Tnmd were expressed in the cellular cytoplasm. In response to myostatin, the cells also showed a tendency to proliferate and migrate more than the control cells. Myostatin (GDF-8) has the ability to increase rat bone marrow mesenchymal stem cell growth and differentiation toward a tenocyte lineage. This information could be useful for future studies regarding tendon repair.

Combined Administration of ASCs and BMP-12 Promotes an M2 Macrophage Phenotype and Enhances Tendon Healing.

Outcomes after intrasynovial tendon repair are highly variable. An intense inflammatory cascade followed by a delayed healing response can cause adhesion formation and repair-site failure that severely impair the function of repaired digits. No effective remedies exist to fully address these issues. Cell- and growth factor-based therapies have been shown to modulate inflammation and improve cell proliferation and matrix synthesis and therefore are promising treatment approaches for intrasynovial tendon repair. (1) Can autologous adipose-derived mesenchymal stromal cells (ASCs) and recombinant bone morphogenetic protein-12 (rBMP-12) be effectively delivered to an intrasynovial flexor tendon repair without adverse effects? (2) Do autologous ASCs modulate the inflammatory response after intrasynovial tendon injury and repair? (3) Does the combined application of autologous ASCs and rBMP-12 modulate the proliferative and remodeling responses after intrasynovial tendon injury and repair? Sixteen 1- to 2-year-old female canines were used in this study. Autologous ASC sheets, with and without rBMP-12, were applied to the surface of sutured flexor tendons. Fourteen days after repair, the effects of treatment were determined using quantitative PCR (six per group) for the expression of genes related to macrophage phenotype or inflammation (IL-4, CD163, VEGF, NOS2, IL-1B, and IFNG), cell proliferation (CCND1), and tendon formation (SCX, TNMD, COL1A1 and COL3A1). Proteomics analysis (four per group) was performed to examine changes in tendon protein abundances. CD146 immunostaining and hematoxylin and eosin staining (four per group) were used to detect tendon stem or progenitor cells and to semiquantitatively evaluate cellularity at the tendon repair; analyses were done blinded to group. Gross inspection and cell tracing showed that autologous ASCs and rBMP-12 were delivered to the flexor tendon repair site without the deleterious effects of adhesion and repair-site gap formation. Quantitative assessment of gene and protein expression showed effects of treatment: ASC-sheet treatment modulated the postrepair inflammatory response and facilitated healing by increasing regenerative M2 macrophages (M2 marker CD204, twofold of normal, p = 0.030), inflammatory inhibitor (prostaglandin reductase 1 [PTRG1], 1.6-fold of normal, p = 0.026), and proteins involved in tendon formation (periostin [POSTN], 1.9-fold of normal, p = 0.035). Consistently, semiquantitative and qualitative evaluations of repaired tissue showed that ASC-sheet treatment reduced mononuclear cell infiltration (12% less than nontreated tendons, p = 0.021) and introduced CD146+ stem or progenitor cells to the repair site. The combined administration of ASCs and rBMP-12 further stimulated M2 macrophages by increasing IL-4 (116-fold of normal, p = 0.002) and led to the increase of M2 effector matrix metalloproteinase-12 involved in matrix remodeling (twofold of normal, p = 0.016) and reduction of a negative regulator of angiogenesis and cell migration (StAR-related lipid transfer domain protein13 [STARD13]; 84% of normal, p = 0.000), thus facilitating the proliferative stage of tendon repair. ASCs and BMP-12 accelerated the progression of healing in the proliferative stage of tendon repair. The effects of ASCs and BMP-12 on tendon functional recovery should be evaluated in future studies. The cell sheet approach is an effective, biocompatible, and surgeon-friendly approach for cell and growth factor delivery during tendon repair. Combined application of ASCs and BMP-12 may accelerate intrasynovial tendon healing while suppressing the adverse inflammatory response.

Ex vivo Tendon Repair Augmented with Bone Marrow Derived Mesenchymal Stem Cells Stimulated with Myostatin for Tenogenesis: N/A - Not a clinical study

Consulting Fee: Arthrex (Yao) We performed an ex vivo study to investigate the effect of bone marrow derived mesenchymal stem cells (BMSC) stimulated with myostatin on tenogenesis in the setting of tendon repair. We hypothesized that BMSC that were delivered to a tendon repair site after being seeded onto sutures would improve tenogenesis if they were stimulated with myostatin. Cadaveric upper limb flexor tendons were harvested, decellularized, and divided into 1cm segments. Sutures seeded with BMSC were passed through 2 tendon segments to simulate repair. The repaired tendons were then cultured either with or without myostatin for 3, 5, and 7 days. The experiment was also repeated with non-decellularized tendons to make a total of 4 groups. The presence of tenomodulin and scleraxis using immunofluorescence analysis was measured at 3, 5, and 7 days for all 4 groups. Viable BMSC were found at all 3 time points in all 4 groups. Myostatin stimulation lead to expression of tenomodulin and scleraxis at 5 and 7 days in both the decellularized and non-decellularized tendons. In the tendons that were not treated with myostatin, tenomodulin and scleraxis were detected only at day 7 for the decellularized tendons and at days 5 and 7 for the non-decellularized tendons. There were also more cells expressing tenomodulin and scleraxis for the groups treated with myostatin at days 5 and 7. For all 4 groups, no tenomodulin or scleraxis was detected at 3 days. •BMSC delivered to tendon repair sites with sutures can survive for at least 7 days.•There is at least a 3 day delay before the markers of tenogenesis are detectable after BMSC delivery to the tendon repair site.•Myostatin results in an earlier, more robust and sustained expression of tenomodulin and scleraxis in this tendon repair model, implying that it facilitated earlier and increased differentiation of BMSC into tenocytes and/or upregulation of tenomodulin and scleraxis production by the tenocytes present.•Treatment of BMSC with myostatin following their delivery using coated sutures to a tendon repair site may result in improved tenogenesis, implying earlier and better healing of the injured tendon.

Cell and Biologic-Based Treatment of Flexor Tendon Injuries

The two primary factors leading to poor clinical results after intrasynovial tendon repair are adhesion formation within the digital sheath and repair-site elongation and rupture. As the outcomes following modern tendon multi-strand repair and controlled rehabilitation techniques are often unsatisfactory, alternative approaches, such as the application of growth factors and mesenchymal stem cells (MSCs), have become increasingly attractive treatment options. Successful biological therapies require carefully controlled spatiotemporal delivery of cells, growth factors, and biocompatible scaffold matrices in order to simultaneously (1) promote matrix synthesis at the tendon repair site leading to increased biomechanical strength and stiffness and (2) suppress matrix synthesis along the tendon surface and synovial sheath preventing adhesion formation. This review summarizes recent cell and biologic-based experimental treatments for flexor tendon injury, with an emphasis on large animal translational studies.

Prevention of Achilles tendon adhesion with nano-curcumin: an experimental study in rats

Objective To study the effect of nano-curcumin on inhibiting tendon adhesion in a rat Achilles tendon injury model and to investigate the related mechanism. Methods The Achilles tendon was cut and repaired in 72 rats that were randomly divided into 3 groups: the control group (group A), the curcumin group (group B), and the nano-curcumin + laser group (group C). The same dose of normal saline, curcumin and nano-curcumin were applied to the tendon suture site, respectively. At different time points of tendon healing (1, 2, 4 and 8 weeks), the Achilles tendons were harvested and subject to gross morphological observation, histological, biomechanical, and immunohistochemical examinations. Statistical analysis was conducted to compare results from various groups. Results The adhesion score of tendons in the nano-curcumin + laser group in gross morphology was significantly lower than that of the control group (P<0.05). Histologically, the inflammatory response score of tendons in the nano-curcumin group was significantly lower than that in the other two groups. Biomechanical tests revealed significantly enhanced tendon gliding distance in the nano-curcumin group comparing to that in the control group (P<0.05). Conclusion Application of nano-curcumin and laser at the tendon repair site can significantly inhibit the early local inflammatory reactions, and prevent tendon adhesion. Key words: Curcumin; Animal experimentation; Tendon adhesion; Nanometer

Low-Dose and Short-Duration Matrix Metalloproteinase 9 Inhibition Does Not Affect Adhesion Formation during Murine Flexor Tendon Healing.

After flexor tendon injury and repair, adhesion formation is a substantial concern, as it can result in loss of motion and functional disability. Matrix metalloproteinase 9 (Mmp9) is a gelatinase that contributes to degradation of extracellular matrix and is expressed during flexor tendon healing. Mmp9(-/-) mice have accelerated remodeling of adhesions during flexor tendon healing, relative to wild-type mice. The purpose of this study was to investigate whether Ro 32-3555, an Mmp9 inhibitor, can improve flexor tendon healing by limiting adhesion formation or enhancing remodeling of scar tissue during murine flexor tendon healing. Flexor digitorum longus laceration and repair was performed in female C57BL/6J mice. Mice were treated with vehicle or the Mmp9 inhibitor Ro 32-3555 for 8 days. Analysis was performed for digit range of motion and gliding function, biomechanics, gene expression, and Mmp9 activity. An Mmp9 activity assay and zymography confirmed suppression of Mmp9 activity in mice treated with Ro 32-3555. There was no significant difference in tendon gliding or range of motion between vehicle and Ro 32-3555-treated mice. There was also no difference in tendon biomechanical properties between the two groups. Local inhibition of Mmp9 gelatinolytic activity at the flexor tendon repair site is insufficient to alter adhesion formation, remodeling of adhesions, or mechanical properties of healing murine flexor tendons.

Extrinsic versus intrinsic hand muscle dominance in finger flexion.

This study aims to identify the patterns of dominance of extrinsic or intrinsic muscles in finger flexion during initiation of finger curl and mid-finger flexion. We recorded 82 hands of healthy individuals (18-74 years) while flexing their fingers and tracked the finger joint angles of the little finger using video motion tracking. A total of 57 hands (69.5%) were classified as extrinsic dominant, where the finger flexion was initiated and maintained at proximal interphalangeal and distal interphalangeal joints. A total of 25 (30.5%) were classified as intrinsic dominant, where the finger flexion was initiated and maintained at the metacarpophalangeal joint. The distribution of age, sex, dominance, handedness and body mass index was similar in the two groups. This knowledge may allow clinicians to develop more efficient rehabilitation regimes, since intrinsic dominant individuals would not initiate extrinsic muscle contraction till later in finger flexion, and might therefore be allowed limited early active motion. For extrinsic dominant individuals, by contrast, initial contraction of extrinsic muscles would place increased stress on the tendon repair site if early motion were permitted.

Rotator cuff repair with a tendon–fibrocartilage–bone composite bridging patch

BackgroundTo compare the mechanical performance of a rotator cuff repaired with a novel tendon–fibrocartilage–bone composite bridging patch vs the traditional Mason–Allen repair in an in vitro canine model. MethodsTwenty shoulders and 10 bridging patches from patellar tendon were harvested. The patches were trimmed and sliced into 2 layers. An infraspinatus tendon tear was created in each shoulder. Modified Mason–Allen sutures were used to repair the infraspinatus tendon to the greater tuberosity, with or without the bridging patch (bridging patch group and controls, respectively). Shoulders were loaded to failure under displacement control at a rate of 0.5mm/s. FindingsThe ultimate tensile load was significantly higher in the bridging patch group than control (mean [SD], 365.46 [36.45] vs 272.79 [48.88] N; P<.001). Stiffness at the greater tuberosity repair site and the patch–infraspinatus tendon repair site was significantly higher than the control repair site (93.96 [27.72] vs 42.62 [17.48] N/mm P<.001; 65.94 [24.51] vs 42.62 [17.48] N/mm P=.02, respectively). InterpretationThe tendon–fibrocartilage–bone composite bridging patch achieved higher ultimate tensile load and stiffness at the patch–greater tuberosity repair site compared with traditional repair in a canine model. This composite tissue transforms the traditional tendon-to-bone healing interface (with dissimilar tissues) into a pair of bone-to-bone and tendon-to-tendon interfaces, which may improve healing quality and reduce retear rate.

Effects of boric acid on the healing of Achilles tendons of rats.

Tendinous lesions are among the most frequent pathologies encountered in sportsmen. The objectives of new treatments are to improve the healing process and reduce the recovery time. Boron plays an important role in the wound repair process by increasing components of extracellular matrix and angiogenesis. This animal study aimed to investigate the effect of boric acid on healing of the Achilles tendon. The right Achilles tendons of 40 rats were completely sectioned, and the rats were randomly divided into five groups. Each group consisted of eight rats. Groups 1 and 2 were oral boric acid groups with the doses of 4 and 8mg/kg/day boric acid, respectively. Group 3 was the local boric acid group (8mg/kg boric acid intratendinous injection). Group 4 was administered both oral and local boric acid (8mg/kg/day orally and 8mg/kg boric acid intratendinous injection), and group 5 was the control group with no boric acid application. At the end of the fourth week, all the rats were killed and histopathological examination of the Achilles tendon repair site was made. Histopathological examination of the tissue sections revealed more properly oriented collagen fibres, more normal cellular distribution of tenocytes and more properly organized vascular bundles in group 1 and group 2, which were the groups administered oral boric acid. Pathological sum scores of groups 1 and 2 were less than those of the other groups, and the differences between the oral boric acid groups (group 1 and group 2) and the other three groups (groups 3, 4 and 5) were statistically significant (p=0.001). As boric acid is safe and toxicity even after very high doses is unusual, oral boric acid may be used as an agent to improve the healing process of tendon injuries. However, biomechanical tests should also be performed to show the effect of boric acid on strength and endurance of the tendon before it can be used in clinical practice.

Multi-layer electrospun membrane mimicking tendon sheath for prevention of tendon adhesions.

Defect of the tendon sheath after tendon injury is a main reason for tendon adhesions, but it is a daunting challenge for the biomimetic substitute of the tendon sheath after injury due to its multi-layer membrane-like structure and complex biologic functions. In this study, a multi-layer membrane with celecoxib-loaded poly(l-lactic acid)-polyethylene glycol (PELA) electrospun fibrous membrane as the outer layer, hyaluronic acid (HA) gel as middle layer, and PELA electrospun fibrous membrane as the inner layer was designed. The anti-adhesion efficacy of this multi-layer membrane was compared with a single-layer use in rabbit flexor digitorum profundus tendon model. The surface morphology showed that both PELA fibers and celecoxib-loaded PELA fibers in multi-layer membrane were uniform in size, randomly arrayed, very porous, and smooth without beads. Multi-layer membrane group had fewer peritendinous adhesions and better gliding than the PELA membrane group and control group in gross and histological observation. The similar mechanical characteristic and collagen expression of tendon repair site in the three groups indicated that the multi-layer membrane did not impair tendon healing. Taken together, our results demonstrated that such a biomimetic multi-layer sheath could be used as a potential strategy in clinics for promoting tendon gliding and preventing adhesion without poor tendon healing.

Do Postoperative Platelet-Rich Plasma Injections Accelerate Early Tendon Healing and Functional Recovery After Arthroscopic Supraspinatus Repair?

Background: Tendon-bone healing after rotator cuff repair directly correlates with a successful outcome. Biological therapies that elevate local growth-factor concentrations may potentiate healing after surgery. Purpose: To ascertain whether postoperative and repeated application of platelet-rich plasma (PRP) to the tendon repair site improves early tendon healing and enhances early functional recovery after double-row arthroscopic supraspinatus repair. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 60 patients underwent arthroscopic double-row supraspinatus tendon repair. After randomization, half the patients received 2 ultrasound-guided injections of PRP to the repair site at postoperative days 7 and 14. Early structural healing was assessed with MRI at 16 weeks, and cuff appearances were graded according to the Sugaya classification. Functional scores were recorded with the Oxford Shoulder Score; Quick Disability of the Arm, Shoulder and Hand; visual analog scale for pain; and Short Form–12 quality-of-life score both preoperatively and at postoperative weeks 6, 12, and 16; isokinetic strength and active range of motion were measured at 16 weeks. Results: PRP treatment did not improve early functional recovery, range of motion, or strength or influence pain scores at any time point after arthroscopic supraspinatus repair. There was no difference in structural integrity of the supraspinatus repair on MRI between the PRP group (0% full-thickness retear; 23% partial tear; 77% intact) and the control group (7% full-thickness retear; 23% partial tear; 70% intact) at 16 weeks postoperatively (P = .35). Conclusion: After arthroscopic supraspinatus tendon repair, image-guided PRP treatment on 2 occasions does not improve early tendon-bone healing or functional recovery.

Zone II Flexor Tendon Repair Using Knotless Barbed Suture: A Comparative Biomechanical Study Evaluating Effect on Tendon Bulking, Gliding Resistance, and Work of Flexion: N/A - Not a clinical study

Knotless barbed suture repairs for zone II laceration are biomechanically equivalent to, or superior than traditional sutures in reducing tendon repair site bulking, gliding resistance, and work of flexion.

Development of biodegradable polycaprolactone film as an internal fixation material to enhance tendon repair: an in vitro study

BackgroundCurrent tendon repair techniques do not provide sufficient tensile strength at the repair site, and thus early active motion rehabilitation after tendon repair is discouraged. To enhance the post-operative tensile strength, we proposed and tested an internal fixation technique using a polycaprolactone (PCL) biofilm. PCL was chosen for its good biocompatibility, excellent mechanical strength, and an appropriate degradation time scale.MethodsPCL biofilms were prepared by a modified melt-molding/leaching technique, and the physical and mechanical properties and in vitro degradation rate were assessed. The pore size distribution of the biofilm and the paratenon of native tendons were observed using scanning electron microscopy. Next, we determined whether this biofilm could enhance the tensile strength of repaired tendons. We performed tensile tests on rabbit Achilles tendons that were first lacerated and then repaired: 1) using modified Kessler suture combined with running peripheral suture (‘control’ group), or 2) using biofilm to wrap the tendon and then fixation with sutures (‘biofilm’ group). The influence of different repair techniques on tendon tensile strength was evaluated by mechanical testing.ResultsThe novel biofilm had supple texture and a smooth surface. The mean thickness of the biofilm was 0.25 mm. The mean porosity of the biofilm was 45.3%. The paratenon of the rabbit Achilles tendon had pores with diameters ranging from 1 to 9 μm, which were similar to the 4–12 μm diameter pores in the biofilm cross-section. The weight loss of the biofilms at 4 weeks was only 0.07%. The molecular weight of PCL biofilms did not change after immersion in phosphate buffered saline for 4 weeks. The failure loads of the biofilm were similar before (48 ± 9 N) and after immersion (47 ± 7 N, P > 0.1). The biofilm group had ~70% higher mean failure loads and 93% higher stiffness compared with the control group.ConclusionsWe proposed and tested an internal fixation technique using a PCL biofilm to enhance tendon repair. Internal fixation with the biofilm followed by standard suturing can significantly increase the tensile strength of tendon repair sites. This technique has the potential to allow active motion rehabilitation during the early post-operative period.

A new TGF‐β3 controlled‐released chitosan scaffold for tissue engineering synovial sheath

The post-operative outcome of flexor tendon healing remains limited by flexor tendon adhesion that reduces joint range of motion. Despite improvement in different methods, peritendinous adhesion formation continues to present a formidable challenge. Recent studies showed that transforming growth factor-β3 (TGF-β3) may be the key factor to reducing adhesion formation in skin or tendon. In this study, we designed a novel type of tissue engineering synovial sheath containing TGF-β3, to prevent flexor tendon adhesion. First, to achieve a stable release of TGF-β3, chitosan microspheres, prepared by crosslinking-emulsion, were used for the delivery of TGF-β3. Second, a three-dimensional chitosan scaffold was prepared by lyophilization, and TGF-β3 microspheres were carefully introduced into the scaffold. Then, synovial cells were cultured and then seeded into the TGF-β3 loaded scaffold to produce TGF-β3 controlled-released tissue engineering synovial sheath. Tests clearly demonstrated that the scaffold has good structure and compatibility with cells. These results expand the feasibility of combinative strategies of controlled protein release and tissue-engineered synovial sheath formation. Application of this scaffold to tendon repair sites may help to prevent adhesion of tendon healing.

The Effects of Hylan G-F 20 Surface Modification on Gliding of Extrasynovial Canine Tendon Grafts In Vitro

Studies have shown that a lubricant exogenously applied on extrasynovial tendon surfaces can reduce the gliding resistance after flexor tendon repair; however, the reagents that have been tested are solely for experimental testing and are not available for clinical use. The purpose of this study was to investigate the effect of exogenously applied hylan G-F 20, a U.S. Food and Drug Administration-approved hyaluronic acid for the treatment of osteoarthritis, on extrasynovial tendon gliding resistance in an in vitro canine model. Twenty-four canine peroneus longus (PL) tendons and proximal pulleys of the ipsilateral paws were treated with 1 of 3 solutions: saline, carbodiimide derivatized hylan G-F 20, or unmodified hylan G-F 20. The gliding resistance of each tendon preparation was then measured over 1000 cycles in a saline bath. After 1,000 cycles, the gliding resistance of the PL tendons treated with unmodified hylan G-F 20 decreased significantly compared with the saline-treated tendons. The gliding resistance of the PL tendons treated with modified hylan G-F 20 increased significantly compared with the saline group. The PL tendons treated with pure hylan G-F 20 showed a positive effect on the gliding resistance. The results of this in vitro canine study suggest that exogenously applied hylan G-F 20 improves gliding of the extrasynovial tendon graft. This material may be capable of reducing friction over flexor tendon repair sites and flexor tendon grafts.

Cell Migration after Synovium Graft Interposition at Tendon Repair Site

We have recently reported that interpositional synovium grafts from tendon sheath have a potential to accelerate tendon healing when implanted at the repair site. The purpose of this study was to investigate the effect of orientation of the synovium after synovium graft transplantation, by comparing the ability of cells from the visceral and parietal surfaces to migrate into the tendon in a canine tissue culture model. The synovium graft was placed within a complete tendon laceration, with either the visceral or parietal surface facing the proximal end of the lacerated tendon. The number of migrating cells was quantified by a cell migration assay. Qualitative immunohistochemistry and confocal laser microscopy were also used at day 10. Many labeled synovial cells were observed within the tendon to which the visceral surface of the synovium graft was facing. Migrated cells were also observed on the parietal side, but there were fewer cells compared to visceral surface cells. Migrating cells all expressed α-smooth muscle actin. We found that graft orientation affected cell migration. Whether this finding has clinical significance awaits in vivo study.

A photoactivated nanofiber graft material for augmented Achilles tendon repair

Suture repair of Achilles tendon rupture can cause infection, inflammation and scarring, while prolonged immobilization promotes adhesions to surrounding tissues and joint stiffness. Early mobilization can reduce complications provided the repair is strong enough to resist re-rupture. We have developed a biocompatible, photoactivated tendon wrap from electrospun silk (ES) to provide additional strength to the repair that could permit early mobilization, and act as a barrier to adhesion formation. ES nanofiber mats were prepared by electrospinning. New Zealand white rabbits underwent surgical transection of the Achilles tendon and repair by: (a) SR: standard Kessler suture + epitendinous suture (5-0 vicryl). (b) ES/PTB: a single stay suture and a section of ES mat, stained with 0.1% Rose Bengal (RB), wrapped around the tendon and bonded with 532 nm light (0.3 W/cm(2) , 125 J/cm(2) ). (c) SR + ES/PTB: a combination of (a) and (b). Gross appearance, extent of adhesion formation and biomechanical properties of the repaired tendon were evaluated at Days 7, 14, or 28 post-operatively (n = 8 per group at each time point). Ultimate stress (US) and Young's modulus (E) in the SR group were not significantly different from the ES/PTB group at Days 7 (US, P = 0.85; E, P = 1), 14 (US, P = 0.054; E, P = 1), and 28 (US, P = 0.198; E, P = 0.12) post-operatively. Adhesions were considerably greater in the SR group compared to the ES/PTB group at Days 7 (P = 0.002), 14 (P < 0.0001), and 28 (P < 0.0001). The combination approach of SR + ES/PTB gave the best outcomes in terms of E at 7 (P < 0.016) and 14 days (P < 0.016) and reduced adhesions compared to SR at 7 (P < 0.0001) and 14 days (P < 0.0001), the latter suggesting a barrier function for the photobonded ES wrap. Photochemical sealing of a ES mat around the tendon repair site provides considerable benefit in Achilles tendon repair. Lasers Surg. Med. 44: 645-652, 2012. © 2012 Wiley Periodicals, Inc.

The role of collagen arrangement change during tendon healing demonstrated by scanning electron microscopy

The dry weight of tendon tissue is accounted for mainly by collagen fibers. Accordingly, the tendon-healing process primarily involves repair of collagen fibers. During the remodeling phase of tendon healing, newly proliferating collagen fibers are transformed into a mature repaired tendon. Despite the importance of this phenomenon, the details of fibrous rebuilding have not been reported previously. The aim of this study was to visualize the ultrastructural changes and to obtain a clear understanding of the reorganization of the collagen fibers in the tendon repair site, using rat Achilles tendons. We used scanning electron microscopy (SEM) with cell maceration as the main method of analysis. Pretreatment with cell maceration removed the cellular components successfully. This allowed precise visualization of each collagen fiber and the three-dimensional network of the fibers. This study was the first to apply the cell-maceration/SEM method to observe tendon tissue. Seven days after surgery, new collagen fibers grew extensively in the repair site in a random arrangement. Fourteen days after surgery, the collagen fibers began to form an axial arrangement. Near the tendon stump, this change progressed from the outer layer to the core region. On the other hand, in the middle of the repair site, it progressed from the core to the outer layer. Change in the axial arrangement of collagen fibers contributes to the connection between the repair site and the tendon stump and to the separation of the repair site from the paratenon.