Introduction: New biotechnologies create opportunities for gene therapy to promote rotator cuff healing. We have previously demonstrated that genetically engineered mesenchymal stem cells (MSCs) over expressing BMP-2 and SMAD8 signaling molecule differentiate to tenocytes in vitro and in vivo. Therefore, we hypothesized that rotator cuff defect could be regenerated using genetically engineered MSCs. Method: Nonviral methods were utilized to establish genetically engineered MSCs that co-express BMP-2 and the Smad8 signaling molecule. A previously validated animal model was utilized to examine rotator cuff healing. A 2mm x2mm full thickness defect was created in the infraspinatus tendon of 8 nude rats. A collagen-I biomembrane (TissueMend) containing 3 x 10. 6. engineered cells was sewn into the defect. An identical control procedure was repeated on the contralateral side with biomembrane containing non-engineered MSCs. Results: 4 weeks post implantation the area of implantation was isolated and analyzed by light microscopy and histochemical staining. Analysis of the engineered implants revealed the formation of dense connective tissue with parallel-organized fibers and spindle shaped cells, unlike the control samples. Proton Double Quantum Filtered Magnetic Resonance Imaging technique of the rotator cuff tendons demonstrated an increased presence of organized collagen fibers within the engineered rotator cuff tissue when compared with either native rotator cuff or those treated with non-engineered MSCs. Conclusion: This is the first report showing rotator cuff tendon repair using genetically engineered MSCs. Moreover these findings may have considerable importance for tendon healing and may indicate a clinical gene therapy platform to augment surgical repair

Rotator cuff disease encompasses a spectrum from partial to full thickness tears. Despite being 2–3 times more common than full–thickness tears, effective non-operative treatment for partial thickness tears has remained elusive. Platelet enriched plasma (PRP) has been proposed to enhance rotator cuff healing by enhancing the natural healing cascade. However, its utility in rotator cuff disease remains controversial. The purpose of this study was to compare the patient reported outcomes between PRP and corticosteroid injection in patients with symptomatic partial thickness tears. This double blind randomized controlled trial enrolled patients with symptomatic, partial thickness rotator cuff tears or rotator cuff tendinopathy proven on ultrasound or MRI. Patients were randomized to either corticosteroid or PRP ultrasound-guided injection of the affected shoulder. Patients completed patient reported outcomes at 6 weeks and 12 weeks. The primary outcome was Visual Analog Scale (VAS) pain scores. Secondary outcomes included the Western Ontario Rotator Cuff (WORC) index, American Shoulder and Elbow Surgeons (ASES) score, and failure of non-operative management as determined by consent for surgery or progression to operative intervention. Ninety-nine patients were enrolled in the study with equal demographics between the two groups. Taking into account pre-injection scores, patients with PRP injections demonstrated a statistically significant improvement in VAS scores compared to patients receiving corticosteroid injections at 12 weeks (p=0.045) but not at 6 weeks (p=0.704). There was no difference in other outcome measures or progression of the two groups to surgical intervention. The use of PRP in the management of partial thickness rotator cuff tears demonstrates significant improvement of pain scores at 12 week follow up compared to corticosteroid injections. However, this did not affect the rate of progression to surgical intervention. Continued study is required to determine the utility of PRP in this patient population

Introduction. It is an example of tendon to bone healing of rotator cuff tears. Low Level Laser Therapy (LLLT) is used in pain literature, pain palliation, tendinopathies, osteoarthritis treatment, implant osteointegration in jaw surgery, wound healing, fracture healing, tendon healing, nerve healing. But; there is not a study on tendon-bone healing. It is aimed to investigate the effects of tendon to bone healing with the rotator cuff experimental tear model. Material and Methods. 60 Wistor Albino Rat right shoulders were used in our project in four groups. Effectiveness of the study in each study group to increase and use the minimum number of animals that would be significant it was planned to use 15 (6 histology + 9 biomechanical) subjects. In our study, there are 4 groups in total. 1. Group 4. Week sacrified control group 2. Group 4. Week sacrificed LLLT group 3. Group 8. Week sacrified control group 4. Group is postoperative LLLT group. The 4 round SSP tendons have been cut with a full course. A total of eight sessions of biostimulation were performed with 24 j energy per session. Biomechanical tensile test and histopathological examination were performed on rats sacrificed at 4 and 8 weeks. In histological examination, cellularity at the repair site with hemotoxylin-eosin staining, extracellular matrix localization with Masson trichrome staining and fibrosis, TRAP (Tartrate Resistance Acid Phosphatase) and osteoclast activity, collagen fibril organization with picrochucine were evaluated. In immunohistological examination, proliferation activity was evaluated by CD-31 (Abcam, Cambridge, MA, USA) through vascular endothelial cells, Ki-67 (Tucson, AZ) and tendon proliferation index. Failure load for comparison of biomechanical stability between groups drawing will be done. Biomechanical pulling applications Linear pulling force over tendon It will be realized by applying. Last failure load (Newton), elongation (mm) and hardness values was recorded. Results. Two rats died in the postoperative first group and one rat died in the other groups. Six animals from each group were examined histopathologically. While the mean of stifness was higher in the patient who underwent LLLT at the 4th week biomechanically compared to the control group, there was no difference in the 8th week between the control group LLLT biomechanically. Histologically, the group with LLLT at 4 weeks showed increased fibroblastic activity and osteoclastic activity, but at 8 weeks there was no significant difference. Discussion. There are studies on the benefits of biostimulation with LLLT in fracture healing, implant integration, wound healing, tendon healing. Biostimulation experiments with LLLT for tendon healing were evaluated in rotator cuff healing as they were not available in literature. Especially early contributions were thought to be beneficial for postoperative rupture

Surgical reattachment of torn rotator cuff tendons can lead to satisfactory clinical outcome but failures remain common. Ortho-R product is a freeze-dried formulation of chitosan (CS) that is solubilized in platelet-rich plasma (PRP) to form injectable implants. The purpose of the current pilot study was to determine Ortho-R implant acute residency, test safety of different implant doses, and assess efficacy over standard of care in a sheep model. The infraspinatus tendon (ISP) was detached and immediately repaired in 22 skeletally mature ewes. Repair was done with four suture anchors in a suture bridge configuration (n = 6 controls). Freeze-dried formulations containing 1% w/v chitosan (number average molar mass 35 kDa and degree of deacetylation 83%) with 1% w/v trehalose (as lyoprotectant) and 42.2 mM calcium chloride (as clot activator) were solubilized with autologous leukocyte-rich PRP and injected at the tendon-bone interface and on top of the repaired site (n = 6 with a 1 mL dose and n = 6 with a 2 mL dose). Acute implant residency was assessed histologically at 1 day (n = 2 with a 1 mL dose and n = 2 with a 2 mL dose). Outcome measures included MRI assessment at baseline, 6 weeks and 12 weeks, histopathology at 12 weeks and clinical pathology. MRI images and histological slides were scored by 2 blinded readers (veterinarian and human radiologist, and veterinarian pathologist) and averaged. The Generalized Linear Model task (SAS Enterprise Guide 7.1 and SAS 9.4) was used to compare the different groups with post-hoc analysis to test for pairwise differences. Ortho-R implants were detected near the enthesis, near the top of the anchors holes and at the surface of ISP tendon and muscle at 1 day. Numerous polymorphonuclear cells were recruited to the implant in the case of ISP tendon and muscle. On MRI, all repair sites were hyperintense compared to normal tendon at 6 weeks and only 1 out 18 repair sites was isointense at 12 weeks. The tendon repair site gap seen on MRI, which is the length of the hyperintense region between the greater tuberosity and tendon with normal signal intensity, was decreased by treatment with the 2 mL dose when compared to control at 12 weeks (p = 0.01). Histologically, none of the repair sites were structurally normal. A trend of improved structural organization of the tendon (p = 0.06) and improved structural appearance of the enthesis (p = 0.1) with 2 mL dose treatment compared to control was seen at 12 weeks. There was no treatment-specific effect on all standard safety outcome measures, which suggests high safety. Ortho-R implants (2 mL dose) modulated the rotator cuff healing processes in this large animal model. The promising MRI and histological findings may translate into improved mechanical performance, which will be assessed in a future study with a larger number of animals. This study provides preliminary evidence on the safety and efficacy of Ortho-R implants in a large animal model that could potentially be translated to a clinical setting

Bone marrow concentrates are being used to augment soft tissue healing. However, only 0.01% of these cells meet the criteria of a mesenchymal stem cell (MSC), which likely accounts for the variability in reported results. Previous studies using an established rat rotator cuff repair model have demonstrated that bone marrow-derived MSCs had no effect on healing. In this study we evaluated the effect of purified human MSCs on rotator cuff healing in an athymic rat model. Hypothesis: Purified human MSCs added to the repair site will improve biomechanical strength and fibrocartilage formation of the healing tendon. Fifty-two athymic rats underwent unilateral detachment and repair of the supraspinatus tendon with either fibrin glue (control) or fibrin glue with 106 hMSCs (experimental) applied at the repair site. Flow cytometry verified the stem cell phenotype of the cells as CD73+, CD90+, CD105+, CD14-, CD34- and CD45-. Rats were sacrificed at 2 and 4 weeks, with 10 used for biomechanical testing and 3 for histologic analysis from each group. Biomechanical testing revealed a significant increase in failure load (11.5±2.4N vs. 8.5±2.4N, p=0.002) and stiffness (7.1±1.2 N/mm vs. 5.7±2.1 N/mm, p0.17). These data demonstrate the potential for stem cells to augment tendon healing. This is the first study to use purified stem cells, rather than simple bone marrow concentrate. In the future, cell sorting techniques and culture expansion could be used to select and expand the small population of true stem cells in bone marrow. Furthermore, healing could potentially be improved with repeat cell injection at an additional post-operative time point

Purpose of the study: Irrespective of the technique used, the average rate of bone-tendon healing after rotator cuff repair is about 50% One of the reasons is the poor vitality of the tissues implicated in repair, particularly progressive destruction of the enthesis. Using the rat Achilles tendon, we destroyed the enthesis mechanically then repaired it with and without local injection of chondrocytes in order to study the effect of cell therapy on healing phenomena. Material and method: Sixty 3-month-old Wistar rats were operated on under general anaesthesia to detach the Achilles tendon and destroy the enthesis. In the first group (RI), the tendon was reinserted via a transosseous tunnel using a 4/0 non absorbable knitted thread. In the second group (RIC), joint chondrocytes, harvested from 4-day-old rats were injected locally during the same repair procedure. Animals were sacrificed every 15 days (n=15 per group) for a biomechanical and histology study. Results: In group RI, the non-healing rate was 50% versus 33% in group RIC; the difference was not significant (n=0.3). Tear resistance was increased significantly at 45 days in the RC group (p=0.04). The histology study showed a statistically significant development of a neoenthesis in the RIC group (p< 0.05), which was not observed in the RI group. Discussion: This animal model is valid for exploring rotator cuff healing with a spontaneous rate of healing to the order of 50%. Addition of chondrocytes during the surgical repair induces the production of an enthesis and increases the healing rate 50% and the value of the different biomechanical parameters at 30 days, with a statistically significant difference at 45 days

Introduction and Aims: Large or recurrent rotator cuff tendon tears are difficult to treat effectively. Collagen bio-scaffolds have become available to reinforce a tendon repair or as an interpositional graft. This study compares the suitability of two collagen bio-scaffolds for autologous tenocyte implantation, and assesses the in vivo rotator cuff healing response with these grafts in a rabbit model. Method: Tenocytes were isolated from rabbit tendon, cultured and seeded onto the Restore patch (DePuy), or the Matricel (Verigen) collagen membrane. Serial scanning electron microscopy examined tenocyte integration with the bio-scaffold, and extra-cellular matrix synthesis over time. A rotator cuff tendon defect was created in 50 rabbits and repaired by either: a) direct suture to tuberosity; b) Matricel interposition graft; c) Matricel interposition with autologous tenocytes; d) Restore patch interposition graft; e) Restore patch interposition with autologous tenocytes. Gross and histological evaluation were performed at four weeks and eight weeks post-surgery. Results: Scanning electron microscopy of the Matricel membrane showed a rough surface characterised by a loose arrangement of collagen fibres capable of cell adhesion. SEM at one, three and five days after cell seeding, showed progressive integration of tenocytes into the three-dimensional membrane structure with extra-cellular matrix neosynthesis in the spaces between the native collagen fibres. SEM of the Restore patch showed a relatively smooth surface of highly compacted collagen fibres. Serial SEM after cell seeding showed relatively less tenocyte integration onto the membrane surface though tenocyte replication and matrix neo-synthesis was observed. All 50 rabbits regained normal gait at two weeks post-surgery. At sacrifice, no tendon ruptures had occurred at either time point in any of the five groups. At four weeks, the Matricel and Restore bio-scaffold membranes were partially absorbed, and a florid lymphocytic inflammatory response was evident surrounding the remaining membrane. By eight weeks, graft tissue had been resorbed further, the inflammatory response had decreased, and the regenerating tendon showed progressive remodelling. Autologous tenocyte implantation on both membranes improved the reparative tendon histological grade at eight weeks compared to membranes without cell implantation, and was equivalent to the direct repair group. Conclusion: Autologous tenocytes can be implanted onto both Matricel and Restore collagen bio-scaffolds. Though both Xeno grafts induce an anti-inflammatory response in vivo, membrane resorption subsequently occurs. The healing response of large rotator cuff defects treated with interpositional collagen grafts is improved with autologous tenocyte implantation in a rabbit model

Large and retracted rotator cuff tendon tears fail to repair, or re-tear following surgical intervention. This study attempted to develop novel tissue engineering approaches using tenocytes-seeded bioscaffolds for tendon reconstruction of massive rotator cuff tendon defect in rabbits. Porcine small intestine submucosa (Restore™) and type I/III collagen bioscaffold (ACI-MaixTM) were chosen as bioscaffold carriers for autologous tenocytes. Biological characterization of autologous tenocytes was conducted prior to the implantation. The tenocyte-seeded bioscaffolds were implanted as interposition grafts to reconstruct massive rotator cuff tendon defects in rabbits. In situ re-implantation of the autologous rotator cuff tendon, excised during defect creation served as a positive control. Histological outcomes were analysed and semi-quantitatively graded at four and eight weeks after surgery. The results demonstrate that at four weeks both tenocyte-seeded bioscaffolds display inflammatory reaction similar to bioscaffold-only cuff reconstruction and the histological grading were inferior to control repair. However, at eight weeks inflammatory reaction of both tenocyte-seeded bioscaffolds were dramatically reduced as compared to bioscaffold alone. In addition, bioscaf-folds seeded with tenocytes generated similar histological appearance to that of the positive control. The implantation of autologous tenocytes on collagen-based bioscaffold offers improved rotator cuff tendon healing and remodelling compared to the implantation of bioscaffold alone

Aims

Many biomechanical studies have shown that the weakest biomechanical point of a rotator cuff repair is the suture-tendon interface at the medial row. We developed a novel double rip-stop (DRS) technique to enhance the strength at the medial row for rotator cuff repair. The objective of this study was to evaluate the biomechanical properties of the DRS technique with the conventional suture-bridge (SB) technique and to evaluate the biomechanical performance of the DRS technique with medial row knots.

Purpose: We hypothesised that the rate of tendon healing after arthroscopic repair of full-thickness tears of the supraspinatus is equivalent to that obtained with open techniques reported in the literature. Material and methods: We studied prospectively a cohort of 65 patients with arthroscopically repaired full-thickness tears of the supraspinatus. The patients were reviewed a mean 19 months (12–43) after repair. At arthroscopy, patients were aged 59.5 years on average (28–79). Bone-tendon sutures were performed with resorbable thread and self-locking anchors positioned on the lateral aspect of the humerus. Repair was protected with an abduction brace for six weeks. Forty-one patients (63%) accepted an arthroscan performed six months to two years after arthroscopy to assess tendon healing. Results: Ninety-four percent of the patients were satisfied with the outcome. The mean Constant score was 51.6±10.6 points preoperatively and 80.2±13.2 at last follow-up (p< 0.001). The arthroscan showed that the rotator cuff had healed in 70% of the cases (29/41). The supra-spinatus had not healed on the trochiter in eight cases (25%) and was partially healed in two (5%). The size of the residual tendon defect was less than the initial tear in all cases except one. The rate of patient satisfaction and function was not significantly different if the tendon had healed (Constant score 81.3/100, satisfaction 93%) or if there was a residual tendon defect (Constant score 77.5/100, satisfaction 92%). Shoulder force in patients with a healed tendon (6±1.9 kg) was better than in those with a tendon defect (4.5±2.8 kg), but the difference was not significant. Factors affecting tendon healing were age > 65 years (43% healing, p< 0.02), and wide tears. Conclusion: Arthroscopic repair of isolated supraspinatus tears enables tendon healing in 70% of cases as demonstrated by arthroscan. This rate was equivalent to those reported in historical series of open repair. Patients aged over 65 years had significantly less satisfactory healing. The absence of tendon healing does not compromise functional and subjective outcome despite reduced force

Aims

Rotator cuff (RC) tears are common musculoskeletal injuries which often require surgical intervention. Noninvasive pulsed electromagnetic field (PEMF) devices have been approved for treatment of long-bone fracture nonunions and as an adjunct to lumbar and cervical spine fusion surgery. This study aimed to assess the effect of continuous PEMF on postoperative RC healing in a rat RC repair model.

Aims

In the context of tendon degenerative disorders, the need for innovative conservative treatments that can improve the intrinsic healing potential of tendon tissue is progressively increasing. In this study, the role of pulsed electromagnetic fields (PEMFs) in improving the tendon healing process was evaluated in a rat model of collagenase-induced Achilles tendinopathy.

The February 2014 Shoulder & Elbow Roundup³⁶⁰ looks at: whether arthroscopic acromioplasty is a cost-effective intervention; shockwave therapy in cuff tear; whether microfracture relieves short-term pain in cuff repair; the promising early results from L-PRF augmented cuff repairs; rehabilitation following cuff repair; supination strength following biceps tendon rupture; whether longer is better in humeral components; fatty degeneration in a rodent model; and the controversial acromioclavicular joint dislocation.

Tendinopathy is a debilitating musculoskeletal condition which can cause significant pain and lead to complete rupture of the tendon, which often requires surgical repair. Due in part to the large spectrum of tendon pathologies, these disorders continue to be a clinical challenge. Animal models are often used in this field of research as they offer an attractive framework to examine the cascade of processes that occur throughout both tendon pathology and repair. This review discusses the structural, mechanical, and biological changes that occur throughout tendon pathology in animal models, as well as strategies for the improvement of tendon healing.

Cite this article: Bone Joint Res 2014;3:193–202.

The February 2014 Research Roundup³⁶⁰ looks at: blood supply to the femoral head after dislocation; diabetes and hip replacement; bone remodelling over two decades following hip replacement; sham surgery as good as arthroscopic meniscectomy; distraction in knee osteoarthritis; whether joint replacement prevent cardiac events; tranexamic acid and knee replacement haemostasis; cartilage colonisation in bipolar ankle grafts; CTs and proof of fusion; atorvastatin for muscle re-innervation after sciatic nerve transection; microfracture and short-term pain in cuff repair; promising early results from L-PRF augmented cuff repairs; and fatty degeneration in a rodent model.