Rotator Cuff Injury Model Research Articles

Allogenous Tendon Stem/Progenitor Cells in Silk Scaffold for Functional Shoulder Repair

Tendon stem/progenitor cells (TSPCs) were recently identified within tendon tissues. The aim of this study was to investigate TSPC-seeded knitted silk-collagen sponge scaffold for functional shoulder repair. The multidifferentiation potential, proliferation, and immune properties of TSPCs were investigated in vitro, while the efficacy of TSPC-seeded knitted silk-collagen sponge scaffolds in promoting rotator cuff regeneration was evaluated in vivo within a rabbit model. TSPCs, which exhibited universal stem cell characteristics (i.e., clonogenicity, high proliferative capacity, and multidifferentiation potential), nonimmunogenicity, and immunosuppression, proliferated well on our scaffold in vitro. Implantation of allogenous TSPC-seeded scaffolds within a rabbit rotator cuff injury model did not elicit an immunological reaction, but instead increased fibroblastic cell ingrowth and reduced infiltration of lymphocytes within the implantation sites at 4 and 8 weeks postsurgery. After 12 weeks, the allogenous TSPC-treated group exhibited increased collagen deposition and had better structural and biomechanical properties compared to the control group. This study thus demonstrated that the allogenous TSPC-seeded knitted silk-collagen sponge scaffold enhanced the efficacy of rotator cuff tendon regeneration by differentiating into tenocytes, and by secreting anti-inflammatory cytokines that prevent immunological rejection. Hence, allogenous TSPC-seeded knitted silk-collagen sponge scaffolds can be a clinically useful application for tendon tissue engineering.

Development of Fatty Atrophy After Neurologic and Rotator Cuff Injuries in an Animal Model of Rotator Cuff Pathology

Detachment of a tendon from its osseous insertion, as can be the case with severe rotator cuff injuries, leads to atrophy of and increased fat in the corresponding muscle. We sought to validate a rotator cuff injury model in the rabbit and to test the hypothesis that tenotomy of a rotator cuff tendon would consistently create muscle atrophy and fatty degeneration analogous to the changes that occur after injury to a nerve innervating the same muscle. New Zealand white rabbits were divided into three groups: (1) partial rotator cuff tear without retraction of the muscle, (2) complete rotator cuff tear with retraction of the muscle, and (3) nerve transection of the subscapular nerve. Animals were killed at two or six weeks after injury, and the muscles were analyzed for weight, cross-sectional area, myosin fiber-type composition, and fat content. In addition, the subscapular nerve was harvested at two weeks and evaluated for neuronal injury. At six weeks after injury, the rabbit muscles in the complete tenotomy and nerve transection groups had significant decreases in wet mass and increases in fat content relative to the control groups. Fat accumulation had a similar spatial pattern at six weeks in both the nerve transection and complete tenotomy groups. Such changes were not seen in the partial tenotomy group. No change was found in muscle myosin fiber-type composition. At two weeks after injury, subscapular nerves in the complete tenotomy group showed gross evidence of neuronal injury. This study establishes the rabbit subscapularis muscle as a valid model to study the muscular changes associated with rotator cuff tears. Our data suggest that the muscular changes associated with complete tenotomy are comparable with those seen with denervation of the muscle and suggest that chronic rotator cuff tears may induce a neurologic injury.

Exercise following a short immobilization period is detrimental to tendon properties and joint mechanics in a rat rotator cuff injury model

Rotator cuff tears are a common clinical problem that can result in pain and disability. Previous studies in a rat model showed enhanced tendon to bone healing with postoperative immobilization. The objective of this study was to determine the effect of postimmobilization activity level on insertion site properties and joint mechanics in a rat model. Our hypothesis was that exercise following a short period of immobilization will cause detrimental changes in insertion site properties compared to cage activity following the same period of immobilization, but that passive shoulder mechanics will not be affected. We detached and repaired the supraspinatus tendon of 22 Sprague-Dawley rats, and the injured shoulder was immobilized postoperatively for 2 weeks. Following immobilization, rats were prescribed cage activity or exercise for 12 weeks. Passive shoulder mechanics were determined, and following euthanasia, tendon cross-sectional area and mechanical properties were measured. Exercise following immobilization resulted in significant decreases compared to cage activity in range of motion, tendon stiffness, modulus, percent relaxation, and several parameters from both a structurally based elastic model and a quasi-linear viscoelastic model. Therefore, we conclude that after a short period of immobilization, increased activity is detrimental to both tendon mechanical properties and shoulder joint mechanics, presumably due to increased scar production.

Repair of a Rotator Cuff Tendon Defect Using an Acellular Human Dermal Graft in a Large Primate Model (SS-44)

A large primate model which resembles human shoulder anatomy, mechanics, and immunogenicity was used to evaluate the use of an acellular dermal human graft for rotator cuff tendon defect repair and augmentation. A rotator cuff defect was created in two groups of baboons. In one group, the defect was repaired with the acellular human dermal graft, while the other group did not have a repair. All grafted specimens healed, the nongrafted defects failed to heal. The graft was successful at restoring tendon integrity at defects sites and demonstrated a favorable histological appearance including neovascularization and graft incorporation into native tendon. Evaluate an acellular human dermal graft for rotator tendon defect repair and augmentation in a large primate model which closely resembles the human shoulder anatomy, mechanics, and immunogenicity. A primate rotator cuff injury model was developed and consisted of full thickness bilateral defects in the infraspinatus and subscapularis tendons. Ten adult female skeletally mature baboons were divided into two groups. In one group (n=5), the defects were repaired using a non-cross-linked human acellular dermis graft (GraftJacket Regenerative Tissue Matrix, Wright Medical). A patch of graft material was cut to cover the tendon width and length and sutured with nonabsorbable suture. At the bone insertion site, the patch was secured to the residual tendon and periosteum by suture placed through superficial bone tunnels. In the other group (n=5), the defects were created, but no graft was applied. The subscapularis tendon was used for histological study, and the infraspinatus tendon was used for mechanical testing (not reported here). The right and left shoulders were operated on 6 weeks apart. After euthanasia at 12 weeks, one 6-week and one 12-week shoulder was available from each animal. Clinical assessment included: (1)grasping for food, limb extension forward, limb extension to shoulder level, limb extension overhead; (2) radiographs under sedation preoperatively, then 0, 6, 12 weeks postoperatively; (3) Passive range of motion measurements under sedation preoperatively, then at 0, 6 12 weeks postoperatively. The subscapularis tendon of each joint was studied histologically using sections stained with H and E, Masson's trichrome and Verhoeff-van Gieson to determine healing of the model defect, incorporation of the graft material into the native tendon, and any immunogenic response to the implanted material. All incisions healed. Progressive improvement in limb function was observed in both groups. At necropsy, all grafted tendons were intact. Grossly, grafted tendons were thickened by residual graft material and fibrous tissue, and the defects were no longer present. In contrast, non-grafted tendons had normal to thinner dimensions, and the central defects were still visible grossly or covered only by a thin membrane. Radiographically, there were no differences between the groups. All shoulders had a smooth ROM with no crepitus or instability. ROM differences from preoperative values were seen in both groups with peak loss occurring at 6 weeks, returning toward, but not completely, to preoperative values at 12 weeks. Histologically, in the grafted group, tendon continuity was re-established with incorporation of the graft into the substance of the tendon. The 12 week grafted specimens were characterized by a greater degree of incorporation and remodeling with collagen fibers oriented in the long axis of the tendon and decreased cellular infiltrate compared to the 6 week specimens. The untreated tendon defects failed to heal after 12 weeks. The acellular human dermal matrix was successful in restoring tendon integrity at defect sites and is supported by the favorable histological appearance. There was no impedance to wound healing from the acellular graft material. The large primate rotator cuff defect model replicated well the human rotator cuff condition.

The localized expression of extracellular matrix components in healing tendon insertion sites: an in situ hybridization study

The localized expression of a number of extracellular matrix genes was evaluated over time in a novel rat rotator cuff injury model. The supraspinatus tendons of rats were severed at the bony insertion and repaired surgically. The healing response was evaluated at 1, 2, 4, and 8 weeks post-injury using histologic and in situ hybridization techniques. Expression patterns of collagens (I, II, III, IX, X, XII), proteoglycans (decorin, aggrecan, versican, biglycan, fibromodulin), and other extracellular matrix proteins (elastin, osteocalcin, alkaline phosphatase) were evaluated at the healing tendon to bone insertion site. Histologic results indicate a poor healing response to the injury, with only partial recreation of the insertion site by 8 weeks. In situ hybridization results indicate a specific pattern of genes expressed in each zone of the insertion site (i.e., tendon, fibrocartilage, mineralized cartilage, bone). Overall, expression of collagen types I and XII, aggrecan, and biglycan was increased, while expression of collagen type X and decorin was decreased. Expression of collagen type I, collagen type XII, and biglycan decreased over time, but remained above normal at 8 weeks. Results indicate that the rat supraspinatus tendon is ineffective in recreating the original insertion site, even at 8 weeks post-injury, in the absence of biological or biomechanical enhancements.