In vivo evaluation of adipose-derived stromal cells delivered with a nanofiber scaffold for tendon-to-bone repair

Rotator cuff tears are common and cause a great deal of lost productivity, pain, and disability. Tears are typically repaired by suturing the tendon back to its bony attachment. Unfortunately, the structural (e.g., aligned collagen) and compositional (e.g., a gradient in mineral) elements that produce a robust attachment in the healthy tissue are not regenerated during healing, and the repair is prone to failure. Two features of the failed healing response are deposition of poorly aligned scar tissue and loss of bone at the repair site. Therefore, the objective of the current study was to improve tendon-to-bone healing by promoting aligned collagen deposition and increased bone formation using a biomimetic scaffold seeded with pluripotent cells. An aligned nanofibrous poly(lactic-co-glycolic acid) scaffold with a gradient in mineral content was seeded with adipose-derived stromal cells (ASCs) and implanted at the repair site of a rat rotator cuff model. In one group, cells were transduced with the osteogenic factor bone morphogenetic protein 2 (BMP2). The healing response was examined in four groups (suture only, acellular scaffold, cellular scaffold, and cellular BMP2 scaffold) using histologic, bone morphology, and biomechanical outcomes at 14, 28, and 56 days. Histologically, the healing interface was dominated by a fibrovascular scar response in all groups. The acellular scaffold group showed a delayed healing response compared to the other groups. When examining bone morphology parameters, bone loss was evident in the cellular BMP2 group compared to other groups at 28 days. When examining repair-site mechanical properties, strength and modulus were decreased in the cellular BMP2 groups compared to other groups at 28 and 56 days. These results indicated that tendon-to-bone healing in this animal model was dominated by scar formation, preventing any positive effects of the implanted biomimetic scaffold. Furthermore, cells transduced with the osteogenic factor BMP2 led to impaired healing, suggesting that this growth factor should not be used in the tendon-to-bone repair setting

A prospective evaluation of survivorship of asymptomatic degenerative rotator cuff tears

BACKGROUND: The purpose of this prospective study was to report the long-term risks of rotator cuff tear enlargement and symptom progression associated with degenerative asymptomatic tears. METHODS: Subjects with an asymptomatic rotator cuff tear in one shoulder and pain due to rotator cuff disease in the contralateral shoulder enrolled as part of a prospective longitudinal study. Two hundred and twenty-four subjects (118 initial full-thickness tears, fifty-six initial partial-thickness tears, and fifty controls) were followed for a median of 5.1 years. Validated functional shoulder scores were calculated (visual analog pain scale, American Shoulder and Elbow Surgeons [ASES], and simple shoulder test [SST] scores). Subjects were followed annually with shoulder ultrasonography and clinical evaluations. RESULTS: Tear enlargement was seen in 49% of the shoulders, and the median time to enlargement was 2.8 years. The occurrence of tear-enlargement events was influenced by the severity of the final tear type, with enlargement of 61% of the full-thickness tears, 44% of the partial-thickness tears, and 14% of the controls (p < 0.05). Subject age and sex were not related to tear enlargement. One hundred subjects (46%) developed new pain. The final tear type was associated with a greater risk of pain development, with the new pain developing in 28% of the controls, 46% of the shoulders with a partial-thickness tear, and 50% of those with a full-thickness tear (p < 0.05). The presence of tear enlargement was associated with the onset of new pain (p < 0.05). Progressive degenerative changes of the supraspinatus muscle were associated with tear enlargement, with supraspinatus muscle degeneration increasing in 4% of the shoulders with a stable tear compared with 30% of the shoulders with tear enlargement (p < 0.05). Nine percent of the shoulders with a stable tear showed increased infraspinatus muscle degeneration compared with 28% of those in which the tear had enlarged (p = 0.07). CONCLUSIONS: This study demonstrates the progressive nature of degenerative rotator cuff disease. The risk of tear enlargement and progression of muscle degeneration is greater for shoulders with a full-thickness tear, and tear enlargement is associated with a greater risk of pain development across all tear types. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence