Tendon injuries account for a significant number of musculoskeletal afflictions each year. While new surgical techniques and rehabilitation protocols have led to improved clinical outcomes, postsurgical scarring remains the most problematic aspect of tendon repair. In contrast to this typical pattern of fibrosis, recent studies have shown that fetal tendon is capable of healing without scar. However, whether this regenerative healing pattern is intrinsic to the fetal tissue itself or the result of its environment is not known. Thus, the objective of this study is to examine the influence of an adult environment on healing in adult and fetal tendons. We hypothesized that injured fetal tendon tissue transplanted into an adult environment would retain a regenerative healing pattern after injury, demonstrating normal histological and mechanical properties. Our results support this hypothesis. Histological analyses revealed considerable alterations in adult tendon transplants after injury while fetal transplants showed no abnormalities. The injured adult tendons also demonstrated elevated levels of TGF-b1, bFGF, and CD44 at the wound site, whereas the fetal specimens showed little or no such changes in response to injury. The data from our biomechanical studies further corroborate these observations, with significant decreases in the stiffness, modulus, and almost all viscoelastic properties in wounded versus unwounded adult tendons, and fetal specimens showing no differences in mechanical properties between the wounded and unwounded groups. Thus, the results of our investigation demonstrate that the adult environment is not an impediment to scarless repair and that this capability is intrinsic to the fetal tendon itself. Our study also begins to provide insight into the mechanisms controlling this regenerative response. ß

Patients who underwent repair of massive rotator cuff tears with interposition porcine acellular dermal matrix graft have good subjective function as assessed by the MASES score. Patients have significant improvement in pain, range of motion, and manual muscle strength. Postoperative ultrasound demonstrated that the repair was completely intact in 91.8% of patients, a vast improvement compared with results previously reported for primary repairs of massive rotator cuff tears.

Few regenerative approaches exist for the treatment of injuries to adult dense connective tissues. Compared to fetal tissues, adult connective tissues are hypocellular and show limited healing after injury. We hypothesized that robust repair can occur in fetal tissues with an immature extracellular matrix (ECM) that is conducive to cell migration, and that this process fails in adults due to the biophysical barriers imposed by the mature ECM. Using the knee meniscus as a platform, we evaluated the evolving micromechanics and microstructure of fetal and adult tissues, and interrogated the interstitial migratory capacity of adult meniscal cells through fetal and adult tissue microenvironments with or without partial enzymatic digestion. To integrate our findings, a computational model was implemented to determine how changing biophysical parameters impact cell migration through these dense networks. Our results show that the micromechanics and microstructure of the adult meniscus ECM sterically hinder cell mobility, and that modulation of these ECM attributes via an exogenous matrix-degrading enzyme permits migration through this otherwise impenetrable network. By addressing the inherent limitations to repair imposed by the mature ECM, these studies may define new clinical strategies to promote repair of damaged dense connective tissues in adults.

The meniscus plays a central load‐bearing role in the knee joint. Unfortunately, meniscus injury is common and can lead to joint degeneration and osteoarthritis (OA). In small animal models, progressive degenerative changes occur with the unloading of the meniscus via destabilization of the medial meniscus (DMM). However, few large animal models of DMM exist and the joint‐wide initiation of the disease has not yet been defined in these models. Thus, the goal of this study is to develop and validate a large animal model of surgically induced DMM and to use multimodal (mechanical, histological, and magnetic resonance imaging) and multiscale (joint to tissue level) quantitative measures to evaluate degeneration in both the meniscus and cartilage. DMM was achieved using an arthroscopic approach in 13 Yucatan minipigs. One month after DMM, joint contact area decreased and peak pressure increased, indicating altered load transmission as a result of meniscus destabilization. By 3 months, the joint had adapted to the injury and load transmission patterns were restored to baseline, likely due to the formation and maturation of a fibrovascular scar at the anterior aspect of the meniscus. Despite this, we found a decrease in the indentation modulus of the tibial cartilage and an increase in cartilage histopathology scores at 1 month compared to sham‐operated animals; these deleterious changes persisted through 3 months. Over this same time course, meniscus remodeling was evident through decreased proteoglycan staining in DMM compared to sham menisci at both 1 and 3 months. These findings support that arthroscopic DMM results in joint degeneration in the Yucatan minipig and provide a new large animal testbed in which to evaluate therapeutics and interventions to treat post‐traumatic OA that originates from a meniscal injury.