Integrative Device for Treating Rotator Cuff Tendon Injuries

This application focuses on the challenge of tendon-to-bone integration for rotator cuff repair and augmentation. The tendon-to-bone insertion in the rotator cuff is often the site of injury in cuff tendon tears. The inability of current repair methods to regenerate the native insertion contributes significantly to the high re-tear rate following repair. As such, there currently exists an unmet demand for integrative fixation devices for rotator cuff repair. Our approach centers on the regeneration of the anatomic insertion site between tendon and bone, which consists of two distinct yet continuous regions of noncalcified and calcified fibrocartilaginous tissue. To address these challenges, we have proposed an innovative approach focused on the regeneration of the tendon-to-bone interface through the design of a novel stratified scaffold coupled with controlled stem cell differentiation.

Current clinically available strategies include graft patches, which focus on mechanical fixation of the injured tendon. Though these designs provide initial stability, they suffer from a lack of mechanical integrity and are ultimately unable to facilitate regeneration of the anatomic insertion. Small intestinal submucosa and dermis are the two most commonly available patches for cuff repair. However, suboptimal outcomes attributed to a mismatch in mechanical properties and rapid matrix remolding have been observed in human trials, limiting the clinical successes of these patches. In a systematic comparison of four commercially available extracellular matrix patches, all were mechanically inferior to the native tendon and underwent premature graft resorption. Moreover, none of the grafts promoted tendon-to-bone integration.

In contrast, the bioinspired technology described in this proposal enables the integrative repair of rotator cuff tears by targeting the regeneration of the critical tendon-to-bone interface. This is essential given that the predominant reason for repair failure and requisite revision surgery is the lack of functional tendon-to-bone integration. Therefore, this technology represents an attractive graft choice that possesses physiologically relevant mechanical properties and the ability to reestablish the tendon-to-bone interface. Through a series of systematic cell and animal studies, this proposal aims to evaluate the potential of this novel graft to harness the regenerative potential of stem cells for functional integrative rotator cuff repair and fixation. The sophisticated design methodologies are useful for other soft tissue injuries and represent a potential paradigm shift in tendon repair from single- to composite-tissue regeneration. In summary, completion of the planned studies will lead to the development of a new generation of fixation devices and demonstrates the potential of stem cells and stratified scaffold design for engineering complex tissue systems that will seamlessly integrate with and function within the body.