ABSTRACT: Rotator cuff tears often heal poorly, leading to re-tears after repair. This is in part attributed to the low proliferative ability of the resident cells (tendon fibroblasts and tendon-stem cells) upon injury to the rotator cuff tissue and the low vascularity of the tendon insertion. In addition, surgical outcomes of current techniques used in clinical settings are often suboptimal, leading to the formation of neo-tissue with poor biomechanics and structural characteristics, which results in re-tears. This has prompted interest in a new approach, which we term as "Regenerative Engineering", for regenerating rotator cuff tendons. In the Regenerative Engineering paradigm, roles played by stem cells, scaffolds, growth factors/small molecules, the use of local physical forces, and morphogenesis interplayed with clinical surgery techniques may synchronously act, leading to synergistic effects and resulting in successful tissue regeneration. In this regard, various cell sources such as tendon fibroblasts and adult tissue-derived stem cells have been isolated, characterized, and investigated for regenerating rotator cuff tendons. Likewise, numerous scaffolds with varying architecture, geometry, and mechanical characteristics of biologic and synthetic origin have been developed. Furthermore, these scaffolds have been also fabricated with biochemical cues (growth factors and small molecules), facilitating tissue regeneration. In this Review, various strategies to regenerate rotator cuff tendons using stem cells, advanced materials, and factors in the setting of physical forces under the Regenerative Engineering paradigm are described.
