Advances in biologic augmentation for rotator cuff repair

Abstract

Rotator cuff tear is a very common shoulder injury that often necessitates surgical intervention for repair. Despite advances in surgical techniques for rotator cuff repair, there is a high incidence of failure after surgery because of poor healing capacity attributed to many factors. The complexity of tendon-to-bone integration inherently presents a challenge for repair because of a large biomechanical mismatch between the tendon and bone and insufficient regeneration of native tissue, leading to the formation of fibrovascular scar tissue. Therefore, various biological augmentation approaches have been investigated to improve rotator cuff repair healing. This review highlights recent advances in three fundamental approaches for biological augmentation for functional and integrative tendon–bone repair. First, the exploration, application, and delivery of growth factors to improve regeneration of native tissue is discussed. Second, applications of stem cell and other cell-based therapies to replenish damaged tissue for better healing is covered. Finally, this review will highlight the development and applications of compatible biomaterials to both better recapitulate the tendon–bone interface and improve delivery of biological factors for enhanced integrative repair.

Tendon healing affects the multiscale mechanical, structural and compositional response of tendon to quasi-static tensile loading

“…It is well established that tendons heal through scar formation, do not regain pre-injury material properties, and often display aberrant phenotypes [20,45,48 -50]. As tendon cells reside within a niche environment that combines mechanical and biochemical cues [51][52][53][54], it is essential to understand how alterations to this microenvironment may drive tendons toward an aberrant differentiation (chondrogenic, osteogenic or adipogenic) [55]. Our results not only add to the understanding of how tendon healing affects the local microenvironment of residing tendon cells in native tissue, but identify the capacity for these cells to biomechanically respond to external mechanical cues.…”

The “other” 15–40%: The Role of Non‐Collagenous Extracellular Matrix Proteins and Minor Collagens in Tendon

“…Despite these challenges, decellularized tendon tissue allografts have been evaluated in small and large animal models and showed some promise in augmenting tendon repair after injury . In addition, overexpression or exogenous addition of individual ECM proteins in combination with a diverse set of growth factors have been shown to enhance tenogenic differentiation of stem cells and augment repair processes in injury models, respectively, and as such could represent an integral part of a comprehensive tendon tissue engineering and repair strategy . An understanding of the dynamic tendon ECM and tenocyte PCM will provide useful guidance to design future therapeutic approaches to augment tendon healing and to invigorate tendon tissue engineering.…”

“…173 OTHER ECM PROTEINS IN TENDON combination with a diverse set of growth factors have been shown to enhance tenogenic differentiation of stem cells and augment repair processes in injury models, respectively, and as such could represent an integral part of a comprehensive tendon tissue engineering and repair strategy. 74,[180][181][182] An understanding of the dynamic tendon ECM and tenocyte PCM will provide useful guidance to design future therapeutic approaches to augment tendon healing and to invigorate tendon tissue engineering.…”

Integrating soft and hard tissues via interface tissue engineering

“…Similar to other tissue engineered grafts, a translation gap remains between promising approaches in the laboratory and successful implementation in the clinical setting. Many of the technologies discussed above have only been evaluated in the preclinical setting . While encouraging, small or large animal results do not necessarily guarantee similar performance when used in humans.…”

“…Many of the technologies discussed above have only been evaluated in the preclinical setting. 66 While encouraging, small or large animal results do not necessarily guarantee similar performance when used in humans. Moreover, adaptation of these integrative design for use with arthroscopy surgery represents another translational challenge.…”