Growth factor delivery strategies for rotator cuff repair and regeneration

Abstract

The high incidence of degenerative tears and prevalence of retears (20-95%) after surgical repair makes rotator cuff injuries a significant health problem. This high retear rate is attributed to the failure of the repaired tissue to regenerate the native tendon-to-bone insertion (enthesis). Biological augmentation of surgical repair such as autografts, allografts, and xenografts are confounded by donor site morbidity, immunogenicity, and disease transmission, respectively. In contrast, these risks may be alleviated via growth factor therapy, which can actively influence the healing environment to promote functional repair. Several challenges have to be overcome before growth factor delivery can translate into clinical practice such as the selection of optimal growth factor(s) or combination, identification of the most efficient stage and duration of delivery, and the design considerations for the delivery device. Emerging insight into the injury-repair microenvironment and our understanding of growth factor mechanisms in healing are informing the design of advanced delivery scaffolds to effectively treat rotator cuff tears. Here, we review potential growth factor candidates, design parameters and material selection for growth factor delivery, innovative and dynamic delivery scaffolds, and novel therapeutic targets from tendon and developmental biology for the structural and functional healing of rotator cuff repair.

Stimuli‐Responsive Delivery of Growth Factors for Tissue Engineering

“…Various GFs including bFGF, VEGF, PDGF and hepatocyte growth factor (HGF) are involved in the regeneration process at different points across the stages of repair. [ 126 ] A variety of unique features in the regenerative muscle microenvironment are deployed as stimuli. The context of tissue ischemia, for example, leads to hypoxia and ROS generation, accompanied by lactic acid accumulation and increase in protease levels.…”

rhBMP-2-Coated Acellular Dermal Graft for Chronic Rotator Cuff Healing: Translational Tendon Repair Research

“…There have been a number of preclinical and clinical trials for the enhanced tendon-bone healing in the shoulder repair surgery [12,21,30]. The augmentation repair of rotator cuff by incorporating growth factors or stem cells into the scaffold is intended to enhance the repair process, improve the mechanical properties, and reduce the possibility of re-rupture [10,24,25].…”

“…And a growth factor should induce host cell infiltration and new tissue formation. Those characteristics are strongly necessary for biological augmentation approaches [9][10][11][12]. The dermal graft, which has been used for wound coverage, maybe applicable for large rotator cuff tears.…”

Spatiotemporal control of growth factors in three-dimensional printed scaffolds

“…(41) This approach is exemplary of many similar growth factor delivery strategies that utilize carriers with differential release kinetics, and many existing reviews have summarized the advances and ongoing pitfalls associated with such strategies. (26,42,43) Ultimately, combining the multibioink systems discussed previously with differentially degradable growth factor vessels can effect a combination of spatial and temporal control over growth factor release.…”