Stem Cell-Based Therapies and Tissue Engineering Innovations for Tendinopathy: A Comprehensive Review of Current Strategies and Future Directions

Abstract

Tendon diseases commonly lead to physical disability, exerting a profound impact on the routine of affected patients. These conditions respond poorly to existing treatments, presenting a substantial challenge for orthopedic scientists. Research into clinical translational therapy has yet to yield highly versatile interventions capable of effectively addressing tendon diseases, including tendinopathy. Stem cell-based therapies have emerged as a promising avenue for modifying the biological milieu through the secretion of regenerative and immunomodulatory factors. The current review provides an overview of the intricate tendon microenvironment, encompassing various tendon stem progenitor cells within distinct tendon sublocations, gene regulation, and pathways pertinent to tendon development, and the pathology of tendon diseases. Subsequently, the advantages of stem cell-based therapies are discussed that utilize distinct types of autologous and allogeneic stem cells for tendon regeneration at the translational level. Moreover, this review outlines the challenges, gaps, and future innovations to propose a consolidated stem cell-based therapy to treat tendinopathy. Finally, regenerative soluble therapies, insoluble bio-active therapies, along with insoluble bio-active therapies, and implantable 3D scaffolds for tendon tissue engineering are discussed, thereby presenting a pathway toward enhanced tissue regeneration and engineering. This review explores the potential of stem cell-based therapies in treating tendon diseases, focusing on the tendon microenvironment, cellular dynamics, and gene regulatory networks essential for tendon integrity and repair. It evaluates autologous and allogeneic stem cells for tendon repair, addressing challenges and future directions in tendinopathy treatment. The review also explores innovative regenerative therapies and 3D scaffolds, aiming to advance tendon regeneration and engineering practices. image