Advancements in Therapeutic Approaches for Degenerative Tendinopathy: Evaluating Efficacy and Challenges

Abstract

Degenerative tendinopathy results from the accumulation of minor injuries following unsuccessful tendon repair during acute tendon injuries. The process of tendon repair is prolonged and varies between individuals, making it susceptible to reinjury. Moreover, treating chronic tendinopathy often requires expensive and extensive rehabilitation, along with a variety of combined therapies to facilitate recovery. This condition significantly affects the quality of life of affected individuals, underscoring the urgent need for more efficient and cost-effective treatment options. Although traditional treatments have improved significantly and are being used as substitutes for surgical interventions, the findings have been inconsistent and conflicting. This review aims to clarify these issues by exploring the strengths and limitations of current treatments as well as recent innovations in managing various forms of degenerative tendinopathy.

Keywords: regenerative medicine; tendinopathy; therapeutic advancements.

Figure 1

Tendinopathy associated changes: The figure provides an overview of the multifactorial causes and pathological changes involved in tendinopathy. Intrinsic factors such as genetic predisposition, aging, and hormonal imbalances, along with extrinsic factors like repetitive mechanical loading, sedentary lifestyle, and drug side effects contribute to the onset and progression of chronic tendon injuries. The degenerative process is marked by a continuum of changes, including failed healing, alterations in cell phenotype, and structural disruptions such as disorganized collagen fibers, altered tendon matrix, and increased or abnormal vascularity. These pathological changes are implicated in various conditions like rotator cuff tear, patellar tendon tear, tennis elbow, and Achilles tendon tear.

Figure 2

Stages of tendon healing: This figure delineates the three primary stages of tendon healing: inflammation, proliferation, and remodeling. During the inflammation stage, which lasts up to 48 h, there is an influx of immune cells, including platelets, neutrophils, monocytes, erythrocytes, and macrophages. These cells are guided by a complex interplay of cytokines and growth factors such as Interleukin 6, Interleukin 1-Beta, Fibroblast Growth Factor, Insulin-like Growth Factor, Platelet-Derived Growth Factor, Transforming Growth Factor Beta, and Vascular Endothelial Growth Factor. The proliferation stage, spanning from 3 days to 4 weeks, is characterized by the activation of fibroblasts, macrophages, and tenocytes, along with contributions from Mesenchymal Stem Cells (MSCs) and Tendon-Derived Stem Cells (TDSCs). This stage is critical for the formation of a provisional collagen III (COL3) scaffold, which serves as a template for new tissue. Finally, the remodeling stage, extending from 12 months to up to 2 years, involves the transition from collagen III to the stronger collagen I (COL1), alongside the organization of the extracellular matrix. This phase ensures the strengthening and proper alignment of the collagen fibers, crucial for restoring the tendon’s mechanical properties and function.