Exogenous Crosslinking of Tendons as a Strategy for Mechanical Augmentation and Repair: A Narrative Review

Collagens constitute a family of triple-helical proteins with a high level of structural polymorphism and a broad diversity of structural and chemical characteristics. Collagens are designed to form supporting aggregates in the extracellular spaces of our body, but they can be isolated from animal sources and processed to become available as biomaterials with wide applications in biomedicine and bioengineering. Collagens can be conveniently modified chemically, and their propensity for participating in crosslinking reactions is an important feature. While the crosslinking promoted by a variety of agents provides a range of collagen-based products, there has been minor interest for therapies based on the crosslinking of collagen while located within living connective tissues, known as exogenous crosslinking. Currently, there is only one such treatment in ocular therapeutics (for keratoconus), and another two in development, all based on mechanical augmentation of tissues due to ultraviolet (UV)-induced crosslinking. As seen in this review, there was some interest to employ exogenous crosslinking in order to reinforce mechanically the lax tendons with an aim to arrest tear propagation, stabilize the tissue, and facilitate the healing. Here we reviewed in details both the early stages and the actual status of the experimental research dedicated to the topic. Many results have not been encouraging, however there is sufficient evidence that tendons can be mechanically reinforced by chemical or photochemical exogenous crosslinking. We also compare the exogenous crosslinking using chemical agents, which was predominant in the literature reviewed, to that promoted by UV radiation, which was rather neglected but might have some advantages.