Glycosaminoglycans in Tendon Physiology, Pathophysiology, and Therapy

Abstract

Although glycosaminoglycans constitute a minor portion of native tissues, they play a crucial role in various physiological processes, while their abnormal expression is associated with numerous pathophysiologies. Glycosaminoglycans have become increasingly prevalent in biomaterial design for tendon repair, given their low immunogenicity and their inherent capacity to stimulate the regenerative processes, while maintaining resident cell phenotype and function. Further, their incorporation into three-dimensional scaffold conformations significantly improves their mechanical properties, while reducing the formation of peritendinous adhesions. Herein, we discuss the role of glycosaminoglycans in tendon physiology and pathophysiology and the advancements achieved to date using glycosaminoglycan-functionalized scaffolds for tendon repair and regeneration. It is evidenced that glycosaminoglycan functionalization has led to many improvements in tendon tissue engineering and it is anticipated to play a pivotal role in future reparative therapies.

The impact of loading, unloading, ageing and injury on the human tendon

“…It has been suggested that force is transferred laterally between adjacent fibrils via proteoglycans and their associated GAG chains, including chondroitin‐ and dermatan‐sulfate (Scott & Thomlinson, ; Ryan et al . ). However, removing this complex in human tendon (Svensson et al .…”

Co-transfection of decorin and interleukin-10 modulates pro-fibrotic extracellular matrix gene expression in human tenocyte culture

“…The pathologic hallmark of tendon fibrosis is underlined by changes in the composition of interstitial extracellular matrix (ECM) 6 7 8 9 10 . This is associated with the failure of timely termination of key molecular processes in the normal healing cascades, presumably due to continuing presence of physical and biochemical triggers and regulators 11 .…”

Insulin immobilized PCL‐cellulose acetate micro‐nanostructured fibrous scaffolds for tendon tissue engineering

“…Though GAGs make up a small percent of native tendon tissue, their presence in tendon ECM serve to protect tendons against shear and compressive forces . Additionally, GAGs have been shown to play a role in collagen fibrillogenesis, fiber diameter, and mechanical integrity . Furthermore, increased expression of collagen I protein was observed to be qualitatively increased with cells grown on electrospun fibers after treatment with insulin or IGF‐1 when compared with the control basal group (Figure ).…”