Effect of Diabetes on Tendon Structure and Function: Not Limited to Collagen Crosslinking

Abstract

Diabetes mellitus (DM) is associated with musculoskeletal complications—including tendon dysfunction and injury. Patients with DM show altered foot and ankle mechanics that have been attributed to tendon dysfunction as well as impaired recovery post-tendon injury. Despite the problem of DM-related tendon complications, treatment guidelines specific to this population of individuals are lacking. DM impairs tendon structure, function, and healing capacity in tendons throughout the body, but the Achilles tendon is of particular concern and most studied in the diabetic foot. At macroscopic levels, asymptomatic, diabetic Achilles tendons may show morphological abnormalities such as thickening, collagen disorganization, and/or calcific changes at the tendon enthesis. At smaller length scales, DM affects collagen sliding and discrete plasticity due to glycation of collagen. However, how these alterations translate to mechanical deficits observed at larger length scales is an area of continued investigation. In addition to dysfunction of the extracellular matrix, tendon cells such as tenocytes and tendon stem/progenitor cells show significant abnormalities in proliferation, apoptosis, and remodeling capacity in the presence of hyperglycemia and advanced glycation end-products, thus contributing to the disruption of tendon homeostasis and healing. Improving our understanding of the effects of DM on tendons—from molecular pathways to patients—will progress toward targeted therapies in this group at high risk of foot and ankle morbidity.

Effects of adipose-derived mesenchymal stem cell conditioned medium on human tenocytes exposed to high glucose

“…This implies an amelioration in the maintenance and restoration of tendon tissue, as well as a reduction of extracellular matrix (ECM) structural and biochemical changes, during diabetic tendinopathy. 72 , 73 …”

Effects of Ribose-Induced Glycation on the Elastic Modulus of Collagen Fibrils Observed by Atomic Force Microscopy

“…Glycated collagen impairs the skin's mechanical properties, leading to increased susceptibility to injury, delayed wound healing and a tendency to develop chronic ulcers -common and debilitating complications of diabetes (Monnier et al, 1999;Burgess et al, 2021). In the context of the musculoskeletal system, the altered biomechanical properties of glycated collagen contribute to the joint stiffness and reduced mobility commonly reported in people with diabetes (Adamska et al, 2022;Vaidya et al, 2023). These changes not only reduce quality of life, but also increase the risk of injury and make physical activity more difficult, further complicating diabetes management (Murray & Coleman, 2019).…”

Biodegradable Polymer Electrospinning for Tendon Repairment

“…In tendon tissue engineering, collagen, as the main component of the human tendon, is a natural degradable polymer with a biomimetic tendon ECM structure. Due to its good cell and growth factor binding sites on the surface, it has the function of supporting cell adhesion, migration, growth, and differentiation [ 34 ]. Tissue engineering technology has been used to combine a collagen scaffold with growth factors to help repair damaged tendons.…”

“…Natural biodegradable polymers, such as collagen and gelatin, usually share the common disadvantage of lacking mechanical properties and having uncontrolled degradation rates [ 43 ]. Collagen, the first naturally occurring biodegradable polymer to be used as a scaffold, is not mechanically strong enough to provide post-operative mechanical support after a tendon tear [ 34 ]. To overcome this disadvantage, electrostatic spinning scaffolds have been extensively researched and applied.…”