Biomaterials and tissue engineering approaches using glycosaminoglycans for tissue repair: Lessons learned from the native extracellular matrix

Glycosaminoglycans (GAGs) are an important component of the extracellular matrix as they influence cell behavior and have been sought for tissue regeneration, biomaterials, and drug delivery applications. GAGs are known to interact with growth factors and other bioactive molecules and impact tissue mechanics. This review provides an overview of native GAGs, their structure, and properties, specifically their interaction with proteins, their effect on cell behavior, and their mechanical role in the ECM. GAGs’ function in the extracellular environment is still being understood however, promising studies have led to the development of medical devices and therapies. Native GAGs, including hyaluronic acid, chondroitin sulfate, and heparin, have been widely explored in tissue engineering and biomaterial approaches for tissue repair or replacement. This review focuses on orthopaedic and wound healing applications. The use of GAGs in these applications have had significant advances leading to clinical use. Promising studies using GAG mimetics and future directions are also discussed. Statement of significance: Glycosaminoglycans (GAGs) are an important component of the native extracellular matrix and have shown promise in medical devices and therapies. This review emphasizes the structure and properties of native GAGs, their role in the ECM providing biochemical and mechanical cues that influence cell behavior, and their use in tissue regeneration and biomaterial approaches for orthopaedic and wound healing applications.