Glycosaminoglycans in hard tissue repair and regeneration: A group of re-emerging natural carbohydrates.

Bone, cartilage, and tooth, can develop hard tissue-related diseases due to tumors, inflammation, and aging. Within the realm of hard tissue engineering, scaffolds play crucial roles in mimicking the properties of natural extracellular matrix (ECM) while meeting strict requirements for mechanical and biological characteristics. As key components of the ECM, the applications of glycosaminoglycans (GAGs) in hard tissue regeneration remained limited due to their inherently weak mechanical properties and stability. With the advances in material manufacturing techniques and a deeper understanding of the regulatory mechanisms in hard tissue development and regeneration, GAGs have been brought back into the spotlight and regarded as promising scaffold materials owing to their adjustable mechanical properties, excellent biocompatibility, and biological effects on cells, growth factors, biomineralization, etc. In this review, a comprehensive overview of the functions and applications of GAGs in bone, cartilage, osteochondral and dental hard tissue repair and regeneration was provided. The review began with the analysis, structure and biological roles of GAGs, followed by an overview of current challenges in hard tissue engineering. Subsequently, it demonstrated the recent research advances of GAGs in these hard tissues separately. Finally, current research trends, limitations, as well as insights into future directions were particularly discussed.