Exploring advancements in polysaccharide-based approaches: The cornerstone of next-generation cartilage regeneration therapeutics.

Cartilage regeneration poses a formidable challenge in orthopaedics due to continuous wear and tear exertion and its limited intrinsic healing capacity, which demand exploration beyond current clinical approaches. Polysaccharides emerged as promising agents for cartilage regeneration, offering biocompatibility, biodegradability, bioactivity, and ECM mimicry. This article provides an overview of the pathophysiology of cartilage diseases and current clinical approaches, followed by polysaccharide-based strategies for cartilage repair, delineating the chemical and biological properties of various polysaccharides like alginates, hyaluronic acid, and chondroitin sulfate. The emphasis lies on innovative strategies such as sulphated and cross-linked polysaccharides, with injectable polysaccharide hydrogels offering adjustable mechanical properties and easy administration. Growth factor and cellular incorporation into hydrogels enhance their therapeutic potential. At the same time, biofabrication techniques, such as filamented light biofabrication, cartilage spheroid generation, and 3D printing, offer precise control over cartilage architecture, with bio-inks comprising alginate, gelatin, and hyaluronic acid showing promise. These advancements underscore the potential of polysaccharides to revolutionize cartilage regeneration strategies, offering hope for improved patient outcomes in the future. The article concludes by addressing regulatory hurdles and the future perspective of polysaccharide-based approaches in clinical translation for cartilage regeneration.