Chondroitin sulfate: From bioactive molecule to versatile drug delivery system for advancing regenerative medicine

Regenerative medicine, a rapidly advancing field, holds immense promise for restoring and revitalizing damaged tissues and organs resulting from aging, diseases, or injuries, ultimately improving patient well-being. Chondroitin Sulfate (CS), a naturally occurring glycosaminoglycan, is a compelling biomaterial due to its natural origin, well-established biocompatibility, and structural complexity. Renowned for its biocompatibility, structural complexity, and varied bioactivities, CS provides significant applications beyond its recognized function in joint health and osteoarthritis treatment. Recent breakthroughs demonstrate its potential in treating complicated disorders such as interstitial cystitis, psoriasis, dry eye syndrome, and cardiovascular diseases by controlling inflammation, facilitating wound healing, and improving tissue repair. Notwithstanding its therapeutic potential, CS remains inadequately investigated in regenerative medicine and tissue engineering. Its capacity to modulate cellular signaling, promote extracellular matrix remodeling, and improve scaffold integration establishes it as a crucial facilitator of sophisticated therapeutic approaches. This review elucidates the progression of CS-based drug delivery systems, encompassing hydrogels, microparticles, nanoparticles, composites, and beads while underscoring their effectiveness in addressing conventional drug delivery obstacles such as non-specific targeting and off-target effects. Integrating CS into advanced platforms enables regulated drug release, accurate targeting, and enhanced cellular absorption while maintaining biodegradability and compatibility with tissue engineering scaffolds. Its inherent antioxidant, anti-inflammatory, and immune-modulating characteristics augment its attractiveness for individualized therapeutic applications. Recent studies highlight the adaptability of CS in developing multimodal drug delivery systems designed for regenerative medicine. Nonetheless, substantial deficiencies persist, especially in clinical validation and extensive applications. Overcoming these hurdles may fully realize CS's potential in transforming drug delivery, establishing a solid basis for the progression of regenerative therapies. By integrating biomaterial science with clinical medicine, CS-based systems are set to transform treatment approaches in regenerative medicine, providing precision, efficiency, and adaptability for individualized care.