Biopolymers in Regenerative Medicine: A Critical Review of Materials, Immunomodulation, and Translational Strategies

Biopolymers—whether derived from natural sources or produced synthetically—combine biodegradability with biocompatibility, positioning them as essential materials for scaffolds and drug delivery systems in regenerative medicine. Although substantial progress has been made in synthesis methodologies and clinical evaluation, comprehensive and critically oriented reviews that systematically consolidate knowledge on biopolymer applications remain scarce. This review synthesizes evidence on natural polymers (collagen, cellulose, chitosan, hyaluronic acid, alginate) and synthetic polymers (polycaprolactone, polylactic acid, polyglycolic acid, their copolymers, and polyethylene glycol). We examine their classification, physicochemical properties, modification strategies, and applications—including tissue engineering, drug delivery, wound healing, and multi-tissue regeneration. Critically, rather than merely cataloging successful case studies, this review identifies and analyzes bottlenecks: the scarcity of head-to-head in vivo comparative studies, the lack of standardized preclinical protocols, poor predictability of long-term immune responses, and ambiguous criteria for material selection that hinder clinical decision-making. The final section discusses emerging hybrid constructs that integrate microcapsules for sustained therapeutic release, representing a paradigm shift from passive structural implants toward actively programmable therapeutic platforms. By bridging materials science, immunology, and translational medicine, this review provides a strategic roadmap for moving biopolymer research beyond proof-of-concept toward clinically viable, scalable, and immunologically smart regenerative systems.