Carrageenan-based hydrogels and composite scaffolds for cartilage and osteochondral regeneration: Mechanisms,...

Articular cartilage and the osteochondral unit have limited intrinsic healing capacity, creating a need for advanced tissue engineering solutions. This systematic review critically evaluates the development and performance of carrageenan (CG)-based biomaterials for cartilage and osteochondral regeneration. Using a structured search of PubMed, Scopus, and Web of Science (2002-2025), we identified and analyzed 140 relevant studies that met predefined inclusion criteria: (1) use of κ-, ι-, or λ-carrageenan in scaffold fabrication, (2) in vitro or in vivo assessment of chondrogenic or osteochondral repair, and (3) reporting of mechanical, biological, or degradation data. Our analysis reveals that the sulfate-rich backbone and ion-sensitive gelation of CG provide a versatile platform for designing biomimetic scaffolds. We provide a comparative assessment of major scaffold classes-including ionic hydrogels, covalent hybrids, polyelectrolyte complexes, pHoto-crosslinkable networks, and multiphasic composites-highlighting distinct trade-offs in mechanical strength, degradation profiles, and bioactivity. CG-based systems consistently support chondrocyte viability (>90%) and enhance the expression of cartilage-specific markers (collagen II, aggrecan, SOX9). However, significant variability exists in reported performance metrics, which often depends on CG type, crosslinking method, and composite formulation. Despite promising preclinical outcomes, key barriers to clinical translation persist. These include limited long-term mechanical stability under physiological loading, insufficient control over degradation kinetics, and a lack of standardized in vivo models for osteochondral defect repair. We conclude that while CG-based hydrogels represent a compelling biomaterial strategy for cartilage regeneration, future progress depends on the rational integration of advanced fabrication techniques, standardized characterization protocols, and targeted immunomodulatory design to address these translational hurdles.