Unraveling the Potential of <i>Chondrosia reniformis</i> Collagen for Tissue Engineering Scaffolds, with Particular Insights into Chondrogenic Differentiation

Evaluating the biomedical potential of marine biopolymers is a promising strategy for their high-value application. This study investigated the ability of collagen derived from <i>Chondrosia reniformis</i> to support cell proliferation and chondrogenic differentiation, assessing its suitability for tissue regeneration. Collagen was isolated, preserving its fibrillar structure and glycosylation features, then cross-linked with EDC, genipin, or glutaraldehyde to produce freeze-dried scaffolds. The resulting structures were characterized in terms of physicochemical properties, morphology, degradation, rheology, and cytocompatibility. While all scaffolds showed comparable degradation and rheological behavior, genipin-cross-linked scaffolds exhibited larger pore sizes, whereas glutaraldehyde-cross-linked scaffolds showed higher water uptake. <i>In vitro</i> assays using ATDC5, BJ, and EA.hy926 cell lines demonstrated superior metabolic activity and proliferation on genipin-cross-linked scaffolds. Additionally, human adipose stem cells displayed early chondrogenic differentiation, evidenced by <i>SOX9</i>, <i>ACAN</i>, and <i>COMP</i> expression under basal conditions. These findings highlight the versatility of <i>C. reniformis</i> collagen for biomedical applications, particularly cartilage regeneration.