Dialdehyde Starch Cross-Linked Collagen with Heparin Conjugation: Characterization and Feasibility Study for Osteochondral Tissue Repair

Collagen is widely used in tissue engineering due to its excellent biocompatibility; however, its limited intrinsic mechanical strength restricts its application in load-bearing environments. This study introduces dialdehyde starch (DAS) as a biocompatible macromolecular cross-linker to enhance the mechanical integrity of collagen hydrogels. Collagen gels were cross-linked with DAS during neutralization under optimized conditions, resulting in a significant increase in compressive stiffness (up to ~125 kPa), thereby improving their suitability for mechanically demanding applications. Degradation studies of DAS-crosslinked collagen confirmed the long-term stability of the gel, while post-neutralization heparin incorporation improved bifunctionality, as evidenced by increased surface retention. FT-IR analysis confirmed the successful DAS cross-linking and heparin conjugation while preserving the native collagen structure. Bioactivity assays of DAS-crosslinked and heparin-conjugated collagen gel demonstrated enhanced chondrocyte migration in PDGF-BB-functionalized gels and improved cell viability, proliferation, and matrix deposition in TGF-β3-treated constructs. Preliminary ex vivo culture using a rabbit osteochondral defect model showed promising tissue integration and glycosaminoglycan accumulation. These results highlight the potential of DAS-crosslinked and heparin-conjugated collagen hydrogels as mechanically robust and biologically supportive scaffolds for osteochondral tissue engineering and regenerative medicine applications.