Structure–Property Relationships in Chemically Interpenetrated Collagen–Polyurethane–Glycosaminoglycan Networks

ABSTRACT

Chemically reinforced collagen–polyurethane–glycosaminoglycan (GAG) interpenetrating polymer network hydrogels are developed to establish how GAG chemistry and concentration regulate network formation, structure, and biological functionality. Collagen–PU–IPNs containing 0–60 wt% hyaluronic acid (HA) or chondroitin sulfate (CS) exhibit complete gelation within 30 min, while HA accelerates fibrillar assembly, reaching a maximum kinetic constant of 0.510 min ^{− 1} at 30 wt% HA. GAG incorporation modulates hydration and crosslinking, with swelling capacities among 1800%–2300% and crosslinking degrees of 75%. These compositional changes translate into distinct viscoelastic responses, with solid‐like behavior maintained across the formulations and an elastic modulus reaching approximately 9.9 kPa at 45 wt% HA. Structural and morphological analyses reveal GAG‐dependent fibrillar, dendritic, and amorphous architectures, which further influence degradation behavior. CS‐containing networks exhibit greater hydrolytic stability, whereas HA‐based systems show enhanced enzymatic susceptibility. Importantly, GAG incorporation reduces hemolytic activity while supporting the metabolic activity and proliferation of monocytes, fibroblasts, and bone marrow‐derived cells. Antibacterial and immunomodulatory responses are also observed, with IL‐10 secretion increasing with HA content and reaching 6672 pg mL ^{− 1} at 60 wt% HA. Overall, GAG chemistry and concentration provide effective control over composition–structure–property–function relationships, enabling tailored multifunctional hydrogels for potential biomedical applications.