On chitosan-agarose-gelatin hydrogels functionalized with tannic acid and metallic ions for regenerative medicine

Abstract:

Tissue defects resulting from trauma and related diseases continue to pose a significant clinical challenge due to their limited capacity for self-healing. Conventional grafts and substitutes remain limited, highlighting the strong demand for affordable, bioactive materials capable of responding to the complex physicochemical conditions of tissue regeneration. Biopolymer-based hydrogels are promising candidates, although their clinical translation requires optimized design. In this study, multifunctional chitosan-agarose-gelatin hydrogels were developed through dual cross-linking and subsequently functionalized with tannic acid (TA) and/or TA-metal complexes (Sr2+, Cu2+, or both). The physicochemical, mechanical, and thermal properties, as well as the biodegradation, hemocompatibility, and cytocompatibility, were investigated. Results show the formation of a dual-architecture structure at both macro- and micro-porosity levels. TA-only functionalization led to insufficient hydrogel stability, whereas incorporation of metal ions significantly improved it, with degradation rates ranging from ~13–25 % at 30 days. Depending on formulation, compressive strengths ranged from 10 to 30 kPa, and Young’s Modulus from 50 to 100 kPa, reflecting the different coordination modes of TA–metal complexes. The biological evaluation confirmed satisfactory outcomes for all functionalized hydrogels. TA + Cu2+/Sr2+ functionalization with a short incubation time emerged as the most promising strategy, achieving an interesting compromise between physicochemical properties, degradation, and mechanical performance. Overall, the developed hydrogels represent a versatile and tunable platform with high potential for application in regenerative medicine.

Bioactive hydrogel; Chitosan; Tannic acid; Metallic ions; Tissue regeneration.