Bioactive human placental ECM hydrogels crosslinked with tannic acid enhance stability and antioxidant properties for diabetic wound healing.

Hydrogels are promising materials for minimally invasive surgical interventions and tissue regeneration. However, hydrogels derived from the extracellular matrix (ECM) frequently suffer from rapid degradation, poor injectability, limited bioactivity, and weak stability. The purpose of this work is to combine decellularized placental extracellular matrix (PECM) hydrogels with tannic acid (TA) to enhance the stability and biological characteristics. PECM hydrogels were subjected to proteomic analysis to detect and describe bioactive proteins. PECM hydrogels crosslinked with TA demonstrated antibacterial efficiency, antioxidant activity, hemocompatibility, and biocompatibility. Notable improvements in stability were observed following enzymatic degradation and rheological characterization. Mice treated with PECM hydrogels crosslinked with TA in a diabetic wound healing model show sustained vascularization, reduced inflammation over time, faster wound closure, and cell infiltration. These findings highlight the synergistic effect of TA crosslinking in modulating both the structural integrity and the biological function of PECM hydrogels. Furthermore, the integration of TA contributes to the controlled degradation profile, enabling prolonged residence time at the wound site for effective tissue regeneration. The enhanced stability, presence of bioactive molecules, and microenvironment for host remodelling, as well as the demonstrated therapeutic efficacy of these hydrogels, suggest significant promise for their clinical application in tissue repair.