Dual Functionalized Injectable Hybrid Extracellular Matrix Hydrogel for Burn Wounds

Low strength and rapid biodegradability of Acellular Dermal Matrix (ADM) restrict wider clinical application as rapid cell delivery platform in situ, for management of burn wounds. Herein, extracted ADM was modified by dual cross-linking approach with ionic crosslinking using chitosan (CTS) and covalent cross-linking using an iodine modified 2, 5-dihydro-2,5-dimethoxy-furan (DHF-I) cross-linker; termed as CsADM-Cl. In addition, inherent growth factors and cytokines were found to be preserved in the CsADM-Cl, irrespective of ionic/covalent crosslinking. CsADM-Cl demonstrated improvement in post crosslinking stiffness with decreased biodegradation rate. This hybrid crosslinked hydrogel supported adhesion, proliferation, and migration of human foreskin derived fibroblasts (HFCs) and keratinocytes (HKC). Also, the angiogenic potential of CsADM-Cl was manifested by chick chorioallantoic membrane (CAM) assay. CsADM-Cl showed excellent antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Moreover, CsADM-Cl treated full thickness (FT) burn wounds demonstrated rapid healing marked with superior angiogenesis, well-defined dermal-epidermal junctions (DEJ), mature basket weave collagen deposition, and development of more pronounced secondary appendages. Altogether, the bioactive CsADM-Cl hydrogel established significant clinical potential to support wound healing as an apt injectable antibacterial matrix to encounter unmet challenges concerning critical burn wounds.