Dual Functionalized Injectable Hybrid Extracellular Matrix Hydrogel for Burn Wounds

Low strength and rapid biodegradability of acellular dermal matrix (ADM) restrict its wider clinical application as a rapid cell delivery platform in situ for management of burn wounds. Herein, the extracted ADM was modified by a dual cross-linking approach with ionic crosslinking using chitosan and covalent crosslinking using an iodine-modified 2,5-dihydro-2,5-dimethoxy-furan cross-linker, termed as CsADM-Cl. In addition, inherent growth factors and cytokines were found to be preserved in CsADM-Cl, irrespective of ionic/covalent crosslinking. CsADM-Cl demonstrated improvement in post crosslinking stiffness with a decreased biodegradation rate. This hybrid crosslinked hydrogel supported adhesion, proliferation, and migration of human foreskin-derived fibroblasts and keratinocytes. Also, the angiogenic potential of CsADM-Cl was manifested by chick chorioallantoic membrane assay. CsADM-Cl showed excellent antibacterial activity against Escherichia coli and Staphylococcus aureus. Moreover, CsADM-Cl treated full thickness bum wounds and demonstrated rapid healing marked with superior angiogenesis, well-defined dermal-epidermal junctions, 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.

Automated summary

The dual cross-linked CsADM-Cl hydrogel, modified with ionic crosslinking using chitosan and covalent crosslinking using an iodine-modified cross-linker, demonstrated improved stiffness and reduced biodegradation rate post-crosslinking. It supported adhesion, proliferation, and migration of human foreskin-derived fibroblasts and keratinocytes, exhibited angiogenic potential, showed excellent antibacterial activity, and promoted rapid healing in full thickness burn wounds with superior angiogenesis and other positive healing indicators. The bioactive CsADM-Cl hydrogel has significant clinical potential as an injectable antibacterial matrix for treating challenging burn wounds.