Bifunctional modified bacterial cellulose-based hydrogel through sequence-dependent crosslinking towards enhanced antibacterial and cutaneous wound healing.

Chronic wounds caused by microbial infection have emerged as a major challenge on patients and medical health system. Bacterial cellulose (BC) characterized by its excellent biocompatibility and porous network, holds promise for addressing complex wound issues. However, lack of inherent antibacterial activity and cross-linking sites in the molecular network of BC have constrained its efficacy in hydrogel design and treatment of bacterial-infected wounds. Additionally, few studies have explored the effects of precursor crosslinking sequences on hydrogel processing. Herein, a quaternary ammonium and aldehyde-biofunctionalized bacterial cellulose (OQBC) was synthesized and utilized for the development of double network (DN) hydrogels, incorporating the crosslinking sequences of thiol-alginate (SASH) and carboxymethyl chitosan (CMCS). Firstly, OQBC was characterized with bifunctional groups, which endows its inherent antibacterial activity and gel-forming property. Subsequently, DN hydrogels formed through thiol-aldehyde addition and amino-aldehyde reactions showed favorable injectability and self-healing ability. The sequential crosslinking via Schiff-base and thiohemiacetal bonds endowed the hydrogels with distinct features, including degradation behavior, pH-responsive swelling, water retention, surface roughness, and cell behavior. With the increasing OQBC content into hydrogels, bacteriostatic rate exceeded 90 % without obvious cytotoxicity. Hydrogels also exhibited antioxidant and sustained drug release properties. Moreover, in infected skin thickness defect rats, the selected hydrogel enhanced wound repair and regeneration by inhibiting inflammation and promoting collagen deposition and angiogenesis. This design of sequence-dependent crosslinked antibacterial DN hydrogel offers a promising tool for the development of advanced materials to treat infected wounds.