Composites based on alginate containing formylphosphazene-crosslinked chitosan and its Cu(II) complex as an antibiotic-free antibacterial hydrogel dressing with enhanced cytocompatibility

Hydrogels based on chitosan or alginate biopolymers are believed to be desirable for covering skin lesions. In this research, we explored the potential of a new composite hydrogels series of sodium alginate (Alg) filled with cross-linked chitosan to use as hydrogel wound dressings. Cross-linked chitosan (CSPN) was synthesized by Schiff-base reaction with aldehydated cyclophosphazene, and its Cu(II) complex was manufactured and identified. Then, their powder suspension and Alg were transformed into hydrogel via ion-crosslinking with Ca2+. The hydrogel constituents were investigated by using FTIR, XRD, rheological techniques, and thermal analysis including TGA (DTG) and DSC. Moreover, structure optimization calculations were performed with the Material Studio 2017 program based on DFT-D per Dmol3 module. Examination of Alg's interactions with CSPN and CSPN-Cu using this module demonstrated that Alg molecules can be well adsorbed to the particle's surface. By changing the dosage of CSPN and CSPN-Cu, the number and size of pores, swelling rate, degradation behavior, protein absorption rate, cytotoxicity and blood compatibility were changed significantly. Subsequently, we employed erythromycin as a model drug to assess the entrapment efficiency, loading capacity, and drug release rate. FITC staining was selected to verify the hydrogels' intracellular uptake. Assuring the cytocompatibility of Alg-based hydrogels was approved by assessing the survival rate of fibroblast cells using MTT assay. However, the presence of Cu(II) in the developed hydrogels caused a significant antibacterial effect, which was comparable to the antibiotic-containing hydrogels. Our findings predict these porous, biodegradable, and mechanically stable hydrogels potentially have a promising future in the wound healing as antibiotic-free antibacterial dressings.