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Smart hydrogel-based DVDMS/bFGF nanohybrids for antibacterial phototherapy with multiple damaging-sites and accelerated wound healing.

Burn infection is one of the commonest causes of death in severely burned patients. Developing multifunctional biological nanomaterials have a great significance for the comprehensive treatment of burn infection. In this paper, we developed a hydrogel-based nano-delivery system with antibacterial activity and skin regeneration function, which was used for photodynamic antimicrobial chemotherapy (PACT) in the treatment of burns. The treatment system is mainly composed of porphyrin photosensitizer DVDMS and PLGA-encapsulated bFGF nanospheres that embedded in carboxymethyl chitosan (CMCS)-sodium alginate to form CSDP hybrid hydrogel. We systematically evaluated the inherent antibacterial performance, rheological properties, fluorescence imaging and biocompatibility of the CSDP nanosystem. Under mild photo-irradiation (30 J/cm2, 5 min), 10 μg/ml CSDP showed excellent antibacterial and antibiofilm activities, which eradicated almost 99.99% of Staphylococcus aureus and multidrug-resistant (MDR) S. aureus in vitro. KEGG analysis identified multiple signaling pathways were changed in MDR S. aureus after PACT. In the burn-infection model, CSDP-PACT successfully inhibited bacteria growth and concurrently promoted wound healing. Moreover, several regenerative factors were increased and some pro-inflammatory factors were reduced in the burn wounds of CSDP hydrogel treatment. These results suggest that the multifunctional CSDP hydrogel is a portable, light-triggered, anti-bacterial theranostic-platform and CSDP-PACT provides a promising strategy or the mechanically-based synergistic treatment of burn infections.