Smart Hydrogel-Based DVDMS/bFGF Nanohybrids for Antibacterial Phototherapy with Multiple Damaging Sites and Accelerated Wound Healing

Abstract

Burn infection is one of the commonest causes of death in severely burned patients. Developing multifunctional biological nanomaterials has a great significance for the comprehensive treatment of burn infection. In this paper, we developed a hydrogel-based nanodelivery 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 sinoporphyrin sodium (DVDMS) and poly(lactic-co-glycolic acid) (PLGA)-encapsulated basic fibroblast growth factor (bFGF) nanospheres that are 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 photoirradiation (30 J/cm 2 , 5 min), 10 μg/mL CSDP showed excellent antibacterial and anti-biofilm activities, which eradicated almost 99.99% of Staphylococcus aureus and multidrug-resistant (MDR) S. aureus in vitro. KEGG analysis identified that multiple signaling pathways were changed in MDR S. aureus after PACT. In the burninfection model, CSDP-PACT successfully inhibited bacteria growth and concurrently promoted wound healing. Moreover, several regenerative factors were increased and some proinflammatory factors were reduced in the burn wounds of CSDP hydrogel treatment. These results suggest that the multifunctional CSDP hydrogel is a portable, light-triggered, antibacterial theranosticplatform and CSDP-PACT provides a promising strategy or the mechanically based synergistic treatment of burn infections.

Multifunctional Hydrogel Nanocomposites for Biomedical Applications

“…Traditional dressings and sealants often require the use of antibiotics to prevent microbial infection [57]. Researchers have demonstrated the incorporation of nanoparticles can endow hydrogels with antipathogenic properties [39,54,[58][59][60], as well as add angiogenic, or adhesive properties [27,29,57,[61][62][63], thus improving their use for wound healing [64][65][66].…”

“…Some metal and metal oxide NPs are naturally bioactive and can add antipathogenic properties to hydrogels, as well as improve mechanical and chemical properties [39,54,[58][59][60]67,68]. AgNPs are commonly used for the development of antibacterial, antiviral, and antifungal hydrogels, due to harsh attack of AgNPs on the microbial respiratory chain that prevents cell division, and the inability of microorganisms to develop resistance to silver [54,58,64,68]. For example, chitosan-polyvinyl alcohol (PVA), carrageenan, and DNA hydrogels modified with AgNPs showed a significant reduction in a variety of bacteria including Escherichia coli and Bacillus [58,59,69].…”

“…Not surprisingly, ZnO NPs have been shown to prevent the growth of a wide variety of bacterial strains (including both Gram positive and Gram negative), as well as the growth of a fungal strain, Candida albicans [39]. Researchers are exploring other methods to create antimicrobial wound dressings using nanoparticles, including pH sensitive drug delivery [40,65] and the use of phototherapy to generate reactive oxygen species (ROS) [64,70]. Zhu et al incorporated ligninbased NPs loaded with trans-resveratrol, a drug with antioxidant, immunomodulatory, anticancer and anti-inflammatory activity, to carboxymethyl chitosan hydrogels.…”

“…The CNTs also added photothermal effects to kill bacteria and electrical conductivity to improve cell proliferation, differentiation, regeneration, and accelerate healing [40]. Other research groups utilized phototherapy to treat wounds by incorporating zeolite imidazolate framework-8 NPs or porphyrin photosensitizer sinoporphyrin sodium (DVDMS) NPs, in addition to adding other biologics or growth factors to improve wound healing [64,70]. In phototherapy, the nanoparticles produce ROS that cause protein dysfunction and DNA degradation, preventing the formation of drug-resistant bacteria and killing any bacteria present in the wound [54,64,68].…”

Sinoporphyrin sodium, a novel sensitizer for photodynamic and sonodynamic therapy

“…The nanocomposite was proved to improve the antibacterial activity of DVDMS. Mai et al [53] developed a hydrogel-based nanodelivery system with antibacterial activity and skin regeneration function, and the system was mainly composed of DVDMS and poly(lactic-coglycolic acid) (PLGA)-encapsulated basic fibroblast growth factor (bFGF) nanospheres, which mediated PACT provided a promising strategy of burn infections. Psoriasis is a chronic inflammatory skin disease that is difficult to cure.…”