Opto-Laser-Responsive Smart NanoGel with Mild Hyperthermia, Vascularization, and Anti-Inflammatory Potential for Boosting Hard-to-Heal Wounds in a Diabetic Mice Model

Abstract

It is well known that impaired wound healing associated with diabetes mellitus has led to a challenging problem as well as a global economic healthcare burden. Conventional wound care therapies like films, gauze, and bandages fail to cure diabetic wounds, thereby demanding a synergistic and promising wound care therapy. This investigation aimed to develop a novel, greener synthesis of a laser-responsive silver nanocolloid (LR-SNC) prepared using hyaluronic acid as a bioreductant. The prepared LR-SNC was embedded into a stimuli-responsive in situ gel (LR-SNC-in situ gel) for easy application to the wound region. The physicochemical characterization of LR-SNC revealed a nanometric hydrodynamic particle size of 25.59 ± 0.72 nm with an -31.8 ± 0.7 mV surface ζ-potential. The photothermal conversion efficiency of LR-SNC was observed up to 62.9 ± 0.1 °C. In vitro evaluation of LR-SNC with and without NIR laser irradiation exhibited >70% cell viability, confirming its cytocompatibility for human keratinocyte cells. The in vitro scratch assay showed significant wound closure of 75.50 ± 0.02%. Further, the addition of cytocompatible LR-SNC into an in situ gel followed by laser irradiation resulted in substantial in vivo wound closure (86.69 ± 2.48%) in a diabetic wound-bearing mouse. Histological evaluation demonstrated salient features of the healed wounds, such as increased neovascularization, collagen density, migration of keratinocytes, as well as growth of hair follicles. Additionally, the findings showed a decrease in the levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) and enhanced angiogenesis gene expression (VEGF and CD31), thereby healing the diabetic wound efficiently. The present study confirmed the potential role of silver nanocolloids followed by laser irradiation in treating diabetic wound mouse models.

Keywords: NIR laser; diabetic wound; hyaluronic acid; in situ gel; inflammation; mild hyperthermia; silver nanocolloid.