In vivo evaluation of bioactive glass-reinforced multifunctional composite hydrogel for thermal burn and chronic diabetic wound repair.

Abstract

Thermal burn injuries and chronic diabetic wounds pose a vast array of pathophysiological problems (low angiogenicity, persistent inflammation, bacterial infection, tissue necrosis) that contribute to delayed healing and poor regeneration as compared to normal wounds. Multifunctional hydrogels have recently gained immense popularity and become viable choices for chronic wound management because of their versatile functionality, like tunable properties, high biocompatibility, soft and moist microenvironment and mimicking natural tissue surrounding properties. We first fabricated a multifunctional composite hydrogel (MCH) consisting of 5 % gelatin, 1 % chitosan, 100 ng/ml Cur-capped silver nanoparticles, and 1.5 % PDA-coated bioactive glass and evaluated its wound healing potential in burn and chronic diabetic wounds in BALB/c mice. The reduction in wound area was assessed at various time intervals. Also, structural changes and cellular responses were evaluated using H & E staining and Masson Trichrome staining. The gene expression of VEGFA, COL1A1, IL-6, IL-10, and TGF-β1 was evaluated using RT-PCR of tissue samples extracted from the healed area. The in vivo wound healing assessment in thermal burn wounds and diabetic wounds showed a significant reduction in wound area (up to 87 % and 80 % respectively) on day 14 in the wounds treated with MCH. These histological and molecular studies confirmed that the presence of bioactive glass in MCH aids in the polarization of macrophages from M1 to M2 phenotype, released Si ions induce blood vessel formation, and collagen deposition and the presence of Cur-AgNPs effectively reduces inflammation and induces collagen deposition in treated groups as compared to control groups. The incorporation of PDA-coated BG endows the adhesivity and angiogenic and Cur-AgNPs provided antibacterial and anti-inflammatory/antioxidative propertied to hydrogel, to regulate the wound microenvironment at cellular and molecular levels render a vital paradigm to facilitate and accelerate the repair and regeneration of burn and chronic diabetic wounds.