A ternary composite hydrogel based on sodium alginate, carboxymethyl cellulose and copper-doped 58S bioactive glass promotes cutaneous wound healing in vitro and in vivo

Abstract

Hydrogels offer a novel approach to wound repair. In this study, we synthesized a ternary composite using sodium alginate (SA), carboxymethyl cellulose (CMC) and copper-doped 58S bioactive glass (BG). According to our mechanical testing results, the composite made of 7 wt% CMC and 7 wt% BG (SA-7CMC-7BG) showed optimal properties. In addition, our in vitro studies revealed the biocompatibility and bioactivity of SA-7CMC-7BG, with a negative zeta potential of -31.7 mV. Scanning electron microscope (SEM) images showed 273-μm-diameter pores, cell adhesion, and anchoring. The SA-7CMC-7BG closed 90.4 % of the mechanical scratch after 2 days. An in vivo wound model using Wistar rats showed that SA-7CMC-7BG promoted wound healing, with 85.57 % of the wounds healed after 14 days. Treatment with the SA-7CMC-7BG hydrogel caused a 1.6-, 65-, and 1.87-fold increase in transforming growth factor beta (TGF-β), Col I, and vascular endothelial growth factor (VEGF) expression, respectively that prevents fibrosis and promotes angiogenesis. Furthermore, interleukin 1β (IL-1β) expression was downregulated by 1.61-fold, indicating an anti-inflammatory effect of SA-7CMC-7BG. We also observed an increase in epidermal thickness, the number of fibroblast cells, and collagen deposition, which represent complementary pathology results confirming the effectiveness of the SA-7CMC-7BG hydrogel in cutaneous wound healing.

Keywords: Bioactive glass; Hydrogels; Sodium alginate; Wound healing.