Abstract
Skin restoration following full-thickness injury poses significant clinical challenges including inflammation and scarring. Medicated scaffolds formulated from natural bioactive polymers present an attractive platform for promoting wound healing. Glibenclamide was formulated in collagen/chitosan composite scaffolds to fulfill this aim. Glibenclamide was forged into nanocrystals with optimized colloidal properties (particle size of 352.2 nm, and polydispersity index of 0.29) using Kolliphor as a stabilizer to allow loading into the hydrophilic polymeric matrix. Scaffolds were prepared by the freeze drying method using different total polymer contents (3–6%) and collagen/chitosan ratios (0.25–2). A total polymer content of 3% at a collagen/chitosan ratio of 2:1 (SCGL3-2) was selected based on the results of in vitro characterization including the swelling index (1095.21), porosity (94.08%), mechanical strength, rate of degradation and in vitro drug release. SCGL3-2 was shown to be hemocompatible based on the results of protein binding, blood clotting and percentage hemolysis assays. In vitro cell culture studies on HSF cells demonstrated the biocompatibility of nanocrystals and SCGL3-2. In vivo studies on a rat model of a full-thickness wound presented rapid closure with enhanced histological and immunohistochemical parameters, revealing the success of the scaffold in reducing inflammation and promoting wound healing without scar formation. Hence, SCGL3-2 could be considered a potential dermal substitute for skin regeneration.
Highlights
Published: 14 September 2021The skin is the largest organ of the body, playing a pivotal role in sensation, thermoregulation and protection from environmental hazards [1]
The results show that increasing the chitosan ratio relative to collagen was accompanied by an increase in the ultimate compressive strength, which was more pronounced in the blank scaffolds with a lower total polymer content
For efficient applicability to full-thickness wounds, the drug was incorporated into bioactive collagen/chitosan composite scaffolds
Summary
The skin is the largest organ of the body, playing a pivotal role in sensation, thermoregulation and protection from environmental hazards [1]. Wounds disrupt this protective barrier, predisposing the body to infections and allowing for protein and water loss [2]. Wound healing is described to have three overlapping stages: inflammation, proliferation and remodeling [3]. The proliferation phase is characterized by the influx of fibroblasts, extracellular matrix (ECM). The last stage, remodeling, outlined by both wound contraction and collagen remodeling, aims to achieve the maximum tensile strength through reorganization, degradation and re-synthesis of the extracellular matrix
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