Bioactive glass based fibre mats for wound healing
Creators: name: Zhao, Xingchen
Publisher: name: Imperial College London
Year: 2022

description: Wounds are one of the most prevailing healthcare problems. Two of the most common wound types, burn injuries and chronic ulcers, are imposing a great threat to the medical systems due to their high incidence, high morbidity, high cost of treatment, and high likelihood to induce further problems, such as infection, loss of sensory nodes, cell mutation, etc. Burn injuries usually have a damaged epidermis with excessive exudates that can become infected and cause severe inflammation while in the meantime, the sensory nodes, follicles, and glands are fully damaged. Diabetic ulcers, the most common type of chronic wounds, have unepithelialized epidermis that causes biofilm colonization, strong accumulation of cytokines and protease, and neuropathy from diabetes. The most important steps in the regeneration of both wounds are the regeneration of the ECM and vascular network, in order to ensure cell attachment and migration as well as the delivery of oxygen and nutrients to the wound site. This thesis describes the development of 3D ECM-mimic bioactive glass fibre mats as strategies for the regeneration of both injuries. Bioactive glasses (BGs) are biodegradable materials that have already been widely used as a synthetic bone graft material that can regenerate bone defects and as the active ingredient for remineralizing toothpastes, but now they are finding use as medical devices (scaffolds or matrices) for wound healing applications. BGs degrade into therapeutic ions that promote individual steps in the wound healing cascades, including hemostasis, antibacterial effect, anti-inflammation, appropriate cell proliferation, angiogenesis, re-epithelialization, and extracellular matrix production. BG fibre mats were obtained through an optimized sol-gel electrospinning approach, in which the electrospinning and material parameters were determined through experimentation. The fabricated fibre mats mimicked the extracellular matrix in the dermis layer and can be easily packed into wound defects. We synthesized zinc-delivering bioactive glass fibre mats as scaffolds for burn regeneration as the controlled release of zinc ions is thought to be antibacterial, and have anti-inflammation and follicle regeneration properties. In vitro studies confirmed the capabilities of the fabricated fibre mats in ECM deposition and angiogenesis. 3 mol% of Zn incorporation reduced the cytotoxic effect of BGs to fibroblasts and stimulated their expression of growth factors (PDGF, VEGF, bFGF, TGF-β, and HIF-1α) from fibroblasts and endothelial cells for ECM deposition and angiogenesis. Media conditioned with HDFs that had been precultured with BG dissolution products influenced the proliferation and migration of endothelial cells and their protein expression, which provides insights into understanding the mechanism of BGs in angiogenesis. We also synthesized borosilicate bioactive glass fibre mats through modified sol-gel electrospinning for diabetic ulcer regeneration. Boron was selected as it promotes epithelialization, tissue granulation, anti-inflammation, ECM deposition, and most importantly, angiogenesis. The incorporation of boron into the BG system stimulated high expressions of angiogenic factors (VEGF, bFGF, HIF-1α) from fibroblasts and promoted the proliferation and migration of endothelial cells. In vivo studies were conducted in order to investigate the efficacy of silicate and borosilicate BGs in healing diabetic ulcers and to understand the mechanism of them to individual phases of wound healing, including wound closure, epithelialization, anti-inflammation, angiogenesis, tissue granulation, and ECM deposition. The assays included imaging the wound areas through optical cameras, histology analysis and immunohistochemistry analysis. BGs were found to stimulate faster wound healing as they highly promoted all the above-mentioned healing steps. The incorporation of boron into the BG system and processing BGs to fibrous structure both impact the healing effect.