Scaffold-based delivery of mesenchymal stromal cells to diabetic wounds

Abstract

Foot ulceration is a major complication of diabetes mellitus, which results in significant human suffering and a major burden on healthcare systems. The cause of impaired wound healing in diabetic patients is multifactorial with contributions from hyperglycaemia, impaired vascularization and neuropathy. Patients with non-healing diabetic ulcers may require amputation, creating an urgent need for new reparative treatments. Delivery of stem cells may be a promising approach to enhance wound healing because of their paracrine properties, including the secretion of angiogenic, immunomodulatory and anti-inflammatory factors. While a number of different cell types have been studied, the therapeutic use of mesenchymal stromal cells (MSCs) has been widely reported to improve delayed wound healing. However, topical administration of MSCs via direct injection has several disadvantages, including low cell viability and poor cell localization at the wound bed. To this end, various biomaterial conformations have emerged as MSC delivery vehicles to enhance cell viability and persistence at the site of implantation. This paper discusses biomaterial-based MSCs therapies in diabetic wound healing and highlights the low conversion rate to clinical trials and commercially available therapeutic products.

Keywords: Biomaterials; Diabetic wound healing; Mesenchymal stromal cells.

Fig. 1

Summarized representations of various scaffolds used for MSC delivery. Enhanced delivery of MSC can be achieved using scaffolds and grafts that mimic or retain the architecture of natural human tissue, providing a favourable microenvironment for MSCs to attach, proliferate, and retain their secretome, as well as guide the host cell migration. The secretome of MSCs stimulate the infiltration and migration of immune cells (macrophages, lymphocytes, and neutrophil) that will modulate the inflammation and immune response in the wound bed, thus promoting angiogenesis and improving wound healing. From left to right, we depicted the main cell carriers used to delivery MSCs in diabetic wound healing studies. Hydrogel scaffolds hold a high fraction of water within its structure; sponge scaffolds exhibit highly uniform interconnected pore network; fibrous scaffolds consist of fibres at microscale or nanoscale level; and decellularized grafts retain their native ECM elements and anatomical structure. (Created in BioRender.com)