Chitosan based extruded nanofibrous bioscaffold for local delivery of mesenchymal stem cells to improve diabetic wound healing

Abstract

Background Mesenchymal stem cells (MSCs)-based treatment strategy has shown promise in bolstering the healing process of chronic wounds in diabetic patients, who are at risk of amputation and mortality. To overcome the drawbacks of suboptimal cell retention and diminished cell viability at the injury site, a novel nanofibrous biomaterial-based scaffold was developed by using a controlled extrusion of a polymeric solution to deliver the cells (human adipose-derived MSCs (ADMSCs) and placenta-derived MSCs (PLMSCs)) locally to the animal model of diabetic ulcers. Methods The physicochemical and biological properties of the nano-bioscaffold were characterized in terms of microscopic images, FTIR spectroscopy, tensile testing, degradation and swelling tests, contact angle measurements, MTT assay, and cell attachment evaluation. To evaluate the therapeutic efficacy, a study using an excisional wound model was conducted on diabetic rats. Results The SEM and AFM images of scaffolds revealed a network of uniform nanofibers with narrow diameters between 100-130 nm and surface roughness less than 5 nm, respectively. ADMSCs and PLMSCs had a typical spindle-shaped or fibroblast-like morphology when attached to the scaffold. Desired characteristics in terms of swelling, hydrophilicity, biodegradation rate, and biocompatibility were achieved with the CS70 formulation. The wound healing process was accelerated according to wound closure rate assay upon treatment with MSCs loaded scaffold resulting in increased re-epithelialization, neovascularization, and less inflammatory reaction. Our findings unequivocally demonstrated that the cell-loaded nano-bioscaffold exhibited more efficacy compared with its acellular counterpart. In summation, our study underscores the potential of this innovative cellular scaffold as a viable solution for enhancing the healing of diabetic ulcers. Conclusion The utilization of MSCs in a nanofibrous biomaterial framework demonstrates significant promise, providing a novel avenue for advancing wound care and diabetic ulcer management.

1. Introduction

The skin, the body's largest organ, plays a crucial role in maintaining hemostasis and defending against microorganisms [1, 2]. Skin injuries and wounds can occur due to various factors including lacerations, burns, pressure, diabetes, and infections [3]. While acute wounds typically resolve without complications, chronic wounds, often resulting from complex diseases or accidents, present a challenge due to delayed healing processes [4, 5]. Diabetic Foot Ulcers (DFU), a form of chronic wound, affect 15%-25% of diabetic patients, with approximately 20% of moderate to severe cases leading to amputation. This significantly impacts both the quality of life and healthcare costs.

The treatment of chronic wounds poses a global challenge due to high costs, increased risk of infection, and elevated inflammation [6–9]. Tissue engineering has emerged as a successful approach for chronic wound healing and skin regeneration. Tissue-engineered grafts, such as biomaterial scaffolds and skin substitutes offer an alternative solution for skin regeneration [10, 11]. Other types of tissue-engineered grafts can include skin substitutes. These skin substitutes are often used in chronic and non-healing wounds and replace the skin function either temporarily or permanently. They can be classified as cellular or acellular. Acellular types, such as dermis tissue without cellular components, include a scaffold or matrix of biopolymers such as collagen or hyaluronic acid. On the other hand, cellular types contain living cells in a matrix, and moreover, these biopolymer components. These cells, like keratinocytes and fibroblasts, can be autologous, allogeneic, and other species. The major categories of skin substitutes include dermal replacement, epidermal replacement, and dermal/epidermal replacement. A variety of skin substitutes