Engineered Biopolymeric Scaffolds for Chronic Wound Healing

Abstract

Skin regeneration requires the coordinated integration of concomitant biological and molecular events in the extracellular wound environment during overlapping phases of inflammation, proliferation, and matrix remodeling. This process is highly efficient during normal wound healing. However, chronic wounds fail to progress through the ordered and reparative wound healing process and are unable to heal, requiring long-term treatment at high costs. There are many advanced skin substitutes, which mostly comprise bioactive dressings containing mammalian derived matrix components, and/or human cells, in clinical use. However, it is presently hypothesized that no treatment significantly outperforms the others. To address this unmet challenge, recent research has focused on developing innovative acellular biopolymeric scaffolds as more efficacious wound healing therapies. These biomaterial-based skin substitutes are precisely engineered and fine-tuned to recapitulate aspects of the wound healing milieu and target specific events in the wound healing cascade to facilitate complete skin repair with restored function and tissue integrity. This mini-review will provide a brief overview of chronic wound healing and current skin substitute treatment strategies while focusing on recent engineering approaches that regenerate skin using synthetic, biopolymeric scaffolds. We discuss key polymeric scaffold design criteria, including degradation, biocompatibility, and microstructure, and how they translate to inductive microenvironments that stimulate cell infiltration and vascularization to enhance chronic wound healing. As healthcare moves toward precision medicine-based strategies, the potential and therapeutic implications of synthetic, biopolymeric scaffolds as tunable treatment modalities for chronic wounds will be considered.

Keywords: acellular matrices; biopolymeric scaffolds; chronic wounds; inflammatory; matrix remodeling; skin regeneration; skin substitutes.

Figure 1

Biopolymeric dextran scaffold facilitates wound healing in murine and porcine burn models. (A) Complete healing was observed in mice by day 21. Dextran treated wounds exhibited mature epithelial structures, including hair follicles (F) and sebaceous glands in the dermal layer as indicated by Masson trichrome staining (left panel; scale bar = 100 μm). By day 35, new hair growth was observed in the center of dextran treated wounds, as shown by photos, compared to wounds treated with dressing only; arrows indicate center of wound. (B) Wound closure was observed by day 14 in a porcine model as shown by representative macroscopic and immunohistological images. Identification of neoepithelium using Masson's trichrome-stained sections (right panel) confirmed that wounds treated with dressing-only had an epithelial gap, whereas dextran-treated wounds were completely re-epithelialized with a thick reticulated epithelium. Scale bar = 1 cm. Modified from Sun et al. (2011b), and modified and reprinted from Shen et al. (2015). Copyright (2015), with permission from Elsevier.