The Use of Biologic Scaffolds in the Treatment of Chronic Nonhealing Wounds

Abstract

Significance: Injuries to the skin as a result of illness or injury, particularly chronic nonhealing wounds, present a major healthcare problem. Traditional wound care approaches attempt to control the underlying causes, such as infection and ischemia, while the application of wound dressings aims to modify a poorly healing wound environment into a microenvironment more closely resembling an acute wound allowing the body to heal the wound naturally. Recent Advances: Regenerative medicine approaches, such as the use of biologic scaffold materials comprising an intact extracellular matrix (ECM) or individual components of the ECM, are providing new therapeutic options that focus upon the provision of biochemical cues that alter the wound microenvironment to facilitate rapid restoration of normal skin architecture. Critical Issues: The incidence of chronic nonhealing wounds continues to increase. For example, between 15% and 20% of diabetics are likely to develop chronic, nonhealing foot wounds creating an increasing burden on healthcare systems worldwide. Future Directions: Developing a thorough understanding of wound microenvironment and the mechanisms by which biologic scaffolds work in vivo has the potential to markedly improve outcomes in the clinical translation for the treatment of chronic wounds.

Stephen F. Badylak, DVM, PhD, MD

Figure 1.

The key differences between the normal wound healing environment and that of a chronic nonhealing wound. Chronic wounds are characterized by prolonged inflammation and infection with delayed epithelialization and impaired fibroblast migration and extracellular matrix (ECM) synthesis. There is increased matrix metalloproteinase (MMP) activity and a decrease in growth factor expression leading to impaired angiogenesis and poor mobilization of circulating progenitor cells. Arrows indicate increase (↑) or decrease (↓). EGF, epidermal growth factor; FGF, fibroblast growth factor; TGFb, transforming growth factor; VEGF, vascular endothelial growth factor. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound

Figure 2.

Diagram showing the current approaches to wound care. Current treatment options include treating the cause such as improving circulation or treating the wound directly by controlling infection and inflammation to promote healing. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound

Figure 3.

Preparation of biologic scaffolds. Biologic scaffolds can be prepared either by the decellularization of tissues and organs (A) or by degrading the ECM and isolating and purifying individual ECM components (B). To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound

Figure 4.

Comparison of a chronic wound and one treated with a biologic scaffold highlighting the importance of the ECM in providing a friendly microenvironment and regulating cell behavior. As the biologic scaffold is degraded, it releases bioactive ECM fragments that sequester MMPs, decrease inflammation, and promote increased cell migration and angiogenesis. Arrows indicate increase (↑) or decrease (↓). To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound