Abstract and Introduction
Abstract
The extracellular matrix (ECM) of the dermis is a critical structural component required for normal wound healing. The ECM, along with its key signaling components, provides the support structure necessary for fibroblasts, immune cells, and keratinocytes. When ECM activity is dysfunctional, the normal wound healing process is compromised, leading to slow, irregular repair, which may result in the development of chronic wounds. To replace dysfunctional ECM, several strategies have been developed to promote the development of a proper ECM or to replace the ECM entirely. One such method is the use of small intestine submucosa (SIS) to replace the nonfunctional ECM. Small intestine submucosa closely mimics the normal ECM of the human dermis despite being of porcine derivation. Small intestine submucosa wound matrix is an example of an available ECM-based biomaterial that has demonstrated improvements in wound management in the clinical setting.
Introduction
Human skin is the largest organ in the human body and acts as a barrier to infection. This barrier function depends on the presence of a properly working dermal extracellular matrix (ECM). The dermis is largely composed of fibroblasts that secrete and maintain ECM components, but also contains epidermal appendages, nerves, vasculature, and inflammatory cells. The ECM provides the epidermis structural support while also playing a key role in the strength, flexibility, and structural support of the dermis. The ECM itself is a complex scaffold of many structural and functional proteins, but is primarily composed of filamentous type I and III collagens and elastin. The lesser components of the ECM consist of glycoproteins, glycosaminoglycans, cytokines, and growth factors, all of which are required under normal and wound healing conditions. Collagen provides structural support to the skin and functions in signaling, while elastin lends elasticity. Fibronectin provides attachment sites for various cell types and helps to coordinate ECM remodeling. Heparin and hyaluronan function in matrix hydration, bind growth factors, and act as signaling molecules during tissue repair and regeneration. Growth factors aid in matrix turnover by stimulating production of matrix components, angiogenesis, and cellular migration. Meanwhile, matrix metalloproteinases (MMPs) also function in matrix turnover by degrading the ECM to facilitate cell migration and ECM remodeling. Collectively, these components of the ECM serve to create a complex and dynamic scaffold that constantly interacts with itself and its surroundings to maintain homeostasis, while regulating the healing process. Restoring these dynamic interactions and returning to this homeostasis is required during injury or tissue loss.