Humans lose the regenerative potential for wound repair early in embryonic life and following that wounds heal by scarring. Although scarring is a protective mechanism that maintains tissue continuity, it has a major adverse impact on health and society, as we witness in myocardial infarction, stroke and post-burn scar contractures, etc. Recently, regenerative medicine and tissue engineering have emerged with the hope of achieving healing by regeneration rather than repair and scarring.
Tissue engineering applies the principles of biology and engineering to the development of functional substitutes for damaged tissue.1 There are three main pillars of tissue engineering: a scaffold, cells, and biological inducers that facilitate cellular migration and growth. Scaffolds are templates that are made of collagen or synthetic polymers and act as a framework for cellular growth. Most of the available skin substitutes are formed only of an acellular template that acts as a scaffold.
History of Skin Substitutes
As patients are increasingly surviving larger burns due to the introduction of early total burn excision, the need for a wound cover material more durable than allografts or xenografts became clear. This resulted in the collaboration of Yannas, a scientist at the Massachusetts Institute of Technology (MIT), and John Burke, a surgeon at the Massachusetts General Hospital and the Shriner's Burns Centre in Boston, in the 1970s, to produce the first regenerative scaffold to be commercially produced: Integra®. A multicenter clinical trial was conducted and published in 1988, followed in 1990 by a histological study of the phases of wound healing and repair in the same group of patients.2,3 Integra is now widely used in acute burns and reconstructive surgery4 since the U.S. Food and Drug Administration (FDA) granted the manufacturer a license in 1996. In 2003, the license was extended to include the use of Integra for full-thickness wound cover. This widened the indications for the use of Integra to include post-burn reconstruction,4,5 trauma,6,7 skin oncology,8 chronic wounds,9 and a host of other applications.10-13 Other skin substitutes have since been introduced. In the late 1970s, Bell et al14 started developing a new type of skin substitute matrix that was bilayered to mimic the epidermal and dermal layers of skin and which housed living fibroblasts and epidermal cells. This led to the development of the bilayer skin substitute Apligraf (formerly known as Graftskin) by Organogenesis, Inc. that received FDA approval in 2000 for use in the treatment of venous and diabetic ulcers. A similar skin substitute, Orcel (Ortec International, Inc.) was granted FDA approval in 2001 for use in the treatment of fresh split-thickness autograft donor sites in burn patients. In 2000, a non-cross-linked collagen elastin matrix was produced by collaborative work in Europe led by Dr Otto Suwelack. This was later marketed as Matriderm and showed promising results ...