Abstract and Introduction
The process of wound healing consists of an orderly sequence of events characterized by the specific infiltration of specialized cells into the wound site. The platelets and inflammatory cells are the first cells to arrive, and they provide key functions and signals needed for the influx of connective tissue cells and a new blood supply. These chemical signals are known as growth factors or cytokines. The fibroblast is the connective tissue cell responsible for collagen deposition needed to repair the tissue injury. Collagen is the most abundant protein in the animal kingdom, as it accounts for 30 percent of the total protein in the human body. In normal tissues, collagen provides strength, integrity, and structure. When tissues are disrupted following injury, collagen is needed to repair the defect and hopefully restore structure and thus function. If too much collagen is deposited in the wound site, normal anatomical structure is lost, function is compromised, and the problem of fibrosis results. Conversely, if insufficient amounts of collagen are deposited, the wound is weak and may dehisce. Therefore, to fully understand wound healing, it is essential to understand the basic biochemistry of collagen metabolism.
Collagen is found in all of our connective tissues, such as dermis, bones, tendons, and ligaments, and also provides for the structural integrity of all of our internal organs.[1,2] Therefore, because of its wide distribution throughout our bodies, it represents one of the most abundant naturally occurring proteins on earth. In addition to its natural abundance, there are well over 1,000 commercial products on the market today that contain collagen and collagen enhancers. These products are represented by body and hand lotions, nail treatments, firming gels, wrinkle injections, eye pads, and even anti-cancer treatments to name but a few. In recent years, new high-tech wound dressing materials and skin substitutes have become available for the treatment of partial-thickness injuries as well as full-thickness and chronic dermal ulcers.
There are close to 20 different types of collagen found in our bodies.[4,5] Each one of these collagens is encoded by a specific gene. The five major types are summarized in Table 1 . The predominant form is Type I collagen. This fibrillar form of collagen represents over 90 percent of our total collagen and is composed of three very long protein chains. Each protein chain is referred to as an "Alpha" chain. Two of the Alpha chains are identical and are called Alpha-1 chains, whereas the third chain is slightly different and is called Alpha-2. The three chains are wrapped around each other to form a triple helical structure called a collagen monomer (Figure 1). This configuration imparts tremendous strength to the protein. To understand the overall structure of the collagen molecule, think of it as the reinforcement rods called re-bar that are used in concrete construction. Indeed if one converts the molecular dimensions of the collagen molecule to measurements that we can relate to, the molecule when scaled up would measure one inch in diameter to approximately 17 feet long. Therefore, collagen is indeed nature's re-bar, because it is responsible for the strength and integrity of all of our connective tissues and organ structures.
The basic structural unit of collagen is a triple-stranded helical molecule. From Molecular Cell Biology by Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J. © 1986, 1990, 1995, 2000 by W. H. Freeman and Company. Used with permission.
Basically all of the collagens share this triple-helical molecular structure as described above. However, the various other types of collagens have slightly different amino acid compositions and provide other specific functions in our bodies. Type II collagen is the form that is found exclusively in cartilaginous tissues. It is usually associated with proteoglycans or "ground substance" and therefore functions as a shock absorber in our joints and vertebrae. Type III collagen is also found in our skin as well as in blood vessels and internal organs. In the adult, the skin contains about 80-percent Type I and 20-percent Type III collagen. In newborns, the Type III content is greater than that found in the adult. It is thought that the supple nature of the newborn skin as well as the flexibility of blood vessels is due in part to the presence of Type III collagen. During the initial period of wound healing, there is an increased expression of Type III collagen.
Type IV collagen is found in basement membranes and basal lamina structures and functions as a filtration system. Because of the complex interactions between the Type IV collagen and the noncollagenous components of the basement membrane, a meshwork is formed that filters cells as well as molecules and light. For example, in the lens capsule of the eye, the basement membrane plays a role in light filtration. In the kidney, the glomerulus basement membrane is responsible for filtration of the blood to remove waste products. The basement membrane in the walls of blood vessels controls the movement of oxygen and nutrients out of the circulation and into the tissues. Likewise, the basal lamina in the skin delineates the dermis from the epidermis and controls the movement of materials in and out of the dermis.
Type V collagen is found in essentially all tissues and is associated with Types I and III. In addition it is often found around the perimeter of many cells and functions as a cytoskeleton. It is of interest to note that there appears to be a particular abundance of Type V collagen in the intestine compared to other tissues.
Wounds. 2001;13(5) © 2001 Health Management Publications, Inc.
Cite this: Collagen Metabolism - Medscape - Sep 01, 2001.