Overview
These are suitable for wounds that require skin grafting. Vivoderm (hyaluronic acid) is developed from the patient’s own skin and dermagraft is developed from human skin. Both can be used to treat large areas of tissue loss. Hyaluronic acid is intrinsically involved in the wound healing process and it enhances neoangiogenesis and cell migration. They are natural product and easily applied. Dermagraft is commonly used to treat diabetic foot ulcers and vivoderm; burns (35). Indication: Leg or foot ulcers: chronic, non-healing wounds, acute wounds. Examples: Vivoderm, Dermagraft and Apligraft. Pros: Uses the body's own cells to promote healing, reduces healing time. Cons: Initially expensive (35).
Description of System
Many growth factors are involved in normal wound healing. Therefore, they have been proposed as therapeutic agents to promote wound repair. Epidermal growth factor (EGF) is a polypeptide of 53 amino acids that was first isolated from the mouse submaxillary gland by Stanley Cohen in 1962 (51). The EGF family comprises four proteins: EGF, TGF-alpha, heparin-binding EGF, and amphiregulin which have similar structures and act upon the same cell-surface receptor, giving similar biological effects (51).
Current EGF delivery matrixes involve the protein together with a gel (typically cellulose based), which is topically applied to wounds. Current research involves modification of the growth factors to allow chemical bonding to a delivery system. Addition a high molecular weight vehicle to the peptide can increase the biological stability and increase its half-life and efficacy. With this increased stability, proteolytic degradation of EGF in the chronic wound environment could be controlled. The manipulation of the chemical structure can determine subsequent bioactivity, and allow for site-specific targeting and activation (51).
Mechanisms Involved
EGF facilitates epidermal cell regeneration and plays an essential role in the process of dermal wound healing through stimulating proliferation and migration of keratinocytes. It also promotes formation of granulation tissue and stimulates fibroblast motility. As a mitogen (chemical substance that triggers mitosis), it first binds strongly to specific cell-surface receptors, induces their dimerization to activate the tyrosine kinase in the receptor cytoplasmic domain, initiating a signal transduction that results in DNA synthesis and cell proliferation. Acute wound healing is a stepwise progression through haemostasis and inflammation, cellular proliferation, extracellular matrix (ECM) production and wound closure and culminating in the maturation of the healed scar tissue (51).
EGF is pivotal in this process and is produced by different sources, including platelets. It is a potent mitogen for fibroblasts, epithelial and endothelial cells. EGF stimulates fibronectin synthesis, angiogenesis, fibroplasia and collagenase activity. This significant regulatory role occurs from the start of the healing cascade after the initial formation of a blood clot. The Exudate drawn from chronic wounds, in contrast to acute wounds, has elevated protease activity, reduced growth factor activity and increased levels of proinflammatory cytokines. It has been suggested that growth factors may become trapped by ECM molecules or may be degraded excessively by proteases. There is also an imbalance between matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases (51). Local causes such as wound infection, dead tissue debris from hypoxia, bacterial products and foreign bodies are powerful chemo-attractants capable of sustaining high levels of inflammatory cytokines like TNF, interleukins, collagenases and other matrix degrading enzymes like elastase (51).
Costs and Evidence
The use of EGF in impaired wound healing by Falanga et al, showed a modest improvement in wound healing times and rate of epithelialisation, but the results were not statistically significant. The effect of EGF in chronic wounds was less pronounced than in the acute wound setting (51). No significant adverse effects have been recorded.Apligraf is supplied as a circular disk approximately 7.5 cm in diameter and is intended for single-use. The cost of Apligraf is $1,000 - $1,200 per use. In a study by Attilasoy, a higher percentage of wounds were healed with Apligraf (55%) compared to the control (40%). Chronic venous leg ulcers were healed to complete closure with an average of 1.41 applications of Apligraf. Diabetic ulcers treated with Apligraf once a week for a maximum of four weeks reduced the median time to complete wound closure from 91 days in the control group to 38.5 days in the Apligraf group (51). This technique is therefore relatively expensive.
