- Collagen vs. other Biological therapies
Collagen Dressings and Growth Factors
Collagen dressings have numerous advantages during each stage of the wound healing process. In contrast, growth factors are very specific in their actions. It may not be possible to generalize the biological response of a single growth factor over the entire area of a wound for the purpose of enhancing wound healing. Although growth factors are an exciting new approach to wound care, they need extensive study before their delivery and use can be practically accomplished.
A wound bed consists of multiple cell types and a specific growth factor may enhance one activity of one cell type while inhibiting the activity of a different cell type. Growth factors are polypeptide molecules which can interact with specific cell receptors to generate specific cell responses in target cells. They are known as growth factors because many of these polypeptides stimulate proliferation of target cells. Local concentration of growth factors changes during the course of wound healing. The objective behind the use of growth factors is to evoke specific responses which could alter the rate of tissue repair. One obvious advantage of growth factors is that, unlike traditional dressings, they act on the wound at a cellular level.
Some growth factors that influence wound healing are the following: epidermal growth factor (EGF), transforming growth factor-α (TFG- α), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF) and transforming growth factor-β (TFG- β). EGF is a 53 amino acid polypeptide that interacts with specific receptors on fibroblasts, epithelial cells and some other cell types. EGF is closely related to TGF- α and is expressed at different times and sites during wound repair. PDGF as the name suggests, is released by the platelets and has strong chemoattractant properties. As a result, a local concentration of PDGF will promote directed movement of cells towards the source. TGF- β promotes migration and differentiation of cells, but can also inhibit epithelial proliferation. FGF affects proliferation of vascular endothelial cells and epithelial cells such as keratinocytes. In some cases, response will depend on the cellular environment.
The advantage of growth factors is being able to initiate a specific cell response. Current complications and limitations related to growth factors are:
(i) Most studies have concentrated on use of single growth factors, while the wound
environment is a continuously changing array of signals. Synergistic effects, if more
than one growth factor is used, are not well understood at this stage. Growth factors
are not individual players, and combination and/or sequential therapy has to be
intensely studied before they can be successfully used in wound care (Davidson,
1995).
(ii) It may be possible to enhance wound healing by the use of a single growth factor. However, wound healing depends on more than one factor. It may take much more than a careful physical evaluation to find out what factor was missing when the wound did not heal. This is because wound healing does not occur in discrete steps and there is always a delicate balance between various events during the course of wound healing.
(iii) Certain growth factors may have undesired effects, e.g., TGF- β inhibits epithelial proliferation (Davidson, 1995)
(iv) The effects of growth factors may, in some cases, be secondary. For example, FGFmay effect proliferation of vascular endothelial cells. However, its expression is
delayed and lags behind the peak of angiogenic activity. Accordingly, the role of
growth factors in tissue repair becomes questionable (Davidson, 1995).
Collagen Dressings and Biological Coverings
Collagen sponges have shown better utility than biological coverings (Norton, 1981). In Second degree burn models on rabbits, a simple collagen sponge performed significantly better than pigskin (Oluwasami, 1976).
Common biological coverings are allografts (taken from the recipient), xenografts (taken from animal sources) and tissue culture derivatives (grown in a culture medium). Some of the advantages of biological coverings are: a reduction in bacteria population, reduction in evaporative losses, and prevention of further contamination (Pruitt, 1984). Such coverings may be very useful in case of individuals who suffer extensive loss of skin (Yannas, 1980). The new covering could serve as a template for synthesis of new connective tissue (Pruitt, 1984).
However, for a majority of wounds, such dressings are neither favorable nor economically practical. Cultured cells or allografts or xenografts have not been perfected. For example, long-term assessment on wounds covered with cultured autologous keratinocytes showed that the wounds lacked anchoring fibrils which resulted in a fragile graft (Herzog, 1988).
Use of such biological coverings offers several other additional challenges:
- (i) The host body could show intolerance to the foreign body. Immunosuppressive drugs can be used to counteract the natural rejection response, however, the advantage of wound sterilization by natural immune response would than be lost (Queen, 1987). This could result in an increased risk of infection.
- (ii) They can be used only on wounds without any infections. The wounds have to be carefully prepared for application of these dressings. They should be used on wounds having full thickness skin loss with a granulating surface and fewer than 105 bacteria per gram of tissue (Peters, 1979). Further, infections cannot be observed after the application of dressing.
- (iii) Skin biopsies from patients with large wounds could be contaminated with microorganisms, which may overgrow in spite of antibiotics (Medstrat, 1989).
- (iv) Patients with extensive burn or related injuries need tissue culture biological dressings within five days to seven days to avoid risk of sepsis (Medstrat, 1989). It may take 14 days to 21 days to grow epidermal cells in a tissue culture medium.
- (v) Secondary and tertiary populations in a culture media may undergo mutagenic changes.
- (vi) Porcine skin is not like the human skin at the microscopic level (Queen, 1987). They have poor mechanical properties and tend to split into separate layers (Chatterjee, 1987). They are not living tissues and do not establish a true vascular connection with the granulation bed (Peters, 1979).
- (vii) Allografts have a shelf life of only seven days to 10 days when the tissue is stored at 4ºC. The possibility of disease transmission requires a very careful donor selection, limiting the pool available for harvest (Pruitt, 1984).
- (viii) The manufacture of biological dressings is a tedious process and biological coverings are prohibitively expensive.
- (ix) Use of biological dressings requires specialized training on the part of the physicians.
