Point-Counterpoint: Are Acellular Dermal Matrices More Effective Than Fibroblast-Derived Dermal Substitutes?
Studies performed on venous ulcer fibroblasts demonstrated that growth factors released from the fibroblasts could stimulate proliferation.1 It stands to reason that providing young/live allogeneic human cells to the chronic wound can improve the healing potential of the chronic wound. These cells are then able to secrete growth factors that are necessary to stimulate wound repair. Researchers have demonstrated that these cells stay within the wound environment for up to six months.2
The importance of growth factors in wound healing has been well established. The number of growth factors and their receptors in chronic ulcers is known to decrease. Experiments have shown that acute wound fluid that is full of various growth factors stimulates proliferation and wound fluid from chronic wounds inhibits proliferation.3,4
Therefore, the number of growth factors found in chronic wounds is less than that found in the acute wounds. The addition of any one single growth factor has not been effective in vivo except for platelet-derived growth factor beta (PDGF-beta).5
However, fibroblast-derived dermal substitutes have multiple growth factors, which allow a greater likelihood of aiding in the induction of angiogenesis, enhancing the formation of granulation tissue, stimulating epithelialization and modulating the inflammatory response.
Inflammation has been implicated as another important factor in the maintenance of the chronic wound. Chronic wounds are typically heavily colonized and have an intense inflammatory infiltrate. Fibroblast-derived dermal substitutes have inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8) and granulocyte colony-stimulating factor (G-CSF). These cytokines in appropriate concentrations have the potential to modulate the inflammatory process within the chronic wound site.
A Few Considerations About Acellular Dermal Matrices
Acellular dermal matrices are biologically active materials that mimic the skin’s natural dermal extracellular matrix by providing growth factors that stimulate host cell proliferation and serve as a scaffold for their migration during wound healing. Acellular dermal matrices are manufactured by purifying human cadaveric or animal skin to remove all cells that could potentially initiate immune rejection of the graft material or serve as vehicles for disease transmission. All xenogeneic acellular dermal matrices that are currently on the market are of either bovine or porcine origin. This is probably due to the lower costs and wider commercial availability. It is important to note that neither the cows nor pigs are considered to be immunologically similar to humans.
Purification techniques have a significant influence on the properties of each acellular dermal matrix and vary depending on the product. Some contain basement membranes and some do not. I have found that some people in the industry believe that acellular dermal matrices with a preserved basement membrane demonstrate better adherence, outgrowth and differentiation of keratinocytes due to the presence of laminin and collagen type IV, which are absent in acellular dermal matrices that undergo more aggressive sterilization.
Another variable affecting the success of acellular dermal matrices is the crosslinking. Chemical crosslinking is a technique employed in the manufacturing of acellular dermal matrices that improves the matrix’s stability and longevity at the wound site. Crosslinking lowers the chances of immune rejection by the host tissue. However, recent research indicates that crosslinking may also result in disruption of the wound healing process by inducing foreign body response and production of toxic degradation products that have a detrimental effect on host cell survival and proliferation.6,7
The above paragraphs demonstrate the effect that fibroblast-derived dermal substitutes have on a chronic wound. However, to a wound care practitioner, successful clinical outcomes are much more important. We learn to practice evidence-based medicine when treating our patients. Based on the level of evidence pyramid, randomized controlled trials are considered to be the best level of evidence.