Skin Substitutes and Wound Healing: Current Status and Challenges

David Eisenbud, MD, CWS; Ngan F. Huang, BS; Sunny Luke, DSc; Melvin Silberklang, PhD


Wounds. 2004;16(1) 

In This Article

Challenges and Future Directions

While currently available cell-based wound therapies are effective in accelerating wound repair and their appropriate use may achieve closure in nonhealing wounds, potential technologic improvements may further enhance the utility of this approach. For example, more effective cell preservation techniques could enhance shelf life and minimize issues related to storage. More specifically, simplified thawing and rinsing of cryopreserved products would make such products more user-friendly.

Studies need to more clearly define the optimal regimen of cell-based wound therapy (e.g., How many applications are useful? At what intervals should the therapy be applied?).

A more complete understanding of the mechanism of therapeutic action of bioengineered skin could lead to even more efficacious products. For example, if growth factor production is the essence of this modality, genetic modification of the cells to overproduce various specific cytokines might be feasible and productive. While preliminary efforts to create such products have been reported,[94] further refinements based upon advanced understanding may lead to substantial improvements.

Efforts by manufacturers to further reduce the cost of cellular skin substitute wound therapy could change the role of this approach dramatically. Rather than a later treatment to be used when other modalities have failed, or are likely to fail, bioengineered skin could be justifiably used earlier in the patient's course. Lower cost could also allow for multiple applications and possibly increase the efficacy of the course of treatment. It is ironic that Medicare guidelines restrict the use of bioengineered skin to one application under most circumstances, while the clinical trials that have provided the basis for FDA approvals have generally used up to six or even eight weekly applications.

Eventually, the individual commercially available bioengineered skin products will be compared to each other, rather than to a non-cell based control treatment. Head-to-head comparison may establish winners and losers in this field, and these may be different for different indications.

Additional attention to the attributes of the healed wound could broaden appeal for the use of bioengineered skin if factors such as cosmesis, wound recurrence and scar thickness prove to be favorably influenced by its use.

Much additional work is required to better define the relative roles of the various wound technologies. In some instances, the beneficial effect of these may be additive; this has been reported, for example, for subatmospheric therapy (VAC®, Kinetic Concepts Inc., San Antonio, Texas) plus cell-based wound therapy.[95]

Published results implying excellent engraftment results using chimaeric syngeneic/allogeneic mixed cultured keratinocyte grafts deserve further investigation as potentially more rapid and cheaper clinical alternatives to pure cultured epithelial autografts.[96,97]

Building upon decades of advances in cell culture technology, cell-based, and cellular skin substitute wound therapy have recently come of age, and they represent the most empirically and scientifically proven of the modern wound care modalities. Certainly, incremental improvements upon current technologies will continue to appear. However, the authors believe that current use of bioengineered skin products is inappropriately low and that these products are too often reserved until patients have suffered pain and nonhealing for many months or even years. The advent of simple methods for early identification of patients who will not heal well with low technology treatment will improve the process of triaging candidates for bioengineered skin and will increase the popularity and cost-effectiveness of this approach.[90,91,92]


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