A Closer Look At The Efficacy Of Bioengineered Alternative Tissues For DFUs

Melissa Skratsky, DPM, and Stephanie Wu, DPM, MSc

A Closer Look At The Evolution Of Bioengineered Alternative Tissues

The term bioengineered alternative tissue (BAT) is the most current and accurate labeling used to describe these non-autologous skin equivalents. Clinicians have adopted this terminology in recent years as it more clearly defines the composition of the tissue product and the situation(s) most applicable for use. The terms “tissue engineered skin,” “bioengineered skin” and “biological skin equivalents” are misnomers and suggest that the product is an exact replica of human skin comprised of both an epidermis and dermis. In contrast, the name bioengineered alternative tissue implies that the wound product has undergone chemical and biological manufacturing processes to yield a substance that is different than split- and full-thickness skin grafts.

   There are growth factors within these engineered tissues that promote granulation and epithelialization, and optimize the wound environment. One can apply bioengineered alternative tissue to ulcerations when serial wound measurements fail to reveal 50 percent improvement in size over a one month duration or when less than 10 to 15 percent wound contraction occurs per week.6

   The initial impetus for the development of bioengineered alternative tissues occurred in the 1980s and stemmed from insufficient sources of full-thickness dermal autologous skin grafts available for burn victims and the poor quality of scars after treatment with split-thickness autografts.7 Autologous skin grafts and flaps are highly effective in the treatment of certain wounds. However, the pain and potential complications associated with harvesting the graft are definite drawbacks.

   Surgeons and wound care specialists envisioned an “off-the-shelf” product that accelerated tissue regeneration, could be applied in the office, was readily available in large quantities, was not subject to host rejection and was inexpensive. While such an ideal wound product does not currently exist, bioengineered alternative tissues did fill some of the void and provided several of the aforementioned desired clinical characteristics.

   Indications for application of these bioengineered alternative tissues have expanded over the past decade. Since many of these alternative tissues rely on allogenic cells from a donor, they are convenient, easily manufactured and close at hand. However, with accessibility, one pays the price for cell persistence as the allogeneic components and cells disappear from the recipient site within two months, making stimulation of healing and production of growth factors only temporary.8

Current Insights On The Key Components And Functional Requirements Of BATs

There are three distinct components inherent to the design and construct of bioengineered alternative tissue: the presence of a matrix, a tissue differentiation-inducing substance and a cell source. In order to create the most viable functional product, various combinations of cells, biopolymers and soluble mediators have been subject to testing. Research in this area has shown that replacement of connective tissue may enhance the mechanical strength of the wound and reduce scar tissue formation with subsequent incorporation of fibroblasts into several of the alternative tissues.9

   Some bioengineered alternative tissues also contain sheets of biomaterial matrix embedded with allogeneic cells derived from neonatal foreskin. Neonatal foreskin cells have minimal antigenicity, a higher content of keratinocyte stem cells, vigorous cell growth and metabolic activity, and are a relatively convenient and logical source.10

   In an article regarding the biological background of dermal substitutes, van der Veen and co-workers described a series of general principles required for adequate function of these advanced wound care technologies.11 Bioengineered alternative tissues need to incorporate various mechanical and physical properties in order for them to meet clinical demands and promote healing. The first of these principles is protection of the wound from fluid loss and infection.

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