Comparative Effectiveness of Two Acellular Matrices (Dermacell vs. Integra) for Management of Deep Diabetic Foot Ulcers

Diabetes-related foot ulcers (DFUs) are a leading cause of hospitalization and amputation
worldwide, and account for 33% of all direct costs of diabetes care in the US. Ulcers
requiring acute care can result in treatment costs of up to US$70,000 per event, varying with
the severity of the wound. Once the skin is ulcerated, it is susceptible to becoming infected
and ultimately amputation in particular in case of deep DFUs. To manage the cost and avoid
hospitalization and amputation, wound should be immediately closed. But this is often
challenging in diabetic foot with deep ulcers.Wound healing is a dynamic process involving
interactions between cells, extracellular matrix (ECM) and growth factors that reconstitutes
tissue following injury. ECM plays an important role in tissue regeneration and is the major
component of the dermal skin layer. Recognition of the importance of the ECM in wound healing
has led to the development of wound products that aim to stimulate or replace the ECM in
particular in case of deep tissue destruction because of deep DFUs. It is known from the
literature that chronic or hard-to-heal wounds are characterized by a disrupted or damaged
ECM that cannot support wound healing. Thus treatment strategies based on use of biologic
scaffold materials for management of chronic and deep wounds has increased dramatically
during the past two decades. These scaffolds include those comprising an intact extracellular
matrix (ECM) or individual components of the ECM, and those comprising hybrids incorporating
a synthetic component with a biologic component. DermACELL (LifeNet Health,Virginia Beach,
VA) is acellular dermal matrices (ADM), which has been shown to be effective in treating
chronic DFUs in a clinical trial.

Another ADM product available in the market is made by Integra® (Bilayer Matrix Wound
Dressing, Integra LifeSciences). However, advantages/disadvantages of one compared to the
other are unclear. In addition, prior studies often focused on wound healing outcomes (e.g.
time to heal, success of wound healing) without considering patient-centered and
physician-centered outcomes such as time and difficulty to apply, likelihood of adverse
events and need for reapplication, poor tissue mechanics outcomes (e.g. presence of scarring
or tissue biomechanics properties leading to increase in shear or pressure post healing thus
increasing likelihood of recurrence of the ulcer), and other patient centered outcomes like
smell, pain, and comfort.

The primary objective of this prospective, randomized trial is to compare the outcomes of
DermaCELL with Integra. The investigators assumed that the wounds outcomes (e.g. weekly wound
size change, time to heal, time to successful wound granulation) are comparable between
DermaCELL and Integra. However, from operation and patient centered outcomes, there may be
some noticeable differences. For instance, DermaCELL, thanks to its mesh structure, thin
thickness, and no need for hydration, may be easier to apply with shorter time than Integra.
The factors are of key importance in operation room (OR) setting and could reduce overall
cost of application and needs in using OR resources. Other important outcomes least addressed
in prior studies are number of grafts failing, adverse events (e.g. amputation, infection,
etc), cost of wound healing treatment, tissue biomechanics, which may lead to recurrence of
ulcers (e.g. formation of tissue scarring), and other patient-centered outcomes (e.g. pain,
quality of sleeping, wound smelling, etc). For instance, many patients are unhappy with
smelling of wounds, which make them embarrassed among their family members like grand kids.
Thus reducing wound smelling during activities of daily living is often considered as an
important patient centered outcomes.