Human-Derived Acellular Dermal Matrix Grafts for Treatment of Diabetic Foot Ulcers

A Systematic Review and Meta-Analysis

Margaret Luthringer, MD; Thayer Mukherjee, BA; Marvin Arguello-Angarita, MD, MPH; Mark S. Granick, MD; Oscar M. Alvarez, PhD, CCT, FAPWCA


Wounds. 2020;32(2):57-65. 

In This Article

Abstract and Introduction


Background: Treating diabetic foot ulcers (DFUs) requires thorough understanding of available surgical tools.

Objective: This meta-analysis compares human-derived acellular dermal matrices (H-ADMs) with standard of care (SOC) to evaluate the number of healed ulcers at 12 and 16 weeks and number of days to complete healing. As a secondary outcome, the efficacy of 3 H-ADM subtypes are studied.

Methods: Two researchers searched PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials for relevant titles from inception through July 2018. Inclusion criteria indicated articles be randomized controlled trials investigating the effects on neuropathic, nonischemic DFUs.

Results: Data from 312 DFUs in total were included in the meta-analysis. The results show H-ADMs are more effective in healing patients within a 12-week (3.14; range, 2.04–4.83) and 16-week period (2.35; range, 1.25–4.43) in comparison with SOC. Further, the mean time to complete healing was shorter in the H-ADM group (-2.31 days; range, -2.67 to -1.95 days) in comparison with SOC. Within the subgroups, 2 H-ADMs were associated with a higher likelihood of complete healing within 12 weeks when compared with SOC. The third H-ADM had a point estimate, which suggested superiority over SOC.

Conclusions: This study shows H-ADMs are associated with a higher likelihood of complete healing and fewer days to complete healing within a 12-week and 16-week periods when compared with SOC. Also, the commercial products performed similarly.


Foot wounds are a common complication associated with diabetes mellitus (DM) and often impose significant economic, health, and quality of life burdens upon patients and health care systems. Diabetes affects more than 22 million people in the United States.[1] Up to 25% of these people are at risk for developing a diabetic foot ulcer (DFU), with an annual prevalence estimated at 13%.[1,2] Armstrong et al[3] posit nearly 40% of people with a DFU experience a recurrence within 1 year from healing. Substantial prevalence paired with a high rate of DFU recurrence leads to high expenditure of health care dollars. In a 2014 study by Rice et al,[4] the results suggest an annual incremental payer burden of up to $13.2 billion in the United States alone. In addition, DFUs can cause enormous personal hardships to patients, such as higher rates of depression, lack of mobility, and increased tensions with caregivers.[5] Thus, it remains an important public health initiative to treat these wounds quickly and effectively.

Treatment of DFUs focuses on pressure offloading, local wound care (standard of care [SOC]), infection control, and surgical intervention when necessary. Peripheral neuropathy commonly associated with DM decreases protective sensation of the foot. Repetitive stress, trauma, or shear forces lead to skin breakdown. Peripheral vascular disease can lead to ischemia of the distal lower extremity, which compromises native wound healing ability. The Wound Healing Society (WHS) 2013 DFU treatment guidelines[1] promote pressure offloading, reduction of bacterial and cellular burden through adequate debridement, local wound care with moist dressings that also absorb wound exudate, topical and systemic antibiotic therapy when needed, and treatment of osteomyelitis. Further, the guidelines[1] state cellular and acellular equivalents improve DFU healing by releasing growth factors, cytokines, and proteins that stimulate the wound bed. Human-derived acellular dermal matrix (H-ADM) products consist of cadaveric skin processed to remove antigenic cells while retaining the dermal extracellular matrix crucial for angiogenesis and structural support of collagen.[6]

This study aimed to provide an updated search of the literature examining local wound care versus treatment with an H-ADM for neuropathic, nonischemic DFUs. A complete meta-analysis comparing superiority of SOC versus H-ADM use, focusing on the number of wounds healed at 12 and 16 weeks of treatment and number of days to complete healing, was conducted. Also, a subgroup analysis comparing the 3 individual H-ADMs was performed.