Treatment of Hard-to-Heal Diabetic Foot Ulcers With a Hepatic-Derived Wound Matrix

Robert Fridman, DPM, FACFAS, CWSP; Payam Rafat, DPM; Carl C. Van Gils, DPM; Deena Horn, DPM; Dean Vayser, DPM; C. Jake Lambert, Jr, MD

Disclosures

Wounds. 2020;32(9):244-252. 

In This Article

Abstract and Introduction

Abstract

Introduction: Difficult-to-heal diabetic foot ulcers (DFUs) increase the likelihood of significant pathology and increased health care costs.

Objective: This study evaluates the ability of a novel hepatic-derived wound matrix (HD-WM) to treat hard-to-heal DFUs.

Materials and Methods: In total, 53 patients were enrolled and 38 completed per protocol. Patients had ulcers that had been present for at least 90 days and were non-responsive to at least 2 applications of an advanced biologic wound care product. Patients were treated with standard of care and offloading for a 2-week run-in phase. If they satisfied criteria, they were enrolled in the trial and treated with the HD-WM, and then seen weekly for assessment and additional treatment as needed. Patients continued weekly visits until the wound healed or went 12-weeks posttreatment without healing.

Results: Mean starting wound size was 3.5 cm2 and mean wound duration was 41.1 weeks. Median previous treatment applications of an advanced biologic were 3.0. Complete closure of the wound occurred in 22 of the 38 patients (57.9%) within the 12-week study period, while 16 of 38 (42.1%) of the wounds had failed to completely heal. The mean time to wound closure was 8.1 weeks; these patients received a median of 1 application of the HD-WM under investigation. Closure of the wound by 50% or greater at week 4 was highly predictive of complete wound closure by 12 weeks. Except for bodily pain (36-Item Short Form Health Survey), which significantly improved in patients whose wounds healed, quality of life measures did not show changes.

Conclusions: The HD-WM under evaluation did well at closing difficult-to-heal wounds with minimal applications. These results are consistent with a previous study on this HD-WM.

Introduction

Current data suggest that there are more than 400 million people worldwide suffering from diabetes, including more than 30 million in the United States.[1,2] Patients with diabetes have lifetime incidence of up to 25% for developing a diabetic foot ulcer (DFU) and at any given time 4% to 10% will have a DFU.[3] Standard treatment, debridement, offloading, daily dressing changes, and infection control[4,5] may only heal up to 24% of these ulcers after 12 weeks of treatment,[6] suggesting standard treatment is generally insufficient. Diabetic foot ulcers are associated with a host of medical, psychological, and social issues, making their successful treatment that much more important. Substantial medical problems include greater likelihood of infection, lower extremity amputation, and increases in mortality rate.[7,8] Patients who have a lower extremity amputation have a 50% 5-year survival rate.[9] Not surprisingly, these patients also report lower satisfaction with life.

Diabetic foot ulcers that have not shown substantial healing after 4 weeks of treatment are often considered nonhealing, with some using data to argue that a wound that fails to close by at least 50% after 4 weeks will not likely heal within 12 weeks.[6,10] The criterion of 50% closure has not only been put forward as a predictor of timely wound healing but also has been used as a surrogate endpoint for successful wound treatment.[11] When wounds do not show substantial healing after 4 weeks, it is recommended to move to treatment with advanced care. The urgency is to close the wound and avoid complications and health care costs as previously described. A number of advanced acellular and cellular wound matrices have been developed to treat DFUs that are considered nonhealing after no substantial improvement is observed after 4 weeks of standard care;[12] however, no currently available advanced wound treatment grafts are perfusion decellularized and hepatic derived.

The hepatic-derived wound matrix (HD-WM; MIRODERM; Miromatrix) is a novel, non-crosslinked, acellular wound graft that is produced by perfusion decellularization of a whole porcine liver. This process removes cellular material, leaving a highly vascularized collagen matrix and an epithelial basement membrane. When a matrix of this type is reseeded with functional cells to produce whole organs, the cells migrate so that there is physiological appropriate organization of the cells. This suggests the decellularized matrix retains some potentially beneficial proteins, eg, anabolic proteins.[13] The utility of this HD-WM was originally demonstrated by Fridman and Engelhardt[14] in a pilot study of patients with difficult-to-heal DFUs. The authors followed patients who had a DFU open more than 3 months and at least 1 previous treatment attempt with an advanced biologic. Fifty percent of the study patients' wounds were closed within the 12-week period, with a fourth wound showing good healing and more than 90% smaller at 12 weeks.[14] These data also suggested that initial treatment response was predictive of the 12-week closure.

This multicenter study was conducted to replicate and expand on Fridman and Engelhardt.[14] The study prospectively assessed hard-to-heal DFUs in a larger, more geographically diverse population. It was hypothesized that the results obtained here would be consistent with the pilot study. This scientific replication would lend confidence to complete a more definitive randomized controlled trial. The primary endpoint of this study is the proportion of wounds that healed at or prior to 12 weeks, and the authors expect it to be similar to that observed in the previous pilot study. The data also will allow for an analysis of the predictive ability of the 50% healed by 4 weeks criterion.

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