Temple University School of Podiatric Medicine Journal Review Club
Editor's note: This post is part of the Temple University School of Podiatric Medicine (TUSPM) journal review club blog series. In each blog post, a TUSPM student will review a journal article relevant to wound management and related topics and provide their evaluation of the clinical research therein.

Article title: The Management of Diabetic Foot Ulcers with Porcine Small Intestine Submucosa Tri-Layer Matrix: A Randomized Controlled Study
Authors: Cazzell Shawn M., Lange Darrell L., Dickerson Jaime E. Jr., and Slade Herbert B
Journal name and issue: Advances in Wound Care, November 2015 (Epub ahead of print).
Reviewed by: Amanda Borrelli, Class of 2018, Temple University School of Podiatric Medicine

Introduction

Diabetic foot ulcers often present in patients with diabetes mellitus, and are a serious and challenging complication that often requires time and costly procedures to treat. Diabetic foot ulcers are very difficult to heal and often become chronic, which increases the incidence of progressing to infection. The goal of diabetic foot ulcer management is to promote reepithelization of ulcerative areas, as well as address deficits of the ulcer such as necrotic tissue, inadequate perfusion, and inflammation. Currently, the standard care for diabetic ulcer management is to debride the necrotic tissue, perform infection control, offload the wound, and maintain a moist wound environment. The standard of care results in healing half of diabetic foot ulcers in around twenty weeks. Furthermore, an alternate solution to diabetic ulcer management with higher outcomes, at an equitable expense, is highly sought after. A present alternative to standard diabetic foot ulcer management is tri-layer porcine small intestine submucosa (SIS). SIS is a cost effective, three-dimensional biomaterial approximately .30mm thick containing collagen-based extracellular matrix. This study evaluated the use of tri-layer SIS on diabetic foot ulcers for podiatric management.

Materials and Methods

82 patients were randomized to either SIS or standard care (SC) and followed for 12 weeks, or until the closure of their diabetic foot ulcer. Additionally, randomization by wound size was achieved to limit various ulcer size distributions between the two treatment groups. Subjects selected for this study were 18 years of age or older, diagnosed with either type 1 or type 2 diabetes, taking medication for glucose control, and presenting with a neuropathic foot ulcer (.5-10cm2 in area) on the plantar aspect of their foot for a time frame of 6 weeks to 1 year.

At the start of the study, patients in the SC group underwent ulcer debridement, however, patients in the SIS group were not allowed per the study. All ulcers were measured for size, and subjects were given an offloading device that they were required to wear for the duration of the study. Subjects returned weekly, for 12 weeks, for ulcer assessment, application of SIS or SC, measurement, and the recording of any adverse effects. Upon closure of an ulcer, either at the end of the 12 weeks or during the study, subjects were placed into a follow up category where the durability of the closure and additional side effects were recorded.

Each week, ulcers in the SIS group were cleaned with saline and SIS was applied with a 1/8 inch overlap on the wound edge. It was then held with adhesive tape, moistened with saline, protected with a non-adherent dressing, and held in place with self-adherent wrap bandage. Patients in the SC group were provided with care deemed appropriate by the investigator.

Results

Ulcers managed with SIS had a significantly greater proportion closed by 12 weeks, and among all treatment visits, than for the standard care control group. Ulcers in the SIS group closed on average 2 weeks earlier, and had a greater median reduction in ulcer area at each visit than the SC group. Adverse effects for both treatment groups were recorded, and there were no associated safety concerns with the SIS group.

Discussion

Extracellular matrix (ECM) is extremely important in wound healing. Non-healing diabetic ulcers tend to have atypical ECM, as well as a deficiency in the formation of new ECM throughout the healing process. By adding SIS, a form of ECM material, it promoted vascular growth and epithelial formations. Consequently, ulcers managed with tri-layer porcine small intestine submucosa were correlated with a more rapid improvement and a higher probability of achieving total ulcer closure than those patients in the standard care group.

About the Authors:
Amanda Borrelli is a third year podiatric medical student at Temple University School of Podiatric Medicine (TUSPM) in Philadelphia, Pennsylvania. She graduated from Rutgers University in 2012 with a Bachelor of Arts in Biology from the School of Environmental and Biological Sciences. Following her degree, Amanda completed her Master’s in Public Health at the Icahn School of Medicine at Mount Sinai. In the fall of 2014, she started her podiatry career at Temple, where she is involved in many activities and has interests in primary podiatric medicine, surgery, and the diabetic patient.

Dr. James McGuire is the director of the Leonard S. Abrams Center for Advanced Wound Healing and an associate professor of the Department of Podiatric Medicine and Orthopedics at the Temple University School of Podiatric Medicine in Philadelphia.