Diabetic foot ulcerations (DFUs) are one of the most common complications associated with diabetes with an annual incidence of 6.3 percent worldwide. Diabetic patients have a 19 to 34 percent likelihood of having lower extremity ulcers in their lifetime.1 Conventional therapies commonly fail to fully treat these complex wounds. In a prospective study analyzing overall healing rates in DFUs, the percent of wounds healed with standard of care treatment was 59.3 percent after 12 weeks.2 More than 50 percent of diabetic ulcers become infected and 20 percent of those with moderate to severe infection result in amputation.1 Strikingly, at least 85 percent of diabetes-related amputations are preceded by an ulceration and complications refractory to standard of care have an enormous effect on our health-care system.3 Annual diabetes care in the United States costs at least $176 billion, of which up to an estimated $58 billion is related to lower extremity care.1 The difficulty of closing these wounds successfully while maintaining a durable therapeutic response has given podiatrists reason to seek, validate and utilize alternative patient management strategies to more effectively heal DFUs.
Harnessing The Power Of The Patient’s Own Skin
Skin is the largest organ in the human body and has one of the most important roles of being the first line of defense to environmental challenges. A breakdown in this barrier function can have massive clinical implications. Although skin is commonly mistaken as a mere barrier and sensory structure, contemporary research has elucidated skin to be an extremely dynamic biological factory.4 Skin reportedly plays a major role in protein synthesis, metabolism, cell signaling and is an essential part of the immune, nervous and endocrine systems.
Therefore, an ideal DFU therapy would recapitulate the complex structure and biologic function of native skin with the ability to treat defects with a wide range of size and severity.
With these points in mind, an autologous homologous skin construct (SkinTE™, PolarityTE) has emerged with the potential to help heal and close complex dermal wounds such as chronic skin defects, burns, reconstructed burn wounds and acute complex traumatic wounds.5
With this technology, one obtains from the patient a small, healthy, full-thickness skin harvest, which is subsequently treated and manufactured into SkinTE at an FDA-registered facility. The tissue processing activates endogenous regenerative cellular niches that are responsible for native wound healing following injury.
SkinTE is not cultured ex-vivo. Following the tissue processing, the clinician would swiftly apply SkinTE to the prepared wound bed. This follows the concept that the patient’s body can support his or her tissue better than exogenous materials. Similar to how one would apply a traditional autologous skin graft, one would apply SkinTE and it expands directly in the wound bed, generating expanding neo-dermal islands that close the wound from the inside out. Conceptually, the patient serves as his or her own bioreactor.6
What A Pilot Study Revealed About An Emerging Treatment Option For DFUs
Following pre-clinical validation in a swine model, colleagues have evaluated the efficacy of SkinTE to close burn wounds as well as acute traumatic and chronic wounds clinically.6 More recently, investigators conducted a pilot trial to evaluate if a single application of SkinTE had the ability to close hard-to-treat DFUs and if the clinical workflow is as feasible and efficacious as the current standard of care for the outpatient setting.7
The pilot trial involved the use of SkinTE in the treatment of 11 DFUs that were classified as full-thickness but not involving bone that were refractory to standard therapies.7 For this study, researchers retrieved 1.5 cm2 of full-thickness donor skin from the proximal calf in the clinic using local anesthetic only and closed the harvest wound primarily. The entire harvest was processed into SkinTE and returned to the clinic within 48 hours of retrieval. After spreading the SkinTE graft evenly across the patient’s wound bed, the investgators dressed the wounds with non-adherent, non-absorbent silicone, absorbent foam and triple compression wrapping. Patients also wore a CAM boot to offload the wound. The researchers completed the donor harvests and SkinTE applications in the clinic setting without issue.
The researchers in the trial study monitored the patients for 12 weeks for wound closure and followed the patients for at least two weeks after wound closure to assess the durability of healing.
Ten of the 11 wounds, ranging in size between 1.3 to 21.7 cm2, demonstrated complete graft take, granulation, rapid reepithelialization and closure by 12 weeks with one SkinTE application (see figure 1).7 One patient with prior lower extremity hardware due to a Charcot foot reconstruction developed an infection unrelated to the SkinTE-treated wound and required extensive debridement, including the DFU treated with SkinTE. All healed wounds remained closed upon inspection at post-closure durability follow-up visits at least two weeks after healing. As of now, there have been no reported adverse reactions related to SkinTE commercially or in this pilot trial.
This novel technology appears to assist in the closure of DFUs ranging in size and severity without the use of adjuncts or advanced wound care products. This may prove to be a promising adjunct for diabetic wounds and has the potential to change conventional approaches to treating refractory chronic wounds that can lead to amputation. On paper, the idea of utilizing the patient’s own cellular niche and corresponding stem cells from his or her own healthy tissue with the patient’s wound bed as a bioreactor may be an ideal avenue to efficiently restore complex wounds to normalcy.
While a great deal more therapeutic and health economic analysis is necessary, this technology has the potential to help reduce the unnecessarily high burden of lower extremity wounds and amputations worldwide.
Dr. Armstrong is a Professor of Surgery at the University of Southern California. He is the founder and Co-Director of the Southwestern Academic Limb Salvage Alliance (SALSA). Dr. Armstrong is the founder and Co-Director of the International Diabetic Foot Conference (DF-Con).
1. Armstrong DG, Boulton AJM, Bus SA. Diabetic foot ulcers and their recurrence. N Engl J Med. 2017;376(24):2367-2375.
2. Ince P, Game FL, Jeffcoate WJ. Rate of healing of neuropathic ulcers of the foot in diabetes and its relationship to ulcer duration and ulcer area. Diabetes Care. 2007;30(3):660-663.
3. Pendsey SP. Understanding diabetic foot. Int J Diabetes Dev Ctries. 2010;30(2):75–79.
4. Liu Y, Panayi AC, Bayer LR, Orgill DP. Current available cellular and tissue-based products for treatment of skin defects. Adv Skin Wound Care. 2019;32(1):19-25.
5. Mundinger GS, Patterson CW. Replacement of contracted split-thickness skin graft and keloid scar with a self-propagating autologous skin construct (SkinTE™). Plast Reconstr Surg Glob Open. 2018;6(8S):95.
6. Granick MS, Baetz NW, Labroo P, Milner S, Li WW, Sopko NA. In vivo expansion and regeneration of full-thickness functional skin with an autologous homologous skin construct: Clinical proof of concept for chronic wound healing. Int Wound J. 2019;16(3);841-846.
7. Armstrong DG, Orgill D, Galiano R, Glat P, Zelen CM. Results of a pilot evaluation of a novel autologous homologous skin construct treatment of diabetic foot wounds refractory to conventional treatments. Poster presented at: 79th Scientific Sessions of the American Diabetes Association; June 7-11, 2019; San Francisco, CA.