Implantable Nanomedical Scaffold Facilitates Healing of Chronic Lower Extremity Wounds

Background. Chronic, nonhealing wounds are a growing health care problem in the United States, affecting more than 6.5 million patients annually. Objective. This retrospective study evaluates the clinical efficacy and utility of an implantable nanomedical scaffold in the treatment of chronic, nonhealing lower extremity wounds in patients with multiple comorbidities. Materials and Methods. Data from patients with chronic wounds that had persisted for ≥ 4 weeks and were unresponsive to existing advanced wound care modalities were included in the study. Wounds received the implantable nanomedical scaffold weekly, or as deemed appropriate, for up to 12 weeks based on physician assessment of wound status. Results. A total of 82 wounds were included in this study; wound types consisted of 34 diabetic foot ulcers, 34 venous leg ulcers, and 14 other wounds. Overall, treated wounds demonstrated progressive and sustained wound area reduction over the course of treatment, with 85% achieving complete closure at 12 weeks. Conclusions. The implantable nanomedical scaffold proved to be an effective alternative to existing wound matrices capable of supporting the natural wound healing process and may provide significant benefits as part of the treatment algorithm for challenging chronic wounds.

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Chronic, nonhealing wounds are a growing health care problem in the United States, affecting more than 6.5 million patients annually. In particular, diseases that compromise skin integrity and impair normal wound healing processes, such as diabetes and peripheral vascular diseases, are becoming more common and leading to an increasing number of chronic, nonhealing wounds. Wounds, including diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs), are often difficult to treat, and patients may fail to heal with standard options.

An implantable nanomedical scaffold that exhibits structural similarities to the native extracellular matrix (ECM) offers a new approach to the treatment of chronic wounds.^1-3 This matrix is the first product to combine advances in material science (eg, resistance to enzymatic degradation, excellent biocompatibility, strength/durability, and controlled degradation) with the positive attributes of biologic materials (eg, architecture similar to human ECM, fibrous architecture optimized to support cellular migration and proliferation, engineered porosity to support tissue ingrowth, and vascularization).¹ These features have been shown to allow the nanofiber material to achieve rapid and complete healing of wounds in preclinical large animal studies, superior to gold standard biologic material with diverse clinical indications in the wound care.^2,3 The unique properties of the matrix also include ease-of-use, flexibility, and clinical versatility with significant logistical advantages over existing amniotic, allogenic, and biologic products.

The present study was designed to evaluate the efficacy and utility of the implantable nanomedical scaffold in the treatment of chronic, nonhealing lower extremity wounds in patients with multiple comorbidities.

This retrospective study was conducted at a single center. Data from patients with chronic wounds that had persisted for ≥ 4 weeks and were unresponsive to existing advanced wound care modalities were included in the study. Comorbidities included diabetes mellitus, obesity, polymyalgia rheumatic, lymphedema, peripheral vascular disease, steroid use, and neuropathy.

Data were retrospectively collected via chart review by the treating physician. Wound care patients treated with the implantable nanomedical scaffold (Restrata Wound Matrix; Acera Surgical, St Louis, MO) between July 2017 and February 2018 were included in the study. Patient eligibility for treatment with the implantable nanomedical scaffold was based on wound type, severity, and duration (≥ 4 weeks). Written consent for use of de-identified data for medical research was provided by all patients.

Wounds received the implantable nanomedical scaffold weekly, or as deemed appropriate, for up to 12 weeks based on physician assessment of wound status. Before treatment, sharp debridement of the wound margins and wound bed was performed. The implantable nanomedical scaffold was applied directly to the wound bed and a nonadherent dressing (ADAPTIC TOUCH Non-Adhering Silicone Dressing; Systagenix, an Acelity Company, Gatwick, UK), saline-moistened gauze, and dry gauze dressing were applied. Proper offloading utilizing a total contact cast, surgical shoe, or CAM walker for DFUs, and/or multilayer compression bandaging for VLUs were provided as clinically indicated. Wound area measurements and observations of wound quality were assessed weekly. Descriptive statistics were used to summarize wound variables; statistical significance was set at P < .05.

Data from 82 chronic wounds of varying etiologies and sizes treated with the implantable nanomedical scaffold were included in the study (Table 1). Wound types included 34 DFUs, 34 VLUs, and 14 other wounds (pressure ulcers, traumatic and postsurgical wounds, nonvenous vascular wounds, and necrotic wounds).

Overall, no adverse events were reported. Gross observations indicated the wounds treated with the implantable nanomedical scaffold resulted in marked improvement in wound quality and significant reduction in local inflammation. Representative cases can be seen in Figure 1.

Case 1 (Figure 1A-1E) illustrates healing in an 80-year-old man with a history of nonhealing wounds. He had a DFU that was open for > 18 months and failed treatment with Grafix Cryopreserved Placental Membrane (CPM; Osiris Therapeutics, Inc, Columbia, MD) and Provant Therapy Systems (Regenesis Biomedical Inc, Scottsdale, AZ). The wound was treated with the implantable nanomedical scaffold and healed in 4 weeks with 3 applications.

Case 2 (Figure 1F-1J) illustrates healing in a 64-year-old man with a history of nonhealing wounds. The patient had a DFU that was open for > 23 months and had failed treatment with CPM and AmnioBand (MTF Biologics, Edison, NJ). The wound was treated with the implantable nanomedical scaffold and healed in 9 weeks with 8 applications.

Case 3 (Figure 1K-1N) illustrates healing in a 75-year-old man with a history of nonhealing wounds. He had a VLU that was open for > 6 months and failed treatment with standard care and compression wrapping. The wound was treated with the implantable nanomedical scaffold and healed in 2 weeks with 2 applications.

Case 4 (Figure 1O-1S) illustrates healing in a 45-year-old man with a history of nonhealing wounds. He had a pressure ulcer that was open for > 8 months and failed treatment with TRITEC Silver (Milliken Healthcare Products, LLC, Spartanburg, SC). The wound was treated with the implantable nanomedical scaffold and healed in 4 weeks with 3 applications.

Overall, treated wounds demonstrated progressive and sustained wound area reduction over the course of treatment, with 85% (n = 68) of the wounds achieving complete closure at 12 weeks (Table 2). For DFUs, 53% (n = 18) achieved complete closure at 4 weeks, 76% (n = 26) achieved complete closure at 8 weeks, and at 12 weeks, 85% (n = 28) achieved complete closure (Table 2). For VLUs, 41% (n = 14) achieved complete closure at 4 weeks, 62% (n = 21) achieved complete closure at 8 weeks, and at 12 weeks, 91% (n = 30) achieved complete closure (Table 2). For other wounds, 64% (n = 9) achieved complete closure at 4 and 8 weeks, and at 12 weeks, 71% (n = 10) achieved complete closure (Table 2).

Treatment with the implantable nanomedical scaffold significantly improved clinical outcomes and supported healing in chronic refractory wounds. The majority of the wounds (85%) achieved complete healing by 12 weeks.Results demonstrate improved outcomes when compared with other published studies examining various treatment modalities, such as human cellular repair matrix (h-CRM),⁴ porcine small intestine submucosa,⁵ and a bilayered cell-based product.⁶ In particular, closure rates observed for VLUs treated with the implantable nanomedical scaffold (91% at 12 weeks) were greater than those of advanced treatment modalities such as h-CRM.⁴ The unique construction of the nanofiber matrix, including its resistance to enzymatic degradation, strength, and persistence in the wound bed, may account for the excellent closure rates observed.

While the results are encouraging, this is only an initial evaluation of the implantable nanomedical scaffold. There are limitations to the study, including the lack of a control group and randomization, which limit the ability to draw conclusions about the effectiveness of the scaffold. Additional clinical studies are planned and ongoing to further evaluate the clinical efficacy of the implantable nanomedical scaffold and inform the hypotheses of a future randomized controlled trial.

The implantable nanomedical scaffold is an effective alternative to existing wound matrices capable of supporting the natural wound healing process. Most wounds were healed after 12 weeks with regular debridement and application of the implantable nanomedical scaffold. This implantable nanomedical scaffold may provide significant benefits as part of the treatment algorithm for challenging chronic wounds.   

Affiliations: Ocean County Foot & Ankle Surgical Associates, Ocean County, NJ; and Acera Surgical,
St Louis, MO

Correspondence: Matthew R. MacEwan, PhD, President/Chief Science Officer, Acera Surgical, Inc, 10880 Baur Boulevard, St Louis, MO 63132; macewan@acera-surgical.com

Disclosure: Dr. MacEwan is President/Chief Science Officer of Acera Surgical. Dr. Regulski is an advisory board member for Acera Surgical. This paper was exhibited as a poster at the 2018 Symposium on Advanced Wound Care Spring in Charlotte, NC.