Efficacy of a Bioresorbable Matrix in Healing Complex Chronic Wounds

An Open-Label Prospective Pilot Study

Sarah W. Manning, MD; David A. Humphrey, MD; William R. Shillinglaw, DO; Eric Crawford; Gaurav Pranami, PhD; Ankit Agarwal, PhD; Michael J. Schurr, MD

Disclosures

Wounds. 2020;32(11):309-318. 

In This Article

Abstract and Introduction

Abstract

Objective: The goal of this prospective clinical study was to assess the effectiveness of a novel bioresorbable polymeric matrix impregnated with ionic and metallic silver as a primary wound contact dressing in healing stagnant or deteriorating chronic wounds.

Materials and Methods: Thirty-two patients with a total of 35 chronic wounds undergoing treatment at the Wound Healing and Hyperbaric Center at Mission Hospital were recruited under a protocol approved by the institutional review board. The wounds included venous stasis ulcers, diabetic foot ulcers, postoperative surgical wounds, burn wounds, and chronic, nonpressure lower extremity ulcers. At baseline, all wounds were nonhealing (ie, stagnant or deteriorating) for a median of 39 weeks (range, 3–137 weeks) and suspected of persistent microbial colonization that had not responded to traditional antimicrobial products and/or antibiotics. The aforementioned matrix was applied to wounds once every 3 days and covered with a secondary dressing. Previously prescribed protocols of care, such as debridement or compression wraps, were continued, but prior antimicrobial dressings or antibiotics were replaced with the matrix. Wound assessments at 3 weeks and 12 weeks post intervention are reported.

Results: Three patients were excluded due to patients lost to follow-up after initial application. At 3 weeks, 72% of wounds (22/32) had significantly improved healing with an average wound area reduction of 66%. By 12 weeks, 91% of wounds (29/32) either healed completely (ie, fully reepithelialized) or improved significantly with an average wound area reduction of 73%. The matrix was well tolerated; no patient reported discomfort with the application of the matrix.

Conclusions: The micrometer-thick bioresorbable matrix presents a new form factor to wound management, conforming intimately to the underlying wound bed to exert localized and sustained antimicrobial action of noncytotoxic levels of silver. The application of the matrix on the wound surface in protocols of care was safe and well tolerated, and it facilitated improvements in healing of a majority of the stagnant or deteriorating complex chronic wounds.

Introduction

The burden of chronic wounds in the United States continues to mount, with annual cost estimates near $25 billion.[1] These chronic wounds are those that are stagnant or deteriorating, increasing in size, exudate, or odor, and generally having clinical signs of infection. They require more frequent clinical visits, costing 2 to 6 times more per week for treatment than acute wounds that are progressing to healing.[2] Standard protocols for the management of such complex wounds are highly variable and often include administering systemic antibiotics to arrest possible evolving wound infection. Effective strategies include wound debridement and cleansing to remove necrotic tissue and reduce bacterial counts. However, debridement is insufficient in removing all bacteria from a wound surface, often resulting in bacterial regrowth from the wound bed interstices. Therefore, a variety of topical antimicrobial formulations and dressings are included as a first-line approach for wound infection management in standard of care protocols with the intent to reduce the use of systemic antibiotics. Such standards of care, however, still suffer from large deficiencies often associated with poor clinical outcomes. The increased prevalence of antibiotic-resistant bacteria stems from the use of systemic antibiotics.[3] Topical antimicrobials require repeated applications due to short residence times in the wound, necessitating frequent and painful dressing changes.[4] Antimicrobial wound dressings with high loadings of antimicrobials, such as silver and iodine,[5,6] have potential to cause high cytotoxicity[7] and have been reported to impair wound healing.[8–13]

The objective of this study was to evaluate the effectiveness of a novel bioresorbable polymeric matrix (Figure 1) within protocols used to manage hard-to-heal chronic wounds. The antimicrobial matrix contains ionic and metallic silver within polymeric multilayers in which metallic silver particles provide sustained release of antimicrobial silver ions over several days. The manufacturer recommends using the term matrix to describe this bioresorbable porous polymeric multilayer architecture as it provides a scaffold for both uniform loading of silver nanoparticles and a template for cells migration. Other published studies have reported that components of the matrix allow growth and proliferation of fibroblasts[14] and migration of keratinocytes[15] on its surface, as well as supporting normal vascularization and granulation tissue formation in the wound bed.[16] The matrix is reported to be less cytotoxic to mammalian cells,[17] containing only 0.16 mg/in2 of total silver, which is 50-fold to 100-fold less than that found in traditional silver dressings (eg, ACTICOAT Antibacterial Barrier Dressing [Smith+Nephew, Inc], 6.7 mg/in2 silver; Silverlon Antimicrobial Dressing [Cura Surgical, an Argentum Medical Company], 35.2 mg/in2 silver).[18] The ultrathin form factor (thickness, 20 μm) of the matrix facilitates a primary mode of action different than conventional silver dressings. As the matrix absorbs wound fluid, it transforms into a micrometer-thick soft gel that intimately conforms to the contours of an underlying wound bed where bacteria colonize.[17] Most of the silver ions in the matrix are, thus, potentially consumed for antimicrobial action on the wound bed in intimate contact with the matrix.[14] The role of silver in the matrix is not to graft into the tissue, but to prevent colonization in the dressing itself. This mode of action reduces loss of silver ions in wound exudate,[14,17] reducing potential silver cytotoxicity, staining, and irritation[19,20] while potentially enabling increased comfort for patients. The matrix is breathable, allows for the transmission of oxygen and water vapor, and maintains a physiologically moist environment.[17]

Figure 1.

A 5cm x 5cm unit of the matrix held with tweezers on a surface.

Accordingly, the scientific premise of this clinical study was that the micrometer- thick form factor of the matrix with antimicrobial silver could efficiently clear persistent microbial colonization on the surface of chronic wounds stalled in the inflammatory phase and aid in progressing the wound healing process. This study is the first institutional review board (IRB)-approved, open-label, prospective clinical evaluation of the aforementioned matrix in protocols of care for complex, chronic, nonhealing wounds (ClinicalTrials.gov identifier: NCT03204851).

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....