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

Discussion

Chronic wounds with persistent microbial colonization on the tissue surface can remain stalled in the inflammatory phase of healing for months and may never progress without significant intervention.[26] Moreover, the longer a chronic wound remains open means the risk of acquiring a multispecies infection increases.[27] Wound care protocols involving combination approaches of debridement and broad-spectrum antimicrobials are increasingly adopted in the management of chronic wounds. Topical antimicrobial formulations play a key role in arresting microbial colonization on the surface of wound tissue as they can reduce the need for systemic antibiotics.[1] However, traditional antimicrobial dressings are designed as large reservoirs that can replenish the loss of cationic antimicrobials (eg, silver, iodine) that were deactivated immediately in protein-rich wound exudate.[14] Thus, the high concentrations of cationic antimicrobials build up in wound tissue and cause high cytotoxicity;[7] also, these antimicrobials are reported to be associated with impairment of wound healing.[8–13]

The novel bioresorbable polymeric matrix evaluated in this study has been designed specifically to address this limitation of traditional antimicrobial dressings. Conventional silver dressings generate high cytotoxic concentrations of silver in wound fluid to achieve antimicrobial action at the wound bed where bacteria colonize.[14] In contrast, conformal contact of the micrometer-thick matrix with wound bed, owing to its large surface area to cross-sectional area ratio, provides intimate contact of silver ions with the microbes on the wound bed.[14,17] This exerts effective antimicrobial therapy while using 50 times to 100 times less silver content than traditional silver dressings. Most of the silver ions in the matrix are potentially consumed for antimicrobial action on the wound bed,[14,17] thus reducing their loss in wound exudate and potential cytotoxicity, staining, and irritation from dressings.[19,20] The matrix is made of nanometer-thick polymeric multilayers impregnated with metallic silver particles, which dissolve over time in wound fluid to release silver ions.[14,17] This allows the matrix to provide sustained antimicrobial activity for up to 3 days in simulated wound fluid in vitro, as listed in the matrix's IFU.

This is the first IRB-approved human clinical study on this bioresorbable matrix that is designed to evaluate its effectiveness in protocols for management of hard-to-heal wounds that were unresponsive for months to traditional antimicrobial dressings and antibiotics. The matrix was employed as a primary wound contact matrix, which replaced the other primary antimicrobial dressing or antibiotics used in the prior treatment plans. Since all of the wounds at baseline were stalled (ie, either stagnant or deteriorating), prior treatment plans with traditional antimicrobial dressings and antibiotics had little impact on wound healing. This is likely indicative of persistent microbial colonization that was tolerant of such traditional antimicrobial dressings and care.

Results of the study show that inclusion of the matrix in the treatment plan helped jump start the healing process of these stalled wounds. Within 3 weeks, 72% of wounds demonstrated significantly improved healing; within 12 weeks, 91% of wounds either healed completely (fully reepithelialized) or significantly improved. The outcome was consistent across various wound etiologies and chronic wound types. The only difference between new and prior treatment plans was the replacement of traditional antimicrobial dressings with the matrix as the primary wound dressing. These outcomes support the scientific premise that the micrometer-thick form factor of the matrix with metallic silver particles enabled antimicrobial silver ions to work more effectively in clearing persistent microbial colonization hidden in crevices of a tissue surface, where traditional antimicrobial dressings used in prior treatment plans were less effective.

An additional key benefit of the matrix is that it is primarily made of bioresorbable polymers,[17] which circumvents the need for its painful removal and facilitates its potential prolonged use in multimodal treatment plans involving compression wraps or negative pressure. This easy and versatile application of the matrix allowed a single clinical investigator in this study to include the matrix as the primary dressing in all wound care plans without changing the remainder of the care plan. Sustained antimicrobial activity of the matrix limited dressing changes to once every 3 days. Secondary outcomes in the study sought to incorporate patient experience into the evaluation of the matrix. Because many patients with chronic wounds have additional comorbidities and a high level of contact with the medical system, the secondary goal was to create an effective, well-tolerated wound care approach that could minimize visits to the clinic for dressing changes. None of the patients in this study reported pain with any application of the matrix or associated dressing changes. These features of the matrix can potentially improve the quality of life for patients with chronic wounds and increase the likelihood that this population may be compliant with their treatment course.

The 3 venous stasis ulcers that enlarged over the first 4 weeks of evaluation with the matrix were highly exuding and had previously been managed unsuccessfully with multiple antimicrobials and antibiotics, including silver dressings and an antimicrobial absorbent pad, under compression. These longstanding wounds ranged in duration from 5 to 21 months. It may be possible that their exuding nature did not respond to the ultrathin polymeric matrix dressing. These ulcers emphasize that chronic wounds might not respond to a change in topical antimicrobial dressing alone because they involve complex comorbidities and systemic diseases that require multimodal treatment plans.

The study outcomes conclude that application of the matrix directly to the wound surface was safe, well tolerated, and facilitated improvements in healing of most of the stagnant or deteriorating complex chronic wounds. The clinical investigators would recommend considering the matrix for the management of complex wounds in conjunction with standard protocols of care, such as debridement in DFUs and compression therapy in venous stasis ulcers. The matrix should be applied to clinically clean ulcers. Wounds should be clinically inspected at each dressing change and appropriately debrided weekly if there are clinical signs of bioburden or slough.

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