Cryopreserved Placental Membranes Containing Viable Cells Result in High Closure Rate of Nonhealing Upper and Lower Extremity Wounds of Non-Diabetic and Non-Venous Pathophysiology

Eric L. Johnson, MD; Molly Saunders, BS; Tanushree Thote, PhD; Alla Danilkovitch, PhD


Wounds. 2021;33(2):34-40. 

In This Article

Materials and Methods

Study Design

This was a single-center retrospective analysis evaluating the clinical outcomes of vCPM plus SOC in the treatment of upper-extremity and lower-extremity wounds of nondiabetic and nonvenous pathophysiology. To be included in the study, patients were required to have a nonhealing wound that was neither a DFU nor a VLU and had to be receiving vCPM as part of their treatment regimen. Nonhealing wounds were defined as either present for at least 4 weeks with no progression toward closure, or those in patients with significant comorbidities that put them at a high risk of nonclosure. Patients could not be receiving any other skin substitutes during the course of vCPM treatment. Data were deidentified and retrospectively collected through chart review. This study was conducted in compliance with the principles outlined in the Declaration of Helsinki. Due to the retrospective nature of this study, Institutional Review Board approval was waived.

Graft Description and Treatment Regimen

Both vCPM-amnion (Grafix PRIME; Osiris Therapeutics, Inc.) and vCPM-chorion (Grafix CORE; Osiris Therapeutics, Inc.) are aseptically processed from donated human placental tissue following rigorous quality-assurance standards. The vCPM product is a minimally manipulated tissue allograft indicated for use as a cover for acute and chronic wounds without restriction to etiology or location. It is supplied in sheet form and packaged within a cryobag contained within a heat-sealed pouch. To thaw, the cryobag is removed from the pouch and placed into room temperature sterile saline or water. Once thawed, the graft is removed from the pouch and placed into a second sterile basin with saline to rinse. After rinsing, the graft is removed from the plastic backing and placed onto the wound. It is supplied in several different sizes (3 cm x 4 cm, 2 cm x 3 cm, 1.5 cm x 2 cm, 16 mm disc) and can be stored between -75°C and -85°C.[7,8]

Wounds were treated and dressed according to the Bozeman Health Wound and Hyperbaric Center SOC which is in accordance with nationally accepted guidelines. Such guidelines state that SOC consists of evaluating wounds for any systemic issues that would impair closure, cleansing and debridement, maintenance of a moist wound environment, infection and biofilm management, nutritional support, management for edema and exudate, and offloading and/or compression dependent on wound location.[3] At the Bozeman Health Wound and Hyperbaric Center, it is routine to use DNA sequencing to identify biofilm and address the findings prior to using any advanced skin substitutes. Based on physician interpretation of the molecular findings, topical antibiofilm agents were utilized before any vCPM allograft was placed. Prior to application of vCPM, wounds were cleaned and debrided with a curette to remove dead and necrotic tissue. Cleansing depended on provider preference, but usual practice involved a hypochlorous acid/sodium chloride cleanser. Patients received vCPM-amnion, vCPM-chorion, or a combination of both. The lack of the epithelial layer makes chorion-derived vCPM "jelly-like," which makes it better suited for deep or tunneling wounds. On the other hand, vCPM-amnion is recommended for more superficial wounds. For patients who received both types, these grafts were not applied simultaneously; rather, the graft type was chosen on a week-to-week basis. The graft was applied weekly as recommended for most cases; however, in some cases, the frequency of applications deviated at the investigator's discretion. The number of grafts used per patient varied based on the size of the wound. Graft was applied to cover the entire wound. Following vCPM application, wounds were typically dressed with either Mepitel (Mölnlycke Health Care) or ADAPTIC TOUCH (KCI, now part of 3M Company) in accordance with manufacturer's instructions. Patients typically returned to the clinic on a weekly or biweekly basis for ulcer assessments, which included ruler measurements and photography of the wound, as well as adverse event (AE) assessments. Patients were followed for clinical and safety outcomes until complete wound closure, or until the investigator terminated vCPM application.

Clinical Outcomes and Statistical Analyses

The primary endpoint was complete wound closure, defined as 100% re-epithelialization, as determined by the investigator. Additional endpoints included time to closure, number of applications, percent area reduction (PAR) for nonclosed wounds, and number of vCPM-related AEs.

Separate analyses were conducted of vCPM-chorion and vCPM-amnion treatment groups as well as of upper-extremity and lower-extremity wounds. Amnion and chorion have been shown to have similar structural and functional properties.[13] Due to this fact, the authors hypothesized that results would suggest no difference in closure outcomes between the 2 comparator groups.

Descriptive statistics for categorical variables are presented as frequencies and percentages, and as means, standard deviations, medians, and ranges for continuous variables. P values were determined using a X2 test and Kruskal-Wallis test for nonparametric samples for categorical and continuous variables, respectively. A P value of less than or equal to .05 was considered significant.