The pilot study lasted 14 weeks. All patients were treated and assessed by the first author in an outpatient setting. Informed written consent was obtained from all patients prior to enrollment in the trial. Patients were selected to receive PDPHD-WM as a treatment for their DFU based on qualifications of the inclusion/exclusion criteria.
Inclusion criteria
Patients ≥ 18 years of age, who had type 1 or 2 diabetes mellitus and glycosylated hemoglobin < 12% within 3 months of PDPHD-WM application, with adequate vascular perfusion of the affected limb as determined by ankle-brachial index (≥ 0.9), willing and able to maintain required offloading of the affected limb and perform necessary dressing changes, with a Wagner grade I or II DFU (full thickness) > 1 cm2, and was present for > 30 days prior to time of screening, and who experienced previous failure of ≥ 1 advanced therapies (PDGF, HBOT, or BAT) to close the wound comprised the inclusion criteria for this study.
Exclusion criteria
Patients were excluded due to the following factors: suspected or confirmed signs of infection of the study ulcer/limb; sensitivity to porcine products; pregnancy; receiving medication or treatment known to affect wound healing within 30 days of treatment visit; excessive lymphedema that could interfere with wound healing; Charcot foot with a bony deformity; Chopart’s amputation; history of bone cancer of the affected limb; treatment with PDGF, HBOT, or BAT within 30 days of treatment visit; or if the size of the ulcer following debridement improved by > 30% during the run-in phase.
The DFU was assessed clinically, photographed, and measured via planimetric tracing software (ImageJ Version 1.50; National Institutes of Health, Bethesda, MD) at the screening visit (day 0 [-14 ± 3 days]). Each wound tracing was scanned into a digital image. Each pixel length was calibrated, and then the polygon tool was used to define the contour of each wound tracing. Finally, the area defined by the polygon was calculated within the software using the measure function. A 2-week run-in period was then allotted, where all wounds were treated with SOC alone. This included sharp surgical debridement, a saline-gel sterile gauze dressing that was changed once daily by the patient, and offloading with a removable CAM boot. At the treatment visit (day 0 ± 3 days), the wound was assessed again. If there was < 30% improvement in wound size, the patient qualified for application of PDPHD-WM. The ulcer was debrided to healthy tissue, and the wound matrix was secured to the wound with adhesive strips, benzoin, sutures, staples, or a combination of these methods. Saline gel was applied to the outside of the graft and a nonadherent contact layer was secured to the wound using a multilayer compression bandage that was left intact until the next treatment visit. Continued offloading with a CAM boot was maintained throughout the study. Thereafter, weekly office assessments were made for the next 11 weeks (12 study weeks in total), and the wounds were photographed, traced, and assessed. If deemed appropriate by the treating physician, additional PDPHD-WMs were applied at subsequent visits for lack of healing, graft loss from shearing, or minimal visible reepithelialization. At the end of the 12-week treatment phase, data on percentage of complete closure and rates of closure were compiled.
Product
The PDPHD-WM is derived from the highly vascular porcine liver utilizing perfusion decellularization. It retains an intact extracellular matrix (ECM) with unique properties such as an epithelial-basement membrane, an open collagen matrix, and vascular ECM. Perfusion decellularization is a new technology used to decellularize whole organs and vascularized tissues, which has enabled numerous advances in tissue engineering of whole organs (heart, lung, liver, and kidney).16-19 This is in contrast to previous methods based on immersion decellularization, which is limited to thin, dense tissues (dermis, small intestine submucosa, urinary bladder, or pericardial tissue) that comprise many advanced wound care products.