Evaluation of Apligraf^® persistence and basement membrane restoration in donor site wounds: a pilot study

Abstract

Apligraf is a bilayered tissue-engineered product consisting of a bovine collagen matrix with neonatal fibroblasts, overlaid by a stratified epithelium containing living keratinocytes. The United States Food and Drug Administration has approved its use for venous leg ulcers and neuropathic diabetic foot ulcers. Apligraf provides a dermal matrix and produces cytokines similar to the human skin. However, its mechanism of action and ultimate fate in host wounds are unclear. The aim of this study was to evaluate the persistence of Apligraf fibroblasts and keratinocytes in human acute partial-thickness wounds (split-thickness donor sites) treated with Apligraf. In an open-label, within-patient, three-centered, controlled pilot study, 10 patients were treated with Apligraf, Apligraf dermis only (without epidermis), and a polyurethane film for donor site wounds of the same size, depth, and anatomical location. Apligraf DNA persistence was the primary outcome measure. Basement membrane components, cosmetic outcome, time to wound healing, and safety parameters were secondary outcome measures. One week after the initial treatment, reverse transcription polymerase chain reaction analysis found that two Apligraf and two Apligraf dermis-only-treated sites had Apligraf DNA present. Four weeks posttreatment, only one Apligraf and one Apligraf dermis-only sites showed the presence of Apligraf DNA. There was no difference between the three treatment modalities in establishing basement membrane in donor site wounds. No differences in other secondary outcomes were found. Apligraf DNA persisted in a minority of patients at 4 weeks in acute partial-thickness wounds. Apligraf's success in speeding healing of acute wounds appears to be related to factors other than the persistence of donor DNA or effect on basement membrane restoration.

Human cell therapy for venous leg ulcers

“…As measured by in situ hybridization for donor cell Y-chromosome, the allogeneic cells persisted in female recipients for only approximately four weeks [85][86][87]. Reports concerning cell persistence [85,87] were contrary to the published academic experience, but eventually it was understood that histologic constructions are not necessary because the cells begin to die very soon after application [88]. Any barrier or water loss function provided by the engineered tissues is very short lived.…”

A Bioengineered Human Skin Tissue for the Treatment of Infected Wounds

“…22,23 However, clinical findings with BSS therapies suggest that cultured skin tissue is unlikely to be acutely rejected in humans. [24][25][26][27][28] Skin substitutes are gradually replaced by the patient's skin with no excessive inflammation or other signs of acute rejection. [25][26][27][28] Finally, a limitation of all cell-based BSS therapies is the high cost of manufacturing.…”

“…[24][25][26][27][28] Skin substitutes are gradually replaced by the patient's skin with no excessive inflammation or other signs of acute rejection. [25][26][27][28] Finally, a limitation of all cell-based BSS therapies is the high cost of manufacturing. However, this may be counterbalanced by an improved wound healing timeline, which would result in shorter patient hospitalization.…”

Clinical Evaluation of NIKS-Based Bioengineered Skin Substitute Tissue in Complex Skin Defects: Phase I/IIa Clinical Trial Results

“…[35][36][37] Because these types of skin substitutes do not contain professional antigen-presenting cells, such as Langerhans cells, acute rejection is not anticipated, and replacement by patient keratinocytes over time is expected. 38 Extensive clinical experience with Apligraf and other allogeneic treatments containing both epithelial cells as well as dermal fibroblasts show a lack of acute immune responses; however, it has also been shown that the cellular components of these treatments are lost within 6 to 8 weeks of placement.…”