Abstract
Chronic ulcerative and hard-healing wounds are a growing global concern. Skin substitutes, including acellular dermal matrices (ADMs), have shown beneficial effects in healing processes. Presently, the vast majority of currently available ADMs are processed from xenobiotic or cadaveric skin. Here we propose a novel strategy for ADM preparation from human abdominoplasty-derived skin. Skin was processed using three different methods of decellularization involving the use of ionic detergent (sodium dodecyl sulfate; SDS, in hADM 1), non-ionic detergent (Triton X-100 in hADM 2), and a combination of recombinant trypsin and Triton X-100 (in hADM 3). We next evaluated the immunogenicity and immunomodulatory properties of this novel hADM by using an in vitro model of peripheral blood mononuclear cell culture, flow cytometry, and cytokine assays. We found that similarly sourced but differentially processed hADMs possess distinct immunogenicity. hADM 1 showed no immunogenic effects as evidenced by low T cell proliferation and no significant change in cytokine profile. In contrast, hADMs 2 and 3 showed relatively higher immunogenicity. Moreover, our novel hADMs exerted no effect on T cell composition after three-day of coincubation. However, we observed significant changes in the composition of monocytes, indicating their maturation toward a phenotype possessing anti-inflammatory and pro-angiogenic properties. Taken together, we showed here that abdominoplasty skin is suitable for hADM manufacturing. More importantly, the use of SDS-based protocols for the purposes of dermal matrix decellularization allows for the preparation of non-immunogenic scaffolds with high therapeutic potential. Despite these encouraging results, further studies are needed to evaluate the beneficial effects of our hADM 1 on deep and hard-healing wounds.
Highlights
Chronic and hard-healing wounds are a pervasive global health concern
48 h, we found a lower frequency of analyzed cells incubated with hADM 3 compared to the unstimulated control, and at 72 h in cells incubated with hADM 2 and hADM 3 (Figure 2C)
No differences in CD163 expression were observed at 24 h. In the latter time points, we found a significantly lower expression level of CD163 on monocytes when compared to unstimulated control
Summary
Wound healing is composed of four overlapping phases: hemostasis, inflammation, proliferation and remodeling [2]. In each of these phases, distinct mechanisms take place to induce effective wound closure and scar formation. The proliferative ability of epidermal keratinocytes and extracellular matrix (ECM)-depositors, including myofibroblasts, facilitates the rapid coverage of the wound area by dermal and epidermal tissue, inducing scar formation. The remodeling of crucial ECM components takes place, resulting in scar maturation. Proliferative coverage of the wound area is significantly inhibited in chronic wounds, and the healing process is blocked in a self-perpetuating cycle of inflammatory reaction. It is well recognized that the ideal dressing for hard-healing wounds should cover the wound and modulate the wound microenvironment through its immunoregulatory effects
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