Decellularized porcine dermal hydrogel enhances implant-based wound healing in the setting of irradiation.

Autor: DeCostanza L; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA., Grogan GM; Department of Plastic Surgery, University of Virginia, Charlottesville, VA, USA., Bruce AC; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA., Peachey CM; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA., Clark EA; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA., Atkins K; Department of Pathology, University of Virginia, Charlottesville, VA, USA., Tylek T; School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA, USA., Solga MD; Flow Cytometry Core Facility, University of Virginia, Charlottesville, VA, USA., Spiller KL; School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA, USA., Peirce SM; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA., Campbell CA; Department of Plastic Surgery, University of Virginia, Charlottesville, VA, USA., Cottler PS; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA; Department of Plastic Surgery, University of Virginia, Charlottesville, VA, USA; Department of Otolaryngology, University of Virginia, Charlottesville, VA, USA. Electronic address: psc5d@uvahealth.org.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2024 Nov 08. Date of Electronic Publication: 2024 Nov 08.
DOI: 10.1016/j.actbio.2024.11.009
Abstrakt: Acellular Dermal Matrix (ADM) provides mechanical and soft tissue support in implant-based breast reconstruction, and has shown to modulate the healing response. However, skin flap necrosis, edema, and previous radiation therapy can hinder ADM integration. Effective biomaterial integration requires regulating the immune response, fibrosis, and adipocyte-driven functionalization. Extracellular matrix (ECM) hydrogels have demonstrated utility in tissue regeneration, and decreasing inflammation and fibrosis in various tissues. Therefore, we hypothesized that a Decellularized Porcine Dermal (DPD) hydrogel to support ADM integration would prevent excessive fibrosis, regulate the macrophage response, and promote adipogenesis. Exploration of DPD hydrogel during ADM implantation in mice (healthy and radiated) revealed long-term effects of irradiation on implant wound healing. DPD hydrogel rescued radiation-induced fibrosis, restoring capsule thickness of healthy mice, and did not increase the fibroblast migration into the ADM. As a modulating soft tissue filler, DPD hydrogel also promoted adipocyte infiltration in healthy and irradiated mice. Detailed macrophage analysis showed that radiation led to the increase in pro-inflammatory, transition, and reparative markers. Despite relatively subtle effects on individual macrophage phenotype markers, multidimensional flow cytometry analysis revealed that DPD hydrogel temporally regulated two subpopulations. he presence of DPD resulted in significantly reduced CD9 Hi Arg1 Hi CD301b Lo and CD163 Hi CD38 Hi CD301b Hi macrophages in healthy mice at one week, and a significant increase in CD9 High macrophages with low expression of other markers at 6 weeks in irradiated mice. DPD hydrogel promotes a decreased fibrotic, and adipocyte-promoting coordination of wound healing in healthy and irradiated wound beds while not disrupting the immunomodulatory effects of ADM. STATEMENT OF SIGNIFICANCE: Acellular Dermal Matrix (ADM) provides mechanical and soft tissue support in post-mastectomy implant-based breast reconstruction, and positively affects wound healing. Following breast reconstruction, skin flap necrosis, edema, and previous radiation therapy can hinder ADM integration. Effective wound healing and biomaterial integration requires regulating the cellular immune response. Extracellular matrix hydrogels have demonstrated utility in tissue regeneration and decreasing inflammation and fibrosis in various tissues, but has yet to be utilized in the setting of breast reconstruction. Here, we demonstrated that a decellularized dermal hydrogel as an adjunct to ADM, decreases fibrosis and promotes adipogenesis during the coordination of wound healing in healthy and clinically relevant microenvironments that have received radiation therapy while not disrupting the immunomodulatory effects of implanted ADM.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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