Journal article
Decellularized porcine dermal hydrogel enhances implant-based wound healing in the setting of irradiation
Acta biomaterialia, v 191, pp 260-275
01 Jan 2025
PMID: 39522628
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 CD9HiArg1HiCD301bLo and CD163HiCD38HiCD301bHi macrophages in healthy mice at one week, and a significant increase in CD9High 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.
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.
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Details
- Title
- Decellularized porcine dermal hydrogel enhances implant-based wound healing in the setting of irradiation
- Creators
- Lillian DeCostanza - University of VirginiaGraham M. Grogan - University of VirginiaAnthony C. Bruce - University of VirginiaCorrina M. Peachey - University of VirginiaEvan A. Clark - University of VirginiaKristen Atkins - University of VirginiaTina Tylek - Drexel University, School of Biomedical Engineering, Science, and Health SystemsMichael D. Solga - University of VirginiaKara L. Spiller - Drexel University, Chemical and Biological EngineeringShayn M. Peirce - University of VirginiaChristopher A. Campbell - University of VirginiaPatrick S. Cottler - University of Virginia
- Publication Details
- Acta biomaterialia, v 191, pp 260-275
- Publisher
- Elsevier
- Number of pages
- 16
- Grant note
- NHLBI: R01 HL130037
PSC acknowledges support from the Plastic Surgery Foundation/MTF Biologics Allograft Tissue Research Grant. KLS acknowledges support from NHLBI R01 HL130037. Graphical abstract was created with BioRender.com .
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Chemical and Biological Engineering
- Web of Science ID
- WOS:001391077300001
- Scopus ID
- 2-s2.0-85209248029
- Other Identifier
- 991021959778604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Engineering, Biomedical
- Materials Science, Biomaterials