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Effects of Radiation on the Macrophage Response to Acellular Dermal Matrix Integration
Conference proceeding   Open access

Effects of Radiation on the Macrophage Response to Acellular Dermal Matrix Integration

Anthony C. Bruce, Lillian DeCostanza, Graham M. Grogan, Kara L. Spiller, Shayn M. Peirce and Patrick S. Cottler
01 Jan 2022
url
https://doi.org/10.6084/m9.figshare.21733139.v1View
Preprint (Author's original) Open Open Access (License Unspecified)

Abstract

Acellular Dermal Matrices (ADMs) have revolutionized post-mastectomy breast reconstructions by providing support to the silicone implant. ADM incorporation creates a host inflammatory response, implicating a significant macrophage response that is poorly understood. However, ADM has been shown to positively modulate inflammation. Many breast reconstruction patients have also undergone radiation treatment, affecting the tissue microenvironment. Here, we investigated the effects of radiation on ADM-initiated macrophage response in vivo. C57BL/6J mice received 0 or 35Gy dorsal skin radiation 12 weeks prior to subcutaneous ADM implantation. Implants were harvested at 1 and 3 weeks for flow cytometry using a robust panel of pro-inflammatory and pro-regenerative macrophage proteins. Fibrotic capsule response at 3 and 6 weeks was evaluated using hematoxylin and eosin-stained implant cross-sections. Radiation led to alterations in the percentages of macrophages (F4/80+) expressing CD192, CD301b, and CD339 at 1 week and CD86, CD301b, and CD339 at 3 weeks. Within the CD38+CD86+ macrophage subpopulation there were changes in CD9, CD192, CD163, CD301b, CD184, and CD339 at 1 week and CD192 at 3 weeks. Median Fluorescent Intensity analysis revealed alterations in expression levels. CD38, CD86, CD192, and Arginase 1 (Arg1) differed at 1 week, and CD86 at 3 weeks. Within CD38+CD86+ macrophages, there were expression shifts in CD38, CD86, CD192, and Arg1 at 1 week and CD86 at 3 weeks. There was no change in fibrotic capsule response. We provide the first investigation into the impact of radiation on macrophage phenotype in the presence of ADM. The shift in balance of macrophage subpopulations and expression of pro-inflammatory and anti-inflammatory proteins demonstrate that the effect of radiation is more complex than increased inflammation. A comprehensive analysis of the macrophage response to ADM implantation will provide critical supporting evidence of the clinical use and identify potential immunomodulatory strategies to improve ADM-associated healing.

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