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The Biological Role Of Acellular Dermal Matrix In Improving Outcomes Of Tissue Expansion When Subject To Radiation Therapy
Sarah A. Applebaum, MD1,2, Joanna K. Ledwon, PhD1,2, Bianka Progri, MS2, Kristof Gutowski, BS2, Arun K. Gosain, MD1,2.
1Northwestern University Feinberg School of Medicine, Chicago, IL, USA, 2Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.

PURPOSE: Tissue expansion is the leading form of post-mastectomy breast reconstruction and often utilizes acellular dermal matrix (ADM) to improve outcomes. When ADM is used in tissue expansion subject to postmastectomy radiation therapy, there is anecdotal and conflicting data regarding capsule formation and increased tissue necrosis. The present study examines changes in molecular and cellular events to characterize the biological response to tissue expansion when subject to radiation, and the effect on surrounding tissues when tissue expanders are wrapped in ADM.
METHODS: Yucatan minipigs underwent placement of subcutaneous tissue expanders along bilateral flanks. Half of the expanders were wrapped in a contoured sheet of ADM and all expanders were inflated with two weekly fills of 45 cc saline. One week after the final inflation, a subset of pigs received unilateral single fraction radiation of 20 Gy to skin tissue overlying expanders with and without ADM ("XRT-ADM" and "XRT-TE", respectively). Contralateral non-irradiated grids served as controls ("ADM" and "TE"). Full-thickness skin biopsies were harvested from the apex of the expanders before and two months after radiation and embedded in paraffin blocks for histological evaluation or preserved in Allprotect Tissue Reagent for RNA extraction. Expression of known pro- and anti-apoptotic genes (BAX and BCL2L1, respectively) was evaluated.
RESULTS: Intraoperative evaluation of non-irradiated skin revealed an organized layer of connective tissue encapsulating the tissue expanders that was absent when the expanders were wrapped with ADM. This observation was confirmed by Trichrome staining (Fig. 1), which demonstrated sheets of connective tissue in TE (white arrow) that were replaced by cells in ADM (black arrow). Two months after radiation, thin layers of connective tissue were encompassing expanders with and without ADM (Fig. 2). The layer above XRT-TE was observed to be thicker and more densely packed with highly aligned fibers (white arrow) compared to the layer above XRT-ADM (black arrow). There was no significant difference in expression of apoptotic genes, BAX and BCL2L1, between irradiated expanders with and without ADM, suggesting that ADM did not increase tissue necrosis when subject to radiation.
CONCLUSION: During tissue expansion, ADM appears to successfully incorporate with nearby tissue and prevent capsule formation at a macro- and microscopic level in non-irradiated skin. In irradiated skin, although ADM does not fully prevent capsule formation, it does appear to prevent pathological alignment of capsules. Furthermore, ADM does not induce additional apoptosis following radiation. These findings indicate that ADM may decrease capsule formation in tissue expansion, and that this benefit is also seen when tissues are subject to radiation. This study lays the groundwork for developing mechanisms to improve clinical outcomes in patients undergoing expander-based breast reconstruction and are subject to post-mastectomy radiation therapy.


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