TY - JOUR
T1 - Acellular Biologic Nipple-Areolar Complex Graft
T2 - In Vivo Murine and Nonhuman Primate Host Response Evaluation
AU - Pashos, Nicholas C.
AU - Graham, David M.
AU - Burkett, Brian J.
AU - O'Donnell, Ben
AU - Sabol, Rachel A.
AU - Helm, Joshua
AU - Martin, Elizabeth C.
AU - Bowles, Annie C.
AU - Heim, William M.
AU - Caronna, Vince C.
AU - Miller, Kristin S.
AU - Grasperge, Brooke
AU - Sullivan, Scott
AU - Chaffin, Abigail E.
AU - Bunnell, Bruce A.
N1 - Funding Information:
N.C.P. and B.O. were supported by an NSF IGERT Fellow training grant in Bioinnovation, DGE-1144646. The Tulane National Primate Research Center; NIH grant number OD 11104. BioAesthetics Corporation provided funding for the NHP pilot study and publication expenses.
Publisher Copyright:
© Copyright 2020, Mary Ann Liebert, Inc., publishers 2020.
PY - 2020/8
Y1 - 2020/8
N2 - There are more than 3 million breast cancer survivors living in the United States of which a significant number have undergone mastectomy followed by breast and nipple-areolar complex (NAC) reconstruction. Current strategies for NAC reconstruction are dependent on nonliving or nonpermanent techniques, including tattooing, nipple prosthetics, or surgical nipple-like structures. Described herein is a tissue engineering approach demonstrating the feasibility of an allogeneic acellular graft for nipple reconstruction. Nonhuman primate (NHP)-derived NAC tissues were decellularized and their extracellular matrix components analyzed by both proteomic and histological analyses. Decellularized NHP nipple tissue showed the removal of intact cells and greatly diminished profiles for intracellular proteins, as compared with intact NHP nipple tissue. We further evaluated the biocompatibility of decellularized grafts and their potential to support host-mediated neovascularization against commercially available acellular dermal grafts by performing in vivo studies in a murine model. A follow-up NHP pilot study evaluated the host-mediated neovascularization and re-epithelialization of onlay engrafted decellularized NAC grafts. The murine model revealed greater neovascularization in the decellularized NAC than in the commercially available control grafts, with no observed biocompatibility issues. The in vivo NHP model confirmed that the decellularized NAC grafts encourage neovascularization as well as re-epithelialization. These results support the concept that a biologically derived acellular nipple graft is a feasible approach for nipple reconstruction, supporting neovascularization in the absence of adverse systemic responses. Currently, women in the United States most often undergo a mastectomy, followed by reconstruction, after being diagnosed with breast cancer. These breast cancer survivors are often left with nipple-areolar complex (NAC) reconstructions that are subsatisfactory, nonliving, and/or nonpermanent. Utilizing an acellular biologically derived whole NAC graft would allow these patients a living and permanent tissue engineering solution to nipple reconstruction.
AB - There are more than 3 million breast cancer survivors living in the United States of which a significant number have undergone mastectomy followed by breast and nipple-areolar complex (NAC) reconstruction. Current strategies for NAC reconstruction are dependent on nonliving or nonpermanent techniques, including tattooing, nipple prosthetics, or surgical nipple-like structures. Described herein is a tissue engineering approach demonstrating the feasibility of an allogeneic acellular graft for nipple reconstruction. Nonhuman primate (NHP)-derived NAC tissues were decellularized and their extracellular matrix components analyzed by both proteomic and histological analyses. Decellularized NHP nipple tissue showed the removal of intact cells and greatly diminished profiles for intracellular proteins, as compared with intact NHP nipple tissue. We further evaluated the biocompatibility of decellularized grafts and their potential to support host-mediated neovascularization against commercially available acellular dermal grafts by performing in vivo studies in a murine model. A follow-up NHP pilot study evaluated the host-mediated neovascularization and re-epithelialization of onlay engrafted decellularized NAC grafts. The murine model revealed greater neovascularization in the decellularized NAC than in the commercially available control grafts, with no observed biocompatibility issues. The in vivo NHP model confirmed that the decellularized NAC grafts encourage neovascularization as well as re-epithelialization. These results support the concept that a biologically derived acellular nipple graft is a feasible approach for nipple reconstruction, supporting neovascularization in the absence of adverse systemic responses. Currently, women in the United States most often undergo a mastectomy, followed by reconstruction, after being diagnosed with breast cancer. These breast cancer survivors are often left with nipple-areolar complex (NAC) reconstructions that are subsatisfactory, nonliving, and/or nonpermanent. Utilizing an acellular biologically derived whole NAC graft would allow these patients a living and permanent tissue engineering solution to nipple reconstruction.
KW - acellular biological matrix
KW - breast cancer
KW - breast reconstruction
KW - nipple reconstruction
KW - nipple-areolar complex
UR - http://www.scopus.com/inward/record.url?scp=85089787350&partnerID=8YFLogxK
U2 - 10.1089/ten.tea.2019.0222
DO - 10.1089/ten.tea.2019.0222
M3 - Article
C2 - 31950890
AN - SCOPUS:85089787350
SN - 1937-3341
VL - 26
SP - 872
EP - 885
JO - Tissue Engineering - Part A
JF - Tissue Engineering - Part A
IS - 15-16
ER -