Viability of acellular biologic graft for nipple-areolar complex reconstruction in a non-human primate model

Vincent C Caronna,Bruce A Bunnell,David M Graham,Scott K Sullivan,Allison F Rosenberg,Abigail E Chaffin,Nicholas C Pashos,William M Heim,Brooke F Grasperge

doi:10.1038/s41598-021-94155-y

Vincent C Caronna, Bruce A Bunnell + Show 7 more

Open Access

https://doi.org/10.1038/s41598-021-94155-y

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Journal: Scientific Reports	Publication Date: Jul 23, 2021
Citations: 4	License type: open-access

Affiliation: Tulane University

Abstract

Many of the > 3.5 million breast cancer survivors in the US have undergone breast reconstruction following mastectomy. Patients report that nipple-areolar complex (NAC) reconstruction is psychologically important, yet current reconstruction techniques commonly result in inadequate shape, symmetry, and nipple projection. Our team has developed an allogeneic acellular graft for NAC reconstruction (dcl-NAC) designed to be easy to engraft, lasting, and aesthetically pleasing. Here, dcl-NAC safety and host-mediated re-cellularization was assessed in a 6-week study in rhesus macaque non-human primates (NHPs). Human-derived dcl-NACs (n = 30) were engrafted on the dorsum of two adult male NHPs with each animal’s own nipples as controls (n = 4). Weight, complete blood counts, and metabolites were collected weekly. Grafts were removed at weeks 1, 3, or 6 post-engraftment for histology. The primary analysis evaluated health, re-epithelialization, and re-vascularization. Secondary analysis evaluated re-innervation. Weight, complete blood counts, and metabolites remained mostly within normal ranges. A new epidermal layer was observed to completely cover the dcl-NAC surface at week 6 (13–100% coverage, median 93.3%) with new vasculature comparable to controls at week 3 (p = 0.10). Nerves were identified in 75% of dcl-NACs (n = 9/12) at week 6. These data suggest that dcl-NAC is safe and supports host-mediated re-cellularization.

Highlights

Many of the > 3.5 million breast cancer survivors in the US have undergone breast reconstruction following mastectomy
Patients who have had mastectomies due to breast cancer indicate that nipple-areolar complex (NAC) preservation or reconstruction is of vital importance to their self-esteem, body image, and quality of life[1,2,3,4,5]
Human NACs (Fig. 1a) were recovered from deceased donors by organizations accredited by the American Association of Tissue Banks (AATB); consent is obtained by these organizations from the donor via a Document of Gift or from of kin via a Document of Authorization; no tissues were obtained from prisoners

Summary

Introduction

Many of the > 3.5 million breast cancer survivors in the US have undergone breast reconstruction following mastectomy. Decellularization removes donor cellular and genetic material while retaining much of the tissue’s endogenous structure and biochemical and biomechanical features[31,32,33,34] Acellular grafts such as dcl-NAC, unlike intact tissue grafts, pose minimal risk of immune rejection and do not require an immediate blood supply to sustain them[33, 35]. In prior studies we demonstrated that our decellularization method successfully preserves the extracellular matrix’s (ECM) gross architecture, micro-structures, and > 150 different peptides, providing a non-immunogenic cell-free graft[33,34,35, 38] This level of complexity cannot be recreated s ynthetically[15, 39, 40]. We demonstrated in two in vivo feasibility studies that, after subcutaneous implantation in mice and onlay engraftment on a non-human primate (NHP), NHP-derived dcl-NACs re-epithelialize and re-vascularize[33]

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