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

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.

A review of bioengineering techniques applied to breast tissue: Mechanical properties, tissue engineering and finite element analysis

“…Moreover, the resultant biological scaffold was cultured with MSCs and a high degree of bioactivity was obtained. More recently, from the same group, Caronna et al (2021) implanted those acellular grafts into two rhesus macaque non-human primates and successfully assessed the safety and host-mediated re-cellularization over 6 weeks, using the native nipples as control.…”

Patient and Surgeon’s Concerns with Post-Mastectomy Nipple Reconstruction: An Alternative to Traditional Nipple Reconstruction

“…In vivo studies confirm the biocompatibility of the NACgraft ™ , as well as its ability to regenerate a living NAC, including full epithelial coverage and integration of vasculature, at 6-weeks post-engraftment. 25,26 Specifically, these reports indicated that the newly re-cellularized graft harbored proliferating skin cells and confirmed the formation of a protective epidermal layer, as well as the presence of factors responsible for integrating the graft with surrounding host tissue. Notably, further analysis identified the presence of nerve regeneration in some of the grafts.…”

Roadmap on biomaterials for women’s health

“…Existing NAC reconstruction techniques often cannot accurately capture the NAC's appropriate size, shape, and tactile properties. Current TE approaches to create lasting NAC projection utilize decellularized matrices, dermal grafts, and bioprinted scaffolds [32,19]. Decellularized NAC scaffolds implanted in non-human primates have shown similar epithelial coverage and vasculature to native tissue after 6 weeks post-engraftment.…”

“…Decellularized NAC scaffolds implanted in non-human primates have shown similar epithelial coverage and vasculature to native tissue after 6 weeks post-engraftment. The projection, shape, color, and sensitivity characteristics of decellularized NAC scaffolds have not yet been reported [32]. Bioprinting allows for the generation of personalized implants fabricated from biocompatible materials and living cells, using an additive manufacturing approach.…”