Abstract P6-14-13: New approach to nipple reconstruction: In vivo evaluation of acellular nipple-areolar complex grafts

Abstract

There are over 3M breast cancer survivors in the US, many of whom have undergone breast reconstructive surgery. With one-third of early stage and two-thirds of late-stage breast cancer patients opting for mastectomies without a standard, viable method to reliably reconstruct a permanent and natural nipple-areolar complex (NAC). NAC reconstruction is of key psychological importance for these patients, decreasing feelings of distress and increasing body image and self-esteem. Current NAC reconstruction options include rubber prostheses, 3D tattoos, and surgical techniques to create NAC-like structures from a patient’s own skin tissue. These approaches produce NACs that either lack physical depth or fail to maintain a protrusion. The objectives of the non-human primate 6 week engraftment studies with our decellularized human nipple areolar complex (hNAC) grafts were 1) to determine the biocompatibility of the hNAC graft and 2) to measure host-mediated recellularization of the hNAC graft on a nearest-to-human model species. If the hNAC graft maintains cell-derived insoluble matrix components yet is devoid of host cells, intracellular material, and pathogenic organisms, then the hNAC graft will not elicit an adverse humoral response and will show both good biocompatibility and recellularization. The methods employed for our studies involved surgical engraftment of the hNAC graft along the dorsal midline of three adult male non-human primates (rhesus macaque). The number of hNAC grafts engrafted for each NHP was 12 for one NHP and 18 for the other two. Gross animal weight, complete blood count data, and metabolite data were collected weekly from periods before, during (span of 6-weeks), and after hNAC engraftment for each animal. In addition, hNACs were surgically removed at defined weekly time points during the study for histological analysis of recellularization. All data was compiled for each study and statistically analyzed separately and combined. Statistical analyses included unpaired, parametric comparisons of systemic indicators (i.e. weight, complete blood count, metabolites) at each period of the study and of re-epithelialization and neovascular content for individual hNAC grafts during host-mediated recellularization over time. The results from this NHP study demonstrate good evidence of biocompatibility of the hNAC on non-human primates. Gross body weight remained unchanged for all NHPs and complete blood counts (e.g. red blood cells, white blood cells, platelets) and metabolites remained mostly within normal ranges for all NHPs. The hNAC grafts did not effect liver, kidney, or pancreas function. The hNAC grafts showed good recellularization during the study with significant increases measured for re-epithelialization and neovascularization. Histological analysis further revealed functioning microvasculature within grafts as early as 3-weeks post-engraftment. These data suggest that the hNAC graft is biocompatible and capable of recellularization. The presence of de novo epithelia and vasculature within the hNAC grafts collectively support recellularization and regeneration of a hNAC. Citation Format: David Graham, William Heim, Vincent Caronna, Abigail Chaffin, Brooke Grasperge, Scott Sullivan, Bruce A Bunnell, Nicholas C Pashos. New approach to nipple reconstruction: In vivo evaluation of acellular nipple-areolar complex grafts [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-14-13.

Orthotopic grafting of decellularized human nipple: Setting the stage and putative mechanism of healing

“…A proposed new solution is to take advantage of the extensive evidence that a decellularized allogeneic or xenogeneic graft, an acellular extracellular matrix scaffold, can serve as the nidus for a healing event when implanted in a human [ 2 ]. Although such scaffolds have long been derived from dermis, small intestinal submucosa, bladder and other organs, recent work has shown that deceased human donor nipples can be successfully decellularized and, when implanted on the surface of the body in a non-human primate model, exhibit complete healing within six weeks [1] . Planned clinical studies will bring this technology to humans, where longed for accurate and complete nipple restoration can be evaluated.…”