Acellular Biologic Nipple–Areolar Complex Graft: In Vivo Murine and Nonhuman Primate Host Response Evaluation

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

“…An onlay engraftment method was used for all grafts, and performed as described previously with the following modifications (Fig. 1 b) 33 . Surgical scissors were used to excise approximately a circular wound bed of 1.2 cm diameter along the NHP’s dorsal midline.…”

“…Re-epithelialization was measured on scans of H&E-stained sections using Aperio ImageScope software (version 12.3.2.8013) [ https://www.leicabiosystems.com/digital-pathology/manage/aperio-imagescope/ ]. The total length of new cellularized epidermis on the exposed surface of the graft was measured and compared to the total length of exposed graft surface (including non-epithelialized and epithelialized surface) to calculate percent re-epithelialization, as previously described 33 .…”

“…Currently, this level of complexity cannot be recreated synthetically 15 , 39 , 40 . We also 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 .…”

“…Decellularization removes donor cellular and genetic material while retaining much of the tissue’s endogenous structure and biochemical and biomechanical features 31 – 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 . Acellular dermal matrices derived from deceased donors have been used commercially in various types of reconstructive surgeries for almost 30 years, and studies have shown that host cells repopulated these scaffolds and formed new blood vessels that sustain the tissue 31 , 32 , 34 , 36 , 37 .…”

“…Acellular dermal matrices derived from deceased donors have been used commercially in various types of reconstructive surgeries for almost 30 years, and studies have shown that host cells repopulated these scaffolds and formed new blood vessels that sustain the tissue 31 , 32 , 34 , 36 , 37 . 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 – 35 , 38 . Currently, this level of complexity cannot be recreated synthetically 15 , 39 , 40 .…”