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Off the Shelf Nipple Engineering
Sarah Caughey1, Nicholas Vernice2, Jason Harris2, Xue Dong2, Ryan Bender2, Nabih Berri2, Jason Spector2
Weill Cornell Medicine LBMS, New York, NY

Introduction: Nipple reconstruction is critical to patient satisfaction after breast reconstruction. Our group has previously demonstrated that nipples with sustained projection and suitable biomechanical properties can be engineered using processed live costal cartilage (LCC) implanted within a PLA scaffold. Because use of LCC limits application to patients undergoing DIEP reconstruction, we sought to determine if processed decellularized costal cartilage (DCC), which could theoretically be obtained “off the shelf”, would provide similar long term projection and biomechanical properties, thereby widening the application of this nipple engineering approach to all patients undergoing nipple reconstruction.
Methods: PLA scaffolds (diameter: 1.0cm, height: 1.0cm) were printed using a PRUSA 3D printer and sterilized. Lamb costal cartilage was minced (1mm3) or zested (<0.2mm3) and then decellularized. The quality of decellularization was assessed using DNA quantification and histological analysis. DCC was then packed into PLA scaffolds and implanted subcutaneously into immunocompetent Sprague Dawley rats using a CV flap technique. The constructs were explanted and evaluated up to 6 months after implantation.
Results: All nipple reconstructions showed well preserved diameter and projection due to persistence of the external PLA scaffolds at 1, 3, and 6 months. Importantly, mass and volume of the engineered nipple tissue was well preserved over all timepoints. Compared to implantation mass, engineered zested nipples demonstrated a 12% mass increase and a 22% volume increase at 6 months. Minced nipples illustrated a similar mass and volume gain with a 21% increase in mass and a 13% increase in volume at 6 months. Mass and volume increases were due to infiltration of healthy fibrovascular tissue which invested the cartilage, and growth through scaffold wall pores, respectively. Histologic analysis demonstrated a mild inflammatory infiltrate 1 month after implantation which was replaced by healthy fibrovascular cartilaginous tissue by 3 months which was stable through 6 months. The processed DCC structure remained unchanged over time without evidence of degradation. Biomechanical studies are ongoing.
Conclusions: Using decellularized rib cartilage and bioabsorbable scaffolds, we have engineered neo-nipples that completely maintain their volume and mass for at least 6 months. The architecture of the DCC is well preserved showing minimal evidence of immune mediated cellular degradation. The lack of change between 3 and 6 month time points suggests that by 6 months after implantation the engineered nipple has reached a steady state. By using decellularized cartilage this novel approach to nipple engineering may now be applied to any patient requiring nipple reconstruction.


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