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Tissue Engineered Neo-nipples Fabricated From Autologous Costal Cartilage Maintain Projection And Biomechanical Properties Of The Native Human Nipple
Ishani D. Premaratne, BA, Arash Samadi, BA, Mariam Gadjiko, BA, Matthew A. Wright, BA, Alexandra J. Lin, MD, Daniel O. Lara, BA, Jaime L. Bernstein, MD, Jason A. Spector, MD.
Weill Cornell Medicine, New York, NY, USA.

PURPOSE: Nipple reconstruction is often cited by post-mastectomy patients as a vital step in their overall reconstruction and recovery. The current gold standard for nipple reconstruction using local skin flaps leads to significant loss of projection and volume. Available commercial scaffolds similarly are unable to maintain projection after only one year post-operatively. We have previously developed a novel technology using biocompatible 3D-printed scaffolds that have demonstrated the ability to maintain the volume, projection and contour of neo-nipples engineered from autologous costal cartilage (CC). Herein, we compare two alternate methods of processing CC, zesting and mincing, and their effect on the ultimate biomechanical properties of the fabricated tissue.
METHODS: Custom external scaffolds were designed and 3D-printed using polylactic acid (PLA). Patient derived CC was minced into approximately 2-3mm3 portions or flaked by processing with a zesting device into larger 5-6mm3 portions. In both the minced and zested groups, half of the samples were packed into 3D-printed PLA scaffolds (the “scaffolded” group), and in the remainder, an equal volume of processed cartilage was wrapped in Surgicel® only (the “naked” group). The constructs were implanted into nude rats by creating a subcutaneous pocket using a CV flap technique. After 3 months, histological, topographical, and gross analysis were performed on explanted neo-nipples. Biomechanical analysis was performed using confined compression with 5% strain per step up to 30% compression. Samples were prepared with 3mm biopsy punches and cut to 2mm in height for placement into the compression chamber.
RESULTS: After 3 months, analysis of biomechanical properties of explanted neo-nipples in the four groups (minced scaffolded, minced naked, zested scaffolded, and zested naked) revealed no significant difference in equilibrium modulus between the native human nipple and minced scaffolded (p = 0.53), minced naked (p = 0.99), zested scaffolded (p = 0.98), or zested naked (p = 0.99) neo-nipples, representing strong recapitulation of native biomechanical properties. Neo-nipples in the zested naked group had the lowest average difference in equilibrium modulus, and thus the greatest similarity to the biomechanical properties of the native human nipple (20.48 kPa) (Figure 1). Hematoxylin and eosin staining in both groups showed the presence of healthy and viable cartilage after 3 months in-vivo which was confirmed by LIVE/DEAD assay. Formation of fibrous tissue around the processed CC was noted in both groups. Furthermore, the resultant tissue was spongy and compressible much like a native nipple.
CONCLUSION: We demonstrate that autologous CC, which is usually discarded during a DIEP procedure, can be processed by either zesting or mincing to tissue engineer a viable implant for nipple reconstruction that maintains the biomechanical properties of the native nipple. While our group has previously shown that tissue engineered neo-nipples preserve volume, projection and contour over time, the ability to tissue engineer nipples with similar biomechanical properties to the native human nipple represents a significant advancement.


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