Creating Engineered NAC Flaps Using in Vivo Revascularization: A Proof-Of-Concept Study

Acellular scaffold revascularization is the most significant challenge in tissue and organ engineering. To achieve successful and durable cell growth within complex three-dimensional scaffolds, a functional vascular network must ensure the supply of oxygen and nutrients within the matrix structure. Several teams have studied in vitro and ex vivo re-endothelialization using dynamic cell seeding and bioreactors, among other techniques. Still, to date, no approach has demonstrated long-term successful and functional vascular tree growth within 3D scaffolds. Herein, we propose a promising alternative using the in vivo implantation of decellularized nipple-areolar complex (NAC) scaffolds on a prepared vascular pedicle, thereby achieving engineered flap creation. We compared two implanted groups, one with and one without vascular micropunctures. After 3 weeks, explanted scaffolds demonstrated successful in-depth capillary growth, supported by contrast angiography, histology (including CD31 staining), and macroscopic bleeding. Flow cytometry assays identified different cell contingents, including CD45 and CD31-positive. No significant difference was found between the two implanted groups. This proof-of-concept study offers valuable insights into the successful engineering of composite tissues and organs.