Dual Extrusion Patterning Drives Tissue Development Aesthetics and Shape Retention in 3D Printed Nipple-Areola Constructs.

ABSTRACT

Breast cancer and its most radical treatment, the mastectomy, significantly impose both physical transformations and emotional pain in thousands of women across the globe. Restoring the natural appearance of a nipple-areola complex directly on the reconstructed breast represents an important psychological healing experience for these women and remains an unresolved clinical challenge, as current restorative techniques render a flattened disfigured skin tab within a single year. To provide a long-term solution for nipple reconstruction, this work presents 3D printed hybrid scaffolds composed of complementary biodegradable gelatin methacrylate and synthetic non-degradable poly(ethylene) glycol hydrogels to foster the regeneration of a viable nipple-areola complex. In vitro results showcased the robust structural capacity and long-term shape retention of the nipple projection amidst internal fibroblastic contraction, while in vivo subcutaneous implantation of the 3D printed nipple-areola demonstrated minimal fibrotic encapsulation, neovascularization, and the formation of healthy granulation tissue. Envisioned as subdermal implants, these nipple-areola bioprinted regenerative grafts have the potential to transform the appearance of the newly reconstructed breast, reduce subsequent surgical intervention, and revolutionize breast reconstruction practices.