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.

Bioprinting a skin patch with dual-crosslinked gelatin (GelMA) and silk fibroin (SilMA): An approach to accelerating cutaneous wound healing

“…It is imperative to develop the skin-specific hydrogel that is compatible with skin-related cells and promotes the cell migration, growth, and proliferation. However, current extrusion-based hydrogels are limited by certain bio-physical properties (mechanical, structural, or biodegradable) that are not conducive to skin regeneration, and a compromise is usually needed between hydrogel printability and cellular compatibility [ 9 ]. Ideally, the skin-specific hydrogel should exhibit biological characterizes of supporting cells migration, adhesion, and proliferation, as well comply with appropriate mechanical and degradation properties [ 10 ].…”

Long-term Maintenance of Projection of Nipples Reconstructed Using 3D-printed Poly-4-Hydroxybutyrate (P4HB) Bioabsorbable Scaffolds

“…This finding is consistent with the histologic analysis of the rebar group, which showed significant P4HB filament degradation by 12 months (see Plastic and Reconstructive Surgery • October 2023 to be crucial for patients' general and aesthetic gratification, with projection of the nipple being the most important attribute that contributes to patient satisfaction. [5][6][7]33 Because "skin flap only" techniques reliably lose a significant degree of projection, the addition of graft material, such as cartilage and fat, 13,18,19 injectable fillers, 15 or synthetic materials, 16,20,34,35 has been described, resulting in superior projection versus local flaps alone. Techniques that incorporate stiffer materials such as autologous auricular or rib cartilage have demonstrated nipple maintenance as high as 80.5% of baseline with a follow-up of 1 to 8 years.…”

3D and 4D Printing in the Fight against Breast Cancer

“…The last step of breast reconstruction concerns the nipple–areola complex, whose restoration significantly impacts the overall satisfaction of the patient. At present, the application of 3DP technology in this area is limited to the production of acellular scaffolds or bio-printable ink loaded with cells, able to support and guide the natural tissue restoration [ 112 , 113 ]. Aiming to avoid possible rejection and achieve a long-term nipple projection, Samadi et al manufactured a cylinder scaffold made of polylactic acid (PLA) embedded with autologous tissue from the costal cartilage.…”