Rational design of 3D-printed scaffolds for breast tissue engineering using structural analysis

Abstract Best cosmetic outcomes of breast reconstruction using tissue engineering techniques rely on the scaffold architecture and material, which are currently both to be determined. This study suggests an approach for a rational design of breast-shaped scaffold architecture, in which structural analysis is implemented to predict its stiffness and adjust it to that of the native tissue. This approach can help achieve the goal of optimal scaffold architecture for breast tissue engineering. 
Based on specifications defined in a preliminary implantation study of a non-rationally designed scaffold, and using analytical modeling and finite element analysis (FEA), we rationally designed a polycaprolactone (PCL) made, 3D-printed, highly porous, breast-shaped scaffold with a stiffness similar to the breast adipose tissue. This scaffold had an architecture of a double-shelled dome connected by pillars, with no bottom to allow direct contact of its fat graft with the host’s blood vessels (Shelled Hemisphere Adaptive Design (SHAD)). To demonstrate the potential of the SHAD scaffold in breast tissue engineering, a proof-of-concept study was performed, in which SHAD scaffolds were embedded with human adipose derived mesenchymal stem cells (hAdMSCs), isolated from lipoaspirates, and implanted in Nod-Scid-Gamma (NSG) mouse model with a delayed fat graft injection. After 4 weeks of implantation, the SHAD implants were vascularized with a viable fat graft, indicating the suitability of the SHAD scaffold for breast tissue engineering.