Pliable, Scalable, and Degradable Scaffolds with Varying Spatial Stiffness and Tunable Compressive Modulus Produced by Adopting a Modular Design Strategy at the Macrolevel

[Image: see text] Clinical results obtained when degradable polymer-based medical devices are used in breast reconstruction following mastectomy are promising. However, it remains challenging to develop a large scaffold structure capable of providing both sufficient external mechanical support and an internal cell-like environment to support breast tissue regeneration. We propose an internal-bra-like prototype to solve both challenges. The design combines a 3D-printed scaffold with knitted meshes and electrospun nanofibers and has properties suitable for both breast tissue regeneration and support of a silicone implant. Finite element analysis (FEA) was used to predict the macroscopic and microscopic stiffnesses of the proposed structure. The simulations show that introduction of the mesh leads to a macroscopic scaffold stiffness similar to the stiffness of breast tissue, and mechanical testing confirms that the introduction of more layers of mesh in the modular design results in a lower elastic modulus. The compressive modulus of the scaffold can be tailored within a range from hundreds of kPa to tens of kPa. Biaxial tensile testing reveals stiffening with increasing strain and indicates that rapid strain-induced softening occurs only within the first loading cycle. In addition, the microscopic local stiffness obtained from FEA simulations indicates that cells experience significant heterogeneous mechanical stimuli at different places in the scaffold and that the local mechanical stimulus generated by the strand surface is controlled by the elastic modulus of the polymer, rather than by the scaffold architecture. From in vitro experiments, it was observed that the addition of knitted mesh and an electrospun nanofiber layer to the scaffold significantly increased cell seeding efficiency, cell attachment, and proliferation compared to the 3D-printed scaffold alone. In summary, our results suggest that the proposed design strategy is promising for soft tissue engineering of scaffolds to assist breast reconstruction and regeneration.