Layer-by-Layer Rotated Scaffolds with Enhanced Cell Seeding for SERS-Based Assessment of Chemotherapy Resistance

The development of advanced three-dimensional (3D) scaffolds for cancer modeling and drug screening remains a critical need in biomedical engineering. Most 3D printed scaffolds for cell growth focus on a tessellated design involving sequentially deposited printed fibers. Although this design offers a high degree of flexibility in scaffold dimensions, including fiber width and inter-fiber spacing, continuous voids in the Z-axis require additional methods to avoid cell sedimentation to the underlying substrate such as the incorporation of support materials. In this work, we present a modified design strategy based on the rotation of the internal infill pattern between successive layers. This strategy yields tessellated scaffolds that significantly improve cell retention and spatial cell distribution with no need for additional support matrices. Using this optimized design, we developed a 3D breast cancer model to investigate chemotherapeutic resistance by comparing MDA-MB-231 cells and their corresponding cancer stem cells, under paclitaxel treatment. The incorporation of gold nanorods in the scaffold matrix allowed us to perform real-time, in situ drug monitoring via surface-enhanced Raman scattering (SERS) sensing. These tessellated plasmonic scaffolds enable the evaluation of chemoresistance by tracking differential drug accumulation in 3D.