Smart Polymeric 3D Microscaffolds Hosting Spheroids for Neuronal Research via Quantum Metrology

Toward the aim of reducing animal testing, innovative in vitro models are required. Here, this study proposes a novel smart polymeric microscaffold to establish an advanced 3D model of dopaminergic neurons. These scaffolds are fabricated with Ormocomp via Two-Photon Polymerization. The scaffolds are further enhanced by functionalization with fluorescent nanodiamonds (FNDs), which can serve as quantum nanosensors for both magnetic and temperature sensing. The material biocompatibility is tested using two different cell lines, SH-SY5Y and A431, with cell viability over 98%. A total of 69% of the FNDs are grafted on the structure compared to those that remained on the glass surface. Cells are tested with the scaffolds in several microenvironments, and the final assembly required for 3D quantum metrology experiments achieved 91% biocompatibility. Subsequently, embryoid bodies containing dopaminergic neurons, the cell type affected by Parkinson's disease (PD), are integrated with FND-functionalized scaffolds. This 3D model is successfully established, demonstrated by strong interactions between dopaminergic neurons and the scaffold, with the directional growth of neurites along the 3D scaffold. Ultimately, this study have developed a 3D platform that enables the readout of signaling in a model that holds great potential for future PD research.