Neural organoids derived from human induced pluripotent stem cells (hiPSCs) offer physiologically relevant models for studying human brain development and neurological diseases. Their spontaneous self-organization allows the formation of neural progenitors, neurons, and glial cells within a three-dimensional environment. However, their scaffold-free nature causes irregular morphology, high variability, and necrotic core formation due to limited oxygen and nutrient diffusion, which reduces reproducibility and maturation potential. To overcome these issues, scaffold-based approaches provide a controllable microenvironment with mechanical support and improved mass transport. In this work, Voronoids, which are Voronoi tessellation-based hydrogel scaffolds fabricated via micro Digital Light Processing (µDLP), were developed as mesoscale microenvironments for neural organoids. The composite 10% GelMA/10% PEGDMA bioink produced soft hydrogels (3.4–6.6 kPa) with stiffness similar to brain tissue. Three Voronoid designs (V1–V3; porosity 84.6–88.6%) were created to study how architecture and seeding strategy influence cell colonization. Confocal and scanning electron microscopy showed that high-density drop seeding (50,000 cells per Voronoid) resulted in the most even colonization, with deep scaffold infiltration, especially in the highly porous V3 scaffolds. After 90 days, scaffold-based organoids were more uniform, structurally stable, and mechanically stronger than scaffold-free controls, while maintaining high RNA integrity (RINe 9.3–9.5), confirming their suitability for downstream transcriptomic analysis. This work shows that Voronoi tessellation-based hydrogel scaffolds fabricated by µDLP can produce tunable, physiologically relevant microenvironments that improve neural organoid uniformity, stability, and reproducibility, providing a promising platform for future neuromechanobiology and disease modeling studies.

Current stroke treatments are limited to acute phase management, and there are few clinically available drugs for neuron protection or damage repair due to restrictions imposed by the blood-brain barrier. This project envisions an implantable DDS for precise drug dispensing to areas of the brain affected by stroke, using light-activated liposomes and microfluidic control to improve therapeutic effectiveness and minimize off-target side effects.

Reviewing literature on microfluidic trap-and-release mechanisms, it became evident that deformable particles often tend to slip out of traps. To accurately predict this behavior, the Young's-Laplace equation and energy stored in the liposome membrane have been assessed. Next, microfluidic devices that were able to manipulate the liposomes to the desired trapping locations were designed and produced. The trapping behavior of liposomes has been assessed by increasing the hydrostatic pressure under a fluorescent microscope. The results show that the experimental pressure of 50-250 Pa is lower than the expected theoretical predictions and that there exists a diameter threshold of 17-18 μm for which the liposomes show lysis behavior. Finally, the entire DDS concept has been demonstrated using a network of traps using the path-of-least-resistance approach.