3D printing assisted by upconversion nanoparticles

A growing need for engineered tissues with complex microarchitectures has driven rapid advances in light-based biomanufacturing. High spatial resolution and biocompatibility make the photopolymerization technique particularly attractive for fabricating tissues. Yet, conventional approaches struggle with limited penetration depth, optical scattering in cell-dense bioinks, and trade-offs between speed and feature size.

To overcome these challenges, my dissertation develops and integrates novel optical and computational strategies that leverage upconversion nanoparticles, wavefront shaping, and tomographic projection techniques. First, a comprehensive study on photopolymerization dynamics based on upconversion nanoparticles (UCNPs) is introduced. By converting near-infrared into ultraviolet/visible photons, I show that UCNPs enable locally triggered polymerization with tunable voxel sizes, from 1.3 to 2.8 micrometers laterally and 7.7 to 59 micrometers axially, simply by adjusting excitation intensity. Based on these results, the second study tackles the challenge of printing through highly scattering media. UCNP-mediated photopolymerization is combined with a non-invasive wavefront-shaping strategy that uses upconverted photoluminescence as a digital guide star. Hydrogel structures with resolution down to ~2 micrometers were demonstrated through 300 micrometers of chicken breast tissue. This method provides a promising route toward high-resolution non-invasive bioprinting.

Finally, we exploit tomographic volumetric additive manufacturing for fast printing in high-density cell-loaded hydrogels. This printing technique works by projecting dynamic light patterns from multiple angles into a liquid photocurable material to solidify a 3D object simultaneously. Printing in an opaque resin is challenging because the light patterns are scrambled and attenuated by scattering along their propagation, distorting the light dose distribution within the photosensitive resin. A physics-driven differentiable ray-tracing framework was developed to iteratively optimize projection patterns to compensate for scattering in the resin. I used my experimental measurements of the scattering parameters of biological cells in the scattering model of the ray-tracing framework. Simulation results have shown that large objects (7 mm in diameter and height) with complex perfusable channels as small as 400 micrometer can be realized in highly scattering media (sigma_s = 2.1 mm^-1, g = 0.98), which is otherwise impossible to realize without scattering correction. I also explored another strategy to mitigate the scattering in tomographic volumetric additive manufacturing by switching the illumination light source to near-infrared light, assisted by UCNPs. An optical setup was designed and built to realize this function, and the upconverted luminescence was characterized to estimate the light dose for printing. Photopolymerization triggered by UCNPs has been demonstrated in a volum