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The additive manufacturing (AM) of yttria-stabilized zirconia (YSZ) microarchitectures with sub-micrometer precision via two-photon lithography (TPL), utilizing custom photoresin containing zirconium and yttrium monomers is investigated. YSZ 3D microarchitectures can be formed at low temperatures (600 °C). The low-temperature phase stabilization of ZrO2 doped with Y2O3 demonstrates that doping ZrO2 with ≈ 10 mol% Y2O3 stabilizes the c-ZrO2 phase. The approach does not utilize YSZ particles as additives. Instead, the crystallization of the YSZ phase is initiated after printing, i.e., during thermal processing in the air at 600 °C – 1200 °C for one and two hours. The YSZ microarchitectures are characterized in detail. This includes understanding the role of defect chemistry, which has been overlooked in TPL-enabled micro-ceramics. Upon UV excitation, defect-related yellowish-green emission is observed from YSZ microarchitectures associated with intrinsic and extrinsic centers, correlated with the charge compensation due to Y3+ doping. The mechanical properties of the microarchitectures are assessed with manufactured micropillars. Micropillar compression yields the intrinsic mechanical strength of YSZ. The highest strength is observed for micropillars annealed at 600 °C, and this characteristic decreased with an increase in the annealing temperature. The deformation behavior gradually changes from ductile to brittle-like, correlating with the Hall–Petch strengthening mechanism.

In vitro cellular models denote a crucial part of drug discovery programs as they aid in identifying successful drug candidates based on their initial efficacy and potency. While tremendous headway has been achieved in improving 2D and 3D culture techniques, there is still a need for physiologically relevant systems that can mimic or alter cellular responses without the addition of external biochemical stimuli. A way forward to alter cellular responses is using physical cues, like 3D topographical inorganic substrates, to differentiate macrophage-like cells. Herein, protein secretion and gene expression markers for various macrophage subsets cultivated on a 3D topographical substrate are investigated. The results show that macrophages differentiate into anti-inflammatory M2-type macrophages, secreting increased IL-10 levels compared to the controls. Remarkably, these macrophage cells are differentiated into the M2d subset, making up the main component of tumour-associated macrophages (TAMs), as measured by upregulated Il-10 and Vegf mRNA. M2d subset differentiation is attributed to the topographical substrates with 3D fractal-like geometries arrayed over the surface, else primarily achieved by tumour-associated factors in vivo. From a broad perspective, this work paves the way for implementing 3D topographical inorganic surfaces for drug discovery programs, harnessing the advantages of in vitro assays without external stimulation and allowing the rapid characterisation of therapeutic modalities in physiologically relevant environments.

Two-photon lithography (TPL) is a promising technique for manufacturing ceramic microstructures with nanoscale resolution. The process relies on tailor-made precursor resins rich in metal–organic and organic constituents, which can lead to carbon-based residues incorporated within the ceramic microstructures. While these are generally considered unwanted impurities, our study reveals that the presence of carbon-rich residues in the form of graphitic and disordered carbon in tetragonal (t-) ZrO2 can benefit the mechanical strength of TPL microstructures. In order to achieve a better understanding of these effects, we deconvolute the structural and materials contributions to the strength of the 3D microarchitectures by comparing them to plain micropillars. We vary the organic content by different thermal treatments, resulting in different crystal structures. The highest compression strength of 3.73 ± 0.21 GPa and ductility are reached for the t-ZrO2 micropillars, which also contain the highest carbon content. This paradoxical finding opens up new perspectives and will foster the development of “brick and mortar”-like ceramic microarchitectures.