Nanocrystalline Yttria-Stabilized Zirconia Ceramics for Cranial Window Applications.

Transparent yttria-stabilized zirconia (YSZ) ceramics are promising for cranial window applications because of their good mechanical and optical properties as well as biocompatibility. YSZ discs with different yttria concentrations were either processed via current-activated pressure-assisted densification (CAPAD) using commercial nanoparticles or densified via spark plasma sintering (SPS) using pyrolysis-synthesized nanoparticles in-house. This study provided critical results to screen composition, processing, microstructure, and cytocompatibility of transparent YSZ discs for cranial window applications. CAPAD-processed YSZ discs with 6 or 8 mol % yttria (6YSZ and 8YSZ) and SPS-densified YSZ discs with 4 mol % yttria (4YSZ_P) showed 200-350 nm polycrystalline grains containing 20-30 nm crystallite domains. SPS-densified YSZ discs with 8 mol % yttria (8YSZ_P) showed larger polycrystalline grains of 819 ± 155 nm with 29 ± 5 nm crystallite domains. CAPAD-processed YSZ discs with 3 mol % yttria (3YSZ) showed 39 ± 9 nm grains. Bone-marrow-derived stem cells (BMSCs) on the polished YSZ discs showed statistically higher spreading areas than those on the unpolished YSZ discs of the same compositions. Generally, polished 8YSZ, 4YSZ_P, and 8YSZ_P discs and unpolished 8YSZ_R, 4YSZ_PR, and 8YSZ_PR discs had lower average cell adhesion densities than other YSZ discs under direct contact conditions. Under indirect contact conditions, all the YSZ disc groups showed similar average cell adhesion densities to the Cell-only control. The groups of polished 4YSZ_P and 8YSZ_P discs, unpolished 4YSZ_PR and 8YSZ_PR discs, and particle control of 8YSZ_Pnp showed higher Y3+ ion concentrations than other groups. No mineral deposition was detected on the polished YSZ discs after cell culture. Considering multiple factors such as cytocompatibility, cell adhesion density, Y3+ ion release, mineral deposition, and optical transparency collectively, 8YSZ may be the best candidate for the cranial window applications. Further studies are needed to evaluate the long-term transparency and biocompatibility of YSZ discs.

Tunable Crosslinking, Reversible Phase Transition, and 3D Printing of Hyaluronic Acid Hydrogels via Dynamic Coordination of Innate Carboxyl Groups and Metallic Ions.

This article reports tunable crosslinking, reversible phase transition, and three-dimensional printing (3DP) of hyaluronic acid (HyA) hydrogels via dynamic coordination of Fe3+ ions with their innate carboxyl groups for the first time. The concentrations of Fe3+ and H+ ions and the reaction time determine the tunable ratios of mono-, bi-, and tridentate coordination, leading to the low-to-high crosslinking densities and reversible solid-liquid phase transition of HyA hydrogels. At the monodentate-dominant coordination, the liquid hydrogels have low crosslinking densities (HyA_L). At the mixed coordination of mono-, bi-, and tridentate bonding, the solid hydrogels have medium crosslinking densities (HyA_M). At the tridentate-dominant coordination, the solid hydrogels have high crosslinking densities (HyA_H). The reversible solid-liquid phase transitions among HyA_L, HyA_M, and HyA_H were achieved via controlling the concentrations of Fe3+ and H+ ions and reaction time. When the crosslinking densities are between HyA_L and HyA_M, the hydrogels become 3D printable (HyA_P). HyA_P hydrogels were 3D-printed successfully using cold-stage or direct writing methods, and the 3D constructs achieved better structural stability using the latter method. In the direct exposure culture with bone marrow-derived mesenchymal stem cells, the 3D-printed HyA_H (HyA_H_3D) and HyA_H hydrogels showed higher average cell adhesion densities than the HyA_M, HyA_P, and HyA_L hydrogel groups under both direct and indirect contact conditions. For all hydrogel groups, cell adhesion densities under direct contact conditions were statistically lower than the same groups under indirect contact conditions. In this article, we elucidated the mechanisms of dynamic coordination and the relationships among the key parameters in controlling the tunable crosslinking, reversible phase transition, and 3DP of HyA hydrogels without blending with other polymers or adding functional groups. This approach can be potentially adapted to crosslink and 3D print other polymeric hydrogels with carboxyl groups, which is promising for a wide range of applications.