ZrO2 Scaffolds Research Articles

Additive manufacturing of magnesium-doped calcium silicate/zirconia ceramic scaffolds with projection-based 3D printing: Sintering, mechanical and biological behavior

The lack of traditional bioactivity in zirconia (ZrO2) and limitations in the personalization capabilities of conventional manufacturing processes pose significant challenges for alveolar bone defect repair. This study aims to investigate whether ZrO2/CSi-Mgx scaffolds, produced by combining magnesium-doped calcium silicate (CSi–Mg) as a doping phase with ZrO2 as the matrix, using projection-based 3D printing (3DPP) technology, exhibit favorable biocompatibility and mechanical properties at low sintering temperatures. The effect of CSi–Mg content (x%), pore structure and heating temperature on the strength of scaffolds were investigated systematically. Incorporation of CSi–Mg could readily adjust the sintering properties of the ZrO2 scaffolds and the scaffolds with low (10–20 %) CSi–Mg possess much higher strength (74–92 MPa) after 1150 °C. Meanwhile, the ZrO2/CSi–Mg10 scaffolds with Triply periodic minimum surfaces (TPMS) pore structure had a compression strength of over 92 MPa and maintained a respectable strength (63 MPa) even after immersion in Tris buffer for 6 weeks. Concurrently, cellular experiments showed that incorporation of CSi–Mg could enhance cellular adhesion, proliferation, and migration of the ZrO2 scaffolds and also promote the osteogenic property of the scaffolds. In conclusion, the ZrO2/CSi–Mg10 scaffold with TPMS pore structure showcases remarkable mechanical performance and bioactivity, holding the potential to facilitate in-situ bone regeneration within the alveolar bone.

RGD and rhBMP-7 immobilized on zirconia scaffold with interweaved human dental pulp stem cells for promoting bone regeneration

Biomimetic surface modification of scaffolds with osteoinductive molecules is a promising strategy for improving the bioactivity of scaffold and stimulating stem cell signals in bone tissue engineering. Zirconia (ZrO2) offers excellent mechanical properties and biocompatibility, but its bio-inert nature hinders its use in bone regeneration applications. Recombinant human bone morphogenetic protein 7 (rhBMP-7) and arginine-glycine-aspartate (RGD) peptide were investigated for their potential use as surface-modifying biomolecules on the ZrO2 scaffold. Our results showed that human dental pulp stem cells (hDPSCs) were induced to osteogenic differentiation by rhBMP-7 and RGD in a dose-dependent manner. Significantly enhanced alkaline phosphatase activity and up-regulated expression of osteogenic genes in hDPSCs were associated with rhBMP-7 and RGD grafting onto the ZrO2 scaffold. Western blot analysis revealed that rhBMP-7 and RGD grafting led to activation of the SMAD1/5, p38 MARK, and ERK signaling pathways during hDPSCs differentiation. After 4 and 8 weeks of transplantation, the hDPSCs-seeded ZrO2-RGD-BMP-7 scaffold facilitated osteogenic differentiation and enhanced in vivo bone formation in critical-sized calvarial bone defects. The results support the simultaneous use of rhBMP-7 and RGD as surface-modifying biomolecules and hDPSCs as a source of osteogenic stem cells in conjugation with ZrO2-based porous scaffold for bone tissue engineering.

The effect of GelMA/alginate interpenetrating polymeric network hydrogel on the performance of porous zirconia matrix for bone regeneration applications

Bone tissue is a natural composite, exhibiting complicated structures and unique mechanical/biological properties. With an attempt of mimicking the bone tissue, a novel inorganic-organic composite scaffolds (ZrO2-GM/SA) was designed and prepared via the vacuum infiltration method and the single/double cross-linking strategy by blending GelMA/alginate (GelMA/SA) interpenetrating polymeric network (IPN) into the porous zirconia (ZrO2) scaffold. The structure, morphology, compressive strength, surface/interface properties, and biocompatibility of the ZrO2-GM/SA composite scaffolds were characterized to evaluate the performance of the composite scaffolds. Results showed that compared to ZrO2 bare scaffolds with well-defined open pores, the composite scaffolds prepared by double cross-linking of GelMA hydrogel and sodium alginate (SA) presented a continuous, tunable and honeycomb-like microstructure. Meanwhile, GelMA/SA showed favorable and controllable water-uptake capacity, swelling property and degradability. After the introduction of IPN components, the mechanical strength of composite scaffolds was further improved. The compressive modulus of composite scaffolds was significantly higher than the bare ZrO2 scaffolds. In addition, ZrO2-GM/SA composite scaffolds had highly biocompatibility and displayed a potent proliferation and osteogenesis of MC3T3-E1 pre-osteoblasts compared to bare ZrO2 scaffolds and ZrO2-GelMA composite scaffolds. At the same time, ZrO2-10GM/1SA composite scaffold regenerated significantly greater bone than other groups in vivo. This study demonstrated that the proposed ZrO2-GM/SA composite scaffolds had great research and application potential in bone tissue engineering.

Fabrication of a zirconia/calcium silicate composite scaffold based on digital light processing

Zirconia (ZrO2) and calcium silicate (CS) are widely used in bone repair. Zirconia has excellent mechanical properties, while calcium silicate has exceptional biological activity. A porous ZrO2/CS composite ceramic scaffold was formed by digital light processing (DLP) technology in this study. The microstructure analysis demonstrated that CS was embedded between ZrO2 particles. Mechanical tests showed that interconnected CS particles could improve mechanical properties, while discrete CS particles led to a decrease in that. Cell experiments showed that adding CS to ZrO2 had a positive effect on cell proliferation and differentiation. In vitro degradation test showed that the weight loss of scaffolds in four weeks increased form −0.63%–1.42% with the increase of CS content. Moreover, the degradation of scaffold promoted the deposition of apatite, which was beneficial to the integration of the scaffold with living bone. In conclusion, the ZrO2/CS composite scaffold had better biocompatibility compared with the ZrO2 scaffold, which showed a potential solution for 3D printing bone repair scaffolds.

Preparation and biological assessment of a ZrO2-based bone scaffold coated with hydroxyapatite and bioactive glass composite

Zirconia (ZrO2) bioceramics has superior stiffness, prominent fracture toughness and fracture strength. However, ZrO2 is almost bioinert material as an alternative scaffolds for repairing bone defects. In this paper, we prepared a porous ZrO2-based bone scaffold coated with hydroxyapatite (HA) and bioactive glass (BG) composite and optimized the quality hybrid proportion of HA and BGs composite coating and sintering temperature. The scaffold has a dense composite coating at the coating sintering temperature of 950 °C and HA content of 70% with Ca2SiO4 and β-TCP, HA and Ca10(PO4)6CO3 phases. The ZrO2 composite scaffold with HA-BG coating was capable of forming rich calcium and phosphorus deposits in the simulated body fluids. Its compression strength was superior to that of the porous ZrO2 scaffold. And the scaffold can promote proliferation of cultured mesenchymal stem cells and the adhesion and propagation of osteosarcoma MG-63 cells. The results exhibited that the excellent mechanical properties, biological activities and good cytocompatibility of the scaffold. Therefore, The composite scaffold represents a potential bone implant for future clinical applications.

Hydroxyapatite-coated ZrO2 scaffolds with a fluorapatite intermediate layer produced by direct ink writing

Zirconia scaffolds with total porosity ranging between 61.1 and 75.3 vol% were fabricated by direct ink writing. The rheology of the ink, as well as the density, morphology and mechanical properties of the produced ZrO2 scaffolds were characterized. The compressive strength was dependent upon the porosity level, and ranged from 20.8 to 62.9 MPa. ZrO2 scaffolds having porosity of 75.3 vol% were then coated with hydroxyapatite (HA) by slurry infiltration. To suppress the reaction upon sintering between HA and ZrO2, fluorapatite (FA) as an intermediate layer was introduced. The ZrO2/FA/HA scaffolds were immersed in simulated body fluid (SBF) and physiological saline solution (0.9% NaCl) for up to 28 days to evaluate their bioactivity and dissolution behavior, respectively. ZrO2/HA/HA scaffolds were also tested, for comparison. The results show that the specimens with FA/HA layers possessed better bioactivity and exhibited slower dissolution rate than the samples with the HA/HA coating.

Variations of Infiltration and Electronic Contact in Mesoscopic Perovskite Solar Cells Revealed by High‐Resolution Multi‐Mapping Techniques

AbstractA combination of high‐resolution mapping techniques is developed to probe the homogeneity and defects of mesoscopic perovskite solar cells. Three types of cells using a one‐step infiltration process with methylammonium lead iodide (MAPbI3) or 5‐ammoniumvaleric acid‐MAPbI3 solutions, or two‐step process with MAPbI3 solution are investigated. The correlation between photoluminescence, photocurrent, electroluminescence, and Raman maps gives a detailed understanding of the different infiltration mechanisms, electronic contact at interfaces, and effect on local photocurrent for the cells. The one‐step MAPbI3 cell has very limited infiltration of the perovskite solution which results in poor device performance. High loading of the mesopores of the TiO2 and ZrO2 scaffold is observed when using 5‐ammoniumvaleric acid, but some micrometer‐sized non‐infiltrated areas remain due to dense carbon flakes hindering perovskite infiltration. The two‐step cell has a complex morphology with features having either beneficial or detrimental effects on the local photocurrent. The results not only provide key insights to achieving better infiltration and homogeneity of the perovskite film in mesoporous devices but can also aid further work on planar devices to develop efficient extraction layers. Moreover, this multi‐mapping approach allows the correlation of the local photophysical properties of full perovskite devices, which would be challenging to obtain by other techniques.

Evaluation of the Possible Synergic Regenerative Effects of Platelet-Rich Plasma and Hydroxyapatite/Zirconia in the Rabbit Mandible Defect Model.

Platelet-rich plasma (PRP) and bioceramics such as hydroxyapatite (HA) and zirconium oxide (ZrO2) are used to reconstruct mandibular defects. We sought to determine the synergistic effects of HA/ZrO2 and PRP and compare their osteogenic activity. ZrO2 scaffolds were constructed by the slurry method and were then coated with HA and impregnated by PRP/heparan sulfate (HS). Bilateral mandibular defects were created in 26 male rabbits. In 20 rabbits, the left defects were treated with HA/ZrO2/PRP (Group 1) and the corresponding right defects were filled with HA/ZrO2 (Group 2). The 6 remaining models were treated with PRP gels at both sides (Group 3). The osteoconductivity of HA/ZrO2/PRP was compared with that of HA/ZrO2 or PRP by radiological and histological methods after the follow-up period, at weeks 2, 6 and 8. The statistical analyses were performed by ANOVA and LSD using SPSS, version 16.0, for Windows (P<0.05). After 2 weeks, the percentage of the surface occupied by bone was significantly higher in the HA/ZrO2/PRP-treated defects than in the PRP-treated defects (P=0.007). Osteoblast and osteocyte counts were higher significantly in the PRP-treated group (P=0.032); however, the cells had not started matrix formation on a large scale and just small islands of osteoid with trapped osteocytes were observed. In the long term, the regenerative potential of all the scaffolds was the same. HA/ZrO2 showed a superior osteoconductive capacity over PRP in the short term; however, they showed no long-term synergic effects.

Processing, structural, and biological evaluations of zirconia scaffolds coated by fluorapatite

AbstractHighly porous zirconia (ZrO2) scaffolds fabricated by the replication method were coated with fluorapatite (FA). The FA coating was obtained by dipping the ZrO2 scaffolds into stabilized aqueous FA slips having different viscosity values (≤5.0 mPa.s). The influence of the FA slip viscosity and the immersion time on the reduction in the scaffold porosity and microstructure of the coated scaffolds were investigated. Cell spreading and survival of bone marrow‐derived stromal cells (BMSC) and pre‐osteoblastic MC3T3‐E1 cells on the uncoated and coated scaffolds were examined using fluorescence and SEM microscopy, and MTT assay.The FA slip with the lowest viscosity value did not lead to a continuous film along the strut network and the macropores remained uncoated. The slips with the highest viscosity value produced a partial blocking of macropores. The porous structure obtained after coating with slips of 2.2 mPa.s viscosity for 2 seconds exhibited a low reduction in porosity and pore size (400‐420 μm), due to the formation of the FA layer, and a continuous film distributed along the strut surfaces. Morphology, spreading, and survival of BMSC and MC3T3‐E1 cells over a 7‐day culture period evidenced good biocompatibility of FA‐coated ZrO2 scaffolds processed by dip coating.

Electroless deposition of Co(Mn)/Pd-decorator into Y2O3-stabilized ZrO2 scaffold as cathodes for solid oxide fuel cells

In this work, we show that higher Co or Mn dopant content of up to 25 mol% on Pd can be obtained without modifying the original crystal structure of Pd via co-reduction synthesis route using hydrazine (N2H4), which is not achievable via conventional sol-gel route. The synthesized Co/Mn-doped Pd alloys can inhibit Pd agglomeration that hinders Pd use as an oxygen reduction reaction (ORR) promoter on solid oxide fuel cell (SOFC) cathode. The presence of Co or Mn on Pd lattice of Co/Mn-doped Pd alloy-decorated YSZ (Y2O3 stabilized ZrO2) cathode provides dual advantages of improving the ORR performance of the cathode and enhancing the ORR performance stability during long term operation. Between 600 °C and 800 °C, Pd0.90Co0.10O-impregnated YSZ cathode displayed the highest ORR performance among PdO-, Pd0.90Co0.10O-, Pd0.75Co0.25O-, Pd0.90Mn0.10O-, and Pd0.75Mn0.25O-impregnated cathodes as indicated by its relatively low area specific resistance of 0.14 Ω cm2 at 700 °C. Our thermal gravimetric analyses and scanning electron microscopy images revealed that the high electrochemical performance stability of Co/Mn-doped Pd alloys during 30 hour-cathodic current test correlates with their higher metal ↔ metal oxide conversion reversibility and microstructure stability under thermal cycling between room temperature and 900 °C (relative to Pd).

Effects of pore connectivity and microstructure on mechanical performance of ZrO2 scaffolds and PMMA-infiltrated ZrO2 composites

To combine the advantages of ceramics and resins, ceramic/resin composites have been explored for dental restorations in recent years. ZrO2 scaffold is considered as a promising candidate porous matrix for polymer-infiltrated composites due to its excellent biocompatibility and mechanical properties. In the present study, porous ZrO2 scaffolds were prepared by adding pore-forming agent and sintered at 1200–1400 °C, the effects of porosity, pore connectivity and microstructure on the mechanical performance of ZrO2 scaffolds and the corresponding PMMA-infiltrated ZrO2 composites were investigated. To obtain a good pore connectivity and favorite mechanical properties of ceramic scaffolds, the content of pore-forming agent and sintering temperature should be well controlled. The flexural strength of ZrO2 scaffolds was simply affected by the total porosity and sintering temperature. While the flexural strength of the infiltrated composites was dominated by both the strength of the porous scaffolds and the amount of closed pores. Crack bridging in the infiltrated composites is one of the important factors to the enhanced mechanical strength. The highest strength of 265.5 MPa was achieved in the composites infiltrated from the 1400°C-sintered scaffolds with an initial pore forming agent content of 30 wt%.

Lamellar-interpenetrated Al−Si−Mg/Al2O3−ZrO2 composites prepared by freeze casting and pressureless infiltration

Using freeze casting and pressureless infiltration methods, we prepared lamellar Al−Si−Mg/Al2O3−ZrO2 composites with initial ceramic loading of 30vol% and different Al2O3:ZrO2 weight ratios (Al2O3:ZrO2=1:9, 3:7, 5:5, 7:3 and 9:1). The resultant composites inherited the lamellar structure of the Al2O3−ZrO2 scaffolds, and the thickness of both metal and ceramic layers showed a trend of first increase and then decrease with increasing Al2O3 content. During pressureless infiltration, multiple chemical reactions took place between ZrO2 and the Al−12Si−10Mg alloy and the main reaction products were (Al1−m, Sim)3Zr, Al2O3 and ZrSi2 phases. The degree of the reaction depended on the ZrO2 content in the ceramic composition. In general, the compressive strength of the composites decreased with increasing Al2O3 content, but three-point bending strength showed a first decrease and then increase. When Al2O3:ZrO2=1:9, the compressive and bending strength of the composites reached about 997±60MPa and 426±10MPa, respectively. A simple model was proposed to illustrate the fracture mode and toughening mechanism of the composites.

Processing of ZrO2 scaffolds coated by glass–ceramic derived from 45S5 bioglass

Three dimensional, highly porous, ZrO2 scaffolds coated by glass–ceramic derived from 45S5 bioglass were fabricated. The surface reactivity of 45S5 in aqueous solution was investigated as a function of the immersion time. The influence of the solid loading on the rheological behavior of 45S5 aqueous slips with ammonium polyacrylate (NH4PA) was studied; besides the effect of poly(vinyl)alcohol (PVA) on the relative viscosity was determined. The structure and microstructure of uncoated and coated ZrO2 scaffolds were characterized. The high ionic exchange capability of 45S5 was demonstrated by the pH rise, the significant weight loss and the amorphous calcium phosphate nucleation, upon its immersion in aqueous solution. The addition of PVA did not affect the dispersion properties of the 45S5 powder, which were basically controlled by its negative surface charge. 30wt% 45S5 slips with 4wt% PVA exhibited a yield stress and an adequate viscosity in the low shear rate range, to produce a bioglass coating into the ZrO2 scaffold. The glass-ceramic coating was distributed along the strut surfaces, forming a thin film without altering the porosity and the strut thickness of the original ZrO2 scaffold structure.

Cover Image, Volume 12, Issue 6

Cover Photograph: Cover photo from Cijun Shuai et al. Photo of Porous CasiO3/nano‐ZrO2 scaffold (Fig. 1a) image

Effects of composition and sintering temperature on the structure and compressive property of the lamellar Al2O3–ZrO2 scaffolds prepared by freeze casting

Using 3 wt% TiO2 nanopowders as sintering aid, we prepared porous lamellar Al2O3–ZrO2 composites with an initial solid loading of 30 vol% and the Al2O3/ZrO2 weight ratios of 1:9, 3:7, 5:5, 7:3, and 9:1 by freeze casting. The viscosity of water-based slurries decreased with increasing Al2O3 content while the porosity and the wavelength of the lamellae in the sintered scaffolds showed first an increase and then decrease with maximum values appearing at Al2O3:ZrO2 = 5:5. A relatively large amount of tetragonal (t) ZrO2 transformed to monoclinic (m) ZrO2 with the increase in the Al2O3 content and sintering temperature, thus reducing stress-induced phase transformation effect during loading. The compressive strength of the sintered scaffolds depended on sintering temperature, porosity, and the phase composition in the composites. A maximum value of 105 ± 10 MPa was achieved in the scaffolds with a composition of Al2O3:ZrO2 = 3:7 after sintering at 1450 °C for 2 h.

Direct write printing of three-dimensional ZrO2 biological scaffolds

Three-dimensional (3D) zirconium dioxide (ZrO2) scaffolds have been fabricated for biological engineering by direct write printing method. The water-based ZrO2 ink with a solid content fraction of 70 wt% was deposited through a fine nozzle on the substrate by a layer-by-layer sequence to produce the 3D microperiodic structures. The preparation and the rheological behavior of this ink, as well as the principles of the direct write printing process were investigated systematically. Sintered at 1250 °C for 4 h was the optimal process for the uniform grain size and a certain amount of pores. No phase change was observed during the sintering process. Under a microscope, the proliferation of HCT116 cells can be observed around the 3D ZrO2 scaffolds. 3D porous internal architecture is beneficial for cell growth by providing more locations for cells attachments and proliferations. The largest value of compressive strength reached 10 MPa, which is more than that of the hydroxyapatite (HAp) scaffold. The ability of printing 3D scaffolds with the high precise control of their internal architecture is the unique characteristics performed by the direct write technique, which will provide potential application of biomaterials and tissue engineering scaffolds.

Nano-composite of silk fibroin–chitosan/Nano ZrO2 for tissue engineering applications: Fabrication and morphology

A scaffold possessing certain desired features such as biodegradation, biocompatibility, and porous structure could serve as a template for tissue engineering. In the present study, silk fibroin (SF), chitosan (CS) and zirconia (Nano ZrO2) were all combined using the freeze drying technique to fabricate a bio-composite scaffold. The composite scaffold (SF/CS/Nano ZrO2) was characterized by SEM, XRD, TGA, BET and FT-IR studies. The scaffold was found to possess a porous nature with pore dimensions suitable for cell infiltration and colonization. The presence of zirconia in the SF/CS/Nano ZrO2 scaffold led to an increase in compressive strength and water uptake capacity while at the same time decreasing the porosity. Cytocompatibility of the SF/CS/Nano ZrO2 scaffold, assessed by MTT assay, revealed non-toxicity to the Human Gingival Fibroblast (HGF, NCBI: C-131). Thus, we suggest that SF/CS/Nano ZrO2 composite scaffold is a potential candidate to be used for tissue engineering.

Functionalized PLGA-doped zirconium oxide ceramics for bone tissue regeneration

Bone tissue engineering is an alternative approach to bone grafts. In our study we aim to develop a composite scaffold for bone regeneration made of doped zirconium oxide (ZrO2) conjugated with poly(lactic-co-glycolic acid) (PLGA) particles for the delivery of growth factors. In this composite, the PLGA microspheres are designed to release a crucial growth factor for bone formation, bone morphogenetic protein-2 (BMP2). We found that by changing the polymer's molecular weight and composition, we could control microsphere loading, release and size. The BMP2 released from PLGA microspheres retained its biological activity and increased osteoblastic marker expression in human mesenchymal stem cells (hMSCs). Uncapped PLGA microspheres were conjugated to ZrO2 scaffolds using carbodiimide chemistry, and the composite scaffold was shown to support hMSCs growth. We also demonstrated that human umbilical vein endothelial cells (HUVECs) can be co-cultured with hMSCs on the ZrO2 scaffold for future vascularization of the scaffold. The ZrO2 composite scaffold could serve as a bone substitute for bone grafting applications with the added ability of releasing different growth factors needed for bone regeneration.

Mechanical and Biological Performance of Calcium Phosphate Coatings on Porous Bone Scaffold

Composite coatings, consisting of calcium phosphate (CaP) ceramics and phosphate‐based glass (P‐glass), were obtained on a strong ZrO2 porous scaffold to improve biocompatibility by combining mechanical properties and biological activity. Powder mixtures of hydroxyapatite (HA) and P‐glass in varying composition and content were dip‐coated on a ZrO2 porous scaffold and heat‐treated above 800°C for 2 h in air. During thermal treatment, substantial reaction and crystallization occurred, resulting in coating phases of HA, tricalcium phosphate (TCP), dicalcium phosphate (DCP), and surrounding glass. The CaP‐glass coating layer was highly dense and uniform and adhered firmly to the ZrO2 scaffold. The adhesion strength of the coating layer as tested on a nonporous disk increased with increasing glass addition and decreasing CaO content in glass. The highest strength was about 40 MPa, an improvement of twice as high as that of pure HA coating. The osteoblastic cells grew and spread actively through the coated scaffolds. The differentiation of cells on the CaP coatings was much higher than that on ZrO2 substrate and comparable to or slightly higher than that on pure HA coating.

Bioactive Porous Bone Scaffold Coated with Biphasic Calcium Phosphates

Calcium phosphates (CaP) were coated on a zirconia (ZrO2) porous scaffold for hard tissue applications. The ZrO2 porous body, intended to be a load-bearing part, was fabricated by a polymeric foam reticulate method. On the framework, Cal? layers were deposited by a powder slurry method to induce bioactivity and osteoconductivity. The compositions of the coating layers were varied to be biphasic, i. e., hydroxyapatite (HA) with tricalcium. phosphate (TCP) and fluorapatite (FA). The coated scaffolds had a porosity of similar to 90 % and pore size of similar to500-600 mum. The compressive strength of the coated ZrO2 scaffolds was similar to5 MPa, which was similar to7 times higher than those of pure HA. The coating layers had a thickness of similar to30 mum. and was firmly adhered to the substrate. The adhesive strength of the coating layer was similar to20-25 MPa. Human osteoblast-like cells grew and proliferated well on the coated scaffolds. The differentiation of the cells on the coated scaffolds was higher than those on pure ZrO2 scaffold, confirming improved cell activity via the calcium phosphate coatings.