Ceramic Scaffolds Research Articles

Nondeterministic multiobjective optimization of 3D printed ceramic tissue scaffolds

Despite significant advances in the design optimization of bone scaffolds for enhancing their biomechanical properties, the functionality of these synthetic constructs remains suboptimal. One of the main challenges in the structural optimization of bone scaffolds is associated with the large uncertainties caused by the manufacturing process, such as variations in scaffolds’ geometric features and constitutive material properties after fabrication. Unfortunately, such non-deterministic issues have not been considered in the existing optimization frameworks, thereby limiting their reliability. To address this challenge, a novel multiobjective robust optimization approach is proposed here such that the effects of uncertainties on the optimized design can be minimized. This study first conducted computational analyses of a parameterized ceramic scaffold model to determine its effective modulus, structural strength, and permeability. Then, surrogate models were constructed to formulate explicit mathematical relationships between the geometrical parameters (design variables) and mechanical and fluidic properties. The Non-Dominated Sorting Genetic Algorithm II (NSGA-II) was adopted to generate the robust Pareto solutions for an optimal set of trade-offs between the competing objective functions while ensuring the effects of the noise parameters to be minimal. Note that the nondeterministic optimization of tissue scaffold presented here is the first of its kind in open literature, which is expected to shed some light on this significant topic of scaffold design and additive manufacturing in a more realistic way.

Porous hydroxyapatite scaffold orchestrated with bioactive coatings for rapid bone repair

Current bioceramic scaffolds for critical-size bone defects are still facing various challenges such as the poor capability of self-resorption, vascularization and osteogenesis. Herein, a composite scaffold (HOD) is fabricated by integrating bioactive coatings of konjac glucomannan (KGM) and deferoxamine (DFO) into porous hydroxyapatite scaffold (HA), where KGM coating induces the self-resorption of HOD after implanting and DFO promoted the vascularization at the defected bone. Porous HA scaffolds with 200–400 μm of pore sizes were prepared and these bioactive coatings were successfully deposited on the scaffold, which was confirmed by SEM. MC3T3-E1 cells could be tightly attached to the pore wall of HOD and the obvious osteogenic differentiation was clearly displayed after 14 days of co-culture. Besides, HOD displayed the potential of promoting the vascularization of HUVECs. Importantly, the accelerated degradation of HOD was observed in a macrophage-associated acidic medium, which led to the self-resorption of HOD in vivo. Micro-CT images showed that HOD was gradually replaced by newly formed bone, achieving a balance between the new bone formation and the scaffold degradation. The rapid bone repairing of the femoral defects in rats was displayed for HOD in comparison to the HA scaffold. Moreover, the therapeutic mechanism of HOD was highly associated with promoted osteogenesis and vascularization. Collectively, the porous ceramic scaffold orchestrated with bioactive coatings may be a promising strategy for repairing of the large bone defect.

CVD nanocrystalline multilayer graphene coated 3D-printed alumina lattices

3D printing technologies have expanded the possibilities of fabricating new composite materials with tailored properties, which depend on both the materials selected and the structural design at multiple length scales. Here, a catalyst-free CVD method has been used to produce hybrid materials based on 3D printed cellular α-Al2O3 substrates decorated by either nanocrystalline graphene or nanocrystalline graphitic films of tunable number of layers. Graphene-based coatings of variable thickness and crystallinity have been controlled by the alteration of the parameters of CVD processing, performed under CH4/H2 flux. Transmission electron microscopy has confirmed the effective growth of nanocrystalline graphene layers on the scaffolds due to the penetration of CVD gases into the open pores. The fully-connected and highly conductive 3D pathways have displayed a room temperature electrical conductivity in the range of 101–103 S m−1. Furthermore, the thermal conductivity has also increased by 50% for the specimen decorated with a 20 nm thick graphitic coating as compared to a bare 3D ceramic scaffold. The developed structures open up new possibilities for expanding the field of application of graphene/ceramic composites for conditions requiring dielectric substrates of various shapes coated with conductive films or graphene-based catalytic supports with good structural stability.

Porous magnetic Fe3O4/bioactive glass–ceramic (CaO-SiO2-P2O5-MgO) scaffold with enhanced self-heating ability for hyperthermia treatment of bone tumor—an in vitro study

Porous magnetic Fe3O4/bioactive glass–ceramic (CaO-SiO2-P2O5-MgO) scaffold with enhanced self-heating ability for hyperthermia treatment of bone tumor—an in vitro study

Bone tissue engineering scaffolds with HUVECs/hBMSCs cocultured on 3D-printed composite bioactive ceramic scaffolds promoted osteogenesis/angiogenesis.

/Objective: Tissue engineering involves scaffolds, cells and growth factors, among which growth factors have limited applications due to potential safety risks and high costs. Therefore, an alternative approach to exogenously induce osteogenesis is desirable. Considering that osteogenesis and angiogenesis are coupled, a system of human umbilical vein endothelial cells (HUVECs) and human bone mesenchymal stem cells (hBMSCs) coculture is more biologically adapted to the microenvironment in vivo and can mediate osteogenesis and angiogenesis via paracrine signalling. Hence, in this study, a HUVECs/hBMSCs coculture system with appropriate cell and medium proportions was established. The substrate for the coculture system was a 3D-printed composite bioceramic scaffold (β-TCP/CaSiO3) based on a previous study. The aim of this study was to explore the potential of this system for bone tissue engineering. Bioactive ceramic scaffolds for tissue engineering were fabricated via a 3D Bioplotter™ system. The coculture system for in vitro and in vivo studies consisted of direct contact between HUVECs and hBMSCs cultured on the 3D-printed scaffolds. The proportions of HUVECs/hBMSCs and medium components were determined by cell viability, and the coculture system showed negligible cytotoxicity. CD31 secreted by HUVECs formed strings, and cells tended to aggregate in island chain-like arrays. Real-time cell tracking showed that HUVECs were recruited by hBMSCs, and the integrin expression by HUVECs was upregulated. Ultimately, osteogenic and angiogenic marker gene expression and protein secretion were upregulated. Moreover, the obtained bone tissue engineering scaffolds could induce early osteogenic protein secretion and capillary tube formation in nude rats. These bone tissue engineering scaffolds without exogenous growth factors exhibited the ability to promote osteogenesis/angiogenesis. The fabricated 3D-printed bioactive ceramic scaffolds could provide mechanical, biodegradable and bioadaptive support for personalized bone regeneration. In addition, the bone tissue engineering scaffolds exhibited the ability to promote osteogenesis/angiogenesis without the addition of exogenous growth factors, thus mitigating safety risks. Although application of the HUVECs/hBMSCs coculture system might be a time-consuming process, further development of cord blood storage could be beneficial for multicell coculture.

3D-printed electrically conductive silicon carbide

The development of electrically conductive ceramics could achieve robust mechanical strength as well as practically high conductivity, offering applications in structural electrodes, conductors, catalyst supports, etc. However, its operating temperature is limited due to the intrinsic dense structures inevitably hindering the thermal management capability, thus resulting in a temperature-dependent electrical behavior in high-temperature environments. We report an additive manufacturing protocol through vat photopolymerization 3D printing to fabricate the architectured conductive silicon carbide (SiC) ceramics that simultaneously possess high electrical conductivity as well as low thermal conductivity, and demonstrate electric reliability under high-temperature environments above 600°C. The percolation of graphene into the ceramic scaffold establishes a uniform conductive network, exhibiting its electrical conductivity up to 1000 S m−1. The bulk density of the 3D-printed ceramic is measured from 0.366 g cm−3 to 0.897 g cm−3, with thermal conductivity ranging from 62 mW m−1 K−1 to 88 mW m−1 K−1. Furthermore, the mechanical performance of conductive ceramic can be effectively reinforced by densifying the microstructures via spark plasma sintering treatment. The proposed additive manufacturing strategy widens the potential of ceramics as a structural and functional material, offering a promising pathway toward high-temperature electronics applications.

Direct utilization of gaseous fuels in metal supported solid oxide fuel cells

Direct utilization and internal reforming of gaseous fuels is investigated on symmetric-architecture metal supported solid oxide fuel cells (MS-SOFCs) with thin ceramic electrolyte and scaffold backbone layers, and low cost ferritic stainless steel supports on both sides. Infiltrated Pr-oxide and Ni/samarium-doped ceria catalysts are added to the cathode and anode electrodes, respectively. Initial performance and durability is evaluated for MS-SOFCs operating with natural gas, propane, ammonia, and dimethyl ether at 700 °C. Cells for natural gas and propane utilize a novel high entropy alloy (HEA) catalyst for internal reforming with performance and degradation rates similar to H2 (0.5 W cm−2 and ∼12%/100 h). Initial testing with sulfur shows reversible degradation for levels found in natural gas and irreversible degradation for higher levels found in commercial propane. Overall, MS-SOFCs show successful fuel flexibility.

Powder injection molded ceramic scaffolds: The role of pores size and surface functionalization on the cytocompatibility

The alumina-based scaffolds prepared by powder injection molding can be preferentially used for preparation of bone grafts. Here, the final architecture of alumina scaffolds was efficiently controlled by powder space holder size and volume ratio. The alumina is not intrinsically cell-instructive material and thus the coating with electrically-conducting polyaniline or polyaniline/biopolymer films prepared in a colloidal dispersion mode was used to provide this advanced property. The component of the extracellular matrix, sodium hyaluronate, or natural biopolymers (sodium alginate or chitosan) were employed, and, subsequently, the cytocompatibility of the native and functionalized alumina scaffolds were determined. Both the absence of cytotoxicity and the cytocompatibility that were revealed demonstrate the application potential of these composites. The scaffolds with pore size greater than 250 µm were more cytocompatibility than those with pores size between 125 and 250 µm. The cytocompatibility was confirmed under in vivo-mimicking dynamic cultivation conditions which further improve the cell distribution and growth.

Fabrication of doped β-tricalcium phosphate bioceramics by Direct Ink Writing for bone repair applications

β-tricalcium phosphate (β-TCP, β-Ca3(PO4)2) is one of the most attractive biomaterials for bone regeneration and β-TCP macroporous scaffolds are very promising for both cell proliferation and mechanical support. The Additive Manufacturing (AM) process called Direct Ink Writing (DIW), based on the extrusion of a concentrated ceramic slurry, is particularly adapted to resolve the main drawbacks associated with conventional shaping of ceramic scaffolds. In this work, co-doped β-TCP powders were synthetized and used to print macroporous scaffolds by DIW. Doped β-TCP powders have been proved to exhibit higher thermal stability, densification and mechanical properties compared to undoped β-TCP. Two co-doped compositions were produced via the aqueous precipitation technique combining magnesium, strontium, silver and copper cations: Mg-Sr (2.0–2.0 mol%) and Mg-Sr-Ag-Cu (2.0–2.0–0.1–0.1 mol%). DIW slurries were optimized with undoped and co-doped β-TCP with the use of a dispersant and a carboxymethylcellulose and polyethyleneimine mixture to obtain aqueous slurries filled with 42 vol% of powder. Complete rheological characterizations were realized to assess the suitability of the β-TCP slurries for the DIW process (shear-thinning and thixotropic behaviour). The whole processing chain including printing, osmotic drying (PEG 10000) and sintering (1100 °C, 3 h) was optimized to successfully print co-doped β-TCP macroporous scaffolds. Characterizations after sintering showed a reduction of macropores and microcracks using co-doped β-TCP powders as well as improved compressive strengths and densities compared to undoped β-TCP. A significant enhancement of compressive strength values was obtained compared to literature data.

Bioinspired inverse enamel-like columnar composites reproducing the mechanical properties and tribological performance of human enamel

The development of high-performance dental materials that mimic human enamel is urgently required for clinical applications, but remains a key challenge. Herein, we present a biomimetic design strategy for creating inverse enamel-like columnar composites that replicate the mechanical properties and tribological performance of the natural enamel. Inverse to the enamel consisting of hard rods and surrounding relatively soft inter-rod, the composites are assembled from a cellular-structured ceramic scaffold and resin columns. This architecture helps to avoid dramatic stiffness and hardness decreases due to the presence of flexible substances and provides an elegant combination of mechanical properties that strikingly resemble that of natural enamel. Consequently, the inverse enamel-like columnar composites have encouraging tribological performance characterized by an enamel-matched coefficient of friction and wear rate, as well as low abrasive potential to opposing natural teeth, demonstrating great promise for next-generation dental restorations/replacements and other applications. More importantly, the proposed design strategy can be extended to other biological prototypes, thus facilitating the development of various high-performance functional materials.

Additive manufacturing of graphene oxide/hydroxyapatite bioceramic scaffolds with reinforced osteoinductivity based on digital light processing technology

In the field of bone tissue engineering, porous hydroxyapatite (HA) bone repair scaffolds with controlled architecture and porosity are challenging to manufacture and lack sufficient osteoinductive activity, which limit its wider clinical application. This study fabricated porous graphene oxide (GO)/HA composite ceramic scaffolds using digital light processing (DLP) technology. The properties of the composite ceramic slurry and the process parameters of curing, degreasing, and sintering were initially examined to ensure molding accuracy. The research showed that a small amount of GO (0.1–0.4 wt%) could better maintain the pore structure and improve the mechanical properties of composite ceramics. Porous scaffolds with pore sizes of 300–400 μm were prepared for co-culture with rat bone marrow mesenchymal stem cells to detect biocompatibility. The results showed that all scaffolds have no cytotoxicity. Compared with HA, the GO/HA ceramic scaffold significantly promoted the cell adhesion, proliferation, and expression of osteogenesis-related genes; GO (0.1–0.2 wt%) /HA scaffolds exhibited superior alkaline phosphatase activity and more effective bone mineralization, showing enhanced osteoinductivity. The porous GO/HA composite scaffold fabricated by DLP presented a strong potential for repairing bone defects.

Optimization of polarization direction on 3D printed 3-3 piezoelectric composites for sensing application

As a typical smart material, 3-3 piezoelectric composite has a wide application in the fields of ultrasonic transducer, underwater acoustic detection and so on. Direct ink writing has great advantages in preparing 3-3 composites because of its straight-forward process and accurate control of the composites structure. In this work, a water-based PZT slurry of 52.0 vol% solid content was prepared with high storage and loss modulus and shear thinning characteristics. PZT ceramic scaffolds with different porosity were realized by direct ink writing, and 3-3 piezoelectric composites were then prepared by compounding PZT scaffold with epoxy resin. Compared with the common Z-polarized samples, the Y-polarized samples show higher piezoelectric coefficients d 33 and piezoelectric voltage coefficient g 33 . When PZT content of the 3-3 composite was 34.4 vol%, the Y-polarized sample showed the highest g 33 of 81.65 mV m/ N, and the sensing sensitivity could reach 9.81 V/N. Structural configuration and design via direct writing process show great potential for tuning and optimizing the piezoelectric properties of piezocomposites.

Synthesis of 3D porous ceramic scaffolds obtained by the sol-gel method with surface morphology modified by hollow spheres for bone tissue engineering applications

In the present work, we modified the surface morphology of 3D porous ceramic scaffolds by incorporating strontium phosphate (SrP) hollow nano-/microspheres with potential application as delivery system for the local release of therapeutic substances. SrP hollow spheres were synthesized by a template-free hydrothermal method. The influence of the reaction temperature, time and concentration of reactants on precipitates' morphology and size were investigated. To obtain a larger number of open hollow spheres, a new methodology was developed consisting of applying a second hydrothermal treatment to spheres by heating them at 120 °C for 24 h. The X-ray diffraction (XRD) analysis indicated that spheres consisted of a main magnesium-substituted strontium phosphate phase ((Sr0.86Mg0.14)3(PO4)2). The scanning electron microscopy (SEM) micrographs confirmed that spheres had hollow interiors (∼350 nm size) and an average diameter of 850 nm. Spheres had a specific surface area of 30.5 m2/g, a mesoporous shell with an average pore size of 3.8 nm, and a pore volume of 0.14 cm3/g. These characteristics make them promising candidates for drug, cell and protein delivery. For the attachment of spheres to scaffolds’ surface, ceramic structures were immersed in an ethanol solution containing 0.1 g of hollow spheres and kept at 37 °C for 4 h. The scaffolds with incorporated spheres were bioactive after being immersed in simulated body fluid (SBF) for 7 days and spheres were still adhered to their surface after 14 days.

Fabrication and characterisation of alumina/aluminium composite materials with a nacre-like micro-layered architecture

Many natural materials demonstrate ideal design inspirations for the development of lightweight composite materials with excellent damage tolerance. One notable example is the layered architecture of nacre, which possesses toughness an order of magnitude higher than its constituent parts. Man-made nacre-like ceramic/polymer composites obtained through direct infiltration of polymer in ceramic scaffolds have been shown to produce improved mechanical properties over other composite architectures. Replacing the polymer phase with metal could provide higher damage tolerance but the infiltration of metal into complex ceramic scaffolds is difficult due to the surface tension of molten metal. To address this, bioinspired nacre-like micro-layered (µL) alumina scaffolds with different ceramic fractions from 18 to 85% were infiltrated with aluminium alloy 5083 via pressureless and squeeze casting infiltrations techniques. The scaffolds were created using a bi-directional freeze-casting and one-step densification method. As a result, the µL alumina/aluminium composites displayed significant extrinsic toughening mechanisms with both high strength and toughness. The mechanical performance was highly dependent on the interface, microstructure, and composition. The nacre-like composites with 18% alumina and AlN interface displayed a maximum resistance‐curve toughness up to around 70 MPa.m½ (35 MPa.m½ at the ASTM limit) and a flexural strength around 600 MPa.

Sintering behavior and mechanical properties of calcium phosphate–alumina composite porous scaffolds

A novel composite ceramic porous scaffold consisting of calcium phosphate ceramics and alumina was fabricated using the gelation freeze-casting method. Notably, the temperature is important for the simultaneous sintering of different ceramics. A denser microstructure with better mechanical properties was obtained at a sintering temperature of 1450 °C. At sintering temperatures above 1500 °C, liquid-phase sintering occurred, resulting in substantial changes to the microstructure. The addition of alumina accelerated the phase transformation of hydroxyapatite into α-tricalcium phosphate. Furthermore, it was suggested that a mixture of calcium phosphate and alumina was formed at a sintering temperature of 1550 °C. Additionally, Young’s modulus and compressive strength increased with increasing sintering temperature. The increase in compressive strength was due to the smoothening of the microstructural surface via liquid-phase sintering.

Recombinant PTH modification: A new strategy for a multifunctional CaP material to enhance bone regeneration

Bone regeneration requires the interaction of osteogenesis, osteolysis, and angiogenesis as well as an appropriate immune microenvironment. Recombinant human parathyroid hormone (PTH1-34) is approved for clinical anti-osteoporosis treatment because of its good osteogenic activity, osteoclastosis, and angiogenesis. However, the phenomenon of net bone resorption limits its use in local bone repair. Our group provides an effective strategy for multifunctional calcium phosphate (CaP) ceramics with modulating M1 macrophage pro-inflammatory effects, and bone regeneration. CaP ceramic scaffold is functionalized with parathyroid hormone related peptide-1 (PTHrP-1) for bone defect repair. First, peptide-functionalized true bone ceramic (TBC) scaffold exhibit limited M1 macrophage pro-inflammatory effects to improve the osteogenic microenvironment. Second, PTHrP-1 retains the osteogenic activity and angiogenic properties of PTH1-34 while downregulating osteoclast activity to induce favorable bone formation. Third, the peptide modified by tri-continuous aspartic acids (D3) and serine phosphorylation (PSer) has high affinity to the natural CaP matrix, achieving a slow release of PTHrP-1 in the TBC scaffold. Fourth, the carboxyl group of aspartate combined with calcium effectively promotes hydroxyapatite (HAP) nucleation and completes self-assembled mineralization. which is beneficial for bone regeneration. The results show that PTHrP-1-TBC is more suitable for bone regeneration than TBC scaffold and unmodified peptide alone.

TISSUE-ENGINEERED BONE IMPLANTS FOR THE REPLACEMENT OF JAWBONE DEFECTS. LITERATURE REVIEW

The purpose of the study:to trace the development of methods of bone implants for the replacement of jawbone defects: from ceramic and polymeric scaffolds to complex tissue-engineered structures with stem cells, growth factors and vascular anastomoses based on literature data.Materials and methods:searching, systematization and analysis of scientific data on various types of 3D-printed bone implants and their effectiveness in replacing bone defects.Conclusions:Modern technologies of 3D-printing, cell and tissue engineering, microvascular surgical techniques closely approach scientists and clinicians to creation of an artificial bone implant which in the body must become a living structure capable of integrating with the patient’s bone. Only complex approach which includes reconstruction of the implant of individual shape and sufficient mechanical strength, giving of osteoinductive and osteogenic properties, providing of internal axial and external angiogenesis is the basis for such tissue-engineered construction.

A 3D-printed molybdenum-containing scaffold exerts dual pro-osteogenic and anti-osteoclastogenic effects to facilitate alveolar bone repair

The positive regulation of bone-forming osteoblast activity and the negative feedback regulation of osteoclastic activity are equally important in strategies to achieve successful alveolar bone regeneration. Here, a molybdenum (Mo)-containing bioactive glass ceramic scaffold with solid-strut-packed structures (Mo-scaffold) was printed, and its ability to regulate pro-osteogenic and anti-osteoclastogenic cellular responses was evaluated in vitro and in vivo. We found that extracts derived from Mo-scaffold (Mo-extracts) strongly stimulated osteogenic differentiation of bone marrow mesenchymal stem cells and inhibited differentiation of osteoclast progenitors. The identified comodulatory effect was further demonstrated to arise from Mo ions in the Mo-extract, wherein Mo ions suppressed osteoclastic differentiation by scavenging reactive oxygen species (ROS) and inhibiting mitochondrial biogenesis in osteoclasts. Consistent with the in vitro findings, the Mo-scaffold was found to significantly promote osteoblast-mediated bone formation and inhibit osteoclast-mediated bone resorption throughout the bone healing process, leading to enhanced bone regeneration. In combination with our previous finding that Mo ions participate in material-mediated immunomodulation, this study offers the new insight that Mo ions facilitate bone repair by comodulating the balance between bone formation and resorption. Our findings suggest that Mo ions are multifunctional cellular modulators that can potentially be used in biomaterial design and bone tissue engineering.

3D calcium silicophosphate porous scaffold: In vitro and in vivo response

The elderly population (65 years and older) is expected to increase from 524 million people in 2010 to 1.5 billion by 2050, with the corresponding increase in bone-related and joint damage problems. Many of these problems can be solved by using scaffolds for bone tissue regeneration, and material selection is a critical step to obtain satisfactory results. This selection is crucial for the cell division process, cell-cell communication pathways, nutrient transport and osteogenic differentiation. In this study, we designed a tridimensional porous ceramic scaffold composed of 85 wt%C2S – 15 wt%TCP by the polymer sponge replica method combined with ceramic slurry, and we analyzed its biocompatibility and osteoinductive capacity by in vitro and in vivo assays. The in vitro tests showed good biocompatibility because the cells that were seeded over the biomaterial had spread over the entire surface. The in vivo results showed no cytotoxicity signs at the implant site, and the percentages of defect closure and residual biomaterial, and the resorption rate, were adequate. All these results demonstrate that 85 wt%C2S – 15 wt%TCP bioceramics can be taken as potential bone substitutes to be employed for a range of medical applications.

Correction of large jawbone defect in the mouse using immature osteoblast-like cells and a 3D polylactic acid scaffold.

Bone tissue engineering has been developed using a combination of mesenchymal stem cells (MSCs) and calcium phosphate-based scaffolds. However, these complexes cannot regenerate large jawbone defects. To overcome this limitation of MSCs and ceramic scaffolds, a novel bone regeneration technology must be developed using cells possessing high bone forming ability and a scaffold that provides space for vertical bone augmentation. To approach this problem in our study, we developed alveolar bone-derived immature osteoblast-like cells (HAOBs), which have the bone regenerative capacity to correct a large bone defect when used as a grafting material in combination with polylactic acid fibers that organize the 3D structure and increase the strength of the scaffold material (3DPL). HAOB-3DPL constructs could not regenerate bone via xenogeneic transplantation in a micromini pig alveolar bone defect model. However, the autogenic transplantation of mouse calvaria-derived immature osteoblast-like cells (MCOBs) isolated using the identical protocol for HAOBs and mixed with 3DPL scaffolds successfully regenerated the bone in a large jawbone defect mouse model, compared to the 3DPL scaffold alone. Nanoindentation analysis indicated that the regenerated bone had a similar micromechanical strength to native bone. In addition, this MCOB-3DPL regenerated bone possesses osseointegration ability wherein a direct structural connection is established with the titanium implant surface. Hence, a complex formed between a 3DPL scaffold and immature osteoblast-like cells such as MCOBs represents a novel bone tissue engineering approach that enables the formation of vertical bone with the micromechanical properties required to treat large bone defects.