Dual-scale porous biphasic calcium phosphate gyroid scaffolds using ceramic suspensions containing polymer microsphere porogen for digital light processing

This study demonstrates a novel type of biphasic calcium phosphate (BCP) gyroid scaffolds featuring of gyroid macroporous structure and micropous BCP walls using poly(methyl methacrylate) (PMMA) microspheres as the porogen for ceramic digital light processing (DLP) technique. To tailor the microporosity of the BCP walls and the overall porosity of the dual-scale porous BCP scaffolds, the PMMA content with regard to the BCP powder was controlled in the range of 40 vol% to 70 vol%. After debinding at 600 °C and sintering at 1200 °C for 3 h, micropores were uniformly created throughout each BCP framework, while preserving 3?dimensional gyroid macroporous structures. As the PMMA content increased from 40 vol% to 70 vol%, the microporosity remarkably increased from 31.9 (±2.5) vol% to 55.2 (±1.4) vol%. This approach allowed the achievement of very high overall porosities (82.2–89.7 vol%) for the dual-scale porous scaffolds. However, all the scaffolds showed reasonable compressive strengths (0.8 MPa ?2.1 MPa), which are comparable to those of cancellous bones.     

Fabrication,characterization and cellular biocompatibility of porous biphasic calcium phosphate bioceramic scaffolds with different pore sizes

Facile wet-chemical methods are applied to synthesize hydroxyapatite and β-tricalcium phosphate nanoparticles, respectively. Porous biphasic calcium phosphate (BCP) bioceramic scaffolds are then fabricated using as-prepared HA and β-tricalcium phosphate nanoparticle powders. The macro pore diameter of BCP bioceramic scaffolds can be controlled by adjusting the amount of surfactants. The average diameter of the macro pores in BCP bioceramic scaffolds increases from 100 to 600 µm with the decrease amount of sodium dodecyl sulfate from 0.8 to 0.5 g, respectively. The BCP bioceramic scaffolds gradually degrade and the calcium-phosphate compounds fully deposit when soaking in simulated body fluid solution. Moreover, The BCP bioceramic scaffolds have outstanding biocompatibility to promote the cellular growth and proliferation of human dental pulp stem cells (hDPSCs). The hDPSCs also demonstrate favorable cellular adhering capacity on the pore surface of scaffolds, especially on the scaffolds with 100–200 µm pore diameter. The porous BCP bioceramic scaffold with inter-connected pore structure, outstanding in vitro cellular biocompatibility, favorable cell viability and adhesion ability will be a promising biomaterial for bone or dentin tissue regeneration.     

Tailoring the pore structure and property of porous biphasic calcium phosphate ceramics by NaCl additive

This study investigated the effects of NaCl additive on the phase composition, pore structure and mechanical property of porous biphasic calcium phosphate (BCP) ceramics, which were prepared by freeze-casting. The results indicated that the addition of NaCl promoted transformation of β-tricalcium phosphate to hydroxyapatite in the BCP ceramics; the OH group in HA phase of BCP ceramic was partially replaced by chloride ion. As the mass fraction of NaCl in the slurry increased from 0 to 3%, the porosity of obtained porous BCP ceramics decreased from 77.76% to 60.22%; the average width of dendritic pores increased from 74.37 µm to 111.27 µm; the compressive strength achieved threefold increase. As the amount of NaCl additive reached 4.5%, the porosity, pore width, and compressive strength of the porous BCP ceramics were comparable with those modified by 3% NaCl. NaCl is regarded as an effective additive to tailor the pore structure and property of freeze-cast porous ceramics.     

Fabrication and characterization of porous β-tricalcium phosphate scaffolds coated with alginate

All porous materials have a common limitation which is lack of strength due to the porosity. In this study, two different methods have been used to produce porous β-tricalcium phosphate (β-TCP) scaffolds: liquid-nitrogen freeze casting and a combination of the direct-foaming and sacrificial-template methods. Among these two methods, porous β-TCP scaffolds with acceptable pore size and compressive strength and defined pore-channel interconnectivity were successfully fabricated by the combined direct-foaming and sacrificial-template method. The average pore size of the scaffolds was in the range of 100–150 µm and the porosity was around 70%. Coating with 4 wt% alginate on porous β-TCP scaffolds led to higher compressive strength and low porosity. In order to make a chemical link between the β-TCP scaffolds and the alginate coating, silane coupling agent was used. Treated β-TCP scaffold showed improvements in compressive strength of up to 38% compared to the pure β-TCP scaffold and 11% compared to coated β-TCP scaffold.     

The effect of macro/micro combination pore structure of biphasic calcium phosphate scaffold on bioactivity

Cellular responses such as adhesion, spreading, growth and proliferation can be altered by macro and micro pores as well as surface patterns on its surface. In this study, the scaffold was prepared with interconnected macro pores by the polymeric sponge method and with interconnected micro pores by BCP slurry coating with different particle sizes on sintered porous body and necking sintering process. Two particle sizes for micro pores, 200–400 nm and 600–800 nm, were coated on a pre-sintered porous body. A combined macro and micro pore structure of the BCP scaffold can improve osteoblast cellular activity. In vitro study of MG63 cells suggest that the modified scaffolds improved cell response such as cell spreading, proliferation and differentiation. The scaffold that has a uniform distribution of micro pores ranging 1~5 µm in diameter on its surface yields the highest rate of cellular response.     

Preparation and characterisation of HA/TCP biphasic porous ceramic scaffolds with pore-oriented structure

Porous hydroxyapatite/tricalcium phosphate (HA/TCP) ceramic scaffolds with a uniform unidirectional pore structure were successfully fabricated by an ice-templating method by using Ca-deficient HA whiskers and phosphate bioglass. HA whiskers showed good dispersibility in the slurry and favoured the formation of interconnected pores in the scaffolds. Addition of bioglass powders enhanced the material sintering process and the phase transformation of Ca-deficient HA to β-TCP. Calcium-phosphate-based scaffolds with a composition from HA to an HA/β-TCP complex could be obtained by controlling the freezing moulding system and slurry composition. The fabricated scaffolds had a porosity of 75–85%, compressive strength of 0.5–1.0 MPa, and a pore size range of 130–200 µm.     

Fabrication of cancellous-bone-mimicking β-tricalcium phosphate bioceramic scaffolds with tunable architecture and mechanical strength by stereolithography 3D printing

It is highly challenging to fabricate bioceramic scaffolds mimicking architecture and mechanical strength of cancellous bone. Gyroid structure, which is based on triply periodic minimal surface, highly resembles the architecture of cancellous bone. Herein, β-tricalcium phosphate (β-TCP) bioceramic scaffolds with gyroid structure were fabricated by stereolithography (SLA) 3D printing. The SLA 3D printing ensured high precision of ceramic part. The porosity (51–87%), pore size (250 – 2400 µm), pore wall thickness (< 300 µm) and compressive strength (0.6 – 16.8 MPa) of gyroid bioceramic scaffolds were readily adjusted to match various sites of cancellous bone. The gyroid bioceramic scaffolds were more favorable for cell proliferation than the grid-like bioceramic scaffolds. The cancellous-bone-mimicking gyroid bioceramic scaffolds with tunable architecture and mechanical strength were expected to efficiently repair the target bone defects.     

In vitro biodegradable and mechanical performance of biphasic calcium phosphate porous scaffolds with unidirectional macro-pore structure

In this study, porous biphasic calcium phosphate (BCP) scaffolds were fabricated by a freeze–gel casting technique using a tertiary-butyl alcohol (TBA) based slurry. After sintering, unidirectional macropore channels of scaffolds aligned regularly along the TBA ice growth direction were tailored simultaneously with micropores formed in the outer wall of the pore channels. The synthesized porous BCP scaffolds (two different sintering temperatures) exhibit compressive strength of 46.8 MPa for 43.0% porosity and 33.1 MPa for 45.9% porosity, respectively. After immersion in Hank's balanced salt solution (HBSS) for 1, 2, 4, 8 weeks, a precipitation started to be formed with individual small granules on the scaffolds surface. In the case of BCP scaffolds sintered at 1200 °C, β-TCP were slowly degraded with increasing the immersing time; on the other hand, α-TCP (from BCP scaffolds sintered at 1300 °C) was extremely degraded within 1 week of immersing. This behavior could be due to a fast hydrolysis (dissolution–reprecipitation) as a phase transformation from α-TCP to brushite or apatite compared to the β-TCP. After immersion in HBSS, overall the compressive strength of the scaffolds reduced by the gradual degradation in biological environment solution. This behavior is consistent with the degradation behavior of scaffolds after immersion in HBSS.     

Subtractive manufacturing of customized hydroxyapatite scaffolds for bone regeneration

An approach to the preparation of customized hydroxyapatite scaffolds for bone regeneration based on subtractive manufacturing has been developed. The developed method is intended as a simple alternative to rapid prototyping based on additive manufacturing methods. The method for the preparation of customized scaffolds consists in computer numerical controlled (CNC) milling of porous hydroxyapatite foam. The machinable foam for customized scaffolds was prepared by direct foaming of a colloidal hydroxyapatite suspension and the foam structure was consolidated by the gelcasting method. The optimal foam after sintering reached a high porosity of 83.3% and the cellular-like structure contained spherical pores with an average diameter of 613 µm, which were connected through windows with an average diameter of 161 µm. The compressive strength of the sintered foam reached an average value of 2 MPa. CNC milling was tested at different stages of the production cycle of the porous foam and after the reinforcing of the foam by impregnation. The best results were obtained by milling the foam presintered at 1100 °C. The milling process was demonstrated and scaffold examples were successfully manufactured.     

3D pore-interconnected calcium phosphate bone blocks for bone tissue engineering

Pore size and connectivity of artificial bone scaffolds play key role in regulating cell ingrowth and vascularization during healing. The objective of this study was to develop a novel process for preparing 3D pore-interconnected open-cell bone substitutes with varying pore sizes. This was achieved by thermal-induced expansion, drying, then sintering the mixture of biphasic calcium phosphate (BCP) and a thermal responsive porogen comprising chitosan (CS) and hydroxypropyl methyl cellulose (HPMC). The interpolymer complexes (IPCs) of CS/HPMC were prepared and investigated by FT-IR. The mixtures of IPCs/BCP were heated up to 100 °C for analyzing their thermal expansion properties. This resulted in ~13% and ~42% volume increment for IPC-1/BCP and IPC-2/BCP, respectively, while ~230% volume increased in the case of IPC-3/BCP (therefore chosen for sintering bone blocks). Heating rate-dependent (0.20–0.25 °C/min range) sintering profiles for IPC-3/BCP were utilized to produce BCP bone blocks. Gasification of IPC during sintering resulted in the formation of interconnected porous structures, and the morphology was investigated by SEM, revealing varying sizes ranging from 106 ± 13 μm to 1123 ± 75 μm. The pore size range of bone blocks from 235 ± 46 μm to 459 ± 76 μm portrayed significantly high MC3T3-E1 cell viability with prominent filopodial extensions, and elongated cells, depicting efficient biocompatibility. Therefore, the process for preparing porous interconnected 3D bone blocks were feasible, thereby serving as an alternative for potential bone tissue engineering applications.     

Fabrication and characterization of honeycomb β-tricalcium phosphate scaffolds through an extrusion technique

In this study, for the first time honeycomb β-tricalcium phosphate (β-TCP) scaffolds were fabricated through an extrusion technique. The physicochemical properties and cell behaviors of the honeycomb β-TCP scaffolds were investigated. The results showed that scaffolds were characterized by ordered channel-like macropores and unidirectional interconnection. The pore structure and mechanical strength could be tailored by changing the parameters of extrusion molds. The pore size of scaffolds was in the range of 400–800 µm approximately, while their compressive strength parallel to the pore direction and porosity ranged from 14 to 20 MPa and 60–70%, respectively. The in vitro cell behavior demonstrated that cells could well attach on the surfaces and grow into the inner channel-like pores of thescaffolds; the scaffolds with higher porosity showed better cell proliferation but poorer cell differentiation. The honeycomb scaffolds fabricated by extrusion technique are potential candidate for bone tissue engineering.     

Fabrication and properties of porous β-tricalcium phosphate ceramics prepared using a double slip-casting method using slips with different viscosities

A new method to enhance the flexural strength of porous β-tricalcium phosphate (β-TCP) scaffolds was developed. This new method provides better control over the microstructures of the scaffolds and enhances the scaffolds’ mechanical properties. Using this technique, we were able to produce scaffolds with mechanical and structural properties that cannot be attained by either the polymer sponge or slip-casting methods alone or by simply combining the polymer sponge and slip-casting methods. The prepared scaffolds had an open, uniform, interconnected porous structure with a bimodal pore size of 100.0–300.0 μm. The flexural strength of the bimodal porous β-TCP scaffold sintered at 1200 °C was 56.2 MPa and had porosity of 61.4 vol%. The scaffolds obtained provide good mechanical support while maintaining bioactivity, and hence, these bioscaffolds hold promise for applications in hard-tissue engineering.     

Compressive strength and biomineralisation improvement by water glass coating on porous calcium phosphate scaffolds

Calcium phosphate (Ca–P) based scaffolds were found to be a favourable alternative for orthopaedic applications because of their similar chemical composition to natural bone. In this study, porous triphasic Ca–P scaffolds containing macropores (∽200?μm) interconnected with micropores (∽20?μm) were fabricated using an extrusion method. The hydroxyapatite/tricalcium phosphate ratio of the porous scaffolds was varied using different ratios of starting materials while keeping the Ca/P ratio fixed (1.5). A water glass coating on the porous Ca–P scaffolds increased the compressive strength by 45% without significantly decreasing the porosity of the H100D50 scaffold. The maximum compressive strength, ～15?MPa, was achieved on the H100D50 scaffold. The ability for apatite formation in simulated body fluid was amplified by the water glass coating on the sintered Ca–P scaffolds. Therefore, a water glass coating can be used to enhance the mechanical properties as well as the biomineralisation of the porous ceramic scaffolds.     

Preparation of high strength lamellar porous calcium silicate ceramics by directional freeze casting

In this study, porous calcium silicate (CS) ceramics with oriented arrangement of lamellar macropore structure were prepared by directional freeze casting method. The lamellar macropores were connected by the micropores on the pore wall, which had good pore interconnectivity. The effects of solid loading of the slurry, freezing temperature, sintering additive content, and sintering temperature on the microstructures and compressive strength of the synthesized porous materials were investigated systematically. The results showed that with the increase of solid loading (≤20 vol%) and sintering additive content, the sizes of lamellar pores and pore walls increased gradually, the open porosity decreased and the compressive strength increased. The sintering temperature had little effect on the pore size of the ceramics, but increasing the sintering temperature (≤1050 °C) promoted the densification of the pore wall, reduced the porosity, and improved the strength. The decrease of freezing temperature had little effect on porosity, but it reduced the size of lamellar pore and pore wall, so as to improve the strength. Finally, porous CS ceramics with lamellar macropores of about 300–600 μm and 2–10 μm micropores on the pore wall were obtained. The porous CS ceramics had high pore interconnectivity, an open porosity of 66.25% and a compressive strength of 5.47 MPa, which was expected to be used in bone tissue engineering.     

A Novel Biphasic Bone Scaffold: β-Calcium Phosphate and Amorphous Calcium Polyphosphate

Calcium polyphosphate (CPP) was added to hydroxyapatite (HA) to develop a novel biphasic calcium phosphate (BCP). The effects of varying CPP dosage on the sintering property, the mechanical strength, and the phase compositions of HA were investigated. Results showed that CPP reacted with HA and produced β-calcium phosphate (β-TCP) and H₂O and that an excessive dosage of CPP (>10 wt%) obtained a novel BCP of β-TCP/amorphous-CPP, while a lesser dosage of CPP (<10 wt%) obtained a traditional BCP (HA/β-TCP). The porous β-TCP/amorphous-CPP scaffolds (porosity of 66.7%, pore diameter of 150–450 μm, and compressive strength of 6.70±1.5 MPa) were fabricated and their in vitro degradation results showed a significant improvement of degradation with the addition of CPP.     

Studies on processing of layered oxide-bonded porous sic ceramic filter materials

Oxide-bonded porous SiC ceramic filter supports were prepared using SiC powder (d₅₀ = 212 µm), Al₂O₃, and clay as bond forming additives and graphite as pore former following reaction bonding of powder compacts at 1400°C in air. Reaction bonding characteristics, phase composition, porosity, pore size, mechanical strength, and microstructure of porous SiC ceramic supports were investigated. Mullite bond phase formation kinetics was studied following the Johnson–Mehl–Avrami–Kolmogorov (JMAK) model using non-isothermal differential thermal analysis (DTA) data. Compared to porous SiC ceramic filter supports having no needle-like mullite bond phase, materials processed by the mullite bonding technique exhibited higher average strength (22.1%) and elastic modulus (5.4%) at a similar porosity level of ~38%, with upper and lower bounds of their strength, modulus, and porosity being 39.1 MPa, 40.2 GPa, and 36.3% and 34.2 MPa, 31.3 GPa, and 33.0%, respectively. Spray coating method was applied for preparation of oxidation-bonded SiC filtration layer having thickness of ~150 µm and pore size of ~5–20 µm over the porous SiC support compacts using aqueous slurry made of fine SiC powder (d₅₀ = 15 µm) followed by sintering. The layered ceramics thus prepared are potential materials for gas filter applications.     

Sintering and characterization of in situ formed porous cordierite ceramics with nano boehmite additions

In this study, we investigated the effect of sintering temperature and nano boehmite additions on the phase composition, densification, and mechanical properties of porous cordierite ceramics. Ceramic samples were sintered at temperatures ranging from 1200 to 1400°C. Carbon powder was used as a pore forming agent to improve the porosity of the ceramic structure. Nano boehmite and carbon additions significantly enhanced ceramic porosity and average pore size in sintered samples. The bulk density and apparent porosity of the sintered samples were found to be 0.96–1.53 g/cm³ and 42.3%–65.6%, respectively. Sintered samples had cold crushing strengths of 1.5–14.3 MPa. The microstructure obtained by scanning electron microscopy was used to measure average pore size in sintered samples and was found to be 41.93 µm for stoichiometric composition (SC), 67.72 µm for SC and nano boehmite, and 102.98 µm for SC, nano boehmite, and carbon. The microstructure of the sintered samples revealed that the crystallinity of the in situ formed phases increased with the increase in nano boehmite additions.     

Novel Layered Hydroxyapatite/Tri‐Calcium Phosphate–Zirconia Scaffold Composite with High Bending Strength for Load‐Bearing Bone Implant Application

The integration of biological and mechanical requirements remains a challenge in developing porous hydroxyapatite (HA) and tri‐calcium phosphate (TCP) scaffolds for load‐bearing bone implant application. With the newly developed slip‐deposition and coating‐substrate co‐sintering technique, a strong layered HA/TCP‐zirconia scaffold composite structure was successfully fabricated. The bending strength (321 MPa) of this composite can match upper strength limit of the natural compact bone. The HA‐based scaffold coating has multiple scale porous structures with pore size ranging 1–10 and 20–50 μm. The zirconia‐based substrate is also porous with submicropores. Focus ion beam micrographs show most of the micropores in the coating are interconnected. Microindentation and primarily adhesive strength tests demonstrate that the scaffold coating strongly bonds with the zirconia based substrate. In vitro cell culture study indicates that the coatings have no cytotoxicity. It is evident that the strong layered HA–zirconia scaffold composite offers new implant options for bone repairs requiring immediate load bearing capacity.     

Tough and hierarchical porous cryogel scaffolds preparation using n-butanol as a non-solvent

Hierarchical porous chitosan cryogels were prepared by combination of cryogelation and phase separation techniques. n-Butanol was included as a non-solvent in the initial polymer solutions to enable phase separation. The internal morphology of the resulting cryogels revealed hierarchical porosity where larger pores of between 25–50?µm were formed via cryogelation, whereas smaller pores of between 4–10?µm were produced by phase separation. The control sample prepared without n-butanol exhibited monotype porosity. Any crack development was not observed when samples were compressed up to 80% strain. The results demonstrated hierarchical porous and tough scaffolds with potential use in tissue engineering.     

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

Highly 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.