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.     

Synthesis and characterisation of β-TCP/bioglass/zirconia scaffolds

Tricalcium phosphate scaffolds reinforced with bioglass were characterised morphologically, physically, and mechanically. The scaffolds were fabricated through powder technology and the polymer foaming technique using 80?wt-% of β-TCP and 20?wt-% of phosphate-based bioglass doped with zirconia in various amounts (0, 0.25, 0.5, 0.75, and 1.0?wt-%). The foaming agent was varied (1, 1.5, 2, 2.5, and 3?wt-%) to determine the optimal amount that ensured an interconnected porosity and pore size suitable for increasing osteoconduction and cell attachment. Promising samples for tissue engineering applications showed a pore size ranging from 1.41 to 303?μm, total porosity of 50–53%, compressive strength values between 0.6 and 1?MPa, Young’s modulus from 357 to 574?MPa, and excellent interconnectivity.     

Mechanical strength and biocompatibility of bredigite (Ca7MgSi4O16) tissue-engineering scaffolds modified by aliphatic polyester coatings

Bredigite (Ca₇MgSi₄O₁₆) is a bioceramic with excellent bioactivity and bioresorbability; nonetheless, its inadequate mechanical strength and biocompatibility limit its tissue-engineering application. In this research, interconnected porous bredigite scaffolds were fabricated by sol-gel, sacrificial sponge replica and sintering processes for bone tissue engineering. In order to improve their strength and cytocompatibility, the scaffolds were coated with poly(lactic-co-glycolic acid) (PLGA) via immersion in acetone-based solutions containing different concentrations (5, 10 and 15% w/v) of the polymer. Based on the results, the PLGA coatings to 10% do not suppress the porosity characteristics of the scaffolds appropriate for tissue engineering. It was also found that the polymeric coatings significantly enhance the compressive strength of the ceramic scaffolds, where this alteration is improved by increasing the PLGA concentration of the coating solution. In addition, the viability of stem cells on the bredigite scaffolds are improved by using the PLGA coatings, with the optimal concentration of 10% PLGA according to MTT and cell attachment studies.     

Improvement of mechanical properties of macroporous β-tricalcium phosphate bioceramic scaffolds with uniform and interconnected pore structures

The biocompatible and degradable macroporous bioceramic scaffolds with high mechanical properties and interconnected porous structures play an important role in hard tissue regeneration and bone tissue engineering applications. In this study, the improvement of mechanical properties of macroporous β-tricalcium phosphate [β-Ca₃(PO₄)₂, β-TCP] bioceramic scaffolds with uniform macropore size and interconnected pores were fabricated by impregnation of the synthesized β-TCP nano-powder slurry into polymeric frames. The microstructures, mechanical properties and in vitro degradation of the fabricated samples were investigated. For a comparison, β-TCP scaffolds were also fabricated from commercial micro-size powders under the same conditions. The resultant scaffolds showed porosities ∼65% with uniform macropore size ranging from 400 to 550 μm and interconnected pore size ∼100 μm. The compressive strength of the samples fabricated from nano-size powders reached 10.87 MPa, which was almost twice as high as those fabricated from commercial micro-size powders, and was comparable to the high-end value (2–10 MPa) of human cancellous bone. Furthermore, the degradation of the β-TCP bioceramics fabricated from nano-size powders was apparently lower than those fabricated from commercial micro-size powders, suggesting the possible control of the degradation of the scaffolds by regulating initial powder size. Regarding the excellent mechanical properties and porous structures, the obtained macroporous β-TCP bioceramic scaffolds can be used in hard tissue regeneration and bone tissue engineering applications.     

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.     

Three-dimensional printing of triply periodic minimal surface structured scaffolds for load-bearing bone defects

The porous and cellular architecture of scaffolds plays a significant role in mechanical strength and bone regeneration during the healing of fractured bones. In this present study, triply periodic minimal surface (TPMS)-based gyroid and primitive lattice structures were used to design the cellular porous biomimetic scaffolds with different unit cell sizes (4, 5, and 6). The fused filament fabrication-based 3D printing technology was used for the fabrication of polylactic acid scaffolds. The surface morphology and mechanical compressive strength of differently structured scaffolds were observed using scanning electron microscopy and a universal testing machine. The unit cell size of 4 showed higher compressive strength in both gyroid and primitive structured scaffolds compared to unit cell sizes 5 and 6. Moreover, the gyroid structured scaffolds have higher compressive strengths as compared to primitive structured scaffolds due to the higher bonding surface area at the intercalated layers of the scaffold. Hence, the mechanical strength of scaffolds can be tailored by varying the unit cell size and cellular structures to avoid stress shielding and ensure implant safety. These TPMS-based scaffolds are promising and can be used as bone substitute materials in tissue engineering and orthopedic applications.     

Development of fibrin conjugated chitosan/nano β‐TCP composite scaffolds with improved cell supportive property for bone tissue regeneration

In the present study, an attempt has been made to improve cell supportive property of chitosan/nano beta tri‐calcium phosphate (β‐TCP) composite scaffolds by modification of scaffold surface with fibrin using ethyl‐3‐(3‐dimethylaminopropyl) carbodimide (EDC) as crosslinking agent. The developed fibrin conjugated chitosan/nano β‐TCP composite scaffolds possess desired pore size and porosity in the range of 45–151 µm and 81.4 ± 4.1%, respectively. No significant change in compressive strength of scaffolds was observed before and after fibrin conjugation. The calculated compressive strength of fibrin conjugated and non‐conjugated chitosan/nano β‐TCP scaffolds are 2.71 ± 0.14 MPa and 2.67 ± 0.11 MPa, respectively. Results of cell culture study have further shown an enhanced cell attachment, cell number, proliferation, differentiation, and mineralization on fibrin conjugated chitosan/nano β‐TCP scaffold. The uniform cell distribution over the scaffold surface and cell infiltration into the scaffold pores were assessed by confocal laser scanning microscopy. Furthermore, higher expression of osteogenic specific genes such as bone sialo protein, osteonectin, alkaline phosphatase, and osteocalcin (OC) on fibrin conjugated scaffolds was observed when compared to scaffolds without fibrin. Altogether, results indicate the potentiality of developed fibrin conjugated composite scaffolds for bone tissue engineering applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41534.     

Compressive strength of β-TCP scaffolds fabricated via lithography-based manufacturing for bone tissue engineering

Bone is a vital organ that is responsible for the support and movement of body as well as the storage and transportation of cells and nutrients. Disease, along with traumatic events, can leave regions of bone with large voids and/or defects. Related surgical procedures, such as allografts, autografts, and arthroplasty, are reported to amount to roughly €9.6bn annually, emphasising the need for bone repair/replacement globally. Tricalcium phosphate (TCP) is a bioactive ceramic that has been identified as a suitable material for bone tissue engineering applications due to its excellent bioresorbability and overall biocompatibility. Through lithography-based ceramic manufacturing (LCM), β -TCP scaffolds were fabricated across nine different designs in this work. Pore size, unit cell size, and unit cell geometry were altered to vary the porosity of these scaffolds. Following fabrication, the material composition, topography, macrostructure, and microstructure of the β-TCP scaffolds were characterised. The effects of porosity and unit cell geometry on the compressive strengths of β -TCP scaffolds were analysed in detail. Compressive strengths of the scaffolds were measured between 1.4 ± 0.5 MPa and 67.6 ± 13.3 MPa across a porosity range of 5.58 ± 0.09% to 59.36 ± 0.18%. The strength of these scaffolds was considerably lower than that of the compressive strength of cortical bone (100–200 MPa), but mimic the compressive strength of cancellous bone well (0.1–16 MPa). While scaffolds of β-TCP alone may not be suitable for load-bearing applications, they demonstrate enough mechanical stability for bone regeneration/tissue engineering applications. They hold more potential in the regeneration of small bone defects/voids or in composite materials.     

3D Composite scaffolds using strontium containing bioactive glasses

In this study, it was aimed to fabricate and characterize three-dimensional composite scaffolds derived from Sr-doped bioactive glass for bone tissue engineering applications. The scaffolds were fabricated by using polymer foam replication technique and coated with gelatin to be able to improve the properties of them. The porous scaffolds were successfully synthesized using optimized process parameters. Both coated and uncoated scaffolds favored precipitation of calcium phosphate layer when they were soaked in simulated body fluid (SBF). Gelatin coating improved the mechanical properties of the scaffold and also it did not change the bioactive behavior of the scaffold. It was observed that there was a good pore interconnectivity maintained in the scaffold microstructure. Results indicated that scaffolds can deliver controlled doses of strontium toward the SBF medium. That is the determinant for bone tissue regeneration, as far as strontium is known to positively act on bone remodeling.     

Effect of the drying process on the compressive strength and cell proliferation of hydroxyapatite‐derived scaffolds

The compressive strength and MC3T3 cell proliferation response of robocast hydroxyapatite‐derived scaffolds was evaluated for samples fabricated by conventional and freeze‐drying methods followed by sintering at 1100 or 1300°C. Both the sintering temperature and, especially, the drying method affected significantly the size and morphology of the residual microporosity within the robocast scaffold's struts. The freeze‐drying method generated a persistent large (1‐10 μm) microporosity of dendritic morphology that was found to improve the biological response of hydroxyapatite‐derived scaffolds. Conversely, conventional drying enhances the compressive strength of the structures. Strength was also increased at the higher sintering temperature, although at the expense of a poorer cell proliferation behavior. The results of this study suggest that the use of a freeze drying process after printing by robocasting provides a very appropriate method for enhancing the biological performance and reliability of bioceramic robocast scaffolds without severely reducing their compressive strength. And, thus, shows promise as an effective method to optimize the performance of robocast scaffolds for bone tissue regeneration.     

Robocasting and surface functionalization with highly bioactive glass of ZrO2 scaffolds for load bearing applications

This work is a proof of concept for making load bearing implants with osseointegration and bone bonding ability. Yttria-stabilized zirconia (YSZ) scaffolds with a percentage of macro porosity of about 70% were fabricated by robocasting. Although a maximum solids volume fraction of 50 vol.% could be achieved, the 3D-printing process revealed to be more reliable when using inks with 48 vol.% solids. The sintered porous structures exhibited an average compressive strength of ~236 MPa. After some preliminary coating experiments, an ethanol slurry of fine bioactive glass (BG) particles (10 wt.%) stabilized with polyvinylpyrrolidone was used to deposit a uniform surface coating onto the filaments, followed by glazing at 850°C. The functionalized scaffolds showed a relatively uniform surface coverage by the bioactive glass. The results of in vitro testing by immersing the scaffolds in simulated body fluid (SBF) showed remarkable morphological surface changes and an extensive deposition of hydroxyapatite layer. The overall results demonstrate the viability of producing porous YSZ scaffolds with excellent bioactivity, which are promising for bone tissue engineering under load bearing applications.     

Synthesis and characterization of a novel freeze‐dried silanated chitosan bone tissue engineering scaffold reinforced with electrospun hydroxyapatite nanofiber

Novel chitosan scaffolds containing different weight ratios of electrospun hydroxyapatite nanofibers (n‐HAs) were fabricated. The fibers possessed diameters in the range 110–170 nm. A fixed concentration of glycidyloxypropyl‐trimethoxysilane (GPTMS) as a crosslinking agent was added to the chitosan solution (CG). The porosity percentage was increased when GPTMS and n‐HAs were added to the chitosan structure. The presence of GPTMS in the chitosan structure caused a decrease in the average pore size. The pores were more irregular in shape than pure chitosan and CG scaffolds when n‐HAs were added. A uniform distribution of n‐HAs was seen for a chitosan‐GPTMS hybrid scaffold containing 25 wt% n‐HAs (CGH25) using energy dispersive X‐ray spectroscopy and mapping. The best values of compressive strength and elastic modulus were achieved for CGH25. The swelling ratio was decreased on adding GPTMS to the chitosan scaffold. Different morphologies of hydroxyapatite deposits on the surface of CG and CGH25 (string‐like versus needle‐like precipitates) were observed after 14 days of soaking in simulated body fluid. For CGH25, the viability of MG‐63 osteoblastic cells improved with respect to CG for up to 72 h of cell culture. These results reveal the potential of the chitosan‐CGH25 scaffold for use in bone tissue engineering. © 2019 Society of Chemical Industry     

仿天然孔径结构氧化铝质人造岩芯的研制

采用氧化铝、矾土等原料为骨料,以丙烯酰胺为单体、聚甲基丙烯酸铵为分散剂、氨水为体系pH值的调节剂、引发剂、造孔剂和催化剂,利用凝胶注模原位固化成型技术、骨料堆积法和添加造孔剂法制备出了仿天然孔径结构的人造岩芯。抗压强度、显气孔率的性能测试和SEM的分析表明:人造岩芯的抗压强度≥50MPa、显气孔率≥25%、微细孔径≤0.lmm。     

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.     

Effects of microwave sintering on the properties of porous hydroxyapatite scaffolds

Microwave sintering was used to process porous hydroxyapatite scaffolds fabricated by the extrusion deposition technique. The effects of microwave sintering on the microstructure, phase composition, degradation, compressive strength and biological properties of the scaffolds were investigated. After rapid sintering, scaffolds with controlled structure, high densification and fine grains were obtained. A significant increase in mechanical strength was observed relative to conventional sintering. The scaffolds (55–60% porosity) microwave sintered at 1200 °C for 30 min exhibited the highest average compressive strength (45.57 MPa). The degradation was determined by immersing the scaffolds in physiological saline and monitoring the Ca²⁺concentration. The results indicated that the microwave-sintered scaffolds possessed higher solubility than conventionally sintered scaffolds, as it released more Ca²⁺ at the same temperature. Furthermore, an in vitro MC3T3-E1 cell culturing study showed significant cell adhesion, distribution, and proliferation in the microwave-sintered scaffolds. These results confirm that microwave sintering has a positive effect on the properties of porous hydroxyapatite scaffolds for bone tissue engineering applications.     

Novel fabrication of hierarchically porous hydroxyapatite scaffolds with refined porosity and suitable strength

Based on extrusion deposition and foaming technique, a novel method for biological hydroxyapatite (HA) scaffolds was introduced in this paper. The scaffolds were primarily characterised by interconnected and hierarchically porous structures with high porosity, adjustable distribution of pore sizes, as well as considerable mechanical strength. In order to confirm that fine control of bulk porosity and mechanical strength was possible and feasible, further analysis of obtained scaffolds was carried out by field emission scanning electron microscope (FESEM), compressive test and calculation of volumetric shrinkage; in particular, the additional porosity resulting from the introduction of pore former was evaluated. The results indicated that this method can have a great potential to construct HA scaffolds of suitable quality for spongy bone in bone tissue engineering.     

Preparation of Porous Scaffolds from Silk Fibroin Extracted from the Silk Gland of Bombyx mori (B. mori)

In order to use a simple and ecofriendly method to prepare porous silk scaffolds, aqueous silk fibroin solution (ASF) was extracted from silk gland of 7-day-old fifth instar larvae of Bombyx mori (B. mori). SDS-page analysis indicated that the obtained fibroin had a molecular weight higher than 200 kDa. The fabrication of porous scaffolds from ASF was achieved by using the freeze-drying method. The pore of porous scaffolds is homogenous and tends to become smaller with an increase in the concentration of ASF. Conversely, the porosity is decreased. The porous scaffolds show impressive compressive strength which can be as high as 6.9 ± 0.4 MPa. Furthermore, ASF has high cell adhesion and growth activity. It also exhibits high ALP activity. This implies that porous scaffolds prepared from ASF have biocompatibility. Therefore, the porous scaffolds prepared in this study have potential application in tissue engineering due to the impressive compressive strength and biocompatibility.     

Evaluation of mechanical behavior,bioactivity, and cytotoxicity of chitosan/akermanite-TiO2 3D-printed scaffolds for bone tissue applications

This report aimed to evaluate the mechanical behavior, bioactivity, and cytotoxicity of novel chitosan/akermanite-TiO₂ (CS/AK/Ti) composite scaffolds fabricated using the 3D-printing method. The morphological and structural properties of these scaffolds were characterized by Fourier transform spectroscopy (FTIR) and scanning electron microscopy (SEM). The mechanical behavior was examined by measuring the compressive strength, while the bioactivity was estimated in the simulated body fluid (SBF), and also the cytotoxicity of the scaffolds was assessed by conducting cell culturing experiments in vitro. It was found that the mechanical properties were considerably affected by the amount of TiO_2. The scaffolds had the possessed bone-like apatite forming ability, which indicated high bioactivity. Furthermore, L929 cells spread well on the surface, proliferated, and had good viability regarding the cell behaviors. The outcomes confirmed that the morphological, biological, and mechanical properties of developed 3D-composite scaffolds nearly mimicked the features of natural bone tissue. In summary, these findings showed that the 3D-printed scaffolds with an interconnected pore structure and improved mechanical properties were a potential candidate for bone tissue applications.     

Fabrication and properties of 3D printed zirconia scaffold coated with calcium silicate/hydroxyapatite

The scaffold of bone repair needs a variety of material combinations to meet its intended performance; a typical single material such as zirconia has excellent mechanical properties, while hydroxyapatite and calcium silicate are bioactive materials with different degradation rates. In this paper, porous zirconia scaffolds were fabricated using 3D printing technology. The surface of the scaffold was coated by dipping with different contents of calcium silicate and hydroxyapatite to improve the biological activity and mechanical properties. Mechanical tests show that the coating material can effectively fill the pores of the porous scaffold, increasing its compressive strength by an average of 55%. The simulated body fluid (SBF) test showed that the higher calcium silicate in the coating increased the degradation rate. Cell experiments showed that the coated scaffolds exhibited good cytocompatibility and were beneficial to the proliferation and differentiation of cells. In conclusion, coated scaffolds have potential applications in the field of bone repair.     

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.