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.     

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.     

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.     

Studies on novel bioactive glasses and bioactive glass-nano-HAp composites suitable for coating on metallic implants

A series of novel zinc oxide (ZnO) containing bioactive glass compositions in SiO₂-Na₂O-CaO-P₂O₅ system and composite with hydroxyapatite (HAp) nano-particles were developed and applied as coating on Ti-6Al-4V substrates. The bioactive glasses and their composites were also processed to yield dense scaffolds, porous scaffolds and porous bone filler materials. The coating materials and the coatings were characterized and evaluated by different in vitro techniques to establish their superior mechanical properties. The cytotoxicity test of the coating material, porous and dense scaffolds and coated specimens showed non-cytotoxicity, biocompatibility and promising in vitro bioactivity for all tested samples. The dissolution behaviour studies of the bioactive glasses and the composites in simulated body fluid showed promising in vitro release pattern and bioactivity for all tested samples. Addition of nanosized HAp improves mechanical properties of the bioactive glass coating without affecting the in vitro bioactivity.     

Porous Hydroxyapatite Scaffolds Coated With Bioactive Apatite–Wollastonite Glass–Ceramics

The objective of this study was to fabricate porous hydroxyapatite (HA) scaffolds coated with bioactive A/W glass–ceramics and to examine their mechanical and biological properties. Firstly, the HA scaffolds were prepared by the polymeric sponge replication method, and then A/W glasses were coated on the surface of the struts. All of the scaffolds had a highly porous structure with well-interconnected pores. It was observed that the bioactive glass coating markedly increased the strength of the HA scaffolds. This enhancement was attributed to the formation of a dense and strong coating layer on the weak HA struts. The in vitro bioactivities of the scaffolds were markedly improved by the coatings. When the coated scaffolds were soaked in a simulated body fluid (SBF), the bone-like apatite crystals were well mineralized on their surfaces. Osteoblast-like cells (MC3T3) adhered, spread, and grew well on the porous scaffolds. The cells placed on the glass-coated HA scaffold showed a higher proliferation rate and alkaline phosphatase (ALP) activity than those on the pure HA scaffold. These results demonstrate that the bioactive glass coating is effective in improving the strength and bioactivity of the porous HA scaffolds.     

β-TCP scaffold coated with PCL as biodegradable materials for dental applications

Requirements for an ideal scaffold include biocompatibility, biodegradability, mechanical strength and sufficient porosity and pore dimensions. Beta tricalcium phosphate (β-TCP) has competent biocompatibility and biodegradability, but has low mechanical strength because of its porous structure. Polycaprolactone (PCL) is a biodegradable polymer with elastic characteristics and good biocompatibility. In this study, β-TCP/PCL composites were prepared in different ratio and their morphology, phase content, mechanical properties, biodegradation and biocompatibility were investigated. After coating, surfaces of β-TCP scaffolds were covered with the PCL while some of the pores were partially clogged. The compression and bending strength of β-TCP scaffolds were significantly enhanced by PCL coating. The degradation rate of the scaffold in Tris buffer was reduced with higher content of the PCL coating. MTT and ALP assays showed that the osteoblast cells could proliferate and differentiate on PCL coated scaffolds as well as on bare β-TCP scaffolds. Based on the comprehensive analysis achieved in this study, it is concluded that the β-TCP/PCL composite scaffold fabricated with 40% β-TCP and 5% PCL exhibits optimum properties suitable for dental applications.     

可注射nHA/PU复合多孔骨修复支架制备及表征

兼具良好孔隙率和原位任意塑形固化的可注射复合多孔骨修复材料在临床不规则骨缺损的治疗方面显示出巨大的优势。本研究通过优化双组分设计,以水为发泡剂制备可注射纳米羟基磷灰石/聚氨酯（nHA/PU）复合多孔支架。利用扫描电子显微镜（SEM）、傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）、力学测试及Gillmore针测试等手段对制备的支架进行结构形貌、化学组成、力学性能和固化时间表征。结果表明,本研究制备的可注射nHA/PU复合多孔支架孔隙率高、孔隙贯通性好,孔径分布在100~700μm,适宜细胞和组织向孔内生长;添加20% nHA显著提高了PU支架的力学强度,但降低了支架的孔隙率;可注射支架在8h固化,适宜临床操作。本研究制备的可注射nHA/PU复合多孔支架在不规则骨缺损修复领域具有较大的应用潜力。     

Wollastonite/hydroxyapatite scaffolds with improved mechanical,bioactive and biodegradable properties for bone tissue engineering

Wollastonite/hydroxyapatite composite scaffolds are proposed as bone graft. An investigation on scaffold with varying reinforcing wollastonite content fabricated by polymeric sponge replica is reported. The composition, sintering behavior, morphology, porosity and mechanical strength were characterized. All the scaffolds had a highly porous well-interconnected structure. A significant increase in mechanical strength is achieved by adding a 50% wollastonite phase. The most mechanically resistant (50/50) wollastonite/hydroxyapatite scaffolds were soaked in both simulated body fluid (SBF) and Tris–HCl solution in order to assess bioactivity and biodegradability. A carbo-hydroxyapatite layer formed on their surfaces when immersed in SBF. The biodegradability tests reveals that the composite scaffold shows a higher degradation rate compared to pure hydroxyapatite used as comparison. These results demonstrate that the incorporation of a 50% of wollastonite phase in hydroxyapatite matrix is effective in improving the strength and the bioactive and biodegradable properties of the porous scaffolds.     

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.     

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.     

In Situ Crosslinking of Highly Porous Chitosan Scaffolds for Bone Regeneration: Production Parameters and In Vitro Characterization

Various methods of chitosan scaffold production are reported in the literature so far. Here, in situ crosslinking with glutaraldehyde is reported for the first time. It combines pore formation and chitosan crosslinking in a single step. This combination allows incorporation of fragile molecules into 3D porous chitosan scaffolds produced by simple and gentle lyophilization. In this study, parameters of in situ crosslinking of porous chitosan scaffold formation as well as their effect on degradation and bioactivity of the scaffolds are examined. The scaffolds are characterized in the context of their prospective application as bone substitute material. The addition of calcium phosphate phases (hydroxyapatite, brushite) to the macroporous chitosan scaffolds allows manipulation of the bioactivity that is investigated by incubation in simulated body fluid (SBF). The bioactivity is significantly influenced by the modus of changing the fluid (static, daily‐, and twice‐a‐week change). Scaffolds are morphologically characterized by means of scanning electron microscopy, and the mechanical stability is tested after incubation in SBF and phosphate‐buffered saline.     

Gelatin-layered and multi-sized porous β-tricalcium phosphate for tissue engineering scaffold

The multi-sized porous β-tricalcium phosphate scaffolds were fabricated by freeze drying followed by slurry coating using a multi-sized porous sponge as a template. Then, gelatin was dip coated on the multi-sized porous β-tricalcium phosphate scaffolds under vacuum. The mechanical and biological properties of the fabricated scaffolds were evaluated and compared to the uniformly sized porous scaffolds and scaffolds that were not coated by gelatin. The compressive strength was tested by a universal testing machine, and the cell viability and differentiation behavior were measured using a cell counting kit and alkaline phosphatase activity using the MC3T3-E1 cells. In comparison, the gelatin-coated multi-sized porous β-tricalcium phosphate scaffold showed enhanced compressive strength. After 14 days, the multi-sized pores were shown to affect cell differentiation, and gelatin coatings were shown to affect the cell viability and differentiation. The results of this study demonstrated that the multi-sized porous β-tricalcium phosphate scaffold coated by gelatin enhanced the mechanical and biological strengths.     

Application of strontium doped calcium polyphosphate bioceramic as scaffolds for bone tissue engineering

The critical success factors for bone tissue engineering in clinical applications are scaffolds. Ion doping is one of the most important methods to modify the properties of bioceramics for better angiogenesis abilities, biomechanical properties, and biocompatibility. This paper presents a novel ion doping method applied in calcium polyphosphate (CPP)-based bioceramic scaffolds substituted by strontium ions to form (SCPP) scaffolds for bone tissue regeneration. The microstructure and crystallization of the scaffolds were detected by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Degradation tests were assessed to evaluate the mechanical and chemical stabilities of SCPP in vitro. The cell biocompatibility was measured with respect to the cytotoxicity of the extractions of scaffolds. Bone implantation was performed to evaluate the biodegradability and osteoconductivity of the scaffolds, and the bone formation examined by using X-ray radiography. The results indicated that the obtained SCPP scaffolds had a single CPP phase. The SCPP scaffolds yielded a better degradation property than the pure CPP scaffold. The MTT assay and in vivo results reveal that the SCPP scaffolds exhibited a better cell biocompatibility and tissue biocompatibility than CPP and hydroxyapatite (HA) scaffolds. The in vivo immunohistochemistry staining for VEGF also showed that SCPP had a potential to promote the formation of angiogenesis and the regeneration of bone. SCPP scaffold could serve as a potential biomaterial with stimulating angiogenesis in bone tissue engineering and bone repair.     

Effect of sodium carbonate addition on the properties of calcium silicate scaffolds fabricated by 3DIP

3D ink printing (3DIP) technology can accurately control the macroscopic size and microstructure of bioceramic scaffolds. However, nonceramic components in the printing ink used in 3DIP severely affect densification, resulting in less desirable mechanical properties of the scaffolds. In this study, a strategy of sintering assisted by a sintering aid (sodium carbonate) was used to prepare calcium silicate (CSi) scaffolds with high strength. The addition of 1% sintering aid to a CSi scaffold sintered at 1100 °C led to an appreciable compressive strength (47.8 MPa) and high elastic modulus (1847 MPa). Moreover, the CSi scaffolds with sintering aids showed better degradation ability and mineralization ability than the CSi scaffolds without sintering aids. It is expected that the method involving strengthening with sintering aids will promote the application of 3DIP bioceramic scaffolds in the repair of bone defects.     

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.     

Electrophoretic deposition of nanocrystalline TiO2 particles on porous TiO2-x ceramic scaffolds for biomedical applications

Nanocrystalline TiO₂ coated scaffolds offers the possibility to be used in bone tissue regeneration providing not only space for new tissue formation, but also to enhance bioactivity of the implant. In the present study, direct current electrophoretic deposition (EPD) was chosen as simple and low cost technique to coat 3D porous structure of TiO_2-x ceramic. Suspension for EPD was prepared suspending nanocrystalline TiO₂ particles in isopropanol and adding triethanolamine as dispersant. TiO₂ particles were electrophoretically deposited on the surface of TiO_2-x scaffolds through varying EPD time and applied voltage. The scaffold pore structure was maintained after applying the coating by EPD. The deposition of nanocrystalline TiO₂ coating can be a smart strategy to impart bioactive properties to the 3D scaffold, allowing formation of spherical hydroxyapatite particles on the coated scaffolds after immersion in simulated body fluid. In vitro cell studies does not show cytotoxic effect of nanocrystalline TiO₂ coated scaffolds.     

Effect of PCL concentration on PCL/CaSiO3 porous composite scaffolds for bone engineering

Porous polycaprolactone (PCL)-coated calcium silicate (CaSiO₃) composite scaffolds were successfully prepared by 3D gel-printing (3DGP) and vacuum impregnation technology in this study. The effect of different PCL concentration on porous CaSiO₃ scaffolds prepared by 3DGP technology was studied. The composition and morphological characteristics of PCL/CaSiO₃ scaffolds were tested by using fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and energy dispersive spectrometer (EDS) analysis. PCL coating amount on the scaffolds surface was calculated by thermogravimetric analysis (TGA). Compressive strength was tested by a universal testing machine, and degradability was tested by immersing the scaffolds in a simulated body fluid (SBF). The results show that PCL coating thickness increased from 7.29 μm to 12.2 μm, and the compressive strength of the corresponding composite scaffolds increased from 17.15 MPa to 24.12 MPa following with PCL concentration increasing from 7.5% to 12.5%. When the porous composite scaffolds were immersed in SBF for 28 days, the degradation ratio was 1.06% (CaSiO₃), 1.63% (CaSiO₃-7.5PCL), 1.81% (CaSiO₃-10PCL) and 1.55% (CaSiO₃-12.5PCL), respectively. It is obviously that PCL/CaSiO₃ composite scaffolds, which are suitable for bone growth in bone repair engineering, are beneficial to improve the mechanical properties and biodegradability of pure CaSiO₃ scaffolds.     

硅酸钙类骨水泥改性研究进展

硅酸钙类骨水泥材料具有良好的自固化性能，能够作为硬组织修复材料对缺损的骨和牙进行填充和修复，但是由于其力学性能不足、固化时间长等缺点限制了其在临床上的应用范围。该文主要综述了硅酸钙粉体的制备方法及硅酸钙类骨水泥的力学强度、凝结时间、可注射性、降解及生物相容性等，并提出今后的研究重点是利用各体系骨水泥间的性能互补关系，将硅酸钙类骨水泥与其他体系骨水泥进行交叉复合，有望获得综合性能优良的无机复合骨水泥。     

3D printing of polycaprolactone/bioactive glass composite scaffolds for in situ bone repair

3D printing technology can fabricate customized scaffolds based on patient-derived medical images, so it has attracted much attention in the field of developing bone repair scaffolds. Polycaprolactone (PCL) is a suitable polymer for preparing bone repair scaffolds because of its good biocompatibility, thermal stability, excellent mechanical properties and degradable properties. However, PCL is a bioinert material and cannot induce new bone formation at the defect site. In this study, the bioactive material 58s bioactive glass was mixed into PCL to form PCL/bioactive glass composite material. The results of contact angle showed that the hydrophilicity of the scaffold was significantly enhanced with the increase of bioactive glass content. In vitro experiment results showed that, with the increase of bioactive glass content, cell adhesion and proliferation were enhanced, the expression levels of Runx2 and Collagen I(COL-I) were upregulated. The experimental results of in vivo radial defect repair in rats also showed that the effect of bone repair was improved with the increase of bioactive glass content. In conclusion, PCL customized bone repair scaffold containing 20% bioactive glass has widely potential used in the field of clinical bone repair.     

Biocompatibility and strengthening of porous hydroxyapatite scaffolds using poly(l-lactic acid) coating

Hydroxyapatite (HA) is a well-known biocompatible bone substitute. Porous HA is more resorbable and osteoconductive compared with non-porous HA, and has been studied both experimentally and clinically. However, the mechanical strength of porous HA scaffolds is known to be weak. In this study, we developed a porous HA scaffold coated with a synthetic biodegradable polymer, poly(l-lactic acid) (PLLA), to strengthen the scaffold. PLLA-coated HA pellets were used to investigate the in vitro proliferation and alkaline phosphatase (ALP) activity of osteoblasts. PLLA-coated porous HA scaffolds were observed using scanning electron microscopy to investigate surface characteristics, porosity, and mechanical strength. PLLA coating concentration varied from 2 to 10 wt%. Osteoblast proliferation was higher in HA samples coated with PLLA compared with non-coated. ALP activity was highest on 8 wt% PLLA-coating after 3 days and on 4 wt% and 6 wt% PLLA after 9 and 12 days. Porous HA scaffolds with higher concentrations of PLLA were found to have a smoother, flatter surface. This enhanced proliferation and attachment of osteoblasts onto the porous HA scaffold. PLLA solution at a concentration of 10 wt% decreased scaffold porosity to half that of HA scaffolds with no PLLA coating. Scaffold mechanical strength was increased two-fold with a PLLA concentration of 2 wt%. Based on in vitro experimentation, it can be concluded that PLLA-coating on porous HA scaffolds enhances both the biocompatibility and the mechanical strength.