Effect Of β-TCP Research Articles

Beta-tricalcium phosphate promotes osteogenic differentiation of bone marrow-derived mesenchymal stem cells through macrophages

Macrophages are vital regulators of skeletal remodeling and osseous repair. Beta-tricalcium phosphate (β-TCP) is a synthetic ceramic biomaterial that has shown promise as bone substitute. However, whether and how β-TCP affects osteogenesis-related responses of macrophages has rarely been studied. The aims of this study were to explore (a) the effects of β-TCP on osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) co-cultured with macrophages and (b) on macrophage polarization as well as macrophage gene and protein expression profiles. BMSC osteogenic differentiation capacity in vitro was enhanced in β-TCP-induced co-cultured BMSCs compared to that in BMSC monocultures. We also found that macrophages induced with 25 mg ml−1 β-TCP extract had more significant immune responses and switched to the M2 phenotype. Expression levels of the Wnt signaling pathway modulators wingless-type MMTV integration site family, member 6 (WNT6) and Wnt inhibitory factor 1 (WIF1) were upregulated and downregulated, respectively, in macrophages treated with β-TCP extract. Our findings suggest that β-TCP enhances osteogenic differentiation of BMSCs by inducing macrophage polarization and by regulating the Wnt signaling pathway, thereby highlighting its therapeutic potential for bone healing through osteoimmunomodulatory properties.

The effects of β-TCP on mechanical properties, corrosion behavior and biocompatibility of β-TCP/Zn-Mg composites.

Zinc has attracted increasing attention in the field of degradable implant materials due to its suitable degradation rate. To further improve the mechanical properties and biocompatibility of zinc, Zn-1Mg-nvol%β-TCP (n = 0, 1, 3, 5) composites were fabricated for biomedical application by the mechanical stirring combined with ultrasonic assisted casting and hot extrusion technology. The microstructure, mechanical properties and corrosion behavior of these composites were systemically investigated and the composite with the best comprehensive performance were selected for biocompatibility evaluation including L-929 cells cytotoxicity test and SD rat model experiment. Tensile test revealed that Zn-1Mg-1vol%β-TCP composite possessed optimal mechanical properties. The yield strength (YS), ultimate tensile strength (UTS), elongation (σ) and elastic modulus (E) of the as-extruded Zn-1Mg-1vol%β-TCP composite are 250.8 MPa, 330.5 MPa, 11.7% and 125.4 GPa respectively. The immersion tests showed that the corrosion resistance of the composite is slightly decreased with the increase of β-TCP content. In addition, the addition of β-TCP makes the cytocompatibility of the composites better than that of the Zn-1Mg alloy matrix. Various blood biochemical parameters in rat serum samples after implantation showed Zn-1Mg alloy and Zn-1Mg-β-TCP composites has not significant tissue inflammation and showed good biocompatibility.

Manufacturing and mechanical characterization of Al2O3/β-TCP/TiO2 biocomposite as a potential bone substitute

This paper focuses on the mechanical characterization of a bioceramic based on commercial alumina (Al2O3) mixed with synthesized tricalcium phosphate (β-TCP) and commercial titania powder (TiO2). The effect of β-TCP and TiO2 addition on the mechanical performance was investigated. After a sintering process at 1600 °C for 1 h, various mechanical properties of the samples have been studied, such as compressive strength, flexural strength, tensile strength, elastic modulus, and fracture toughness. The measurements of the elastic modulus (E) and the tensile strength (σ t ) were conducted using the modified Brazilian test while the compressive strength (σ c ) was determined through a compression test. Also, semi-circular bending (SCB) specimens were used to evaluate the flexural strength (σ f ) and the opening mode fracture toughness (K IC). From the main results, it was found that the best mechanical performance is obtained with the addition of 10 wt.% TCP and 5 wt.% TiO2. Alumina/10 wt.% tricalcium phosphate/5 wt.% titania composites displayed the highest values of mechanical properties and a good combination of compressive strength (σ c ≈ 352 MPa), flexural strength (σ f ≈ 98 MPa), tensile strength (σ t ≈ 86.65 MPa), and fracture toughness (K IC ≈ 13 MPa m1/2).

Characterization of beta-tricalcium phosphate as a novel immunomodulator

Calcium phosphate (CaP) ceramics including hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP) have been widely used for bone substitution in orthopedic, maxillofacial and dental surgery, as well as in tumor resections. CaP particles are also known to cause inflammatory responses, which are thought to be an unfavorable characteristic of prosthetic coating materials. On the other hand, the immunostimulatory effect of β-TCP induces an anti-tumor effect in xenograft tumor models in athymic mice. To date, in depth analysis of the biological effects of β-TCP has not been studied in mice. In the present study, in vivo biological effects of β-TCP were investigated by subcutaneously injecting β-TCP particles into mice. This induced extensive migration of immune cells to the area surrounding the injection. In addition, we found that in vitro treatment with β-TCP in murine monocyte/macrophage cells (J774A.1) induced up-regulation of surface expression of CD86, and increased production of TNF-α, MIP-1α, and sICAM-1. Furthermore, conditioned medium from J774A.1 cells treated with β-TCP facilitated migration of murine splenocytes in a transwell migration assay. These findings clarify that β-TCP induces an immunostimulatory effect in mice, and suggest a potential for β-TCP as a novel adjuvant for cancer therapy.

Osteogenic and angiogenic potentials of monocultured and co-cultured human-bone-marrow-derived mesenchymal stem cells and human-umbilical-vein endothelial cells on three-dimensional porous beta-tricalcium phosphate scaffold

The use of biodegradable beta-tricalcium phosphate (β-TCP) scaffolds holds great promise for bone tissue engineering. However, the effects of β-TCP on bone and endothelial cells are not fully understood. This study aimed to investigate cell proliferation and differentiation of mono- or co-cultured human-bone-marrow-derived mesenchymal stem cells (hBMSCs) and human-umbilical-vein endothelial cells (HUVECs) on a three-dimensional porous, biodegradable β-TCP scaffold. In co-culture studies, the ratios of hBMSCs:HUVECs were 5:1, 1:1 and 1:5. Cellular morphologies of HUVECs, hBMSCs and co-cultured HUVECs/hBMSCs on the β-TCP scaffolds were monitored using confocal and scanning electron microscopy. Cell proliferation was monitored by measuring the amount of double-stranded DNA (dsDNA) whereas hBMSC and HUVEC differentiation was assessed using the osteogenic and angiogenic markers, alkaline phosphatase (ALP) and PECAM-1 (CD31), respectively. Results show that HUVECs, hBMSCs and hBMSCs/HUVECs adhered to and proliferated well on the β-TCP scaffolds. In monoculture, hBMSCs grew faster than HUVECs on the β-TCP scaffolds after 7days, but HUVECs reached similar levels of proliferation after 14days. In monoculture, β-TCP scaffolds promoted ALP activities of both hBMSCs and HUVECs when compared to those grown on tissue culture well plates. ALP activity of cells in co-culture was higher than that of hBMSCs in monoculture. Real-time polymerase chain reaction results indicate that runx2 and alp gene expression in monocultured hBMSCs remained unchanged at days 7 and 14, but alp gene expression was significantly increased in hBMSC co-cultures when the contribution of individual cell types was not distinguished.