Enhancement in the osteogenesis and angiogenesis of calcium phosphate cement by incorporating magnesium-containing silicates

Based on the good osteogenic and angiogenic effects of silicon and magnesium elements, three types of micro-nano magnesium-containing silicates (MS), including akermanite (Ake, Ca₂MgSi₂O₇), diopside (Dio, CaMgSi₂O₆) and forsterite (For, Mg₂SiO₄), were incorporated into calcium phosphate cement (CPC) to improve its osteogenic and angiogenic performances for clinical application. In this present work, the physicochemical properties, osteogenesis and angiogenesis of MS/CPCs (Ake/CPCs, Dio/CPCs and For/CPCs) were investigated systematically and comparatively. The results showed that all MS/CPCs had good biomineralization and significantly stimulated the osteogenic differentiation of mBMSCs and angiogenic differentiation of HUVECs, respectively. Besides, the stimulating effects were related to not only the category of MS, but also the content of MS. The For/CPCs had a good angiogenic property but their initial setting times were beyond 60 min. The Dio/CPCs showed the lowest biological performance among the three groups of MS/CPCs due to the lower ion release (Si and Mg). The Ake was the ideal modifier that could provide CPC with appropriate physicochemical properties, better osteogenesis and angiogenesis. Simultaneously, a higher addition (10 wt%) of akermanite resulted in the best potential to bone regeneration. Taken together, this research provides an effective approach to improve the overall performance of CPC, and 10Ake/CPC is of great promising prospect in bone repair.     

Adjusting physicochemical and cytological properties of biphasic calcium phosphate by magnesium substitution: An in vitro study

Biphasic calcium phosphate (BCP) is a highly study bone defect repair material with adjustable degradation, perfect osteoconduction and good osteoinduction. As one of the essential trace elements, magnesium (Mg) possesses the abilities of pro-osteogenesis and pro-angiogenesis. Therefore, Mg doping may further expand the application of BCP in bone defect repair, but few studies focus on promoting the osteogenesis and angiogenesis of BCP simultaneously by Mg doping, and the optimal doping amount of Mg remains to be explored. In this study, the physicochemical and biological properties of BCP scaffold affected by Mg doping were systematically study. Results showed that Mg doping enhanced the sintering of BCP scaffold, resulting in the decrease of degradation rate at the initial soaking period. However, the introduction of Mg damaged the lattice stability of BCP, leading to the increase of BCP degradation rate at the later soaking period. BCP scaffolds with Mg doping content ≥3 mol.% could achieve a long-term sustained release of Mg. The ion microenvironment created by Mg-doped scaffolds was simultaneously conducive to the osteogenic differentiation of stem cells and the enhanced angiogenic activity of endothelial cells. The scaffold doped with 5 mol.% of Mg (Mg5–S) showed the highest efficiency in promoting osteogenic differentiation. Mg-doped BCP scaffolds with a doping content ≥3 mol.%, especially Mg5–S, significantly improved the proliferation and angiogenic differentiation of endothelial cells. Based on these, we believe that the optimal doping content of Mg in BCP is 5 mol.%, and Mg5–S has great application potential in bone defect repair.     

Effects of Z-value on physicochemical and biological properties of β-SiAlONs ceramics

This study evaluated the effects of different Z-values on the physical, chemical, and biological properties of β-SiAlON ceramics. Increasing the Z-value of the β-Si₃N₄ solid solution's main phase resulted in the replacement of Si–N bonds with Al–O bonds. The number of columnar crystals decreased, bulk density increased, and porosity decreased, thus transforming the fine-particle microstructure of β-Si₃N₄ into the columnar structure of β-SiAlON. The compressive strength increased, which facilitated sintering at 1500 °C without sintering auxiliaries. H⁺ and OH⁻ ions in deionized water broke the covalent bonds on the β-SiAlON surface, thereby forming new Si–OH, Al–OH, and N–H bonds on the β-SiAlON surface and producing SiO₄⁴⁻, AlO₂⁻, and NH₄⁺ groups in the solution. Increasing the soaking time changed the compositions of ionized H⁺ and OH⁻ ions, thus increasing the pH. MC3T3-E1 cells were cultured on the β-SiAlON surface, and it was observed that the increase in the Z-value of β-SiAlON had no influence on cell adhesion and spreading, but it may slightly suppress cell proliferation at high Z-values. At low Z-values, the low AlO₂⁻ concentration helps promote osteogenic differentiation and mineralized nodule formation. Thus, β-SiAlON ceramics possess excellent physical, chemical, and biological properties and are considered excellent bone-repairing materials.     

Boron-containing bioactive glasses in bone and soft tissue engineering

Boron is considered to influence the performance of several metabolic enzymes and boron deficiency is associated with impaired growth and abnormal bone development. As such, boron is a beneficial bioactive element for animals and humans. It is also well known that boron stimulates wound healing and improves bone health. The addition of boron in different proportions to bioactive glasses has significant effects on glass structure, glass processing parameters, biodegradability, biocompatibility, bioactivity and cytotoxicity. Different compositions of bioactive glasses (BGs) containing boron, including boron-doped, borosilicate and borate glasses, are being investigated for bone and soft tissue engineering under the premise that these BGs are suitable carriers of boron, indicating controlled release of B species in the biological environment. This paper reviews up to date research and applications of borate, borosilicate, and boron doped silicate and phosphate BGs focussing on their physical, structural, degradation and biological properties for hard and soft tissue regeneration.     

Exosomes derived from osteoclasts under compression stress inhibit osteoblast differentiation

Orthodontic tooth movement is triggered by orthodontic force loading on the periodontal ligament and is achieved by alveolar bone remodeling, which is regulated by intimate crosstalk between osteoclastogenesis and osteoblast differentiation. Whether the communication between osteoclasts and osteoblasts is influenced by orthodontic compression stress requires further clarification. In this study, osteoclasts were differentiated for 10 days. On day 4 of differentiation, the number of pre-osteoclasts peaked, as determined by the increased expression of RANK and the number of multinucleated cells. After 24 h of compression stress loading, on day 4, the number of osteoclasts increased, and the optimal magnitude of stress to promote osteoclastogenesis was determined as 1 g/cm2. Moreover, the results of RNA-sequencing analysis showed that the miRNA expression profile changed markedly after compression loading and that many of the altered miRNAs were associated with cell communication functions. A series of indirect co-culture experiments showed an inhibitory effect of osteoclasts on osteoblast differentiation, especially after compression. Next, we added osteoclast-derived exosomes to hPDLSCs during osteoblast differentiation. Exosomes derived from osteoclasts under compression (cEXO) showed a greater inhibitory effect on osteoblast differentiation, compared to exosomes from osteoclasts without compression (EXO). Therefore, we analyzed differentially expressed miRNAs associated with bone development functions in exosomes: miR-223-5p and miR-181a-5p were downregulated, whereas miR-133a-3p, miR-203a-3p, miR-106a-5p, and miR-331-3p were upregulated; these altered expressions may explain the enhanced inhibitory effect of compression stress.     

Design and in vitro evaluation of polymeric formulae of simvastatin for local bone induction

Simvastatin (SVS), a cholesterol-lowering drug, has been shown to stimulate bone formation. This study deals with the design and in vitro evaluation of local delivery systems for simvastatin. They are intended to treat bony defects resulting from periodontitis or to induce osteogenesis around the titanium implants. Granules and gels were formulated using bioerodible/biocompatible polymers, namely hydroxypropylmethyl cellulose (H), sodium carboxymethyl cellulose (C), and chitosan (Ch). The in vitro release profiles and kinetics were evaluated and the swelling and/or erosion was monitored. Differential scanning calorimetry (DSC) and infrared (IR) were used to detect any SVS/polymer interactions that may affect drug release. The results revealed variable extents of controlled drug release from the designed formulae depending on the polymer nature. About 50% cumulative SVS was released from both H granules and gel formulae within 24 h and ∼66% and ∼88% from C granules and gel, respectively. Ch formulae exhibited ∼50% release from granules and ∼30% from gel.     

In Vitro Characterizations of PLLA/β-TCP Porous Matrix Materials and RMSC-PLLA-β-TCP Composite Scaffolds

To develop a novel degradable poly (L-lactic acid)/β-tricalcium phosphate (PLLA/β-TCP) bioactive materials for bone tissue engineering, β-TCP powder was produced by a new wet process. Porous scaffolds were prepared by three steps, I.e. Solvent casting, compression molding and leaching stage. Factors influencing the compressive strength and the degradation behavior of the porous scaffold, e.g. Weight fraction of pore forming agent-sodium chloride (NaCl), weight ratio of PLLA: β-TCP, the particle size ofβ-TCP and the porosity, were discussed in details. Rat marrow stromal cells (RMSC) were incorporated into the composite by tissue engineering approach. Biological and osteogenesis potential of the composite scaffold were determined with MTT assay, alkaline phosphatase (ALP) activity and bone osteocalcin (OCN) content evaluation. Results show that PLLA/β-TCP bioactive porous scaffold has good mechanical and pore structure with adjustable compressive strength needed for surgery. RMSCs seeding on porous PLLA/β-TCP composite behaves good seeding efficacy, biocompatibility and osteoinductive potential. Osteoprogenitor cells could well penetrate into the material matrix and begin cell proliferation and osteogenic differentiation. Osseous matrix could be formed on the surface of the composite after culturing in vitro. It is expected that the PLLA/β-TCP porous composites are promising scaffolds for bone tissue engineering in prosthesis surgery.     

微/纳米结构含锌硅酸钙基涂层成骨性能研究

骨科植入物涂层的表面形貌和化学组成对炎症反应的进程和骨形成的发生都发挥着重要调节作用。为综合利用微/纳米仿生结构和生物活性元素的优势,将含锌(Zn)的纳米结构物质引入到经水热处理后的等离子喷涂硅酸钙(calcium silicate, CS)涂层表面,对所制备涂层的物相组成、表面和截面形貌、比表面积、Zeta电位和生理环境下离子溶出等物理化学性能进行了表征。相比于常规CS涂层,具有微/纳米复合结构的CS和含锌CS涂层拥有更高比表面积和孔容,可吸附更多血清蛋白和纤维连接蛋白,通过刺激细胞内整合素以及下游vinculin和FAK基因表达,提高了骨髓间充质干细胞(BMSCs)铺展能力。涂层中锌的引入进一步提高了其表面BMSCs的增殖能力和与成骨细胞分化相关的基因表达。具有微/纳米复合结构的涂层明显上调了RAW264.7巨噬细胞中M2表型因子(CD206和ARG)基因表达,而涂层中溶出的Zn²⁺显著提高了RAW264.7细胞中抑炎症因子(IL-1ra和IL-10)基因表达,促使其向抑炎症表型转化。骨科植入物涂层表面锌元素和纳米结构的引入有利于创建良好的骨免疫微环境,促进骨...     

Design and In Vitro Evaluation of Polymeric Formulae of Simvastatin for Local Bone Induction

ABSTRACT

Simvastatin (SVS), a cholesterol-lowering drug, has been shown to stimulate bone formation. This study deals with the design and in vitro evaluation of local delivery systems for simvastatin. They are intended to treat bony defects resulting from periodontitis or to induce osteogenesis around the titanium implants. Granules and gels were formulated using bioerodible/biocompatible polymers, namely hydroxypropylmethyl cellulose (H), sodium carboxymethyl cellulose (C), and chitosan (Ch). The in vitro release profiles and kinetics were evaluated and the swelling and/or erosion was monitored. Differential scanning calorimetry (DSC) and infrared (IR) were used to detect any SVS/polymer interactions that may affect drug release. The results revealed variable extents of controlled drug release from the designed formulae depending on the polymer nature. About 50% cumulative SVS was released from both H granules and gel formulae within 24 h and ～66% and ～88% from C granules and gel, respectively. Ch formulae exhibited ～50% release from granules and ～30% from gel.