A novel CKIP-1 SiRNA slow-release coating on porous titanium implants for enhanced osseointegration.

Osseointegration between implants and bone tissue lays the foundation for the long-term stability of implants. The incorporation of a porous structure and local slow release of siRNA to silence casein kinase-2 interacting protein-1 (CKIP-1), a downregulator of bone formation, is expected to promote osseointegration. Here, porous implants with a porous outer layer and dense inner core were prepared by metal coinjection molding (MIM). Mg-doped calcium phosphate nanoparticles (CaPNPs)-grafted arginine-glycine-aspartate cell adhesion sequence (RGD) and transcribed activator (TAT) (MCPRT)/CKIP-1 siRNA complex and polylysine (PLL) were coated onto the surface of the porous implants by layer-by-layer (LBL) self-deposition. The in vitro results showed that the MCPRT-siRNA coating promoted MG63 cell adhesion and proliferation, enhanced the protein expressions (ALP and OC) and bone formation-related gene expression (OPN, OC and COL-1α) in vitro. The in vivo results demonstrated that the porous structure enhanced bone ingrowth and that the local slow release of MCPRT-siRNA accelerated new bone formation at the early stage. The porous structure coupled with local CKIP-1 siRNA delivery constitutes a promising approach to achieve faster and stronger osseointegration for dental implants.

Polydopamine-modified ZIF-8 nanoparticles as a drug carrier for combined chemo-photothermal osteosarcoma therapy.

Single chemotherapy often causes severe adverse effects and chemoresistance which limits therapeutic efficacy. Recently, combination of chemotherapy with photothermal therapy (PTT) have received broad attention for synergistic treatment of osteosarcoma, ultimately resulting in the enhancement of therapeutic efficacy of anticancer drugs. In this study, we have developed a novel drug delivery system based on polydopamine (pDA)-modified ZIF-8 nanoparticles loaded with methotrexate (MTX) (pDA/MTX@ZIF-8 NPs). Herein, pDA modification avoided the explosive release of the drug, and improved the biocompatibility and near-infrared (NIR) light absorbance performance of nanoparticles. The as-prepared pDA/MTX@ZIF-8 NPs could be used as drug targeting delivery system and simultaneously displayed excellent photothermal effects under NIR irradiation. Biology assays in vitro indicated that the pDA/MTX@ZIF-8 NPs were able to efficiently induce MG63 cell apoptosis through reducing mitochondrial membrane potentials (MMPs), and the introduction of photothermal agents enhanced the antitumor effect and decreased the dose of chemotherapeutic drugs. Moreover, the optimized pDA/MTX@ZIF-8 NPs (40 µg/mL) exhibited better photothermal conversion performance and facilitated tumor cells death. These results triumphantly exhibit that the pDA/MTX@ZIF-8 NPs have a synergistic effect of chemo-photothermal therapy (combination index CI = 0.346) and excellent biocompatibility, which has unexceptionable prospects for the therapy of osteosarcoma.

Bone response in vivo of Ti-45Zr alloy as dental implant material.

Ti-Zr alloys have gained increasing attention as a new metallic biomaterial, being used as implants for both orthopedics and dentistry. More recently, our group found promising results for the Ti-45Zr alloy, which presented a low elastic modulus, a pronounced and excellent mechanic character, and excellent cell compatibility in vitro. However, its biocompatibility and potential to promote osteogenesis in vivo remained unclear. In the present study, the biocompatibility, osteointegration ability, and immune response effects of the Ti-45Zr alloy were evaluated in animal experiments. The results showed that the alloy had good blood compatibility and no body side effects. After implantation in vivo, the inflammation turned out well and was beneficial to the polarization of macrophages. Additionally, the Ti-45Zr alloy presented a good osteointegration ability. Overall, these results confirmed that the Ti-45Zr alloy can be used as a dental implant material.

Microstructure, mechanical properties and osseointegration ability of Ta-20Zr alloy used as dental implant material.

The aim of this study was to evaluate the application prospect of a tantalum (Ta) and zirconium (Zr) alloy as a dental implant material. The Ta-20Zr (wt.%) alloy was prepared by powder metallurgy, and its microstructure and mechanical properties were analyzed by standard techniques. The effect of Ta-20Zr alloy on inflammation, bone remodeling and osseointegration was analyzed in rat and rabbit models by biochemical, histological and imaging tests. The Ta-20Zr alloy showed excellent mechanical compatibility with the bone tissue on account of similar elastic modulus (49.2 GPa), thereby avoiding the 'stress shielding effect'. Furthermore, Ta-20Zr alloy enhanced the inflammatory response by promoting secretion of interleukin-6 (IL-6) and IL-10, and facilitated the balance between the M1/M2 macrophage phenotypes. Finally, Ta-20Zr also showed excellent osseointegration and osteogenic ability without any systemic side effects, making it an ideal dental implant material.

Arecoline Enhances Phosphodiesterase 4A Activity to Promote Transforming Growth Factor-ß-Induced Buccal Mucosal Fibroblast Activation via cAMP-Epac1 Signaling Pathway.

Chewing areca nut (betel quid) is strongly associated with oral submucous fibrosis (OSF), a pre-cancerous lesion. Among the areca alkaloids, arecoline is the main agent responsible for fibroblast proliferation; however, the specific molecular mechanism of arecoline affecting the OSF remains unclear. The present study revealed that arecoline treatment significantly enhanced Transforming growth factor-ß (TGF-ß)-induced buccal mucosal fibroblast (BMF) activation and fibrotic changes. Arecoline interacts with phosphodiesterase 4A (PDE4A) to exert its effects through modulating PDE4A activity but not PDE4A expression. PDE4A silence reversed the effects of arecoline on TGF-ß-induced BMFs activation and fibrotic changes. Moreover, the exchange protein directly activated by cAMP 1 (Epac1)-selective Cyclic adenosine 3',5'-monophosphate (cAMP) analog (8-Me-cAMP) but not the protein kinase A (PKA)-selective cAMP analog (N6-cAMP) remarkably suppressed α-smooth muscle actin(α-SMA) and Collagen Type I Alpha 1 Chain (Col1A1) protein levels in response to TGF-ß1 and arecoline co-treatment, indicating that cAMP-Epac1 but not cAMP-PKA signaling is involved in arecoline functions on TGF-ß1-induced BMFs activation. In conclusion, arecoline promotes TGF-ß1-induced BMFs activation through enhancing PDE4A activity and the cAMP-Epac1 signaling pathway during OSF. This novel mechanism might provide more powerful strategies for OSF treatment, requiring further in vivo and clinical investigation.

Hydroxyapatite nanoparticle based fluorometric determination and imaging of cysteine and homocysteine in living cells.

Fluorescent hydroxyapatite nanoparticles (HAP-NPs) were prepared by reacting calcium ion with phosphate in the presence of Eu(III) ion. The HAP-NPs display large Stokes' shift and two strong fluorescence emissions with peaks at 590 nm and 615 nm when excited at 250 nm. The HAP-NPs also have good photostability and water solubility. The HAP-NPs combined with Cu(II) were applied to fluorometric determination of cysteine and homocysteine in biological samples and in living cells. In this detection scheme, the fluorescence of HAP-NPs is initially quenched by Cu(II). The addition of biothiols results in the formation of Cu(II)-thiol complexes and leads to fluorescence recovery. The assay allows cysteine to be detected with a 110 nM detection limit, and homocysteine with a 160 nM detection limit. The assay was successfully applied to the analysis of cysteine in spiked human serum samples and to imaging of cysteine in HeLa cells, and this demonstrates its potential for clinical testing and in biomedical research. Graphical abstract Fluorescent hydroxyapatite nanoparticles were synthesized and combined with Cu2+ for fluorescence sensing of biothiols (cysteine and homocysteine) in complex biological samples and in living cells.

Improved osteoblasts growth on osteomimetic hydroxyapatite/BaTiO3 composites with aligned lamellar porous structure.

Osteoblasts growing into bone substitute is an important step of bone regeneration. This study prepared porous hydroxyapatite (HA)/BaTiO3 piezoelectric composites with porosity of 40%, 50% and 60% by ice-templating method. Effects of HA/BaTiO3 composites with different porosities, with and without polarizing treatment on adhesion, proliferation and differentiation of osteoblasts were investigated in vitro. Results revealed that cell densities of the porous groups were significantly higher than those of the dense group (p<0.05), so did the alkaline phosphate (ALP) and bone gla protein (BGP) activities. Porosity of 50% group exhibited higher ALP activity and BGP activity than those of the 40% and 60% groups. Scanning electron microscopy (SEM) observations revealed that osteoblasts adhered and stretched better on porous HA/BaTiO3 than on the dense one, especially HA/BaTiO3 with porosity of 50% and 60%. However, there was no significant difference in the cell morphology, cell densities, ALP and BGP activities between the polarized group and the non-polarized group (p>0.05). The absence of mechanical loading on the polarized samples may account for this. The results indicated that hierarchically porous HA/BaTiO3 played a favorable part in osteoblasts proliferation, differentiation and adhesion process and is a promising bone substitute material.

[Cephalometric analysis of the soft tissue profile in Hunan Han adults with normal occlusion].

OBJECTIVE: To analyze the characteristics soft tissue profile in Hunan Han adults with normal occlusion and to explore the differences of the soft tissue profile in gender, region and race. METHODS: Lateral cephalometric radiographs were performed for 323 volunteers (164 females and 159 males) from Hunan Province. The digital cephalometric radiographs were imported into the WinCeph8.0 measurement and analysis system in a same computer. According to the Holdaway analysis method, the mean and standard deviation were calculated. Then the results were compared to the data from Liaoning, Nepalese, Japanese, North American Caucasians. RESULTS: The normal value of cephalometric facial soft tissue profile in Han population adults with normal occlusion in Hunan Province were obtained. There were significant differences in subnasale to H line (Sn-H), upper lip tension, lower lip sulcus depth (Si-PgsLs), and soft tissue chin thickness (Pg-Pgs) between males and females (all P<0.05). Compared with Liaoning Province, significant regional differences in soft tissue facial angle (FH-NsPgs), upper lip sulcus depth (Ss-Ls), Sn-H, lower lip thickness, upper lip thickness, H angle, lower lip to H line (Li-PgsLs), Si-PgsLs, and Pg-Pgs were found in Hunan Province (all P<0.05). Compared with the Japan, significant regional differences in FH-NsPgs, nose prominence (Sn-Pn), lower lip thickness, upper lip tensity, H angle, Li-PgsLs, Si-PgsLs, and Pg-Pgs were found in Hunan Province (all P<0.05). Compared with the Nepalese, significant regional differences in Sn-Pn, Ss-Ls, Sn-H, skeletal profile convexity (A-NPs), basic upper lip thickness, upper lip tensity, H angle, Li-PgsLs and Pg-Pgs were found in Hunan Province (all P<0.05). Compared with the North America, significant regional differences in Sn-Pn, Ss-Ls, Sn-H, A-NPs, basic upper lip thickness, upper lip tensity, H angle, Li-PgsLs, Si-PgsLs and Pg-Pgs were found in Hunan Province (all P<0.05). CONCLUSION: There are both similarities and differences in facial soft tissue profile between males and females with normal occlusion in Hunan Province. The characteristics of facial soft tissue profile in Hunan Province are different from that in Liaoning area, Nepal, Japan and North America.