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Titanium (Ti) and its alloys are believed to be promising scaffold materials for dental and orthopedic implantation due to their ideal mechanical properties and biocompatibility. However, the host immune response always causes implant failures in the clinic. Surface modification of the Ti scaffold is an important factor in this process and has been widely studied to regulate the host immune response and to further promote bone regeneration. In this study, a calcium-strontium-zinc-phosphate (CSZP) coating was fabricated on a Ti implant surface by phosphate chemical conversion (PCC) technique, which modified the surface topography and element constituents. Here, we envisioned an accurate immunomodulation strategy via delivery of interleukin (IL)-4 to promote CSZP-mediated bone regeneration. IL-4 (0 and 40 ng/mL) was used to regulate immune response of macrophages. The mechanical properties, biocompatibility, osteogenesis, and anti-inflammatory properties were evaluated. The results showed that the CSZP coating exhibited a significant enhancement in surface roughness and hydrophilicity, but no obvious changes in proliferation or apoptosis of bone marrow mesenchymal stem cells (BMMSCs) and macrophages. In vitro, the mRNA and protein expression of osteogenic related factors in BMMSCs cultured on a CSZP coating, such as ALP and OCN, were significantly higher than those on bare Ti. In vivo, there was no enhanced bone formation but increased macrophage type 1 (M1) polarization on the CSZP coating. IL-4 could induce M2 polarization and promote osteogenesis of BMMSCs on CSZP in vivo and in vitro. In conclusion, the CSZP coating is an effective scaffold for BMMSCs osteogenesis, and IL-4 presents the additional advantage of modulating the immune response for bone regeneration on the CSZP coating in vivo., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Lack of bioactivity and monomer toxicity are limiting factors of polymethyl methacrylate (PMMA) bone cement in orthopedic applications. Herein, we address these shortcomings by proposing two-dimensional magnesium phosphate (MgP) nanosheets and hydroxyapatite (HA) nanofibers as novel fillers in PMMA bone cement nanocomposites. Two-dimensional MgP nanosheets and one-dimensional HA nanofibers were synthesized by tuning the crystallization of the sodium-magnesium-phosphate ternary system and hydrothermal homogeneous precipitation, respectively. We show that MgP nanosheets exhibit antibacterial properties against Escherichia coli (E. coli). In addition, HA nanofibers with high level of bioactivity are the proper choice to induce cell viability in the nanocomposite. Results indicate that the combination of both fillers can act as deformation locks enhancing the compressive strength of the nanocomposites. The synthesized nanocomposite possesses excellent bioactivity, mechanical properties, and cytocompatibility potentially opening new paradigm in the design of next generation bone cement composites., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2019 Elsevier B.V. All rights reserved.)

With the increasing requirement of bone repair materials, hydroxyapatite (HA) has been paid widely attention to investigation because of its good bioactivity and osteoconductivity. The structure of HA is a vital factor to expand its application in the field of hard tissue therapy. Thus, many strategies have been utilized in fabricating one-dimensional (1D) and three-dimensional (3D) nanostructured HA. In this paper, we successful synthesize HA with 1D nanofibers and 3D nanostructured microspheres using stearic acid as a template and different phosphates as phosphorus sources under the same synthetic system. The morphology of HA changes from nanofibers with high flexibility to nanostructured microspheres with good sphericity under the synergistic effect of stearic acid and various phosphates. The HA nanofibers and microspheres are promising for applications in biomedical fields. Base on characterization results, the formation mechanisms of HA nanofibers and HA microspheres self-assembled by nanorods are proposed. Furthermore, the HA morphology transition from nanofibers to nanostructured microspheres may be attributed to the formation of polyphosphate-induced water-in-oil microemulsion system in the synthesis process. The finding may provide a new direction to control HA morphology from 1D nanofibers to 3D microspheres based on previous strategies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Thermal oxidation technology was widely investigated as one of effective surface modification method for improving the bioactivity and biocompatibility of titanium and its alloys. In this work, the induction heat oxidization method, a fast, efficient, economical and environmental protective technology, was applied to prepare the submicron-morphological oxide coating with variable rutile TiO 2 equiaxed crystallites on the surface of pure Ti substrates after cold-drawing with 10-20% deformations. The results showed the plastic-deformed Ti cylinders recrystallized during induction heating treatment (IHT) for 10-20s which resulted in evolution of microstructures as well as slight improvement of microhardness. The surface characteristics of TiO 2 crystallites in oxidation layers were determined by the microstructural evolutions of Ti substrate in terms of the nucleation and growth of TiO 2 crystallites. Specially, the oxidized surface with 50-75nm roughness and more uniform and finer equiaxed oxide grains remarkablely improved the apatite deposition after bioactive evaluation in 1.5 × SBF for 7 days. This work provided a potential method to create controlled bioactive oxide coatings with submicro-/nano-scaled TiO 2 crystallites on titanium substrate in terms of the role of metallographic microstructure in the formation process of titanium oxides., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A scholzite (CaZn 2 (PO 4 ) 2 ·2H 2 O) coating was prepared in situ on commercially pure titanium (cpTi) and Ti-6Al-4V (Ti64) substrates using the chemical conversion technology, and its phase composition and microstructure, as well as mechanical, chemical and biological properties were investigated to explore potential applications as a bioactive coating on bone implants. It is indicated that the coating consists mainly of monoclinic scholzite crystals with nano-thick laminar morphology. The crystals on cpTi aggregate to flower-like particles with the diameter of 5-10μm, while form a network structure homogeneously on Ti64. The scratch test shows that the interfacial bonding strength between the coatings and substrates is higher than 40N. Electrochemical measurements indicate that the corrosion behavior of the coatings is not inferior compared with that of oxide film on substrates. MG63 osteoblast-like cells show good adherence and significantly proliferation and differentiation characteristics on the scholzite coated cpTi and Ti64 (p<0.05) in in-vitro cell tests, demonstrating the cytocompatibility of Ti is significantly improved by the scholzite coating. It is suggested that the scholzite coating might be a promising option in hard tissue replacements for early osteogenesis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Phosphate chemical conversion (PCC) technology has been investigated for improving the surface performance of metallic implants in the biomedical field over the last decade. The metallic materials, such as magnesium and its alloys, titanium, pure iron and stainless steel are widely used as orthopedic devices for immobilization of bone fractures in clinic. They were previously studied as metal substrates for PCC coating aiming to modify their biocompatibility and osteoconductivity. Zinc, calcium and zinc-calcium PCC coatings are frequently utilized considering their nature and the end-use. Although PCC coating has been confirmed to potentially improve the bio-performance of metallic implants in vitro and in vivo by many researchers, there are no unified standards or regulations to give quantitative appraisal of its quality and property. As such, an overview of several main phosphate phases together with their properties and behaviors in vitro and in vivo was conducted. The mechanism of phosphating was also briefly discussed. Critical qualities of PCC coating used for biomedical application including corrosion resistance, wettability and bonding strength were analyzed separately. Biological response including in vitro cell investigations and in vivo tissue response were discussed in terms of the cytocompatibility and bioactivity of PCC coating. Further investigations are proposed to develop appropriate performance evaluation measurements by combining conventional technologies and biomedical procedures., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Plasma electrolytic oxidation (PEO) is one of the most applicable methods to produce bioceramic coating on a dental implant and sandblasting is a primary technique to modify metal surface properties. This study aims to deposit bioceramic Ca- and P-containing coatings on sandblasted commercially pure titanium by PEO technique to improve its bioactive performance. The time-dependent modified surfaces are characterized in terms of their microstructure, phase, chemical composition, mechanical properties and bioactivities. The results show that the combination-treated coating exhibits better properties than the PEO-treated one, especially in bioactivities, as evidenced by the HA formation after immersion in simulated body fluid (SBF) for 5 days and the cell viability after seeding for 1 or 3 days. The enhancement of the modified surface is attributed to a combination of the mechanical sandblasting and the microplasma oxidation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Hydroxyapatite (HA) and HA coated microcarriers for cell culture and delivery have attracted more attention recently, owing to the rapid progress in the field of tissue engineering. In this research, a dense and uniform HA coating with the thickness of about 2 μm was successfully deposited on hollow glass microspheres (HGM) by biomimetic process. The influences of SBF concentration, immersion time, solid/liquid ratio and activation of HGM on the deposition rate and coating characteristics were discussed. X-ray diffraction (XRD) and Fourier transform infrared spectrum (FTIR) analyses revealed that the deposited HA is poorly crystalline. The thickness of HA coating showed almost no increase after immersion in 1.5SBF for more than 15 days with the solid/liquid ratio of 1:150. At the same time, SBF concentration, solid/liquid ratio and activation treatment played vital roles in the formation of HA coating on HGM. This poorly crystallized HA coated HGM could have potential use as microcarrier for cell culture., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Nanocharactered biomaterials, such as nanopowders, nanocrystalline compacts and nanostructured films, as well as materials with nanoscale roughness, have attracted much attention recently, due to their clear effects on cell response. Surface nanocrystallization of plasma-sprayed hydroxyapatite (HA) coating can be realized by conventional post-heat treatment. This study reveals that 20-30nm nanocrystals formed on HA coatings post-heat treated at 650 degrees C, and the increase in holding time increased the number of surface nanocrystals and intensified their aggregation. Hard aggregation occurred when HA coatings were repetitively post-heat treated. This indicates that the surface nanocrystallization is controllable. Cell experiments were carried out with rat calvarial osteoblasts. The post-heat treated HA coatings exhibit an obviously better osteoblast response than the as-sprayed coatings. Well-flattened cells attached themselves to the coating surfaces, with a good interaction between their filopodia and the nanocrystallized region. It is proposed that the surface nanocrystallization should be taken into account when the post-heat treatment process is introduced for the fabrication of HA coatings.