Wenxiao He

Local release of magnesium from mesoporous TiO2 coatings stimulates the peri-implant expression of osteogenic markers and improves osteoconductivity in vivo.

Local release of Mg ions from titanium implant surfaces has been shown to enhance implant retention and integration. To clarify the biological events that lead to this positive outcome, threaded implants coated with mesoporous TiO2 thin films were loaded with Mg-ions and placed in the tibia of rabbits for 3weeks, after surface characterization. Non-loaded mesoporous coated implants were used as controls. Peri-implant gene expression of a set of osteogenic and inflammatory assays was quantified by means of real-time quantitative polymerase chain reaction. The expression of three osteogenic markers (OC, RUNX-2 and IGF-1) was significantly more pronounced in the test specimens, suggesting that the release of Mg ions directly at the implant sites may stimulate an osteogenic environment. Furthermore, bone healing around implants was evaluated on histological slides and by diffraction-enhanced imaging (DEI), using synchrotron radiation. The histological analysis demonstrated new bone formation around all implants, without negative responses, with a significant increase in the number of threads filled with new bone for test surfaces. DEI analysis attested the high mineral content of the newly formed bone. Improved surface osteoconductivity and increased expression of genes involved in the bone regeneration were found for magnesium-incorporation of mesoporous TiO2 coatings.

Mesoscopically Ordered Bone‐Mimetic Nanocomposites

A sustainable approach that highly mimics bone-material deposition is reported to produce mechanically stable, degradable composites with nanostructures resembling that of natural bone. Molecular self-assembly combining intermolecular crosslinking leads to resilient matrices possessing long-range ordered aqueous domains, inside which moderately aligned poorly crystalline apatite is converted from the transient amorphous calcium phosphate phase.

Osteoconductive Potential of Mesoporous Titania Implant Surfaces Loaded with Magnesium: An Experimental Study in the Rabbit

BACKGROUND Mesoporous coatings enable incorporation of functional substances and sustainedly release them at the implant site. One bioactive substance that can be incorporated in mesoporous is magnesium, which is strongly involved in bone metabolism and in osteoblast interaction. PURPOSE The aim of this experimental study was to evaluate the effect of incorporation of magnesium into mesoporous coatings of oral implants on early stages of osseointegration. MATERIAL AND METHODS Titanium implants were coated with thin films of mesoporous TiO2 having pore diameters of 6 nm and were loaded with magnesium. The implant surfaces were extensively characterized by means of interferometry, atomic force microscopy, scanning electron microscopy, and energy-dispersive spectroscopy and then placed in the tibiae of 10 rabbits. After 3 weeks of healing, osseointegration was evaluated by means of removal torque testing and histology and histomorphometry. RESULTS Histological and biomechanical analyses revealed no side effects and successful osseointegration of the implants. The biomechanical evaluation evidenced a significant effect of magnesium doping on strengthening the implant-bone interface. CONCLUSIONS A local release of magnesium from the implant surfaces enhances implant retention at the early stage of healing (3 weeks after implantation), which is highly desirable for early loading of the implant.

In vitro evaluation of human fetal osteoblast response to magnesium loaded mesoporous TiO2 coating

This work aimed to evaluate the in vitro response of Transfected Human Foetal Osteoblast (hFOB) cultured on a magnesium-loaded mesoporous TiO2 coating. The application of mesoporous films on titanium implant surfaces has shown very promising potential to enhance osseointegration. This type of coating has the ability to act as a framework to sustain bioactive agents and different drugs. Magnesium is the element that, after calcium, is the most frequently used to dope titanium implant surfaces, since it is crucial for protein formation, growth factor expression, and aids for bone mineral deposition on implant surfaces. Mesoporous TiO2 films with an average pore-size of 6 nm were produced by the evaporation-induced self-assembly method (EISA) and deposited onto titanium discs. Magnesium loading was performed by soaking the mesoporous TiO2 discs in a magnesium chloride solution. Surface characterization was conducted by SEM, XPS, optical interferometry, and AFM. Magnesium release profile was assessed at different time points using a Magnesium Detection kit. Cell morphology and spreading were observed with SEM. The cytoskeletal organization was stained with TRITC-conjugated Phalloidin and cell viability was evaluated through a mitochondrial colorimetric (MTT) assay. Furthermore, gene expression of bone markers and cell mineralization were analyzed by real time RT-PCR and alizarin-red staining, respectively. The surface chemical analysis by XPS revealed the successful adsorption of magnesium to the mesoporous coating. The AFM measurements revealed the presence of a nanostructured surface roughness. Osteoblasts viability and adhesion as well as the gene expression were unaffected by the addition of magnesium possibly due to its rapid burst release, however, were enhanced by the 3D nanostructure of the TiO2 layer.

Magnesium release from mesoporous carriers on endosseus implants does not influence bone maturation at 6 weeks in rabbit bone

OBJECTIVES The release of magnesium ions (Mg2+ ) from titanium surfaces has been shown to boost the initial biological response of peri-implant bone and to increase the biomechanical strength of osseointegration. The objective of the present paper was to investigate if the initial improvement in osseointegration would influence the bone remodeling also during the maturation stage of bone healing. METHODS Titanium implants were coated with mesoporous titania layers and either loaded with Mg2+ (test group) or left untreated (control group). The implants were inserted in the tibiae of 10 New Zealand White rabbits. Osseointegration was assessed after 6 weeks by means of biomechanical testing (RTQ), non-decalcified histology and histomorphometry (BIC%, BA%, NBA%). The expression of genes involved in the bone formation and remodeling was quantified using qPCR. RESULTS Mg2+ releasing mesoporous titania coatings showed, on average, higher removal torques and histomorphometrical outcomes (RTQ: 17.2 Ncm vs. 15 Ncm; BIC: 38.8% vs. 32.1%; BA%: 71.6% vs. 64%; NBA% 62.5% vs. 54% for the tests vs the controls); however, the differences were not statistically significant. Three osteogenic markers, osteocalcin (OC), collagen 1 alpha 1 (COL1A1), and alkalin phosphatase (ALPL), were respectively 2-fold, 1.53-fold, and 1.13-fold up-regulated in the control group compared to the test. The expression of COL1A1 was particularly high in both groups, while the biomarkers for remodeling and inflammation showed a low expression in both groups. SIGNIFICANCE The results suggested that the initial enhancement in osseointegration induced by magnesium release from mesoporous titania coatings has no detrimental effects during bone maturation.

Correction to: The effect of magnesium on early osseointegration in osteoporotic bone: a histological and gene expression investigation

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Biomimetic Synthesis of Nanostructured Calcium Phosphates

When illness or trauma results in bone non-union that surpasses the self-regenerative capacity of tissue, a substitute material is needed to fill the void and favorably induce bone regeneration. Synthetically produced biomaterials with better reproducibility and availability are clinically needed as an alternative to human- and animal-derived scaffolds. Such materials often comprise some form of calcium phosphate (CaP) owing to their resemblance to bone-minerals. Of special interest is the development of new formation strategies with the aim of forming materials that to a high extent mimics that of the bone tissue it restores. Such strategies often include some level of biomimetics where naturally occurring processes are used as inspiration. In this review, the current state-of-the-art in biomimetic formation techniques using molecular self-assembly and biomimetic mineralization with the effort of forming hierarchical CaP bone-like structures are summarized. It is focused on, but not limited to, the use of amphiphiles as structure-directing agents to achieve control over the CaP mineralization process, i.e. CaP morphogenesis, polymorphism as well as the orientation and organization of CaP crystallites in hybrids. In conclusion, some preclinical data are presented, which clearly demonstrate the positive outlook for bone-like synthetic biomaterials formed using molecular self-assembly techniques.