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High proportion strontium-doped micro-arc oxidation coatings enhance early osseointegration of titanium in osteoporosis by anti-oxidative stress pathway.

ABSTRACT: The excessive accumulation of reactive oxygen species (ROS) under osteoporosis precipitates a microenvironment with high levels of oxidative stress (OS). This could significantly interfere with the bioactivity of conventional titanium implants, impeding their early osseointegration with bone. We have prepared a series of strontium (Sr)-doped titanium implants via micro-arc oxidation (MAO) to verify their efficacy and differences in osteoinduction capabilities under normal and osteoporotic (high OS levels) conditions. Apart from the chemical composition, all groups exhibited similar physicochemical properties (morphology, roughness, crystal structure, and wettability). Among the groups, the low Sr group (Sr25%) was more conducive to osteogenesis under normal conditions. In contrast, by increasing the catalase (CAT)/superoxide dismutase (SOD) activity and decreasing ROS levels, the high Sr-doped samples (Sr75% and Sr100%) were superior to Sr25% in inducing osteogenic differentiation of MC3T3-E1 cells and the M2 phenotype polarization of RAW264.7 cells, thus enhancing early osseointegration. Furthermore, the results of both in vitro cell co-culture and in vivo studies also showed that the high Sr-doped samples (especially Sr100%) had positive effects on osteoimmunomodulation under the OS microenvironment. Ultimately, the collated findings indicated that the high proportion Sr-doped MAO coatings were more favorable for osteoporosis patients in implant restorations.

SUBMITTER: Shen X

PROVIDER: S-EPMC8636681 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Titanium (Ti)-based alloys are widely used in tissue regeneration with advantages of improved biocompatibility, high mechanical strength, corrosion resistance, and cell attachment. To obtain bioactive bone-implant interfaces with enhanced osteogenic capacity, various methods have been developed to modify the surface physicochemical properties of bio-inert Ti and Ti alloys. Nano-structured hydroxyapatite (HA) formed by micro-arc oxidation (MAO) is a synthetic material, which could facilitate osteoconductivity, osteoinductivity, and angiogenesis on the Ti surface. In this paper, we applied MAO and steam-hydrothermal treatment (SHT) to produce HA-coated Ti, hereafter called Ti-M-H. The surface morphology of Ti-M-H1 was observed by scanning electron microscopy (SEM), and the element composition and the roughness of Ti-M-H1 were analyzed by energy-dispersive X-ray analysis, an X-ray diffractometer (XRD), and Bruker stylus profiler, demonstrating the deposition of nano-HA particles on Ti surfaces that were composed of Ca, P, Ti, and O. Then, the role of Ti-M-H in osteogenesis and angiogenesis in vitro was evaluated. The data illustrated that Ti-M-H1 showed a good compatibility with osteoblasts (OBs), which promoted adhesion, spreading, and proliferation. Additionally, the secretion of ALP, Col-1, and extracellular matrix mineralization was increased by OBs treated with Ti-M-H1. Ti-M-H1 could stimulate endothelial cells to secrete vascular endothelial growth factor and promote the formation of capillary-like networks. Next, it was revealed that Ti-M-H1 also suppressed inflammation by activating macrophages, while releasing multiple active factors to mediate osteogenesis and angiogenesis. Finally, in vivo results uncovered that Ti-M-H1 facilitated a higher bone-to-implant interface and was more attractive for the dendrites, which promoted osseointegration. In summary, MAO and SHT-treated Ti-M-H1 not only promotes in vitro osteogenesis and angiogenesis but also induces M2 macrophages to regulate the immune environment, which enhances the crosstalk between osteogenesis and angiogenesis and ultimately accelerates the process of osseointegration in vivo.

Project description:BackgroundThree-dimensional (3D) printing technology has been widely used in orthopedics; however, it is still limited to the change of macroscopic structures. In order to further improve the biological properties of 3D-printed porous titanium scaffolds, this study introduced micro-arc oxidation (MAO) technology to modify the surface of porous titanium scaffolds and construct bioactive coatings on the surface of porous titanium scaffolds to improve the biocompatibility and osseointegration ability of the material.MethodsFor in vitro experiments, human bone marrow stem cells (hBMSCs) were seeded onto untreated scaffolds (control group) and MAO-treated scaffolds (experimental group). After 24 h of co-culture, cytotoxicity was observed using live/dead staining, and cell/scaffold constructs were retrieved and processed for the assessment of cell morphology by using scanning electron microscopy (SEM). Cell proliferation was detected using the Cell Counting Kit-8 (CCK-8) assay after 3, 7, and 14 days of co-culture. The levels of alkaline phosphatase (ALP) in the cell supernatant were detected after 7 and 14 days of co-culture. For in vivo experiments, micro-computed tomography (micro-CT) and Masson Goldner's staining were used to evaluate bone ingrowth and osseointegration at 4 and 8 weeks postoperatively.ResultsIn vitro experiment results confirmed that the two groups of scaffolds were non-cytotoxic and the cell adhesion status on the MAO-treated scaffolds was better. Over time, cell proliferation and ALP levels were higher in the MAO-treated group than in the untreated scaffolds. In the in vivo experiments, the MAO-treated scaffolds showed better bone ingrowth and osseointegration than the untreated group at different time points.ConclusionsThe MAO-treated porous titanium scaffold formed a uniform and dense bioactive coating on the surface, which was more conducive to cell adhesion, proliferation, and differentiation and showed better osseointegration and bone ingrowth in vivo.

Project description:BackgroundTitanium (Ti) is now widely used as implant material due to its excellent mechanical properties and superior biocompatibilities, while its inert bioactivities might lead to insufficient osseointegration, and limit its performance in dental applications.MethodsWe introduced a robust and simple approach of modifying titanium surfaces with polysaccharide complexes. Titanium samples were subjected to hydrothermal treatment to create a uniform porous structure on the surface, followed by coating with a bioinspired and self-assembly polydopamine layer. Strontium Eucommia Ulmoides Polysaccharide (EUP-Sr) complexes are then introduced to the polydopamine-coated porous titanium. Multiple morphological and physiochemical characterizations are employed for material evaluation, while cell proliferation and gene expression tests using macrophages, primary alveolar bone osteoblasts, and vascular endothelial cells are used to provide an overall insight into the functions of the product. The significances of statistical differences were analyzed using student's t-test.ResultsMicroscopic and spectrometric characterizations confirmed that the Ti surface formed a porous structure with an adequate amount of EUP-Sr loading. The attachment was attributed to hydrogen bonding between the ubiquitous glycosidic linkage of the polysaccharide complex and the ring structure of polydopamine, yet the loaded EUP-Sr complex can be gradually released, consequently benefiting the neighboring microenvironment. Cell experiments showed no cytotoxicity of the material, and the product showed promising anti-inflammation, osseointegration, and angiogenesis properties, which were further confirmed by in vivo evaluations.ConclusionWe believe the EUP-Sr modified titanium implant is a promising candidate to be used in dental applications with notable osteoimmunomodulation and angiogenesis functions. And the novel technique proposed in this study would benefit the modification of metal/inorganic surfaces with polysaccharides for future research.

Project description:Innovative nanomaterials are required for the coatings of titanium (Ti) implants to ensure the activation of Ti surfaces for improved osseointegration, enhanced bone fracture healing and bone regeneration. This paper presents a systematic investigation of biomimetic composite (BC) coatings on Ti implant surfaces in a rat model of a diaphyseal femoral fracture. Methodological approaches of surface modification of the Ti implants via the usual joining methods (e.g., grit blasting and acid etching) and advanced physicochemical coating via a self-assembled dip-coating method were used. The biomimetic procedure used multi-substituted hydroxyapatite (ms-HAP) HAP-1.5 wt% Mg-0.2 wt% Zn-0.2 wt% Si nanoparticles (NPs), which were functionalized using collagen type 1 molecules (COL), resulting in ms-HAP/COL (core/shell) NPs that were embedded into a polylactic acid (PLA) matrix and finally covered with COL layers, obtaining the ms-HAP/COL@PLA/COL composite. To assess the osseointegration issue, first, the thickness, surface morphology and roughness of the BC coating on the Ti implants were determined using AFM and SEM. The BC-coated Ti implants and uncoated Ti implants were then used in Wistar albino rats with a diaphyseal femoral fracture, both in the absence and the presence of high-frequency pulsed electromagnetic shortwave (HF-PESW) stimulation. This study was performed using a bone marker serum concentration and histological and computer tomography (micro-CT) analysis at 2 and 8 weeks after surgical implantation. The implant osseointegration was evaluated through the bone-implant contact (BIC). The bone-implant interface was investigated using FE-SEM images and EDX spectra of the retrieved surgical implants at 8 weeks in the four animal groups. The obtained results showed significantly higher bone-implants contact and bone volume per tissue volume, as well as a greater amount of newly formed bone, in the BC-coated Ti implants than in the uncoated Ti implants. Direct bone-implant contact was also confirmed via histological examination. The results of this study confirmed that these biomimetic composite coatings on Ti implants were essential for a significant enhancement of osseointegration of BC-coated Ti implants and bone regeneration. This research provides a novel strategy for the treatment of bone fractures with possible orthopedic applications.

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High proportion strontium-doped micro-arc oxidation coatings enhance early osseointegration of titanium in osteoporosis by anti-oxidative stress pathway.

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