Synergistic Improvement of Antibacterial and Osteogenic Differentiation of Thermomechanically Processed Mg-Zr-Sr-Ce Alloy: Insights into the Role of Precipitate Evolution Supported by AIMD Simulation Study.

In the present study, we have discussed the influence of forging temperature (623 K (FT623), 723 K (FT723) and 823 K (FT823)) on microstructure and texture evolution and its implication on mechanical behavior, in vitro-in vivo biocorrosion, antibacterial response, and cytocompatibility of microalloyed Mg-Zr-Sr-Ce alloy. Phase analysis, SEM, and TEM characterization confirm the presence of Mg12Ce precipitate, and its stability was further validated by performing ab initio molecular dynamic simulation study. FT723 exhibits strengthened basal texture, higher fraction of second phases, and particle-stimulated nucleation-assisted DRX grains compared to other two specimens, resulting in superior strength with comparable ductility. FT723 also exhibits superior corrosion resistance mainly due to the strengthened basal texture and lower dislocation density. All the specimens exhibit excellent antibacterial behavior with Gram-negative E. coli, Gram-positive Staphylococcus aureus, and Pseudomonas aeruginosa bacteria. 100% reduction of bacterial growth is observed within 24 h of culture of the specimens. Cytocompatibility was determined by challenging specimen extracts with the MC3T3-E1 cell lines. FT723 specimen exhibits the highest cell proliferation and alkaline phosphatase activity (ALP) because of its superior corrosion resistance. The ability of the specimens to be used in orthopedic implant application was evaluated by in vivo study in rabbit femur. Neither tissue-related infection nor the detrimental effect surrounding the implant was confirmed from histological analysis. Significant higher bone regeneration surrounding the FT723 specimen was observed in SEM analysis and fluorochrome labeling. After 60 days, the FT723 specimen exhibits the highest bone formation, suggesting it is a suitable candidate for orthopedic implant application.

Osteosarcoma cell death induced by innovative scaffolds doped with chemotherapeutics.

Osteosarcoma (OS) cancer treatments include systemic chemotherapy and surgical resection. In the last years, novel treatment approaches have been proposed, which employ a drug-delivery system to prevent offside effects and improves treatment efficacy. Locally delivering anticancer compounds improves on high local concentrations with more efficient tumour-killing effect, reduced drugs resistance and confined systemic effects. Here, the synthesis of injectable strontium-doped calcium phosphate (SrCPC) scaffold was proposed as drug delivery system to combine bone tissue regeneration and anticancer treatment by controlled release of methotrexate (MTX) and doxorubicin (DOX), coded as SrCPC-MTX and SrCPC-DOX, respectively. The drug-loaded cements were tested in an in vitro model of human OS cell line SAOS-2, engineered OS cell line (SAOS-2-eGFP) and U2-OS. The ability of doped scaffolds to induce OS cell death and apoptosis was assessed analysing cell proliferation and Caspase-3/7 activities, respectively. To determine if OS cells grown on doped-scaffolds change their migratory ability and invasiveness, a wound-healing assay was performed. In addition, the osteogenic potential of SrCPC material was evaluated using human adipose derived-mesenchymal stem cells. Osteogenic markers such as (i) the mineral matrix deposition was analysed by alizarin red staining; (ii) the osteocalcin (OCN) protein expression was investigated by enzyme-linked immunosorbent assay test, and (iii) the osteogenic process was studied by real-time polymerase chain reaction array. The delivery system induced cell-killing cytotoxic effects and apoptosis in OS cell lines up to Day 7. SrCPC demonstrates a good cytocompatibility and it induced upregulation of osteogenic genes involved in the skeletal development pathway, together with OCN protein expression and mineral matrix deposition. The proposed approach, based on the local, sustained release of anticancer drugs from nanostructured biomimetic drug-loaded cements is promising for future therapies aiming to combine bone regeneration and anticancer local therapy.

Effect of strontium on transcription factors identified by transcriptome analyses of bovine ruminal epithelial cells.

BACKGROUND: Strontium (Sr) has similar physicochemical properties as calcium (Ca) and is often used to evaluate the absorption of this mineral. Because the major route of Ca absorption in the bovine occurs in the rumen, it is essential to understand whether Sr impacts the ruminal epithelial cells and to what extent. RESULTS: In the present study, RNA sequencing and assembled transcriptome assembly were used to identify transcription factors (TFs), screening and bioinformatics analysis in bovine ruminal epithelial cells treated with Sr. A total of 1405 TFs were identified and classified into 64 families based on an alignment of conserved domains. A total of 174 differently expressed TFs (DE-TFs) were increased and 52 DE-TFs were decreased; the biological process-epithelial cell differentiation was inhibited according to the GSEA-GO analysis of TFs; The GO analysis of DE-TFs was enriched in the DNA binding. Protein-protein interaction network (PPI) found 12 hubs, including SMAD4, SMAD2, SMAD3, SP1, GATA2, NR3C1, PPARG, FOXO1, MEF2A, NCOA2, LEF1, and ETS1, which verified genes expression levels by real-time PCR. CONCLUSIONS: In this study, SMAD2, PPARG, LEF1, ETS1, GATA2, MEF2A, and NCOA2 are potential candidates that could be targeted by Sr to mediate cell proliferation and differentiation, as well as lipid metabolism. Hence, these results enhance the comprehension of Sr in the regulation of transcription factors and provide new insight into the study of Sr biological function in ruminant animals.

Ion-incorporated titanium implants for staged regulation of antibacterial activity and immunoregulation-mediated osteogenesis.

Antibacterial properties and osteogenic activity are considered as two crucial factors for the initial healing and long-term survivability of orthopedic implants. For decades, various drug-loaded implants to enhance biological activities have been investigated extensively. More importantly, to control the drug release timing is equally significant due to the sequential biological processes after implantation. Hence, developing a staged regulation system on the titanium surface is practically significant. Here, we prepared TiO2 nanotubes (TiO2 NTs) on the titanium surface by anodization, followed by the incorporation of zinc (Zn) and strontium (Sr) sequentially through a hydrothermal process. Surface characterization confirmed the successful fabrication of Zn and Sr-incorporated TiO2 NTs (Zn-Sr/TiO2) on the titanium surface. The ion release results exhibited the differential release characteristic of Zn and Sr, which meant the early-stage release of Zn and the long-term release of Sr. It was exactly in accord with  the biological process after implantation, laying the basis of staged regulation after implantation. Zn-Sr/TiO2 showed favorable anti-early infection properties both in vitro and in vivo. Its inhibition effect on bacterial biofilm formation was attributed to the resistance against bacteria's initial adhesion and the killing effect on planktonic bacteria. Additionally, the release of Sr could alleviate infection-induced damage via immunoregulation. The biocompatibility and osteogenic activity mediated by M2 macrophage activation were confirmed with in vitro and in vivo studies. Therefore, it exhibited great potential in staged regulation for antibacterial activity in the early stage and the M2 activation-mediated osteogenic activity in the late stage. The staged regulation process was based on the differential release of Zn and Sr to achieve the early antibacterial effect and the long-term immune-induced osteogenic activity, to prevent implant-related infection and achieve better osseointegration. These two kinds of ions played their roles synergistically and complement mutually. This work is expected to provide an innovative idea for realizing sequential regulation after implantation.

Strontium-Doped Hydroxyapatite Coating Improves Osteo/Angiogenesis for Ameliorative Graft-Bone Integration via the Macrophage-Derived Cytokines-Mediated Integrin Signal Pathway.

Polyethylene terephthalate (PET) artificial ligaments, renowned for their superior mechanical properties, have been extensively adopted in anterior cruciate ligament (ACL) reconstruction surgeries. However, the inherent bio-inertness of PET introduces formidable barriers to graft-bone integration, a critical aspect of rehabilitation. Previous interventions, ranging from surface roughening to chemical modifications, have aimed to address this challenge; however, consistently effective techniques for inducing graft-bone integration remain scarce. Our study employed advanced surface-coating methodologies to introduce strontium-doped hydroxyapatite (SrHA) onto PET ligaments. Detailed scanning electron microscopy (SEM) examinations revealed a uniform and integrative coating of SrHA on PET fibers. Furthermore, spectroscopic analysis confirmed the steady release of strontium ions from the coated surface under physiological conditions. In-depth cellular studies proved that extracellular strontium emanating from SrHA-coated PET (PET@SrHA) ligaments actively steers the M2 macrophage polarization. Additionally, macrophages (Mφs) manifested a heightened secretion of prohealing cytokines when exposed to PET@SrHA. Subsequent investigations showed that these cytokines acted as mediators, activating integrin signaling pathways among macrophages, vascular endothelial cells, and osteoblasts. As a direct consequence, an increased rate of angiogenesis and osteogenic differentiation was observed, vital for graft-bone integration following ACL reconstruction with PET@SrHA ligaments. From a biochemical standpoint, our results pinpoint strontium ions as influential immunomodulators, sculpting the graft-bone interface's immune environment. This insight presents the SrHA-coating technique as a viable therapeutic strategy, holding sound promise for improving angiogenesis and osseointegration outcomes during ACL reconstruction using PET-based grafts.

A Multifunctional Metal-Phenolic Nanocoating on Bone Implants for Enhanced Osseointegration via Early Immunomodulation.

Surface modification is an important approach to improve osseointegration of the endosseous implants, however it is still desirable to develop a facile yet efficient coating strategy. Herein, a metal-phenolic network (MPN) is proposed as a multifunctional nanocoating on titanium (Ti) implants for enhanced osseointegration through early immunomodulation. With tannic acid (TA) and Sr2+ self-assembled on Ti substrates, the MPN coatings provided a bioactive interface, which can facilitate the initial adhesion and recruitment of bone marrow mesenchymal stem cells (BMSCs) and polarize macrophage toward M2 phenotype. Furthermore, the TA-Sr coatings accelerated the osteogenic differentiation of BMSCs. In vivo evaluations further confirmed the enhanced osseointegration of TA-Sr modified implants via generating a favorable osteoimmune microenvironment. In general, these results suggest that TA-Sr MPN nanocoating is a promising strategy for achieving better and faster osseointegration of bone implants, which can be easily utilized in future clinical applications.

Effect of strontium fluoride on mechanical and remineralization properties of enamel: An in-vitro study on a modified orthodontic adhesive.

OBJECTIVES: Evaluate the ability of strontium fluoride on bond strength and enamel integrity after incorporation within orthodontic adhesive system as a delivery vehicle. METHODS: Experimental orthodontic adhesive system Transbond™ XT were modified with 1% Sr2+, 0.5% SrF2, 1% strontium, 0.5% Sr2+, 1% F-, 0.5% F-, and no additions were control. Mixing of formulation was monitored using Fourier transform infrared spectroscopy. Small-molecule drug-discovery suite was used to gain insights into Sr2+, F-, and SrF2 binding. Shear bond testing was performed after 6-months of ageing. Enamel blocks were cut, and STEM pictures were recorded. Specimens were indented to evaluate elastic modulus. Raman microscope was used to collect Raman spectra and inspected using a scanning electron microscope. Crystal structural analysis was performed using X-ray diffraction. Effect of material on cellular proliferation was determined. Confocal was performed to evaluate the effect of formulation on biofilms. RESULTS: FTIR of modified adhesives depicted peak changes within range due to various functional groups existing within samples. TEM represented structurally optimized hexagonal unit-cell of hydroxyapatite. Mean shear bond strength is recorded highest for Transbond XT with 1% SrF2. Dead bacterial percentage appeared higher in 0.5% SrF2 and 1% F- specimens. Crystal lengths showed an increase in 0.5% and 1% SrF2 specimens. Phase contrast within TEM images showed a union of 0.5% SrF2 crystal with enamel crystal with higher elastic modulus and highly mineralized crystalline hydroxyapatite. Intensity of ν1 PO43- and ν1 CO32- along with carbonate - / ν1PO43- ratio displayed good association with strontium fluoride. The formulation showed acceptable cell biocompatibility (p < 0.353). All specimens displayed characteristic diffraction maxima of different apatite angles within XRD. SIGNIFICANCE: Experimental results suggested good biocompatibility, adequate mechanical strength, and far-ranging crystallization ability. This would provide a new strategy to overcome the two major challenges of fixed orthodontics, biofilm growth, and demineralization of enamel.

Janus Membrane with Intrafibrillarly Strontium-Apatite-Mineralized Collagen for Guided Bone Regeneration.

Commercial collagen membranes face difficulty in guided bone regeneration (GBR) due to the absence of hierarchical structural design, effective interface management, and diverse bioactivity. Herein, a Janus membrane called SrJM is developed that consists of a porous collagen face to enhance osteogenic function and a dense face to maintain barrier function. Specifically, biomimetic intrafibrillar mineralization of collagen with strontium apatite is realized by liquid precursors of amorphous strontium phosphate. Polycaprolactone methacryloyl is further integrated on one side of the collagen as a dense face, which endows SrJM with mechanical support and a prolonged lifespan. In vitro experiments demonstrate that the dense face of SrJM acts as a strong barrier against fibroblasts, while the porous face significantly promotes cell adhesion and osteogenic differentiation through activation of calcium-sensitive receptor/integrin/Wnt signaling pathways. Meanwhile, SrJM effectively enhances osteogenesis and angiogenesis by recruiting stem cells and modulating osteoimmune response, thus creating an ideal microenvironment for bone regeneration. In vivo studies verify that the bone defect region guided by SrJM is completely repaired by newly formed vascularized bone. Overall, the outstanding performance of SrJM supports its ongoing development as a multifunctional GBR membrane, and this study provides a versatile strategy of fabricating collagen-based biomaterials for hard tissue regeneration.

Strontium-loaded 3D intramedullary nail titanium implant for critical-sized femoral defect in rabbits.

The treatment of critical-sized bone defects has long been a major problem for surgeons. In this study, an intramedullary nail shaped three-dimensional (3D)-printed porous titanium implant that is capable of releasing strontium ions was developed through a simple and cost-effective surface modification technique. The feasibility of this implant as a stand-alone solution was evaluated using a rabbit's segmental diaphyseal as a defect model. The strontium-loaded implant exhibited a favorable environment for cell adhesion, and mechanical properties that were commensurate with those of a rabbit's cortical bone. Radiographic, biomechanical, and histological analyses revealed a significantly higher amount of bone ingrowth and superior bone-bonding strength in the strontium-loaded implant when compared to an untreated porous titanium implant. Furthermore, one-year histological observations revealed that the strontium-loaded implant preserved the native-like diaphyseal bone structure without failure. These findings suggest that strontium-releasing 3D-printed titanium implants have the clinical potential to induce the early and efficient repair of critical-sized, load-bearing bone defects.

Repair of a rat calvaria defect with injectable strontium (Sr)-doped polyphosphate dicalcium phosphate dehydrate (P-DCPD) ceramic bone grafts.

The trace element strontium (Sr) enhances new bone formation. However, delivering Sr, like other materials, in a sustained manner from a ceramic bone graft substitute (BGS) is difficult. We developed a novel ceramic BGS, polyphosphate dicalcium phosphate dehydrate (P-DCPD), which delivers embedded drugs in a sustained pattern. This study assessed the in vitro and in vivo performance of Sr-doped P-DCPD. In vitro P-DCPD and 10%Sr-P-DCPD were nontoxic and eluents from 10%Sr-P-DCPD significantly enhanced osteoblastic MC3T3 cell differentiation. A sustained, zero-order Sr release was observed from 10%Sr-P-DCPD for up to 70 days. When using this BGS in a rat calvaria defect model, both P-DCPD and 10% Sr-P-DCPD were found to be biocompatible and biodegradable. Histologic data from decalcified and undecalcified tissue showed that 10%Sr-P-DCPD had more extensive new bone formation compared with P-DCPD 12-weeks after surgery and the 10%Sr-P-DCPD had more organized new bone and much less fibrous tissue at the defect margins. The new bone was formed on the surface of the degraded ceramic debris within the bone defect area. P-DCPD represented a promising drug-eluting BGS for repair of critical bone defects.

Enhancing immune modulation and bone regeneration on titanium implants by alleviating the hypoxic microenvironment and releasing bioactive ions.

Bone implantation inevitably causes damage to surrounding vasculature, resulting in a hypoxic microenvironment that hinders bone regeneration. Although titanium (Ti)-based devices are widely used as bone implants, their inherent bioinert surface leads to poor osteointegration. Herein, a strontium peroxide (SrO2)-decorated Ti implant, Ti_P@SrO2, was constructed through coating with poly-L-lactic acid (PLLA) to alleviate the hypoxic microenvironment and transform the bioinert surface of the implant into a bioactive surface. PLLA degradation resulted in an acidic microenvironment and the release of SrO2 nanoparticles. The acidic microenvironment then accelerated the decomposition of SrO2, resulting in the release of O2 and Sr ions. O2 released from Ti_P@SrO2 can alleviate the hypoxic microenvironment, thus enhancing cell proliferation in an O2-insufficient microenvironment. Furthermore, under hypoxic and normal microenvironments, Ti_P@SrO2 enhanced alkaline phosphatase activity and bone-related gene expression in C3H10T1/2 cells with the continuous release of Sr ions. Meanwhile, Ti_P@SrO2 suppressed M1 polarization and promoted M2 polarization of bone marrow-derived monocytes under hypoxic and normal conditions. Furthermore, in a rat implantation model, the implant enhanced new bone formation and improved osteointegration after modification with SrO2. In summary, the newly designed O2- and Sr ion-releasing Ti implants are promising for applications in bone defects.

Enhanced remineralisation ability and antibacterial properties of sol-gel glass ionomer cement modified by fluoride containing strontium-based bioactive glass or strontium-containing fluorapatite.

OBJECTIVES: This study aimed to compare two types of bioactive additives which were strontium-containing fluorinated bioactive glass (SrBGF) or strontium-containing fluorapatite (SrFA) added to sol-gel derived glass ionomer cement (SGIC). The objective was to develop antibacterial and mineralisation properties, using bioactive additives, to minimize the occurrence of caries lesions in caries disease. METHODS: Synthesized SrBGF and SrFA nanoparticles were added to SGIC at 1 wt% concentration to improve antibacterial properties against S. mutans, promote remineralisation, and hASCs and hDPSCs viability. Surface roughness and ion-releasing behavior were also evaluated to clarify the effect on the materials. Antibacterial activity was measured via agar disc diffusion and bacterial adhesion. Remineralisation ability was assessed by applying the material to demineralised teeth and subjecting them to a 14-day pH cycle, followed by microCT and SEM-EDS analysis. RESULTS: The addition of SrFA into SGIC significantly improved its antibacterial property. SGIC modified with either SrBGF or SrFA additives could similarly induce apatite crystal precipitation onto demineralised dentin and increase dentin density, indicating its ability to remineralise dentin. Moreover, this study also showed that SGIC modified with SrBGF or SrFA additives had promising results on the in vitro cytotoxicity of hASC and hDPSC. SIGNIFICANT: SrFA has superior antibacterial property as compared to SrBGF while demonstrating equal remineralisation ability. Furthermore, the modified SGIC showed promising results in reducing the cytotoxicity of hASCs and hDPSCs, indicating its potential for managing caries.

A novel porous titanium with engineered surface for bone defect repair in load-bearing position.

Porous titanium exhibits low elastic modulus and porous structure is thought to be a promising implant in bone defect repair. However, the bioinert and low mechanical strength of porous titanium have limited its clinical application, especially in load-bearing bone defect repair. Our previous study has reported an infiltration casting and acid corrosion (IC-AC) method to fabricate a novel porous titanium (pTi) with 40% porosity and 0.4 mm pore diameter, which exerts mechanical property matching with cortical bone and interconnected channels. In this study, we introduced a nanoporous coating and incorporated an osteogenic element strontium (Sr) on the surface of porous titanium (named as Sr-micro arch oxidation [MAO]) to improve the osteogenic ability of the pTi by MAO. Better biocompatibility of Sr-MAO was verified by cell adhesion experiment and cell counting kit-8 (CCK-8) test. The in vitro osteogenic-related tests such as immunofluorescence staining, alkaline phosphatase staining and real-time polymerase chain reaction (RT-PCR) demonstrated better osteogenic ability of Sr-MAO. Femoral bone defect repair model was employed to evaluate the osseointegration of samples in vivo. Results of micro-CT scanning, sequential fluorochrome labeling and Van Gieson staining suggested that Sr-MAO showed better in vivo osteogenic ability than other groups. Taking results of both in vitro and in vivo experiment together, this study indicated the Sr-MAO porous titanium could be a promising implant load-bearing bone defect.

Polydopamine-Functionalized Strontium Alginate/Hydroxyapatite Composite Microhydrogel Loaded with Vascular Endothelial Growth Factor Promotes Bone Formation and Angiogenesis.

Critical-size bone defects are a common and intractable clinical problem that typically requires filling in with surgical implants to facilitate bone regeneration. Considering the limitations of autologous bone and allogeneic bone in clinical applications, such as secondary damage or immunogenicity, injectable microhydrogels with osteogenic and angiogenic effects have received considerable attention. Herein, polydopamine (PDA)-functionalized strontium alginate/nanohydroxyapatite (Sr-Alg/nHA) composite microhydrogels loaded with vascular endothelial growth factor (VEGF) were prepared using microfluidic technology. This composite microhydrogel released strontium ions stably for at least 42 days to promote bone formation. The PDA coating can release VEGF in a controlled manner, effectively promote angiogenesis around bone defects, and provide nutritional support for new bone formation. In in vitro experiments, the composite microhydrogels had good biocompatibility. The PDA coating greatly improves cell adhesion on the composite microhydrogel and provides good controlled release of VEGF. Therefore, this composite microhydrogel effectively promotes osteogenic differentiation and vascularization. In in vivo experiments, composite microhydrogels were injected into critical-size bone defects in the skull of rats, and they were shown by microcomputed tomography and tissue sections to be effective in promoting bone regeneration. These findings demonstrated that this novel microhydrogel effectively promotes bone formation and angiogenesis at the site of bone defects.

Effects of aligned PLGA/SrCSH composite scaffolds on in vitro growth and osteogenic differentiation of human mesenchymal stem cells.

Strontium (Sr) has important functions in bone remodeling. Incorporating strontium-doped α-calcium sulfate hemihydrate (SrCSH) into poly(lactic-co-glycolic acid) (PLGA) fibrous scaffolds were expected to increase its bio-activity and provide a potential material for bone tissue engineering. In the present study, Sr-containing aligned PLGA/SrCSH fibrous scaffolds similar to the architecture of natural bone were prepared via wet spinning. CCK-8 assay revealed that Sr-containing scaffolds possessed better bioactivity and supported favorable cell growth effectively. The aligned PLGA/SrCSH fibers exerted a contact effect on cell attachment, inducing regular cell alignment and influencing a series of cell behaviors. Releasing of high concentration Sr from a-PLGA/SrCSH scaffolds could induce high expression levels of BMP-2, increase ALP activity and upregulate RUNX-2 expression, and further promote the expressions of COL-I and OCN and the maximum mineralization. This study demonstrated that Sr and ordered structure in a-PLGA/SrCSH fibrous scaffolds could synergistically enhance the osteogenic differentiation of umbilical cord mesenchymal stem cells (UCMSCs) by regulating cell arrangement and expressions of osteogenic genes.

Enhanced Mechanical Properties, Corrosion Resistance, Cytocompatibility, Osteogenesis, and Antibacterial Performance of Biodegradable Mg-2Zn-0.5Ca-0.5Sr/Zr Alloys for Bone-Implant Application.

Magnesium (Mg) alloys are widely used in bone fixation and bone repair as biodegradable bone-implant materials. However, their clinical application is limited due to their fast corrosion rate and poor mechanical stability. Here, the development of Mg-2Zn-0.5Ca-0.5Sr (MZCS) and Mg-2Zn-0.5Ca-0.5Zr (MZCZ) alloys with improved mechanical properties, corrosion resistance, cytocompatibility, osteogenesis performance, and antibacterial capability is reported. The hot-extruded (HE) MZCZ sample exhibits the highest ultimate tensile strength of 255.8 ± 2.4 MPa and the highest yield strength of 208.4 ± 2.8 MPa and an elongation of 15.7 ± 0.5%. The HE MZCS sample shows the highest corrosion resistance, with the lowest corrosion current density of 0.2 ± 0.1 µA cm-2 and the lowest corrosion rate of 4 ± 2 µm per year obtained from electrochemical testing, and a degradation rate of 368 µm per year and hydrogen evolution rate of 0.83 ± 0.03 mL cm-2 per day obtained from immersion testing. The MZCZ sample shows the highest cell viability in relation to MC3T3-E1 cells among all alloy extracts, indicating good cytocompatibility except at 25% concentration. Furthermore, the MZCZ alloy shows good antibacterial capability against Staphylococcus aureus.

Improved Biocompatibility and Angiogenesis of the Bone Titanium Scaffold through ERK1/2 Signaling Mediated by an Attached Strontium Element.

The promotion of early osseointegration is crucial for the success of biomedical titanium implants. Physical and chemical modifications to the material surface can significantly compensate for the lack of biocompatibility and early osseointegration of the implant. In this study, we implanted strontium onto titanium plates and analyzed the effect of strontium-doped materials on angiogenesis and biocompatibility in the human bone structure. Our findings demonstrated that strontium-loaded titanium sheet materials effectively promote human umbilical vein endothelial cell (HUVEC) biocompatibility and vascular differentiation ability, as evidenced by proliferation-apoptosis assays, RT-qPCR for vascular neogenesis markers, ELISA for vascular endothelial growth factor (VEGF) levels, and nitric oxide (NO) analysis. Mechanism studies based on RNAseq and Western blotting analysis revealed that strontium can promote titanium material biocompatibility with HUVEC cells and vascular neovascularization ability by activating the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Meanwhile, blocking the ERK1/2 signaling pathway could reverse the promotional effect of vascular formation. Overall, we have successfully fabricated a multifunctional biocompatible bone implant with better histocompatibility and angiogenesis compared to uncoated implants.

Effect of Strontium-Substituted Calcium Phosphate Coatings Prepared by One-Step Electrodeposition at Different Temperatures on Corrosion Resistance and Biocompatibility of AZ31 Magnesium Alloys.

As potential degradable biomaterials, magnesium (Mg) alloys have development prospects in the field of orthopedic load-bearing, whereas the clinical application has encountered a bottleneck due to a series of problems caused by its rapid corrosion. In this study, strontium-substituted calcium phosphate (CaP) coatings with different structures were prepared on the surface of the Mg matrix by a simple one-step electrodeposition method at different temperatures, which enhanced the poor corrosion resistance of the Mg matrix. The coated sample prepared at 65 °C reduced the corrosion current density by 3 orders of magnitude and increased the impedance by nearly 2 orders of magnitude compared with bare Mg alloy, thanks to its dense fibrous structure similar to that of natural bones. Although the coating composition varies with different preparation temperatures, CaP, as an inorganic component similar to natural bone, has good cytocompatibility. Doping the right amount of strontium, which is a trace element in human bones, is beneficial to stimulate osteoblast differentiation, inhibit the activity of osteoclasts, and induce the formation of bone tissues. This provides a new option for modifying the Mg alloy with CaP coatings as a base.

Strontium-doped hydroxyapatite and its role in osteogenesis and angiogenesis.

For the past 50 years, hydroxyapatite (HA) has been widely used in bone defect repair because it is the main inorganic component of the mineral phase of a human bone. Extensive preclinical and clinical studies have shown that strontium (Sr) can safely and effectively help prevent and treat bone diseases, including osteoporosis. These findings have resulted in the concept of integrating Sr and HA for bone disease management. The doped Sr can improve the physicochemical properties of HA and enhance its angiogenic and bone regeneration ability. Nevertheless, no study has reviewed the design strategy of Sr-doped HA (Sr-HA) to understand its biological roles. Therefore, in this article, we review recent developments in Sr-HA preparation and its effect on osteogenesis and angiogenesis in vitro and in vivo along with key suggestions for future research and development.

Synthesis and Antimicrobial Analysis of High Surface Area Strontium-Substituted Calcium Phosphate Nanostructures for Bone Regeneration.

Continuous microwave-assisted flow synthesis has been used as a simple, more efficient, and low-cost route to fabricate a range of nanosized (<100 nm) strontium-substituted calcium phosphates. In this study, fine nanopowder was synthesized via a continuous flow synthesis with microwave assistance from the solutions of calcium nitrate tetrahydrate (with strontium nitrate as Sr2+ ion source) and diammonium hydrogen phosphate at pH 10 with a time duration of 5 min. The morphological characterization of the obtained powder has been carried out by employing techniques such as transmission electron microscopy, X-ray diffraction, and Brunauer-Emmett-Teller surface area analysis. The chemical structural analysis to evaluate the surface properties was made by using X-ray photoelectron spectroscopy. Zeta potential analysis was performed to evaluate the colloidal stability of the particles. Antimicrobial studies were performed for all the compositions using four bacterial strains and an opportunistic human fungal pathogen Macrophomina phaseolina. It was found that the nanoproduct with high strontium content (15 wt% of strontium) showed pronounced antibacterial potential against M. luteus while it completely arrested the fungal growth after 48 h by all of its concentrations. Thus the synthesis strategy described herein facilitated the rapid production of nanosized Sr-substituted CaPs with excellent biological performance suitable for a bone replacement application.