Titanium-doped phosphate glasses containing zinc and strontium applied in bone regeneration.

Phosphate bioactive glass has been studied for its advanced biodegradability and active ion release capability. Our previous research found that phosphate glass containing (P2O5)-(Na2O)-(TiO2)-(CaO)-(SrO) or (ZnO) showed good biocompatibility with MG63 and hMSCs. This study further investigated the application of 5 mol% zinc oxide or 17.5 mol% strontium oxide in titanium-doped phosphate glass for bone tissue engineering. Ti-Ca-Na-Phosphate glasses, incorporating 5% zinc oxide or 17.5% strontium oxide, were made with melting quenching technology. The pre-osteoblast cell line MC3T3-E1 was cultured for indirect contact tests with graded diluted phosphate glass extractions and for direct contact tests by seeding cells on glass disks. The cell viability and cytotoxicity were analysed in vitro over 7 days. In vivo studies utilized the tibial defect model with or without glass implants. The micro-CT analysis was performed after surgery and then at 2, 6, and 12 weeks. Extractions from both zinc and strontium phosphate glasses showed no negative impact on MC3T3-E1 cell viability. Notably, non-diluted Zn-Ti-Ca-Na-phosphate glass extracts significantly increased cell viability by 116.8% (P < 0.01). Furthermore, MC3T3-E1 cells cultured with phosphate glass disks exhibited no increase in LDH release compared with the control group. Micro-CT images revealed that, over 12 weeks, both zinc-doped and strontium-doped phosphate glasses demonstrated good bone incorporation and longevity compared to the no-implant control. Titanium-doped phosphate glasses containing 5 mol% zinc oxide, or 17.5 mol% strontium oxide have promising application potential for bone regeneration research.

Strontium-doped bioactive glass-functionalized polyetheretherketone enhances osseointegration by facilitating cell adhesion.

In the field of orthopedics, surgeons have long been facing the challenge of loosening of external fixation screws due to inherent material characteristics. Despite Polyetheretherketone (PEEK) being employed as an orthopedic implant material for many years, its bio-inert nature often hinders bone healing due to the limited bioactivity, which restricts its clinical applications. Herein, a new type of orthopedic implant (Sr-SPK) was developed by introducing strontium (Sr)-doped mesoporous bioactive glass (Sr-MBG) onto the surface of PEEK implants through a simple and feasible method. In vitro experiments revealed that Sr-SPK effectively promotes osteogenic differentiation while concurrently suppressing the formation of osteoclasts. The same results were validated in vivo with Sr-SPK significantly improving bone integration. Upon investigation, it was found that Sr-SPK promotes adhesion among bone marrow mesenchymal stem cells (BMSCs) thereby promoting osteogenesis by activating the regulation of actin cytoskeletal and focal adhesion pathways, as identified via transcriptome analysis. In essence, these findings suggest that the newly constructed Sr-doped biofunctionalized PEEK implant developed in this research can promote osteoblast differentiation and suppress osteoclast activity by enhancing cell adhesion processes. These results underline the immense potential of such an implant for wide-ranging clinical applications in orthopedics.

Sr-Incorporated Bioactive Glass Remodels the Immunological Microenvironment by Enhancing the Mitochondrial Function of Macrophage via the PI3K/AKT/mTOR Signaling Pathway.

The repair of critical-sized bone defects continues to pose a challenge in clinics. Strontium (Sr), recognized for its function in bone metabolism regulation, has shown potential in bone repair. However, the underlying mechanism through which Sr2+ guided favorable osteogenesis by modulating macrophages remains unclear, limiting their application in the design of bone biomaterials. Herein, Sr-incorporated bioactive glass (SrBG) was synthesized for further investigation. The release of Sr ions enhanced the immunomodulatory properties and osteogenic potential by modulating the polarization of macrophages toward the M2 phenotype. In vivo, a 3D-printed SrBG scaffold was fabricated and showed consistently improved bone regeneration by creating a prohealing immunological microenvironment. RNA sequencing was performed to explore the underlying mechanisms. It was found that Sr ions might enhance the mitochondrial function of macrophage by activating PI3K/AKT/mTOR signaling, thereby favoring osteogenesis. Our findings demonstrate the relationship between the immunomodulatory role of Sr ions and the mitochondrial function of macrophages. By focusing on the mitochondrial function of macrophages, Sr2+-mediated immunomodulation sheds light on the future design of biomaterials for tissue regenerative engineering.

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.

Study on the performance and mechanism of cobaltous ion removal from water by a high-efficiency strontium-doped hydroxyapatite adsorbent.

In this study, a high-efficiency strontium-doped hydroxyapatite (Sr-HAP) adsorbent was synthesized by a sol-gel method for removing cobaltous ions (Co(II)) from water. The effects of adsorbent dose, initial solution pH, initial Co(II) concentration and temperature on the removal performance of Co(II) were investigated. Experimental results indicated that the optimum Sr-HAP dose was 0.30 g/50 mL solution, the Sr-HAP adsorbent could effectively remove Co(II) in a wide pH range of 3-8. Increasing temperature was conducive to the adsorption, and the maximum Co(II) adsorption capacity by Sr-HAP reached 48.467 mg/g at 45 °C. The adsorption of Co(II) followed the pseudo-second-order kinetic model, indicating that the Co(II) adsorption by Sr-HAP was attributed mainly to chemisorption. The isothermal adsorption results showed that at lower Co(II) equilibrium concentration, the Langmuir model fitted the data better than the Freundlich model but opposite at higher Co(II) equilibrium concentration. Therefore, the adsorption of Co(II) was a process from monolayer adsorption to multilayer adsorption with the increase of the Co(II) equilibrium concentration. The diffusion analysis of Co(II) to Sr-HAP indicated that the internal diffusion and surface adsorption were the rate-controlled steps of Co(II) adsorption. Thermodynamic study demonstrated that the Co(II) adsorption process was spontaneous and endothermic. The mechanism study revealed that in addition to chemisorption, Sr-HAP also removed Co(II) ions from water via ion exchange and surface complexation.

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.

Near-Infrared Dual-Modal Sensing of Force and Temperature in Total Knee Replacement Using Mechanoluminescent Phosphor of Sr3Sn2O7: Nd, Yb.

Knee replacement surgery confronts challenges including patient dissatisfaction and the necessity for secondary procedures. A key requirement lies in dual-modal measurement of force and temperature of artificial joints during postoperative monitoring. Here, a novel non-toxic near-infrared (NIR) phosphor Sr3Sn2O7:Nd, Yb, is designed to realize the dual-modal measurement. The strategy is to entail phonon-assisted upconversion luminescence (UCL) and trap-controlled mechanoluminescence (ML) in a single phosphor well within the NIR biological transmission window. The phosphor is embedded in medical bone cement forming a smart joint in total knee replacements illustrated as a proof-of-concept. The sensing device can be charged in vitro by a commercial X-ray source with a safe dose rate for ML, and excited by a low power 980 nm laser for UCL. It attains impressive force and temperature sensing capabilities, exhibiting a force resolution of 0.5% per 10 N, force detection threshold of 15 N, and a relative temperature sensitive of up to 1.3% K-1 at 309 K. The stability against humidity and thermal shock together with the robustness of the device are attested. This work introduces a novel methodological paradigm, paving the way for innovative research to enhance the functionality of artificial tissues and joints in living organisms.

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.

Effects of Zinc and Strontium Doping on In Vitro Osteogenesis and Angiogenesis of Calcium Silicate/Calcium Phosphate Cement.

Based on multiple biological functions (mainly osteogenesis and angiogenesis) of bioactive ions, Zn/Sr-doped calcium silicate/calcium phosphate cements (Zn/Sr-CS/CPCs, including 10Zn-CS/CPC, 20Sr-CS/CPC, and 10Zn/20Sr-CS/CPC) were prepared by the addition of Zn and Sr dual active ions into CS/CPC to further accelerate its bone regeneration in this study. The physicochemical and biological properties of the Zn/Sr-CS/CPCs were systematically investigated. The results showed that the setting time was slightly prolonged, the compressive strength and porosity did not change much, and all groups maintained good injectability after the doping of Zn and Sr. Besides, the doping of Zn and Sr had little effect on the phase and microstructure of hydrated products of CS/CPC. The degradation rate of Zn/Sr-CS/CPCs decreased after doping with Zn and Sr. In mouse bone marrow mesenchymal stem cells (mBMSC) experiments, all Zn/Sr-CS/CPCs stimulated the viability, adhesion, proliferation, and alkaline phosphatase (ALP) activity together with osteogenesis-related genes (ALP, Runx2, Col-I, OCN, and OPN). The further addition of Zn and Sr played better and synergistic roles in in vitro osteogenesis. Thereinto, 10Zn/20Sr-CS/CPC manifested the optimum in vitro osteogenic performance. As for human umbilical vein endothelial cell (HUVEC) experiments, the incorporation of CS doped with Zn and Sr into CPC possessed good vascularization properties of proliferation, NO secretion, tube formation, and the expression of angiogenesis-related genes (VEGF, bFGF, and eNOS). In conclusion, the doping of Zn and Sr into CS/CPC could exhibit excellent osteogenesis and good angiogenesis potentials and 10Zn/20Sr-CS/CPC could be considered as a promising candidate in bone repair.

Strontium-driven physiological to pathological transition of bone-like architecture: A dose-dependent investigation.

Whilst strontium (Sr2+) is widely investigated for treating osteoporosis, it is also related to mineralization disorders such as rickets and osteomalacia. In order to clarify the physiological and pathological effects of Sr2+ on bone biomineralization , we performed a dose-dependent investigation in bone components using a 3D scaffold that displays the hallmark features of bone tissue in terms of composition (osteoblast, collagen, carbonated apatite) and architecture (mineralized collagen fibrils hierarchically assembled into a twisted plywood geometry). As the level of Sr2+ is increased from physiological-like to excess, both the mineral and the collagen fibrils assembly are destabilized, leading to a drop in the Young modulus, with strong implications on pre-osteoblastic cell proliferation. Furthermore, the microstructural and mechanical changes reported here correlate with that observed in bone-weakening disorders induced by Sr2+ accumulation, which may clarify the paradoxical effects of Sr2+ in bone mineralization. More generally, our results provide physicochemical insights into the possible effects of inorganic ions on the assembly of bone extracellular matrix and may contribute to the design of safer therapies for treating osteoporosis. STATEMENT OF SIGNIFICANCE: Physiological-like (10% Sr2+) and excess accumulation-like (50% Sr2+) doses of Sr2+ are investigated in 3D biomimetic assemblies possessing the high degree of organization found in the extracellular of bone. Above the physiological dose, the organic and inorganic components of the bone-like scaffold are destabilized, resulting in impaired cellular activity, which correlates with bone-weakening disorders induced by Sr2+.

A comparative analysis of 3D printed scaffolds consisting of poly(lactic-co-glycolic) acid and different bioactive mineral fillers: aspects of degradation and cytocompatibility.

Their excellent mechanical properties, degradability and suitability for processing by 3D printing technologies make the thermoplastic polylactic acid and its derivatives favourable candidates for biomaterial-based bone regeneration therapies. In this study, we investigated whether bioactive mineral fillers, which are known to promote bone healing based on their dissolution products, can be integrated into a poly(L-lactic-co-glycolic) acid (PLLA-PGA) matrix and how key characteristics of degradation and cytocompatibility are influenced. The polymer powder was mixed with particles of CaCO3, SrCO3, strontium-modified hydroxyapatite (SrHAp) or tricalcium phosphates (α-TCP, ß-TCP) in a mass ratio of 90 : 10; the resulting composite materials have been successfully processed into scaffolds by the additive manufacturing method Arburg Plastic Freeforming (APF). Degradation of the composite scaffolds was investigated in terms of dimensional change, bioactivity, ion (calcium, phosphate, strontium) release/uptake and pH development during long-term (70 days) incubation. The mineral fillers influenced the degradation behavior of the scaffolds to varying degrees, with the calcium phosphate phases showing a clear buffer effect and an acceptable dimensional increase. The amount of 10 wt% SrCO3 or SrHAp particles did not appear to be appropriate to release a sufficient amount of strontium ions to exert a biological effect in vitro. Cell culture experiments with the human osteosarcoma cell line SAOS-2 and human dental pulp stem cells (hDPSC) indicated the high cytocompatibility of the composites: For all material groups cell spreading and complete colonization of the scaffolds over the culture period of 14 days as well as an increase of the specific alkaline phosphatase activity, typical for osteogenic differentiation, were observed.

Strontium Ion-Functionalized Nano-Hydroxyapatite/Chitosan Composite Microspheres Promote Osteogenesis and Angiogenesis for Bone Regeneration.

Critical-size bone defects are an important problem in clinical practice, which usually occurs in severe trauma, or tumor resection, and cannot heal completely and autonomously. Implantation of grafts is often required to promote the regeneration of critical-size bone defects. Metal ions play an important role in human health, as they affect the body's metabolism and the tissue function. Strontium ions (Sr2+) can promote osteogenesis and angiogenesis. Herein, we prepared nano-hydroxyapatite (nHA)/chitosan (CS) composite microspheres with a uniform particle size distribution and an extracellular matrix-like nanofiber structure using microfluidic technology and direct alkali-induced gelation. Strontium ions were stably added into the microspheres by using polydopamine (PDA) to chelate metal ions forming a bone repair material (nHA/CS@PDA-Sr) with good bioactivity. The coordination reaction of PDA can effectively control the release of strontium ions and avoid the negative effects caused by the high strontium concentration. Our in vitro experiments showed that the composite microspheres had good biocompatibility and that the PDA coating promotes cell adhesion. The slow release of strontium ions can effectively promote mesenchymal stem cells osteogenic differentiation and the vascularization of endothelial cells. In addition, we injected composite microspheres into cranial defects of rats to evaluate osseointegration in vivo. The results showed that nHA/CS@PDA-Sr could effectively promote bone regeneration in the defect area. This study demonstrates that composite microspheres stimulate bone repair providing a promising way for bone-defect regeneration.

Bone Regeneration in Small and Large Segmental Bone Defect Models after Radiotherapy Using Injectable Polymer-Based Biodegradable Materials Containing Strontium-Doped Hydroxyapatite Particles.

The reconstruction of bones following tumor excision and radiotherapy remains a challenge. Our previous study, performed using polysaccharide-based microbeads that contain hydroxyapatite, found that these have osteoconductivity and osteoinductive properties. New formulations of composite microbeads containing HA particles doped with strontium (Sr) at 8 or 50% were developed to improve their biological performance and were evaluated in ectopic sites. In the current research, we characterized the materials by phase-contrast microscopy, laser dynamic scattering particle size-measurements and phosphorus content, before their implantation into two different preclinical bone defect models in rats: the femoral condyle and the segmental bone. Eight weeks after the implantation in the femoral condyle, the histology and immunohistochemistry analyses showed that Sr-doped matrices at both 8% and 50% stimulate bone formation and vascularization. A more complex preclinical model of the irradiation procedure was then developed in rats within a critical-size bone segmental defect. In the non-irradiated sites, no significant differences between the non-doped and Sr-doped microbeads were observed in the bone regeneration. Interestingly, the Sr-doped microbeads at the 8% level of substitution outperformed the vascularization process by increasing new vessel formation in the irradiated sites. These results showed that the inclusion of strontium in the matrix-stimulated vascularization in a critical-size model of bone tissue regeneration after irradiation.

Zn-Sr-sintered true bone ceramics enhance bone repair and regeneration.

Bone defects are one of the toughest challenges faced by orthopedic surgeons worldwide, especially at critical sizes, which are caused by severe trauma, malignancy, or congenital disease. The ideal bone tissue-engineered scaffold for bone regeneration is the one that has good osteoconductivity, osteoinductivity, pore structure, and antibacterial properties. Metal ions have been recognized in recent years to be essential regulators of bone metabolism, and they are widely used for bone tissue engineering. In particular, zinc ions are of interest because of their ideal biocompatibility, osteogenesis-promoting properties, and antibacterial properties. Moreover, the dual role of strontium (Sr) in promoting osteogenesis and inhibiting osteolysis provides academic support for Zn-Sr co-doped scaffolds. Based on true bone ceramics (TBC), Zn-Sr-sintered scaffolds with good pore structures were prepared using immersion-calcination. The biocompatibility, cell adhesion, osteogenic properties, and antibacterial activity of Zn-Sr-sintered TBC scaffolds in bone marrow mesenchymal stem cells (BMSCs) are superior to those of control TBC scaffolds. The Zn-Sr-sintered TBC scaffold was used to repair rat cranial defects. Its good in vivo repair performance was confirmed by osseointegration and inward bone growth compared with that of the control TBC scaffold. Zn0.25Sr0.20-TBC is an ideal material for bone repair because of its good biocompatibility and favorable in vitro osteogenic properties.

In vitro release of silver ions and expression of osteogenic genes by MC3T3-E1 cell line cultured on nano-hydroxyapatite and silver/strontium-coated titanium plates.

Attempts are ongoing to improve the surface properties of dental implants by application of different coatings, aiming to enhance osseointegration, and decrease the adverse effects of titanium and its alloys used in dental implants. Coating of implant surface with hydroxyapatite (HA) is one suggested strategy for this purpose due to its high biocompatibility and similar structure to the adjacent bone. This study aimed to quantify the release of silver ions and expression of osteogenic genes by MC3T3-E1 cells cultured on nano-HA and silver/strontium (Ag/Sr)-coated titanium plates via the electrochemical deposition method. Plates measuring 10 × 10 × 0.9 mm were fabricated from Ti-6Al-4 V alloy, and polished with silicon carbide abrasive papers before electrochemical deposition to create a smooth, mirror-like surface. After applying homogenous nano-HA coatings with/without silver/strontium on the surface of the plates, the composition of coatings was confirmed by energy-dispersive X-ray spectroscopy (EDS), and their morphological properties were analyzed by scanning electron microscopy (SEM). The coated specimens were then immersed in simulated body fluid (SBF), and the concentration of released sliver ions was quantified by spectroscopy at 7-14 days. The MC3T3-E1 osteoblastic cell line was cultured in osteogenic medium for 7-14 days, and after RNA extraction and cDNA synthesis, the expression of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN); osteogenic genes was quantified by polymerase chain reaction (PCR) using SYBR Green Master Mix kit. The expression of genes and the released amount of silver ions were compared between the two groups using the Mann-Whitney U test. The two groups were not significantly different regarding silver ion release at 14 days (P > 0.05). However, silver ion release was significantly higher from nano-HA coatings with silver/strontium at 7 days (P = 0.03). The difference in expression of RUNX2 (P = 0.04), OPN (P = 0.04), and OCN (P = 0.03) genes was also significant between nano-HA coating groups with and without silver/strontium at 7 days, and the expressions were higher in nano-HA with silver/strontium group, but this difference was not significant at 14 days. Addition of silver and strontium to specimens coated with nano-HA increased the release of silver ions within the non-toxic range, and enhanced the expression of osteogenic genes particularly after 7 days.

Microstructure, Mechanical, In Vitro Biodegradation, and Antimicrobial Behavior of a Mg-Zn-Ca-Sr/ZrO2 Composite Prepared Using Powder Metallurgy.

Biodegradable materials, especially Mg alloys, have an exceptional advantage over nonbiodegradable materials in orthopedic applications, such as avoiding second surgery for removal/replacement, stress shielding, but not enough mechanical strength, and so forth. By further improving the Mg alloy to get all the remaining required properties, it can be used for better biodegradable implants, which depend adequately on material optimization, processing, and so forth. A Mg-Zn-Ca-Sr/ZrO2 composite has been prepared using powder metallurgy by adding 0, 1, 2, and 3 wt % of ZrO2, which also contains Zn, Ca, and Sr as nutrient elements. Microstructure characterization, as well as mechanical and in vitro biodegradation, have been investigated by hardness, compression, and immersion tests. The highest compressive strength, contraction, and hardness of about 185.6 MPa, 9.5%, and 65.2 HRB are observed in the 2% ZrO2-containing composite, respectively, whereas a minimum biodegradation rate of 2.76 mm/year is observed on the same. The antibiotic sensitivity observations against Staphylococcus aureus suggest that the alloy C3 has superior biological activity against the pathogen which ranks this alloy on top in merit. Overall, Mg-Zn-Ca-Sr/ZrO2 exhibits impressive potential for use as a biodegradable and antibiotic material for orthopedic applications.

Strontium Substituted ß-Tricalcium Phosphate Ceramics: Physiochemical Properties and Cytocompatibility.

Sr2+-substituted ß-tricalcium phosphate (ß-TCP) powders were synthesized using the mechano-chemical activation method with subsequent pressing and sintering to obtain ceramics. The concentration of Sr2+ in the samples was 0 (non-substituted TCP, as a reference), 3.33 (0.1SrTCP), and 16.67 (0.5SrTCP) mol.% with the expected Ca3(PO4)2, Ca2.9Sr0.1(PO4)2, and Ca2.5Sr0.5(PO4)2 formulas, respectively. The chemical compositions were confirmed by the energy-dispersive X-ray spectrometry (EDX) and the inductively coupled plasma optical emission spectroscopy (ICP-OES) methods. The study of the phase composition of the synthesized powders and ceramics by the powder X-ray diffraction (PXRD) method revealed that ß-TCP is the main phase in all compounds except 0.1SrTCP, in which the apatite (Ap)-type phase was predominant. TCP and 0.5SrTCP ceramics were soaked in the standard saline solution for 21 days, and the phase analysis revealed the partial dissolution of the initial ß-TCP phase with the formation of the Ap-type phase and changes in the microstructure of the ceramics. The Sr2+ ion release from the ceramic was measured by the ICP-OES. The human osteosarcoma MG-63 cell line was used for viability, adhesion, spreading, and cytocompatibility studies. The results show that the introduction of Sr2+ ions into the ß-TCP improved cell adhesion, proliferation, and cytocompatibility of the prepared samples. The obtained results provide a base for the application of the Sr2+-substituted ceramics in model experiments in vivo.

Enhanced ectopic bone formation by strontium-substituted calcium phosphate ceramics through regulation of osteoclastogenesis and osteoblastogenesis.

To explore how strontium influences osteoclastogenesis and osteoblastogenesis during material-induced ectopic bone formation, porous strontium-substituted biphasic calcium phosphate (Sr-BCP) and BCP ceramics with equivalent pore structures and comparable grain size and porosity were prepared. In vitro results showed that compared with BCP, Sr-BCP inhibited the osteoclastic differentiation of osteoclast precursors by delaying cell fusion, down-regulating the expression of osteoclast marker genes, and reducing the activity of osteoclast specific proteins, possibly due to the activated ERK signaling pathway but the suppressed p38, JNK and AKT signaling pathways. Meanwhile, Sr-BCP promoted the osteogenic differentiation of mesenchymal stem cells (MSCs) by up-regulating the osteogenic gene expression. Sr-BCP also mediated the expression of important osteoblast-osteoclast coupling factors, as evidenced by the increased Opg/Rankl ratio in mMSCs, and the reduced Rank expression and enhanced EphrinB2 expression in osteoclast precursors. Similar results were observed in an in vivo study based on a murine intramuscular implantation model. The sign of ectopic bone formation was only seen in Sr-BCP at 8 weeks. Compared to BCP, Sr-BCP obviously hindered the formation of TRAP- and CTSK-positive multinucleated osteoclast-like cells during the early implantation time up to 6 weeks, which is consistent with the in vivo PCR results. This suggested that Sr-BCP could clearly accelerate the ectopic bone formation by promoting osteogenesis but suppressing osteoclastogenesis, which might be closely related to the expression of osteoblast-osteoclast coupling factors regulated by Sr2+. These findings may help in the design and fabrication of smart bone substitutes with the desired potential for bone regeneration through modulating both osteoclastic resorption and osteoblastic synthesis.

Surface Modification of Poly(ether ether ketone) by Simple Chemical Grafting of Strontium Chondroitin Sulfate to Improve its Anti-Inflammation, Angiogenesis, Osteogenic Properties.

Besides inducing osteogenic differentiation, the surface modification of poly(ether ether ketone) (PEEK) is highly expected to improve its angiogenic activity and reduce the inflammatory response in the surrounding tissue. Herein, strontium chondroitin sulfate is first attempted to be introduced into the surface of sulfonated PEEK (SPEEK-CS@Sr) based on the Schiff base reaction between PEEK and ethylenediamine (EDA) and the amidation reaction between EDA and chondroitin sulfate (CS). The surface characteristics of SPEEK-CS@Sr implant are systematically investigated, and its biological properties in vitro and in vivo are also evaluated. The results show that the surface of SPEEK-CS@Sr implant exhibits a 3D microporous structure and good hydrophilicity, and can steadily release Sr ions. Importantly, the SPEEK-CS@Sr not only displays excellent biocompatibility, but also can remarkably promote cell adhesion and spread, improve osteogenic activity and angiogenic activity, and reduce the inflammatory response compared to the original PEEK. Therefore, this study presents the surface modification of PEEK material by simple chemical grafting of strontium chondroitin sulfate to improve its angiogenesis, anti-inflammation, and osteogenic properties, and the as-fabricated SPEEK-CS@Sr has the potential to serve as a promising orthopedic implant in bone tissue engineering.