Search

Bone graft substitutes to repair critical-sized bone fractures have experienced significant development over the last few decades. Among them, whitlockite (WH)-based bone grafts have proven to be effective in mediating bone healing. In the current study, a next generation, nature-inspired scaffold was developed with strontium-functionalized whitlockite nanoparticles (nSrWH) to enhance the intrinsic properties of WH. A series of nSrWH (with 2.5, 5, 7.5% Sr atomic substitution) were fabricated using a rapid-mixing wet precipitation route. Subsequently, the functionalized whitlockite was integrated into a gelatin-chondroitin sulfate scaffold and subjected to both in vitro and in vivo studies to investigate its osteogenic potential. Results indicated that nSrWH-containing scaffolds promoted osteogenic differentiation while inhibiting osteoclast activity. The positive impact of nSrWH was found to be dose-dependent, with the 7.5% Sr atomic substitution exhibiting the most significant results. Furthermore, the scaffold induced superior de novo bone regeneration compared to its undoped counterpart in the mouse calvarial critical-sized defect model. Collectively, these findings suggest that nSrWH nanoparticles inherit the beneficial properties of whitlockite, coupled by the therapeutic effects of Sr 2+ , operating in concert for an overall enhanced bone regeneration. As such, they constitute promising candidates to meet the biomedical requirements for bioactive bone graft substitutes.

One way to effectively address endophyte infection and loosening is the creation of multifunctional coatings that combine anti-inflammatory, antibacterial, and vascularized osteogenesis. This study started with the preparation of strontium-doped titanium dioxide nanotubes (STN) on the titanium surface. Next, tannic acid (TA), gentamicin sulfate (GS), and pluronic F127 (PF127) were successfully loaded into the STN via layer-by-layer self-assembly, resulting in the STN@TA-GS/PF composite coatings. The findings demonstrated the excellent hydrophilicity and bioactivity of the STN@TA-GS/PF coating. STN@TA-GS/PF inhibited E. coli and S. aureus in vitro to a degree of roughly 80.95 % and 92.45 %, respectively. Cellular investigations revealed that on the STN@TA-GS/PF surface, the immune-system-related RAW264.7, the vasculogenic HUVEC, and the osteogenic MC3T3-E1 showed good adhesion and proliferation activities. STN@TA-GS/PF may influence RAW264.7 polarization toward the M2-type and encourage MC3T3-E1 differentiation toward osteogenesis at the molecular level. Meanwhile, the STN@TA-GS/PF coating achieved effective removal of ROS within HUVEC and significantly promoted angiogenesis. In both infected and non-infected bone defect models, the STN@TA-GS/PF material demonstrated strong anti-inflammatory, antibacterial, and vascularization-promoting osteogenesis properties. In addition, STN@TA-GS/PF had good hemocompatibility and biosafety. The three-step process used in this study to modify the titanium surface for several purposes gave rise to a novel concept for the clinical design of antimicrobial coatings with immunomodulatory properties., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The application of titanium (Ti) implants for patients with diabetes mellitus (DM) is still facing a significant challenge due to obstacles such as hyperglycemia, reactive oxygen species (ROS), and chronic inflammation, which hinders osseointegration. To address this issue, a Ti implant with dual functions of regulating polarization of macrophages and facilitating osseointergration is developed via hydrothermal reaction and hydrogel coating. The reactive oxygen species (ROS) and glucose (Glu) responsive hydrogel coating can locally deliver adenosine (ADO) in the early stage of implantation. The controlled release of ADO regulated the phenotype of macrophages, restored oxidative balance, and enhanced mitochondrial function during the early stages of implantation. Subsequently, strontium (Sr) ions will be released to promote osteogenic differentiation and proliferation of mesenchymal stem cells (MSCs), as the hydrogel coating degraded. It eventually leads to bone reconstruction during the late stages, aligning with the biological cascade of bone healing. The modified Ti implants showed effective osteogenesis for bone defects in DM patients, shedding light on the design and biological mechanisms of surface modification. This research offers promising potential for improving the treatment of bone-related complications in diabetic patients., (© 2024 Wiley‐VCH GmbH.)

Treatment of large-size bone defects is difficult, and acquiring autografts may be challenging due to limited availability. A synthetic patient-specific bone substitute can be developed by using 3D printing technologies in such cases. In the present study, we have developed photocurable composite resins with poly(trimethylene carbonate) (PTMC) containing a high percentage of biodegradable bioactive strontium-substituted nanohydroxyapatite (SrHA, size 30-70 nm). These photocurable resins have then been employed to develop high-surface-area 3D-printed bone substitutes using the digital light processing (DLP) technique. To enhance the surface area of the 3D-printed substitute, cryogels alone and functionalized with bioactive components of bone morphogenetic protein (BMP) and zoledronic acid (ZA) were filled within the 3D-printed scaffold/substitute. The scaffolds were tested in vitro for biocompatibility and functionality in vivo in two therapeutically relevant rat models with large bone defects (4 mm). The porosities of 3D printed scaffolds were found to be 60.1 ± 0.9%, 72.9 ± 0.5%, and 74.3 ± 1.6% for PTMC, PTMC-HA, and PTMC-SrHA, respectively, which is in the range of cancellous bone (50-95%). The thermogravimetric analysis demonstrated the fabrication of 3D printed composites with HA and SrHA concentrations of 51.5 and 57.4 wt %, respectively, in the PTMC matrix. The tensile Young's modulus ( E ), compressive moduli, and wettability increased post incorporation of SrHA and HA in the PTMC matrix. In vitro and in vivo results revealed that SrHA integrated into the PTMC matrix exhibited good physicochemical and biological properties. Furthermore, the osteoactive molecule-functionalized 3D printed composite scaffolds were found to have an adequate osteoconductive and osteoinductive surface that has shown increased bone regeneration and defect repair in both tibial and cranial bone defects. Our findings thus support the use of PTMC-SrHA composites as next-generation patient-specific synthetic bioactive biodegradable bone substitutes.

Osteoporotic fractures and arthritis represent a major socioeconomic health burden. Fragility fracture fixation and joint replacement are often undertaken using titanium (Ti) or Ti alloy implants. Ideally these should induce bone formation and reduce osteoclast formation. Nanoscale topographies are potent inducers of osteogenesis, and strontium (Sr) has both osteogenic and antiosteoclastic effects. We incorporated strontium into a titanium surface with an osteogenic disordered nanoscale topography. The surface comprises 120 nm diameter, 100 nm deep pits in a near-square order with deliberate offset from the center pit position up to ±50 nm, providing a pattern with an average center-center pit spacing of 300 nm (called near-square 50, NSQ50). Several surfaces were assessed, including NSQ50 alone, strontium incorporated alone, and combined, compared with control surfaces. We assessed the surfaces using a human bone marrow stromal cell (BMSC)/ bone marrow hematopoietic cell (BHSC) coculture capable of osteogenesis and osteoclastogenesis. The samples eluted Sr over long-term culture, and uptake of Sr was better with eluted Sr than with Sr added to the culture media. The NSQ50 pattern in Ti was osteogenic, and addition of Sr elution increased osteogenesis further for both flat and NSQ50 samples. Interestingly, BMSCs on all Ti samples did not secrete the receptor activator of nuclear factor kappa-Β ligand (RANKL) or macrophage colony-stimulating factor (M-CSF) while secreting osteoprotegrin (OPG) at high levels. This meant that no osteoclast formation was observed on any Ti surface. Therefore, using Sr-incorporated nanotopographical imprinting, we generated highly osteogenic Ti surfaces that inhibited osteoclast formation.

Background: Delayed healing and non-healing of bone defects pose significant challenges in clinical practice, with metal materials increasingly recognized for their significance in addressing these issues. Among these materials, Strontium (Sr) and Zinc (Zn) have emerged as promising agents for promoting bone repair. Building upon this insight, this research evaluates the impact of a porous Sr@Zn@SiO 2 nanocomposite implant on bone regeneration, aiming to advance the field of bone repair., Methods: The preparation of the Sr@Zn@SiO 2 composite implant involves various techniques such as roasting, centrifugation, and washing. The material's composition is examined, and its microstructure and element distribution are analyzed using TEM and elemental scanning technology. In vitro experiments entail the isolation and characterization of BMSCs followed by safety assessments of the implant material, evaluation of cell migration capabilities, and relevant proliferation markers. Mechanistically, this study delves into key targets associated with significant changes in the osteogenic process. In vivo experiments involve establishing a rat femur bone defect model, followed by assessment of the osteogenic potential of Sr@Zn@SiO 2 using Micro-CT imaging and tissue section staining., Results: Through in vivo and in vitro investigations, we validate the osteogenic efficacy of the Sr@Zn@SiO 2 composite implant. In vitro analyses demonstrate that porous Sr@Zn@SiO 2 nanocomposite materials upregulate BMP-2 expression, leading to the activation of Smad1/5/9 phosphorylation and subsequent activation of downstream osteogenic genes, culminating in BMSCs osteogenic differentiation and bone proliferation. And the migration of BMSCs is closely related to the high expression of CXCL12/CXCR4, which will also provide the conditions for osteogenesis. In vivo, the osteogenic ability of Sr@Zn@SiO 2 was also confirmed in rats., Conclusion: In our research, the porous Sr@Zn@SiO 2 composite implant displays prominent osteogenic effect and promotes the migration and differentiation of BMSCs to promote bone defect healing. This bioactive implant has surgical application potential in the future., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Wang et al.)

Objective: Patients receiving head and neck radiation are at high risk for radiation caries. This study aimed to evaluate the remineralizing effects of an experimental 1.1% NaF (5000 ppmF) toothpaste containing Sr/F-doped bioactive glass nanoparticles (BAG or B) on demineralized irradiated dentin., Materials and Methods: Fluoride concentration and pH stability of materials upon mixing with water were assessed using a fluoride-specific electrode (n = 3) for up to 3 months. Elemental release of materials in water was determined using ICP-OES (n = 3). Fourteen extracted molars were irradiated with a cumulative dose of 70 Gy. Each tooth was sectioned into 4 specimens (n = 14/group), demineralized, and subjected to pH cycling for 14 days. Groups were treated with Prevident (PV), E5000, E5000B, and deionized water twice daily. Remineralization was assessed using ATR-FTIR (mineral-to-collagen ratio) (n = 14). Mineral precipitation was additionally examined with SEM-EDX. The in vitro cytotoxicity of the materials on L929 mouse fibrosarcoma was evaluated with the MTT test (n = 3). Kruskal-Wallis test, followed by Dunn's procedure, was used to compare the data between groups., Result: PV demonstrated greater pH and fluoride release stability than the experimental materials. E5000B exhibited a slight reduction of fluoride release (p < 0.01, R²=0.656) and an increase in pH with time (p = 0.006, R²=0.233). The highest increase in mineral-to-collagen ratio at 14 days was detected with PV (p < 0.05). E5000B also showed a significantly higher ratio than E5000 (p = 0.014). SEM-EDX detected mineral precipitation on dentin treated with PV and E5000B but not in E5000 and DI. The cell viability of PV (56%) was significantly lower than that of E5000 (94%) and E5000B (89%) (p < 0.05)., Conclusion: The use of 5000 ppm fluoride toothpaste enhanced the remineralization of irradiated demineralized dentin, highlighting a potentially valuable strategy for preventing radiation caries. Adding bioactive glass further promoted remineralization but may require formulation adjustments to maintain toothpaste stability for clinical use., Competing Interests: Declarations Ethical approval and consent to participate This study was approved by the Human Research Ethics Committee of Thammasat University (Science), Thailand (COE number 022/2566). Written informed consent was waived from the committee because the patient identification of the extracted teeth was not required. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Endowing titanium surfaces with multifunctional properties can reduce implant-related infections and enhance osseointegration. In this study, titanium dioxide nanotubes with strontium doping (STN) were first created on the titanium surface using anodic oxidation and hydrothermal synthesis techniques. Next, casein phosphopeptide (CCP) and an antimicrobial peptide (HHC36) were loaded into the STN with the aid of vacuum physical adsorption (STN-CP-H), giving the titanium surface a dual function of "antimicrobial-osteogenic". The surface of STN-CP-H has a suitable roughness and good hydrophilicity, which is conducive to osteoblasts. STN-CP-H had a 99 % antibacterial rate against S. aureus and E. coli and effectively prevented the growth of bacterial biofilm. Meanwhile, the antibacterial mechanism of STN-CP-H was initially explored with the help of transcriptome sequencing technology. STN-CP-H could greatly increase osteoblast adhesion, proliferation, and expression of osteogenic markers (alkaline phosphatase, runt-related transcription) when CCP and Sr worked together synergistically. In vivo, the STN-CP-H coating could effectively promote new osteogenesis around titanium implant bone and had no toxic effects on heart, liver, spleen, lung and kidney tissues. A potential anti-infection bone healing material, STN-CP-H bifunctional coating developed in this work efficiently inhibited bacterial infection of titanium implants and encouraged early osseointegration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Biomineralization has been increasingly adopted for the synthesis of advanced materials with superior properties. Hierarchical architecture growth mimicking biomineralization has been studied using various organic molecules to template inorganic materials with controlled morphology. In our previous study, self-assembled Sr/CS/G(SrCO 3 -chitosan-gelatin) aggregates were fabricated using electrophoretic deposition (EPD). This study is a further step toward understanding the morphogenesis of Sr/CS/G aggregates and its biomineralization., Methods: Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD) were used to investigate the biomimetic morphogenesis of Sr/CS/G composite under various EPD parameters, such as polymer concentration, time, and voltage. The Sr/CS/G aggregates were immersed in H 2 O, phosphate-buffered saline (PBS), and simulated body fluid (SBF) to study the bioactive apatite formation ability. In addition, biocompatibility of the composites were evaluated by Fluorescence staining, SEM in vitro. The osteogenic ability of the coatings induced by PBS were tested in vivo., Results: The CS/G weight ratio, EPD time, and voltage were found to influence the morphogenesis of Sr/CS/G aggregates. SEM and TEM results showed that the Sr/CS/G aggregates exhibited fractal growth characteristics and morphological self-similarity. XRD results confirmed the formation of SrCO 3 crystals within the framework of chitosan and gelatin organic templates. Chitosan played a vital role in branching growth of the crystals, whereas gelatin guided the formation of composite spheres. The microstructural and compositional results reveal that the Sr/CS/G-induced apatite coating yielded a large quantity of apatite. These apatite coatings promote the cytocompatibility and osteogenesis of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. The coatings induced by PBS enhanced proliferation and mineralization in vitro, and enhanced angiogenesis and osteogenesis in vivo., Conclusion: Sr/CS/G composites prepared via EPD are promising organic-inorganic templates for biomineralization. These findings provide important insights into understanding the mineralization process and optimizing the design of advanced biological materials., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Gong et al.)

The aim of the present study is to synthesize Cu 1-x Sr x S (x = 0.00, 0.025, 0.05, 0.075, and 0.1) nanoparticles (NPs) using an easy chemical co-precipitation method in an efficient, inexpensive, and simple technique. The structural, morphological, and optical properties of the prepared samples were investigated using XRD, TEM, XRF, UV-Vis DRS, and PL characterization techniques. XRD spectra confirmed the Sr-doped copper sulfide nanoparticles have a hexagonal structure with crystallite sizes ranging from 15.15 to 16.04 nm, and, by XRF, the presence of the dopant was detected. TEM analysis confirmed that strontium ions had an effect on the shape of the CuS nanostructure, and the particle size increased from 16.27 to 17.32 nm after doping. A study using UV-Vis showed the presence of Sr doping increased the optical energy band gap (1.38 eV to 1.59 eV). At room temperature, one photoluminescence (PL) band was found at 826 nm. The antibacterial activity of CuS nanostructures against E. coli, P. aeruginosa, Klebsiella pneumonia, and S. aureus was evaluated by zone of inhibition. Sr doped CuS NPs exhibited the highest antibacterial activity against S. aureus (17 to 29 mm). Also, the results demonstrated that samples doped with 5, 7.5, and 10% Sr exhibited inhibitory effects against all the tested microbial strains higher than the antibiotic., (© 2024. The Author(s).)

Bone defect repair and postoperative infections are among the most challenging issues faced by orthopedic surgeons. Thus, the antibacterial agent Cu and the osteogenic promoter Sr have been widely incorporated into biodegradable alloys separately. However, to the best of our knowledge, the synergistic effects of Cu and Sr on zinc alloys have not been investigated. Therefore, we have developed a series of novel Zn-4Cu-xSr (x = 0.05, 0.1, and 0.3 wt %) alloys. Our results showed that the addition of Cu and Sr significantly increased the strength of pure zinc while maintaining a certain level of ductility. Plastic deformation further enhanced the strength and ductility of the alloys. The tensile strength of HR Zn-4Cu-xSr alloys remains between 233.34 ± 1.31 MPa and 235.81 ± 3.0 MPa, with elongation values ranging from 45.7 ± 1.56% to 49.6 ± 6.22%. The HE Zn-4Cu-0.05Sr alloy exhibits a high elongation of 95.05 ± 11.1%. Furthermore, the HE Zn-4Cu-0.1Sr alloy demonstrates the best overall mechanical performance with ultimate tensile strength ( σ uts ), yield strength ( σ ys ), and elongation (ε) values of 252.73 ± 0.12 MPa, 181.0 ± 0.79 MPa, and 42.8 ± 1.13%, respectively. The corrosion rate of HE Zn-4Cu-xSr alloys increases with an increase in Sr content. All samples exhibit satisfactory cytocompatibility with the cells displaying a healthy spindle-like morphology. In vitro antibacterial tests show that the HE Zn-4Cu-xSr alloys exhibit significant antibacterial effects against Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ), with the antibacterial properties strengthening as the Sr content increases. Therefore, this study demonstrates the tremendous potential application of Zn-4Cu-xSr alloys in biodegradable zinc alloys for bone fracture fixation and repair.

This study investigates the correlation between the biomedical and structural properties of Zn/Sr-modified Calcium Phosphates (ZnSr-CaPs) synthesized via the sol-gel combustion method. X-ray diffraction (XRD) analysis revealed the presence of Ca 10 (PO 4 ) 6 (OH) 2 (HAp), CaCO 3 , and Ca(OH) 2 phases in the undoped sample, while the additional phase, Ca 3 (PO 4 ) 2 (β-TCP) was formed in modified samples. X-ray absorption near-edge structure (XANES) analysis demonstrated the incorporation of Sr into the lattice, with a preference for occupying the Ca1 sites in the HAp matrix. The introduction of Zn, furthermore, led to the formation of ZnO and CaZnO 2 species. The ZnSr-CaPs exhibited significant antibacterial activity attributed to the generation of reactive oxygen species by ZnO, the oxidation reaction of CaZnO 2 , and the presence of Sr ions. Cytotoxicity tests revealed a correlation between the variation in ZnO content and cellular viability, with lower ZnO concentrations corresponding to higher cell viability. Additionally, the cooperative effects of Zn and Sr ions were found to enhance the bioactivity of CaPs, despite ZnO hindering the apatite formation process. These findings contribute to the deep understanding of the diverse role in modulating the antibacterial, cytotoxic, and bioactive properties of ZnSr-CaPs, offering potential applications in the field of biomaterials., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Strontium, cobalt, and manganese ions are present in the composition of bone and useful for bone metabolism, even when combined with calcium phosphate in the composition of biomaterials. Herein we explored the possibility to include these ions in the composition of apatitic materials prepared through the cementitious reaction between ion-substituted calcium phosphate dibasic dihydrate, CaHPO 4 ·2H 2 O (DCPD) and tetracalcium phosphate, Ca 4 (PO 4 ) 2 O (TTCP). The results of the chemical, structural, morphological and mechanical characterization indicate that cobalt and manganese exhibit a greater delaying effect than strontium (about 15 at.%) on the cementitious reaction, even though they are present in smaller amounts within the materials (about 0.8 and 4.5 at.%, respectively). Furthermore, the presence of the foreign ions in the apatitic materials leads to a slight reduction of porosity and to enhancement of compressive strength. The results of biological tests show that the presence of strontium and manganese, as well as calcium, in the apatitic materials cultured in direct contact with human mesenchymal stem cells (hMSCs) stimulates their viability and activity. In contrast, the apatitic material containing cobalt exhibits a lower metabolic activity. All the materials have a positive effect on the expression of Vascular Endothelial Growth Factor (VEGF) and Von Willebrand Factor (vWF). Moreover, the apatitic material containing strontium induces the most significant reduction in the differentiation of preosteoclasts into osteoclasts, demonstrating not only osteogenic and angiogenic properties, but also ability to regulate bone resorption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Bone defects, resulting from trauma, inflammation, tumors, and various other factors, affect both health and quality of life. Although autologous bone transplantation is the gold-standard treatment for bone defects, it has disadvantages such as donor site limitations, prolonged surgical durations, and potential complications, necessitating the development of alternative bone tissue engineering materials. In this study, we used 3D printing technology to fabricate porous titanium implants characterized by superior biocompatibility and mechanical properties. Sodium alginate (SA) and strontium ions (Sr 2+ ) were integrated into mineralized collagen matrices (MCs) to develop strontium-functionalized alginate-mineralized collagen hydrogels (SAMs) with high mechanical strength and sustained metal ion release ability. SAMs were seamlessly incorporated into the porous structures of 3D-printed titanium scaffolds, establishing a novel organic-inorganic bioactive interface. This composite system exhibited high biocompatibility in vitro and increased the expression of genes important for osteogenic differentiation and angiogenesis. In a rabbit model of femoral defect, the titanium implants effectively promoted bone and vascular regeneration on their surface, highlighting their potential in facilitating bone-implant integration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chronic osteomyelitis (OM) represents a severe and persistent infectious bone disease. Effective treatment requires controlled anti-inflammatory releases and bone regeneration across disease phases. A Sr@Ag-based scaffold was successfully printed, featuring micron-scale coaxial fibers containing Ag-doped hydroxyapatite (HA) in the outer layer of PLLA and Sr-doped HA in the inner layer of PLLA, facilitating the spatiotemporal and sequential release of Ag and Sr ions during OM treatment. Most antibacterial agent (Ag) was released during the first 20 days, followed by a slow-release plateau over the next 40 days in phosphate-buffered saline solution (PBS). Meanwhile, the pro-angiogenic agent (Sr) was released in minimal amounts during the initial 20 days, followed by a rapid and considerable release in the following 40 days. The coaxial design effectively inhibited the growth of Staphylococcus aureus and Escherichia coli while preserving the viability of bone cells. The ion-based scaffold exhibited broad-spectrum antibacterial effects and enhanced bone-regenerating gene expression in a complex air-bacteria environment. The Sr@Ag-based coaxial scaffold demonstrated effective antibacterial activity during the early stage and exhibited excellent non-toxic bone regeneration results during the middle and late stages in vivo. This work offered a promising treatment strategy through sequential anti-inflammatory and pro-osteogenic effects for infectious bone-defect diseases., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Xiaodan Sun reports financial support was provided by National Natural Science Foundation of China. Xiaodan Sun reports financial support was provided by Hainan Provincial Department of Science and Technology. Xiaodan Sun reports financial support was provided by Tsinghua University Beijing Union Medical College Hospital. Jingyun Wang reports financial support was provided by China Postdoctoral Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The development of injectable, dual-component formulations based on natural-based polysaccharides is a promising strategy for the localized treatment of rheumatoid arthritis (RA). In the present study, biomimetic formulations consisting of aldehyde-functionalized hyaluronic acid (AHA) and O-carboxymethyl chitosan (OCC) were developed, presenting rapid in situ gelation rates and finely tunable physicochemical properties. These two properties allowed for the controlled delivery of anti-inflammatory, antioxidant, and pro-regenerative agents (i.e., strontium-methotrexate (SrMTX) and europium-tannic acid nanocomplexes (EuTA NCs), making them suitable for application in in vivo RA-models. Biological analyses demonstrated the system's cytocompatibility and its ability to modulate the activity of human articular chondrocytes at the secretome level and scavenge nitric oxide (NO). Moreover, the loaded cargoes not only extended the anti-inflammatory properties of the formulation but also the radiolabeling of EuTA NCs with 68 Ga allowed the visualization of the gel by positron emission tomography (PET). Overall, this work presents the design and in vitro evaluation of an easily modulable polymeric system that allows the in situ release of a multifunctional therapy with promising perspectives for RA treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Titanium and its alloys are widely used as orthopedic implants owing to their good mechanical properties and excellent corrosion resistance. However, the insufficient osteogenic activity and antibacterial properties hinder their clinical applications. To address these issues, TiO 2 nanotube arrays (TNT) were first fabricated on the TA2 alloy surface via an anodizing technique, and strontium ions (Sr 2+ ) were then loaded by hydrothermal reaction (TNT + Sr) and annealing treatment (TNT + A). Subsequently, the polydopamine layer (TNT + PDA) was constructed to immobilize the carboxymethyl chitosan and alendronate sodium (TNT + CA) mixture. The prepared coatings were thoroughly characterized by scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), X-ray photoelectron spectrometer (XPS), attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffractometer (XRD), and water contact angle measurement. The results confirmed that Sr 2+ ions, polydopamine, and carboxymethyl chitosan/alendronate sodium were successfully immobilized on the nanotubes. The coating of TNT + CA significantly enhanced the hydrophilicity, and effectively delayed the release of Sr 2+ and alendronate. The TNT + CA coating significantly promoted osteoblast adhesion and proliferation, and up-regulated the expressions of alkaline phosphatase (ALP), osteocalcin (OCN), and osteoblast-specific transcription factor (RUNX2). TNT + CA was able to rapidly induce in situ hydroxyapatite deposition from the simulated body fluid (SBF). Moreover, TNT + CA coating showed inhibition against Escherichia coli and Staphylococcus aureus (especially against Escherichia coli). The prepared TNT + CA coating provides a novel strategy for enhancing bone affinity, improving osteoblast behaviors, and antibacterial properties of titanium-based biomaterials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Osseointegration is significantly impeded in osteoporotic conditions due to the elevated levels of reactive oxygen species (ROS) and inflammation at the site of injury. To enhance bone regeneration in osteoporotic conditions, a modified polyether ether ketone (PEEK) implants was prepared, denoted as PEEK-PDA-Sr. The implants consisted of mussel adhesion layer with the conjugation of strontium (Sr) ions, which can constantly release Sr ions for up to 3 weeks. PEEK-PDA-Sr demonstrated excellent biocompatibility and effectively regulated intracellular ROS levels and macrophage differentiation. In addition, the PEEK-PDA-Sr facilitated the osteogenesis of bone marrow stromal cells (BMSCs). In the ovariectomized (OVX) rat model of osteoporosis, the PEEK-PDA-Sr exhibited raised osseointegration in the femoral bone defects. The PEEK-PDA-Sr can be used as an immunoregulator with enhanced osseointegration and osteogenesis both in vivo and in vitro, which provides an available approach to treat osteoporotic bone defects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: This study aimed to investigate the osseointegration of titanium (Ti) implants with micro-nano textured surfaces functionalized with strontium additions (Sr) in a pre-clinical rat tibia model., Methodology: Ti commercially pure (cp-Ti) implants were installed bilaterally in the tibia of 64 Holtzman rats, divided into four experimental groups (n=16/group): (1) Machined surface - control (C); (2) Micro-nano textured surface treatment (MN); (3) Micro-nano textured surface with Sr2+ addition (MNSr); and (4) Micro-nano textured surface with a higher complementary addition of Sr2+ (MNSr+). In total, two experimental euthanasia periods were assessed at 15 and 45 days (n=8/period). The tibia was subjected to micro-computed tomography (μ-CT), histomorphometry with the EXAKT system, removal torque (TR) testing, and gene expression analysis by PCR-Array of 84 osteogenic markers. Gene expression and protein production of bone markers were performed in an in vitro model with MC3T3-E1 cells. The surface characteristics of the implants were evaluated by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and laser scanning confocal microscopy., Results: SEM, confocal, and EDS analyses demonstrated the formation of uniform micro-nano textured surfaces in the MN group and Sr addition in the MNSr and MNSr+ groups. TR test indicated greater osseointegration in the 45-day period for treated surfaces. Histological analysis highlighted the benefits of the treatments, especially in cortical bone, in which an increase in bone-implant contact was found in groups MN (15 days) and MNSr (45 days) compared to the control group. Gene expression analysis of osteogenic activity markers showed modulation of various osteogenesis-related genes. According to the in vitro model, RT-qPCR and ELISA demonstrated that the treatments favored gene expression and production of osteoblastic differentiation markers., Conclusions: Micro-nano textured surface and Sr addition can effectively improve and accelerate implant osseointegration and is, therefore, an attractive approach to modifying titanium implant surfaces with significant potential in clinical practice.

Despite the numerous studies on biocompatibility with nano-biomaterials, the biological effects of strontium-substituted HA nanoparticles (nSrHA) need to be better understood. So, we conducted an embryotoxicity test using zebrafish (Danio rerio) according to the OECD 236 guideline, a model that represents a viable alternative that bridges the gap between in vitro and mammalian models. Zebrafish embryos were exposed for 120 h to microspheres containing nSrHA nanoparticles with low and high crystallinity, synthesized at temperatures of 5°C (nSrHA5) and 90°C (nSrHA90). We evaluated lethality, developmental parameters, and reactive oxygen species (ROS) production. The larval behavior was assessed at 168 hpf to determine if the biomaterials affected motor responses and anxiety-like behavior. The results showed that the survival rate decreased significantly for the nSrHA5 group (low crystalline particles), and an increase in ROS was also observed in this group. However, none of the biomaterials caused morphological changes indicative of toxicity during larval development. Additionally, the behavioral tests did not reveal any alterations in all experimental groups, indicating the absence of neurotoxic effects from exposure to the tested biomaterials. These findings provide valuable insights into the biosafety of modified HA-based nanostructured biomaterials, making them a promising strategy for bone tissue repair. As the use of hydroxyapatite-based biomaterials continues to grow, it is crucial to ensure rigorous control over the quality, reliability, and traceability of these materials., (© 2024 Wiley Periodicals LLC.)

Cartilage tissue engineering holds great promise for efficient cartilage regeneration. However, early inflammatory reactions to seed cells and/or scaffolds impede this process. Consequently, managing inflammation is of paramount importance. Moreover, due to the body's restricted chondrogenic capacity, inducing cartilage regeneration becomes imperative. Thus, a controlled platform is essential to establish an anti-inflammatory microenvironment before initiating the cartilage regeneration process. In this study, we utilized fifth-generation polyamidoamine dendrimers (G5) as a vehicle for drugs to create composite nanoparticles known as G5-Dic/Sr. These nanoparticles were generated by surface modification with diclofenac (Dic), known for its potent anti-inflammatory effects, and encapsulating strontium (Sr), which effectively induces chondrogenesis, within the core. Our findings indicated that the G5-Dic/Sr nanoparticle exhibited selective Dic release during the initial 9 days and gradual Sr release from days 3 to 15. Subsequently, these nanoparticles were incorporated into a gelatin methacryloyl (GelMA) hydrogel, resulting in GelMA@G5-Dic/Sr. In vitro assessments demonstrated GelMA@G5-Dic/Sr's biocompatibility with bone marrow stem cells (BMSCs). The enclosed nanoparticles effectively mitigated inflammation in lipopolysaccharide-induced RAW264.7 macrophages and significantly augmented chondrogenesis in BMSCs cocultures. Implanting BMSCs-loaded GelMA@G5-Dic/Sr hydrogels in immunocompetent rabbits for 2 and 6 weeks revealed diminished inflammation and enhanced cartilage formation compared to GelMA, GelMA@G5, GelMA@G5-Dic, and GelMA@G5/Sr hydrogels. Collectively, this study introduces an innovative strategy to advance cartilage regeneration by temporally modulating inflammation and chondrogenesis in immunocompetent animals. Through the development of a platform addressing the temporal modulation of inflammation and the limited chondrogenic capacity, we offer valuable insights to the field of cartilage tissue engineering.

Estrogen deficiency, long-term immobilization, and/or aging are commonly related to bone mass loss, thus increasing the risk of fractures. One option for bone replacement in injuries caused by either traumas or pathologies is the use of orthopedic cement based on polymethylmethacrylate (PMMA). Nevertheless, its reduced bioactivity may induce long-term detachment from the host tissue, resulting in the failure of the implant. In view of this problem, we developed an alternative PMMA-based porous cement (pPMMA) that favors cell invasion and improves osteointegration with better biocompatibility. The cement composition was changed by adding bioactive strontium-nanoparticles that mimic the structure of bone apatite. The nanoparticles were characterized regarding their physical-chemical properties, and their effects on osteoblasts and osteoclast cultures were assessed. Initial in vivo tests were also performed using 16 New Zealand rabbits as animal models, in which the pPMMA-cement containing the strontium nanoparticles were implanted. We showed that the apatite nanoparticles in which 90% of Ca 2+ ions were substituted by Sr 2+ (NanoSr 90%) upregulated TNAP activity and increased matrix mineralization. Moreover, at the molecular level, NanoSr 90% upregulated the mRNA expression levels of, Sp7, and OCN. Runx2 was increased at both mRNA and protein levels. In parallel, in vivo tests revealed that pPMMA-cement containing NanoSr 90%, upregulated two markers of bone maturation, OCN and BMP2, as well as the formation of apatite minerals after implantation in the femur of rabbits. The overall data support that strontium nanoparticles hold the potential to up-regulate mineralization in osteoblasts when associated with synthetic biomaterials., (© 2024 Wiley Periodicals LLC.)

Subacute ruminal acidosis (SARA) is a common nutritional metabolic disease in ruminants that causes significant economic losses to dairy farming. Strontium (Sr) is known to be involved in bone metabolism and exhibits potent anti-inflammatory effects. To evaluate the effect of Sr on inflammation in bovine ruminal epithelial cells, a model of LPS-induced inflammation was established in this study, and the cell viability of bovine ruminal epithelial cells was measured using CCK-8. The production of pro-inflammatory cytokines was measured by ELISA and real-time PCR, respectively. The related proteins of the TLR4/MyD88/NF-κB pathway were assayed through Western blotting, and the fluorescence of p-p65 and p-IκB were assayed by immunofluorescence. Molecular docking of Sr and TLR4/MyD88/NF-κB pathway-related proteins was performed using MIB2 ( http://bioinfo.cmu.edu.tw/MIB2/ ). Results showed that after treatment for 24 h, the cell viability was decreased at the high concentration of Sr (≥ 10 mmol/L). Sr significantly decreased the production of TNF-α, IL-1β, and IL-6, downregulated the related proteins expression of the TLR4/MyD88/NF-κB pathway, and reduced the fluorescence levels of p-p65 and p-IκB. The NF-κB pathway inhibitor PDTC and molecular docking further revealed that Sr reduced LPS-induced pro-inflammatory cytokines production via the TLR4/MyD88/NF-κB pathway. These results suggest that Sr reduces LPS-induced pro-inflammatory cytokines production via the TLR4/MyD88/NF-κB pathway, thereby exerting an anti-inflammatory effect in bovine ruminal epithelial cells, providing a basis for Sr in the treatment of bovine rumen acidosis disease., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The primary emphasis of this study was on the innovative and scientifically valuable hydrothermal synthesis of MIL-101(Co) as a metal-organic framework (MOF) material. Subsequently, the CuFe 2 O 4 was incorporated into the MOF by a reduction-precipitation technique. The SrTiO 3 /CuFe 2 O 4 /MIL-101(Co) composite was synthesized by using hydrothermal in situ growth process. The XRD and FESEM investigations of the SrTiO 3 /CuFe 2 O 4 /MIL-101(Co) composite definitively verified its crystalline structure and proved its production with exact shape and dimensions. The data indicated that Candida albicans displayed the greatest vulnerability to all three produced materials, with reported Minimum Inhibitory Concentration (MIC) values of 500 µg mL -1 for MIL-101(Co). The CuFe 2 O 4 /MIL-101(Co) compound, when produced, exhibits MIC values of 200 µg mL -1 . Additionally, the combination of CuFe 2 O 4 /MIL-101(Co) with SrTiO 3 , shows MIC values of 50 µg mL -1 . The results also indicated that the MIC values for MIL-101(Co), and CuFe 2 O 4 /MIL-101(Co) against S. aureus were 100 µg mL -1 . Ultimately, SrTiO 3 /CuFe 2 O 4 /MIL-101(Co) exhibited identical MIC values of 50 µg mL -1 against S. aureus. The concentration of the bacterial protein was increased by adding MIL-101(Co), CuFe 2 O 4 /MIL-101(Co), and SrTiO 3 /CuFe 2 O 4 /MIL-101(Co). The antibacterial capabilities of the SrTiO 3 /CuFe 2 O 4 /MIL-101(Co) were increased after being subjected to gamma doses of 100.0 kGy. This process paves a ways for manufacturing innovation in near future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Calcium silicate-based bioceramics have been applied in endodontics as advantageous materials for years, many chemical components and new synthesizing methods were used to improve the base formulation of the materials for positively affecting the sealers properties. Recently, a novel biomaterial formulation, grounded in strontium silicate, has been introduced to the market, offering potential advancements in the field., Objective: To comparatively analyze the cytotoxicity and cell migration effects of a novel strontium silicate-based bioceramic material (CRoot SP) and those of calcium silicate-based (iRoot SP) and epoxide amine resin (AH Plus) sealers on stem cells derived from rat apical papilla(rSCAPs)., Methods: rSCAPs were isolated and characterized in vitro and subsequently cultured in the presence of various concentrations of CRoot SP, iRoot SP and AH Plus extracts. Cytotoxicity was assessed by CCK-8 assay, and cell-migration capacity was assessed by using wound healing assays ., Results: No significant differences in cell viability were observed in the 0.02 mg/mL and 0.2 mg/mL sealer groups. The cell viability of CRoot SP was consistently greater than that of iRoot SP at concentrations of 5 mg/mL and 10 mg/mL across all time points. Maximum cytotoxic effect was noted on day 5 with 10 mg/mL AH Plus.The scratch was partly healed by cell migration in all groups at 24 h, and the 0.02 mg/mL, and 0.2 mg/mL CRoot SP exerted beneficial effects on rSCAPs migration., Conclusions: CRoot SP exhibited less cytotoxic than the iRoot SP and AH Plus extracts after setting. A lower concentration of CRoot SP thus promotes the cell migration capacity of rSCAPs, and it may achieve better tissue repair during root canal treatment., (© 2024. The Author(s).)

Biodegradable metals, including magnesium, iron, and zinc alloys, have attracted extensive attention due to their good biodegradability and biocompatibility. However, the mechanical properties and corrosion rates of most biodegradable metallic materials have not yet reached the ideal level required for clinical applications. Strontium, as an element of Group IIA in the periodic table of elements, has similar chemical and biological properties to calcium. It can promote bone tissue development and increase bone strength. In addition, strontium can also promote angiogenesis and facilitate the repair of infarcted heart activity. Thus, strontium is commonly used as one of the most alloying elements to improve the in vitro and in vivo properties of biodegradable metals. Besides, strontium is also widely used in various bioactive coatings to improve the comprehensive properties of biodegradable metals. This paper outlines the role of strontium in the human body and summarizes recent research and applications of strontium-containing biodegradable metallic materials. Finally, this paper also provides an outlook on the challenges faced in applying and researching strontium in biodegradable metals.

Large bone defects resulting from fractures and diseases have become a significant medical concern, usually impeding spontaneous healing through the body's self-repair mechanism. Calcium phosphate (CaP) bioceramics are widely utilized for bone regeneration, owing to their exceptional biocompatibility and osteoconductivity. However, their bioactivities in repairing healing-impaired bone defects characterized by conditions such as ischemia and infection remain limited. Recently, an emerging bioceramics zinc-strontium phosphate (ZSP, Zn 2 Sr(PO4) 2 ) has received increasing attention due to its remarkable antibacterial and angiogenic abilities, while its plausible biomedical utility on tissue regeneration is nonetheless few. In this study, gallic acid-grafted gelatin (GGA) with antioxidant properties was injected into hydrogels to scavenge reactive oxygen species and regulate bone microenvironment while simultaneously incorporating ZSP to form GGA-ZSP hydrogels. The GGA-ZSP hydrogel exhibits low swelling, and in vitro cell experiments have demonstrated its favorable biocompatibility, osteogenic induction potential, and ability to promote vascular regeneration. In an in vivo bone defect model, the GGA-ZSP hydrogel significantly enhanced the bone regeneration rates. This study demonstrated that the GGA-ZSP hydrogel has pretty environmentally friendly therapeutic effects in osteogenic differentiation and massive bone defect repair.

Regenerating periodontal defects in osteoporosis patients presents a significant clinical challenge. Unlike the relatively straightforward regeneration of homogeneous bone tissue, periodontal regeneration requires the intricate reconstruction of the cementum-periodontal ligament-alveolar bone interface. Strontium (Sr)-doped biomaterials have been extensively utilized in bone tissue engineering due to their remarkable pro-osteogenic attributes. However, their application in periodontal tissue regeneration has been scarcely explored. In this study, we synthesized an innovative injectable Sr-BGN/GNM scaffold by integrating Sr-doped bioactive glass nanospheres (Sr-BGNs) into the nanofiber architecture of gelatin nanofiber microspheres (GNMs). This design, mimicking the natural bone extracellular matrix (ECM), enhanced the scaffold's mechanical properties and effectively controlled the sustained release of Sr ions (Sr 2+ ), thereby promoting the proliferation, osteogenic differentiation, and ECM secretion of PDLSCs and BMSCs, as well as enhancing vascularization in endothelial cells. In vivo experiments further indicated that the Sr-BGNs/GNMs significantly promoted osteogenesis and angiogenesis. Moreover, the scaffold's tunable degradation kinetics optimized the prolonged release and pro-regenerative effects of Sr 2+ in vivo, matching the pace of periodontal regeneration and thereby facilitating the regeneration of functional periodontal tissues under osteoporotic conditions. Therefore, Sr-BGNs/GNMs emerge as a promising candidate for advancing periodontal regeneration strategies.

Bone tissue engineering offers a promising alternative to stimulate the regeneration of damaged tissue, overcoming the limitations of conventional autografts and allografts. Recently, titanium alloy (Ti) implants have garnered significant attention for treating critical-sized bone defects, especially with the advancement of 3D printing technology. Although Ti alloys have impressive versatility, their lack of cellular adhesion, osteogenic and antibacterial properties are significant factors that contribute to their failure. Hence, to overcome these obstacles, this study aimed to incorporate osteoinductive and antibacterial cue-loaded hydrogels into 3D-printed Ti (3D-Ti) scaffolds. 3D-Ti scaffolds were synthesized using the direct metal laser sintering method and loaded with a gelatin (Gel) hydrogel containing strontium-doped silver nanoparticles (Sr-Ag NPs). Compared with Ag NPs, Sr-doped Ag NPs increased the expression of Runx2 mRNA, which is a key bone transcription factor. We subjected the bioactive 3D-hybrid scaffolds (3D-Ti/Gel/Sr-Ag NPs) to physicochemical and material characterization, followed by cytocompatibility and osteogenic evaluation. The microporous and macroporous topographies of the scaffolds with Sr-Ag NPs showed increased Runx2 expression and matrix mineralization, with potent antibacterial properties. Therefore, the 3D-Ti scaffolds incorporated with Sr-Ag NP-loaded Gel hydrogels favored osteoblast differentiation and antibacterial activity, indicating their potential for orthopedic applications., (© 2024 Wiley‐VCH GmbH.)

Successful implementation of X-ray-activated photodynamic therapy (X-PDT) is challenging because most photosensitizers (PSs) absorb light in the blue region, but few nanoscintillators produce efficient blue scintillation. Here, efficient blue-emitting SrF 2 :Eu scintillating nanoparticles (ScNPs) are developed. The optimized synthesis conditions result in cubic nanoparticles with ≈32 nm diameter and blue emission at 416 nm. Coating them with the meso-tetra(n-methyl-4-pyridyl) porphyrin (TMPyP) in a core-shell structure (SrF@TMPyP) results in maximum singlet oxygen ( 1 O 2 ) generation upon X-ray irradiation for nanoparticles with 6TMPyP depositions (SrF@6TMPyP). The 1 O 2 generation is directly proportional to the dose, does not vary in the low-energy X-ray range (48-160 kVp), but is 21% higher when irradiated with low-energy X-rays than irradiations with higher energy gamma rays. In the clonogenic assay, cancer cells treated with SrF@6TMPyP and exposed to X-rays present a significantly reduced survival fraction compared to the controls. The SrF 2 :Eu ScNPs and their conjugates stand out as tunable nanoplatforms for X-PDT due to the efficient blue emission from the SrF 2 :Eu cores; the ability to adjust the scintillation emission in terms of color and intensity by controlling the nanoparticle size; the efficient 1 O 2 production when conjugated to a PS and the efficacy of killing cancer cells., (© 2024 Wiley‐VCH GmbH.)

Objectives: To explore the antimicrobial potential of strontium (Sr)-functionalized wafers against multiple bacteria associated with per-implant infections, in both mono- and multispecies biofilms., Materials and Methods: The bactericidal and bacteriostatic effect of silicon wafers functionalized with a strontium titanium oxygen coating (Sr-Ti-O) or covered only with Ti (controls) against several bacteria, either grown as a mono-species or multispecies biofilms, was assessed using a bacterial viability assay and a plate counting method. Mono-species biofilms were assessed after 2 and 24 h, while the antimicrobial effect on multispecies biofilms was assessed at Days 1, 3, and 6. The impact of Sr functionalization on the total percentage of Porphyromonas gingivalis in the multispecies biofilm, using qPCR, and gingipain activity was also assessed., Results: Sr-functionalized wafers, compared to controls, were associated with statistically significant less viable cells in both mono- and multispecies tests. The number of colony forming units (CFUs) within the biofilm was significantly less in Sr-functionalized wafers, compared to control wafers, for Staphylococcus aureus at all time points of evaluation and for Escherichia coli at Day 1. Gingipain activity was less in Sr-functionalized wafers, compared to control wafers, and the qPCR showed that P. gingivalis remained below detection levels at Sr-functionalized wafers, while it consisted of 15% of the total biofilm on control wafers at Day 6., Conclusion: Sr functionalization displayed promising antimicrobial potential, possessing bactericidal and bacteriostatic ability against bacteria associated with peri-implantitis grown either as mono-species or mixed in a multispecies consortium with several common oral microorganisms., (© 2024 The Author(s). Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

The aim of this study is to explore the therapeutic effects of Mg-Sr-Ca containing bioactive glass nanoparticles sodium alginate hydrogel modified mineralized collagen scaffold (Mg-Sr-Ca-BGNs-SA-MC) on the repair of osteoporotic bone defect. During the study, Mg-Sr-Ca containing bioactive glass nanoparticles (Mg-Sr-Ca-BGNs) were synthesized using the sol-gel method, and the Mg-Sr-Ca-BGNs-SA-MC scaffold was synthesized by a simple method. The Mg-Sr-Ca-BGNs and the Mg-Sr-Ca-BGNs-SA-MC scaffold were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The elements of Mg, Sr, Ca and Si were effectively integrated into Mg-Sr-Ca-BGNs. SEM analysis revealed the presence of Mg-Sr-Ca-BGNs on the scaffold's surface. Furthermore, the cytotoxicity of the scaffolds were assessed using a live/dead assay. The result of the live/dead assay demonstrated that the scaffold materials were non-toxic to cell growth. More importantly, the in vivo study indicated that implanted scaffold promoted tissue regeneration and integration with newly formed bone. Overall, the Mg-Sr-Ca-BGNs-SA-MC scaffold is suitable for guided bone regeneration and beneficial to repair of osteoporotic bone defects., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Articular cartilage defects are a global challenge, causing substantial disability. Repairing large defects is problematic, often exceeding cartilage's self-healing capacity and damaging bone structures. To tackle this problem, a scaffold-mediated therapeutic ion delivery system is developed. These scaffolds are constructed from poly(ε-caprolactone) and strontium (Sr)-doped bioactive nanoglasses (SrBGn), creating a unique hierarchical structure featuring macropores from 3D printing, micropores, and nanotopologies due to SrBGn integration. The SrBGn-embedded scaffolds (SrBGn-µCh) release Sr, silicon (Si), and calcium (Ca) ions, which improve chondrocyte activation, adhesion, proliferation, and maturation-related gene expression. This multiple ion delivery significantly affects metabolic activity and maturation of chondrocytes. Importantly, Sr ions may play a role in chondrocyte regulation through the Notch signaling pathway. Notably, the scaffold's structure and topological cues expedite the recruitment, adhesion, spreading, and proliferation of chondrocytes and bone marrow-derived mesenchymal stem cells. Si and Ca ions accelerate osteogenic differentiation and blood vessel formation, while Sr ions enhance the polarization of M2 macrophages. The findings show that SrBGn-µCh scaffolds accelerate osteochondral defect repair by delivering multiple ions and providing structural/topological cues, ultimately supporting host cell functions and defect healing. This scaffold holds great promise for osteochondral repair applications., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Mesoporous bioactive glass nanoparticles (MBGNs) doped with therapeutical ions present multifunctional systems that enable a synergistic outcome through the dual delivery of drugs and ions. The aim of this study was to evaluate influence of co-doping with strontium and magnesium ions (SrMg-MBGNs) on the properties of MBGNs. A modified microemulsion-assisted sol-gel synthesis was used to obtain particles, and their physicochemical properties, bioactivity, and drug-loading/release ability were evaluated. Indirect biological assays using 2D and 3D cell culture models on human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and endothelial EA.hy926 cells, respectively, were used to determine biocompatibility of MBGNs, their influence on alkaline phosphatase (ALP) production, calcium deposition, and cytoskeletal organization. Results showed that Sr,Mg-doping increased pore volume and solubility, and changed the mesoporous structure from worm-like to radial-dendritic, which led to a slightly accelerated drug release compared to pristine MBGNs. Biological assays confirmed that particles are biocompatible, and have ability to slightly induce ALP production and calcium deposition of hBM-MSCs, as well as to significantly improve the proliferation of EA.hy926 compared to biochemical stimulation via vascular endothelial growth factor (VEGF) administration or regular media. Fluorescence staining revealed that SrMg-MBGNs had a similar effect on EA.hy926 cytoskeletal organization to the VEGF group. In conclusion, Sr,Mg-MBGNs might be considered promising biomaterial for biomedical applications.

This study aimed to compare the biological properties of newly synthesized cements based on calcium phosphate with a commercially used cement, mineral trioxide aggregate (MTA). Strontium (Sr)-, Copper (Cu)-, and Zinc (Zn)-doped hydroxyapatite (miHAp) powder was obtained through hydrothermal synthesis and characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectrometry (EDX). Calcium phosphate cement (CPC) was produced by mixing miHAp powder with a 20 wt.% citric acid solution, followed by the assessment of its compressive strength, setting time, and in vitro bioactivity. Acetylsalicylic acid (ASA) was added to the CPC, resulting in CPCA. Biological tests were conducted on CPC, CPCA, and MTA. The biocompatibility of the cement extracts was evaluated in vitro using human dental pulp stem cells (hDPSCs) and in vivo using a zebrafish model. Antibiofilm and antimicrobial effect (quantified by CFUs/mL) were assessed against Streptococcus mutans and Lactobacillus rhamnosus . None of the tested materials showed toxicity, while CPCA even increased hDPSCs proliferation. CPCA showed a better safety profile than MTA and CPC, and no toxic or immunomodulatory effects on the zebrafish model. CPCA exhibited similar antibiofilm effects against S. mutans and L. rhamnosus to MTA.

Acrylic resins are widely used as the main components in removable orthodontic appliances. However, poor oral hygiene and maintenance of orthodontic appliances provide a suitable environment for the growth of pathogenic microorganisms. In this study, strontium-modified phosphate-based glass (Sr-PBG) was added to orthodontic acrylic resin at 0% (control), 3.75%, 7.5%, and 15% by weight to evaluate the surface and physicochemical properties of the novel material and its in vitro antifungal effect against Candida albicans (C. albicans). Surface microhardness and contact angle did not vary between the control and 3.75% Sr-PBG groups (p > 0.05), and the flexural strength was lower in the experimental groups than in the control group (p < 0.05), but no difference was found with Sr-PBG content (p > 0.05). All experimental groups showed an antifungal effect at 24 and 48 h compared to that in the control group (p < 0.05). This study demonstrated that 3.75% Sr-PBG exhibits antifungal effects against C. albicans along with suitable physicochemical properties, which may help to minimize the risk of adverse effects associated with harmful microbial living on removable orthodontic appliances and promote the use of various materials., (© 2024. The Author(s).)

Titanium-based orthopedic implants are gaining popularity in recent years due to their excellent biocompatibility, superior corrosion resistance and lightweight properties. However, these implants often fail to perform effectively due to poor osseointegration. Nanosurface modification approaches may help to resolve this problem. In this work, TiO 2 nanotube (NT) arrays were fabricated on commercially available pure titanium (Ti) surfaces by anodization and annealing. Then, zinc (Zn) and strontium (Sr), important for cell signaling, were doped on the NT surface by hydrothermal treatment. This very simple method of Zn and Sr doping takes less time and energy compared to other complicated techniques. Different surface characterization tools such as scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectroscopy (EDS), static water contact angle, X-ray diffraction (XRD) and nanoindentation techniques were used to evaluate the modified surfaces. Then, adipose derived stem cells (ADSCs) were cultured with the surfaces to evaluate cell adhesion, proliferation, and growth on the surfaces. After that, the cells were differentiated towards osteogenic lineage to evaluate alkaline phosphatase (ALP) activity, osteocalcin expression, and calcium phosphate mineralization. Results indicate that NT surfaces doped with Zn and Sr had significantly enhanced ADSC adhesion, proliferation, growth, and osteogenic differentiation compared to an unmodified surface, thus confirming the enhanced performance of these surfaces.

Bone defects persist as a significant challenge in the field of clinical orthopedics. This study focuses on the fabrication and characterization of 3D-printed composite hydrogel scaffolds composed of sodium alginate, gelatin, and α-tricalcium phosphate (α-TCP) with varying ratios of Strontium ions (Sr 2+ ). These scaffolds aim to address the clinical challenges associated with bone defect repair by providing mechanical support and promoting bone formation and vascularization. The degradation, swelling, mechanical properties, and release profiles of Sr 2+ from the hydrogel scaffolds were comprehensively characterized. In vitro tests were conducted to assess cell viability and proliferation, as well as osteogenic and angiogenic gene expression, to investigate the osteogenic and pro-angiogenic potential of the composite hydrogel scaffolds. Furthermore, skull defect simulations were performed, and composite scaffolds with varying Sr 2+ ratios were implanted to evaluate their effectiveness in bone repair. This research establishes a foundation for advancing bone tissue engineering through composite scaffolds containing biological macromolecules and strontium, with alginate serving as a key element in enhancing performance and expanding clinical applicability., Competing Interests: Declaration of competing interest The authors declare that we have no conflict of interest related directly or indirectly to this paper., (Copyright © 2024. Published by Elsevier B.V.)

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., (© 2024 Wiley Periodicals LLC.)

Purpose: Functional inorganic nanomaterials (NMs) are widely exploited as bioactive materials and drug depots. The lack of a stable form of application of NMs at the site of skin injury, may impede the removal of the debridement, elevate pH, induce tissue toxicity, and limit their use in skin repair. This necessitates the advent of innovative wound dressings that overcome the above limitations. The overarching objective of this study was to exploit strontium-doped mesoporous silicon particles (PSiSr) to impart multifunctionality to poly(lactic-co-glycolic acid)/gelatin (PG)-based fibrous dressings (PG@PSiSr) for excisional wound management., Methods: Mesoporous silicon particles (PSi) and PSiSr were synthesized using a chemo-synthetic approach. Both PSi and PSiSr were incorporated into PG fibers using electrospinning. A series of structure, morphology, pore size distribution, and cumulative pH studies on the PG@PSi and PG@PSiSr membranes were performed. Cytocompatibility, hemocompatibility, transwell migration, scratch wound healing, and delineated angiogenic properties of these composite dressings were tested in vitro. The biocompatibility of composite dressings in vivo was assessed by a subcutaneous implantation model of rats, while their potential for wound healing was discerned by implantation in a full-thickness excisional defect model of rats., Results: The PG@PSiSr membranes can afford the sustained release of silicon ions (Si 4+ ) and strontium ions (Sr 2+ ) for up to 192 h as well as remarkably promote human umbilical vein endothelial cells (HUVECs) and NIH-3T3 fibroblasts migration. The PG@PSiSr membranes also showed better cytocompatibility, hemocompatibility, and significant formation of tubule-like networks of HUVECs in vitro. Moreover, PG@PSiSr membranes also facilitated the infiltration of host cells and promoted the deposition of collagen while reducing the accumulation of inflammatory cells in a subcutaneous implantation model in rats as assessed for up to day 14. Further evaluation of membranes transplanted in a full-thickness excisional wound model in rats showed rapid wound closure (PG@SiSr vs control, 96.1% vs 71.7%), re-epithelialization, and less inflammatory response alongside skin appendages formation (eg, blood vessels, glands, hair follicles, etc.)., Conclusion: To sum up, we successfully fabricated PSiSr particles and prepared PG@PSiSr dressings using electrospinning. The PSiSr-mediated release of therapeutic ions, such as Si 4+ and Sr 2+ , may improve the functionality of PLGA/Gel dressings for an effective wound repair, which may also have implications for the other soft tissue repair disciplines., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Li et al.)

Phosphate bioactive glass has been studied for its advanced biodegradability and active ion release capability. Our previous research found that phosphate glass containing (P 2 O 5 )-(Na 2 O)-(TiO 2 )-(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., (© 2024. The Author(s).)

Infection and aseptic loosening caused by bacteria and poor osseointegration remain serious challenges for orthopedic implants. The advanced surface modification of implants is an effective strategy for addressing these challenges. This study presents a "pneumatic nanocannon" coating for titanium orthopedic implants to achieve on-demand release of antibacterial and sustained release of osteogenic agents. SrTiO 3 nanotubes (SrNT) were constructed on the surface of Ti implants as "cannon barrel," the "cannonball" (antibiotic) and "propellant" (NH 4 HCO 3 ) were codeposited into SrNT with assistance of mussel-inspired copolymerization of dopamine and subsequently sealed by a layer of polydopamine. The encapsulated NH 4 HCO 3 within the nanotubes could be thermally decomposed into gases under near-infrared irradiation, propelling the on-demand delivery of antibiotics. This coating demonstrated significant efficacy in eliminating typical pathogenic bacteria both in planktonic and biofilm forms. Additionally, this coating exhibited a continuous release of strontium ions, which significantly enhanced the osteogenic differentiation of preosteoblasts. In an implant-associated infection rat model, this coating demonstrated substantial antibacterial efficiency (>99%) and significant promotion of osseointegration, along with alleviated postoperative inflammation. This pneumatic nanocannon coating presents a promising approach to achieving on-demand infection inhibition and sustained osseointegration enhancement for titanium orthopedic implants.

Borate glass transforms into hydroxycarbonate apatite more rapidly than silicate glass. This research aims to evaluate strontium's structural and biological effects on borate bioactive glass (BBG) and the influence of strontium concentrations (0%, 5%, 10%, and 15% Sr) prepared via the sol-gel method. The study reveals significant findings related to the physicochemical properties of the glass. Immersion of the glass powders in a simulated body fluid (SBF) led to the development of a hydroxyapatite (HAP) layer on the glass surfaces. This transformation was verified through X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) analyses. In particular, 5% strontium exhibited gradual degradation, resulting in particle sizes below 100 nm. The BBG-15%Sr demonstrates heightened pathogenic activity as it shows a significant inhibition zone of 14 mm at 250 μg/mL, surpassing other substituted BBGs. It effectively combats Gram-positive bacteria, completely inhibiting MRSA growth at 50 μg/mL. This underscores its robust biofilm disruption capabilities, eradicating biofilms, even at minimal concentrations after prolonged exposure. C. elegans when subjected to BBG-15%Sr shows less ROS production when compared with the others. Moreover, the results suggest that the modified glass could be a potential material for the treatment of osteomyelitis-affected bone repair.

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 Sr 2+ 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, Sr 2+ -mediated immunomodulation sheds light on the future design of biomaterials for tissue regenerative engineering.

The limited regulation strategies of the regeneration microenvironment significantly hinder bone defect repair effectiveness. One potential solution is using biomaterials capable of releasing bioactive ions and biomolecules. However, most existing biomaterials lack real-time control features, failing to meet high regulation requirements. Herein, a new Strontium (Sr) and epigallocatechin-3-gallate (EGCG) based metal-phenolic network with polydopamine (PMPNs) modification is prepared. This material reinforces a biomimetic scaffold made of extracellular matrix (ECM) and hydroxyapatite nanowires (nHAW). The PMPNs@ECM/nHAW scaffold demonstrates exceptional scavenging of free radicals and reactive oxygen species (ROS), promoting HUVECs cell migration and angiogenesis, inducing stem cell osteogenic differentiation, and displaying high biocompatibility. Additionally, the PMPNs exhibit excellent photothermal properties, further enhancing the scaffold's bioactivities. In vivo studies confirm that PMPNs@ECM/nHAW with near-infrared (NIR) stimulation significantly promotes angiogenesis and osteogenesis, effectively regulating the microenvironment and facilitating bone tissue repair. This research not only provides a biomimetic scaffold for bone regeneration but also introduces a novel strategy for designing advanced biomaterials. The combination of real-time photothermal intervention and long-term chemical intervention, achieved through the release of bioactive molecules/ions, represents a promising direction for future biomaterial development., (© 2024 Wiley‐VCH GmbH.)

Implant-associated osteomyelitis (IAOM) is characterized by bone infection and destruction; current therapy of antibiotic treatment and surgical debridement often results in drug resistance and bone defect. It is challenging to develop an antibiotic-free bactericidal and osteogenic-enhanced strategy for IAOM. Herein, an IAOM-tailored antibacterial and osteoinductive composite of copper (Cu)-strontium (Sr) peroxide nanoparticles (CSp NPs), encapsulated in polyethylene glycol diacrylate (PEGDA) (CSp@PEGDA), is designed. The dual functional CSp NPs display hydrogen peroxide (H 2 O 2 ) self-supplying and Fenton catalytic Cu 2+ ions' release, generating plenty of hydroxyl radical ( • OH) in a pH-responsive manner for bacterial killing, while the released Sr 2+ promotes the in vitro osteogenicity regarding cell proliferation, alkaline phosphatase activity, extracellular matrix calcification, and osteo-associated genes expression. The integration of Cu 2+ and Sr 2+ in CSp NPs together with the coated PEGDA hydrogel ensures the stable and sustainable ion release during short- and long-term periods. Benefitted from the injectablity and photo-crosslink ability, CSp@PEGDA is able to thoroughly fill the infectious site and gelate in situ for bacterial elimination and bone regeneration, which is verified through in vivo evaluation using a clinical-simulating IAOM mouse model. These favorable abilities of CSp@PEGDA precisely meet the multiple therapeutic needs and pave a promising way for implant-associated osteomyelitis treatment., (© 2024 Wiley‐VCH GmbH.)

Introduction: There is an ongoing need for improved healing response and expedited osseointegration on the Ti implants in acetabular fracture sites. To achieve adequate bonding and mechanical stability between the implant surface and the acetabular fracture, a new coating technology must be developed to promote bone integration and prevent bacterial growth., Methods: A cylindrical Ti substrate mounted on a rotating specimen holder was used to implant Ca 2+ , P 2+ , and Sr 2+ ions at energies of 100 KeV, 75 KeV and 180 KeV, respectively, using a low-energy accelerator to synthesize strontium-substituted hydroxyapatite at varying conditions. Ag 2+ ions of energy 100 KeV were subsequently implanted on the as-formed surface at the near-surface region to provide anti-bacterial properties to the as-formed specimen., Results: The properties of the as-formed ion-implanted specimen were compared with the SrHA-Ag synthesized specimens by cathodic deposition and low-temperature high-speed collision technique. The adhesion strength of the ion-implanted specimen was 43 ± 2.3 MPa, which is well above the ASTM standard for Ca-P coating on Ti. Live/dead cell analysis showed higher osteoblast activity on the ion-implanted specimen than the other two. Ag in the SrHA implanted Ti by ion implantation process showed superior antibacterial activity., Discussion: In the ion implantation technique, nano-topography patterned surfaces are not concealed after implantation, and their efficacy in interacting with the osteoblasts is retained. Although all three studies examined the antibacterial effects of Ag 2+ ions and the ability to promote bone tissue formation by MC3T3-E1 cells on SrHA-Ag/Ti surfaces, ion implantation techniques demonstrated superior ability. The synthesized specimen can be used as an effective implant in acetabular fracture sites based on their mechanical and biological properties., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Swain et al.)

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 Mg 12 Ce 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.

It remains an obstacle to induce the regeneration of hard dentin tissue in clinical settings. To overcome this, a P(VDF-TrFE) piezoelectric film with 2 wt% SrCl 2 addition is designed. The biofilm shows a high flexibility, a harmonious biocompatibility, and a large piezoelectric d 33 coefficient of 14 pC N -1 , all contributing to building an electric microenvironment that favor the recruitment of dental pulp stem cells (DPSCs) and their differentiation into odontoblasts during normal chewing, speaking, etc. On the other hand, the strontium ions can be gradually released from the film, thus promoting DPSC odonto-differentiation. In vivo experiments also demonstrate that the film induces the release of dentin minerals and regeneration of dentin tissue. In the large animal dentin defect models, this piezoelectric film induces in situ dentin tissue formation effectively over a period of three months. This study illustrates a therapeutic potential of the piezoelectric film to improve dentin tissue repair in clinical settings., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)