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1.
J Mater Sci Mater Med ; 35(1): 33, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38900208

RESUMEN

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.


Asunto(s)
Regeneración Ósea , Supervivencia Celular , Vidrio , Fosfatos , Estroncio , Titanio , Estroncio/química , Estroncio/farmacología , Regeneración Ósea/efectos de los fármacos , Animales , Ratones , Fosfatos/química , Fosfatos/farmacología , Vidrio/química , Titanio/química , Supervivencia Celular/efectos de los fármacos , Ensayo de Materiales , Zinc/química , Línea Celular , Osteoblastos/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ingeniería de Tejidos/métodos , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacología , Microtomografía por Rayos X
2.
Colloids Surf B Biointerfaces ; 241: 114042, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38924850

RESUMEN

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.


Asunto(s)
Benzofenonas , Adhesión Celular , Vidrio , Cetonas , Células Madre Mesenquimatosas , Oseointegración , Osteogénesis , Polietilenglicoles , Polímeros , Estroncio , Estroncio/farmacología , Estroncio/química , Oseointegración/efectos de los fármacos , Polímeros/química , Polímeros/farmacología , Adhesión Celular/efectos de los fármacos , Cetonas/química , Cetonas/farmacología , Polietilenglicoles/química , Polietilenglicoles/farmacología , Animales , Osteogénesis/efectos de los fármacos , Vidrio/química , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Diferenciación Celular/efectos de los fármacos , Propiedades de Superficie , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/química , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoclastos/citología , Ratones , Células Cultivadas , Tamaño de la Partícula
3.
ACS Biomater Sci Eng ; 10(6): 3923-3934, 2024 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-38766805

RESUMEN

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.


Asunto(s)
Vidrio , Macrófagos , Mitocondrias , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Estroncio , Serina-Treonina Quinasas TOR , Serina-Treonina Quinasas TOR/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/inmunología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Estroncio/farmacología , Estroncio/química , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Células RAW 264.7 , Vidrio/química , Osteogénesis/efectos de los fármacos , Regeneración Ósea/efectos de los fármacos , Andamios del Tejido/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/química , Microambiente Celular/efectos de los fármacos
4.
J Cell Physiol ; 239(5): e31256, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38591855

RESUMEN

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.


Asunto(s)
Antineoplásicos , Apoptosis , Neoplasias Óseas , Fosfatos de Calcio , Doxorrubicina , Metotrexato , Osteogénesis , Osteosarcoma , Andamios del Tejido , Humanos , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Fosfatos de Calcio/administración & dosificación , Fosfatos de Calcio/química , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Osteosarcoma/metabolismo , Estroncio/farmacología , Estroncio/química , Andamios del Tejido/química , Sistemas de Liberación de Medicamentos , Metotrexato/administración & dosificación , Metotrexato/farmacología
5.
Environ Sci Pollut Res Int ; 31(20): 30059-30071, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38594560

RESUMEN

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.


Asunto(s)
Cobalto , Durapatita , Estroncio , Contaminantes Químicos del Agua , Purificación del Agua , Adsorción , Cobalto/química , Estroncio/química , Contaminantes Químicos del Agua/química , Durapatita/química , Purificación del Agua/métodos , Cinética , Concentración de Iones de Hidrógeno , Iones , Agua/química
6.
Adv Sci (Weinh) ; 11(18): e2307269, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38445899

RESUMEN

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.


Asunto(s)
Inmunomodulación , Células Madre Mesenquimatosas , Oseointegración , Titanio , Oseointegración/efectos de los fármacos , Animales , Titanio/química , Inmunomodulación/efectos de los fármacos , Taninos/farmacología , Taninos/química , Propiedades de Superficie , Prótesis e Implantes , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Osteogénesis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Ratones , Estroncio/química , Estroncio/farmacología , Modelos Animales , Ratas
7.
BMC Vet Res ; 20(1): 88, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459489

RESUMEN

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


Asunto(s)
Estroncio , Factores de Transcripción , Humanos , Bovinos , Animales , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Estroncio/farmacología , Estroncio/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Perfilación de la Expresión Génica/veterinaria , Células Epiteliales/metabolismo , Transcriptoma , Calcio/metabolismo
8.
Small ; 20(25): e2310180, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38342676

RESUMEN

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.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Temperatura , Humanos , Estroncio/química , Iterbio/química , Luminiscencia , Neodimio/química , Mediciones Luminiscentes/métodos , Rayos Infrarrojos
9.
J Biomed Mater Res B Appl Biomater ; 112(2): e35388, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38334714

RESUMEN

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


Asunto(s)
Sustitutos de Huesos , Fosfatos de Calcio , Fosfatos , Polifosfatos , Ratas , Animales , Polifosfatos/farmacología , Sustitutos de Huesos/farmacología , Estroncio/farmacología , Cerámica/farmacología , Cráneo
10.
ACS Biomater Sci Eng ; 10(2): 825-837, 2024 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-38267012

RESUMEN

This study aimed to evaluate the bioactivity of poly(ether ether ketone) (PEEK) after surface modification by persistent photoconductive strontium titanate (SrTiO3) magnetron sputtering and ultraviolet (UV) C irradiation. According to the different modifications, the PEEK specimens were randomly divided into five groups (n = 38/group): PEEK, Sr100-PEEK, Sr200-PEEK, UV/PEEK, and UV/Sr200-PEEK. Then, the specimens of Sr100-PEEK and Sr200-PEEK groups were, respectively, coated with 100 and 200 nm thickness photocatalyst SrTiO3 on the PEEK surface by magnetron sputtering. Subsequently, UV-C light photofunctionalized the specimens of PEEK and Sr200-PEEK groups to form UV/PEEK and UV/Sr200-PEEK groups. The specimens were characterized by a step meter, scanning electron microscopy (SEM), atomic force microscopy (AFM), energy dispersive X-ray spectroscopy (EDX), and a water contact angle meter. The release test of the Sr ion was performed by inductively coupled plasma mass spectrometry (ICP-MS). In vitro study, osteogenic activity (MC3T3-E1 osteoblast-like cells) and epithelial and connective tissue attachment (gingival epithelial cells GE1 and fibroblasts NIH3T3) were analyzed in five groups. Surface morphology of the specimens was changed after coating, and the Sr content on the Sr-PEEK surface was increased with increasing coating thickness. In addition, the contact angle was increased significantly after magnetron sputtering. After UV-C photofunctionalization, the content of surface elements changed and the contact angle was decreased. The release of Sr ion was sustained, and the final cumulative release amount did not exceed the safety limit. In vitro experiments showed that SrTiO3 improved the cell activity of MC3T3-E1 and UV-C irradiation further enhanced the osteogenic performance of PEEK. Besides, UV-C irradiation also significantly promoted the cell viability, development, and expression of adhesion proteins of GE1 and NIH3T3 on PEEK. The present investigation demonstrated that nano SrTiO3 coating with UV-C photofunctionalization synergistically enhanced the osteogenic properties and soft tissue sealing function of PEEK in vitro.


Asunto(s)
Benzofenonas , Cetonas , Óxidos , Polietilenglicoles , Polímeros , Estroncio , Titanio , Ratones , Animales , Cetonas/farmacología , Polietilenglicoles/farmacología , Polietilenglicoles/química , Éter , Células 3T3 NIH , Éteres de Etila , Éteres
11.
Adv Healthc Mater ; 13(12): e2303975, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38235953

RESUMEN

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.


Asunto(s)
Aleaciones , Antibacterianos , Magnesio , Ensayo de Materiales , Osteogénesis , Antibacterianos/farmacología , Antibacterianos/química , Aleaciones/química , Aleaciones/farmacología , Corrosión , Animales , Osteogénesis/efectos de los fármacos , Ratones , Magnesio/química , Magnesio/farmacología , Staphylococcus aureus/efectos de los fármacos , Implantes Absorbibles , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Zinc/química , Zinc/farmacología , Línea Celular , Estroncio/química , Estroncio/farmacología , Circonio/química , Circonio/farmacología
12.
ACS Appl Mater Interfaces ; 16(4): 4462-4477, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38240605

RESUMEN

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


Asunto(s)
Indoles , Osteogénesis , Polímeros , Factor A de Crecimiento Endotelial Vascular , Ratas , Animales , Factor A de Crecimiento Endotelial Vascular/farmacología , Alginatos/farmacología , Microtomografía por Rayos X , Angiogénesis , Regeneración Ósea , Cráneo , Hidroxiapatitas/farmacología , Estroncio/farmacología
13.
Biol Trace Elem Res ; 202(4): 1559-1567, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37491616

RESUMEN

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.


Asunto(s)
Estroncio , Titanio , Humanos , Titanio/farmacología , Titanio/química , Estroncio/farmacología , Estroncio/química , Factor A de Crecimiento Endotelial Vascular , Proteína Quinasa 3 Activada por Mitógenos , Angiogénesis , Sistema de Señalización de MAP Quinasas , Propiedades de Superficie
14.
Small Methods ; 8(1): e2301134, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37840374

RESUMEN

The efficacy of sonodynamic therapy (SDT) mainly relies on the sonosensitizers, which generate reactive oxygen species (ROS) upon ultrasound (US) stimulation. However, the limited availability of high-efficiency sonosensitizers hampers the therapeutic effectiveness of SDT as a standalone modality. In this work, a robust sonodynamic and gas cancer therapeutic platform is constructed based on strontium (Sr) doped barium titanate (BST) piezoelectric nanoparticles functionalized with L-arginine (BST@LA). The doping of Sr into A site of the ABO3 piezoelectric nanocrystals not only introduces oxygen vacancies into the nanoparticles and enhance the intrinsic piezoelectricity, but also narrows the semiconductor band gap and enhances charge carrier migration, all of which facilitate the sonodynamic production of superoxide anion (•O2 - ) and hydroxyl radical (•OH). In addition, the generated ROS promotes the decomposition of the surface-tethered LA, enabling the controlled release of nitric oxide (NO) gas at the tumor site, thereby achieving a combination therapeutic effect. In vivo experiments exhibit remarkable tumor suppression rate (89.5%) in 4T1 tumor mice model, demonstrating the effectiveness of this strategy. The ion doping and oxygen vacancy engineering to improve sonosensitizers, along with the synergistic combination of sonodynamic and gas therapy, provides promising avenues for improving cancer therapy.


Asunto(s)
Neoplasias , Estroncio , Animales , Ratones , Óxido Nítrico , Especies Reactivas de Oxígeno , Ácido Linoleico , Oxígeno , Neoplasias/terapia
15.
ACS Biomater Sci Eng ; 9(11): 6225-6240, 2023 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-37906514

RESUMEN

There is an urgent demand for antibacterial bone grafts in clinics. Worryingly, the misuse and overuse of antibiotics accelerate the emergence of drug-resistant bacteria. Therefore, this study prepared a novel injectable bioceramic cement without antibiotics (FS-BCS), which showed good antibacterial properties by loading iron and strontium onto a matrix composed of brushite and calcium sulfate. The setting time, injectability, microstructure, antibacterial properties, anti-biofilm properties, and cytocompatibility of the novel bioceramic cement were evaluated thoroughly. The results showed that the material was highly injectable and antiwashout. The antibacterial tests revealed that FS-BCS inhibited the growth of 99.9% E. coli and S. aureus separately in the broth due to the synergistic effect of strontium and iron. Simultaneously, crystal violet and fluorescent staining tests revealed that the material could significantly inhibit the formation of E. coli and S. aureus biofilms. In addition, the co-incorporation of iron and strontium promoted the proliferation and migration of osteoblasts. Therefore, FS-BCS has good application potential in antibiotic-free anti-infection bone grafting using minimally invasive surgery.


Asunto(s)
Escherichia coli , Staphylococcus aureus , Cementos para Huesos/química , Cementos para Huesos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Biopelículas , Hierro/farmacología , Estroncio/farmacología , Procedimientos Quirúrgicos Mínimamente Invasivos
16.
ACS Biomater Sci Eng ; 9(10): 5761-5771, 2023 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-37676927

RESUMEN

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.


Asunto(s)
Calcio , Osteogénesis , Ratones , Animales , Humanos , Calcio/farmacología , Fosfatos/farmacología , Estroncio/farmacología , Estroncio/química , Zinc/farmacología , Fosfatos de Calcio/farmacología , Fosfatos de Calcio/química , Cementos para Huesos/farmacología , Cementos para Huesos/química
17.
Sci Total Environ ; 904: 166948, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37696404

RESUMEN

Cadmium (Cd) contamination of rice is an urgent ecological and agricultural problem. Strontium (Sr) has been shown to promote plant growth. However, the effect of Sr on rice seedlings under Cd stress is currently unclear. In this work hydroponic experiments were used to assess the impact of Sr on rice seedling growth under Cd stress. The findings demonstrated that foliar application of 0.5 mg L-1 Sr had no discernible impact on the development of rice seedlings. However, Sr significantly alleviated growth inhibition and toxicity in rice seedlings when threatened by Cd. Compared with the Cd treatment (Cd, 2.5 mg L-1), the root length, shoot height, and whole plant length of rice seedlings in the Cd + Sr treatment (Cd, 2.5 mg L-1; Sr, 0.5 mg L-1) increased by 4.96 %, 12.47 % and 9.60 %, respectively. The content of Cd in rice decreased by 23.34 % (roots) and 5.79 % (shoots). Sr lessened the degree of membrane lipid peroxidation damage (lower MDA concentration) among the seedlings of rice under Cd stress by controlling the activities of antioxidant enzymes and GSH content. By changing the expression of antioxidant enzyme-encoding genes and downregulating the heavy metal transporter gene (OsNramp5), Sr reduced accumulation and the detrimental effects of Cd on rice seedlings. Our study provides a new solution to the problem of Cd contamination in rice, which may promote the safe production of rice and benefit human health.


Asunto(s)
Cadmio , Oryza , Humanos , Cadmio/metabolismo , Antioxidantes/metabolismo , Plantones , Estrés Oxidativo , Estroncio/toxicidad , Estroncio/metabolismo , Raíces de Plantas/metabolismo
18.
Chemosphere ; 340: 139925, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37619756

RESUMEN

Nonradioactive strontium (Sr) are produced as a result of radioactive decay of heavier elements such as uranium and thorium. Nonradioactive Sr shares physicochemical similarities with Ca and can replace it during bone formation, which may cause bone cancer in humans. Hence, concerning the potential hazards associated with strontium, it is imperative to eliminate it. The present study aimed to investigate the removal mechanisms of hematite-adsorbed strontium by calcium solution. Strontium was adsorbed to hematite at pH 8 and 10 and washed with calcium solution. X-ray absorption near-edge structure (XANES), extended X-ray absorption fine structure (EXAFS), scanning electron microscopy, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (after Ca washing) were performed on the samples before and after washing. Analyses and fitting by XANES and EXAFS confirmed the formation of an inner-sphere complex of strontium at pH 10. The XRD spectra showed that SrCO3 and SrFe2O4 formed at pH 8 and 10, respectively. After washing with the calcium solution, strontium was directly substituted to form CaCO3 and CaFe2O4. The X-ray photoelectron spectroscopy results provided a systematic analysis of the proportions of hematite and strontium, confirming the substitution of strontium with calcium. This substitution could be attributed to the physicochemical similarities between calcium and strontium. This study confirms the substitution of Sr with Ca, highlighting the physicochemical similarity of the Sr and Ca that facilitates substitution reactions.


Asunto(s)
Neoplasias Óseas , Calcio , Humanos , Calcio de la Dieta , Estroncio
19.
Acta Biomater ; 169: 579-588, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37516416

RESUMEN

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+.


Asunto(s)
Osteoporosis , Estroncio , Humanos , Estroncio/farmacología , Estroncio/química , Huesos/patología , Calcificación Fisiológica , Osteoporosis/patología , Colágeno/farmacología
20.
Biomater Sci ; 11(16): 5590-5604, 2023 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-37403758

RESUMEN

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.


Asunto(s)
Osteogénesis , Andamios del Tejido , Humanos , Andamios del Tejido/química , Glicoles , Fosfatos de Calcio/química , Minerales , Diferenciación Celular , Estroncio/química , Impresión Tridimensional
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