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1.
ACS Appl Mater Interfaces ; 16(13): 15687-15700, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38511302

RESUMO

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


Assuntos
Integrinas , Osteogênese , Citocinas , 60489 , Células Endoteliais , Hidroxiapatitas/química , Estrôncio/farmacologia , Estrôncio/química , Transdução de Sinais , Íons/farmacologia
2.
Dalton Trans ; 53(15): 6501-6506, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38511607

RESUMO

In the crystals of alkaline earth metal compounds strontium and barium with the non-steroidal anti-inflammatory drug nimesulide, the strontium cation is nine-coordinated with a distorted tricapped trigonal prismatic geometry TCTPR-9, whereas the ten-coordinated barium ion exhibits a distorted tetracapped trigonal prismatic geometry TCTPR-10.


Assuntos
Metais Alcalinoterrosos , Estrôncio , Sulfonamidas , Bário/química , Estrôncio/química , Metais Alcalinoterrosos/química , Anti-Inflamatórios não Esteroides
3.
Dent Mater ; 40(4): 716-727, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38395738

RESUMO

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


Assuntos
Cárie Dentária , Fluoretos , Humanos , Fluoretos/farmacologia , Fluoretos/química , Cimentos de Ionômeros de Vidro/farmacologia , Cimentos de Ionômeros de Vidro/química , Estrôncio/farmacologia , Estrôncio/química , Antibacterianos/farmacologia , Antibacterianos/química , Apatitas/farmacologia , Cárie Dentária/terapia , Teste de Materiais
4.
Molecules ; 29(3)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38338415

RESUMO

Tissue engineering is an interdisciplinary field of science that has been developing very intensively over the last dozen or so years. New ways of treating damaged tissues and organs are constantly being sought. A variety of porous structures are currently being investigated to support cell adhesion, differentiation, and proliferation. The selection of an appropriate biomaterial on which a patient's new tissue will develop is one of the key issues when designing a modern tissue scaffold and the associated treatment process. Among the numerous groups of biomaterials used to produce three-dimensional structures, hydroxyapatite (HA) deserves special attention. The aim of this paper was to discuss changes in the double electrical layer in hydroxyapatite with an incorporated boron and strontium/electrolyte solution interface. The adsorbents were prepared via dry and wet precipitation and low-temperature nitrogen adsorption and desorption methods. The specific surface area was characterized, and the surface charge density and zeta potential were discussed.


Assuntos
Boro , Hidroxiapatitas , Humanos , Hidroxiapatitas/química , Tecidos Suporte/química , Durapatita , Materiais Biocompatíveis/química , Estrôncio/química , Propriedades de Superfície
5.
Int J Biol Macromol ; 254(Pt 3): 127780, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37907172

RESUMO

Dentine hypersensitivity (DH) is a common oral health issue and occlusion of the exposed dentinal tubules (DTs) is regarded as the most effective therapeutic treatment nowadays. However, it is still difficult to develop easy and effective strategies for deep occlusion of DTs. In this study, we develop a strategy for occluding DTs deeply and compactly via simple application of occlusion media including (poly-L-aspartic acid)­strontium (PAsp­strontium) and phosphate/fluoride. The bonding of strontium ions to poly-L-aspartic acid formed a positively charged PAsp­strontium complexes. After application of 15 min each, the PAsp­strontium and phosphate/fluoride rapidly penetrated into the DTs in turn via the electrostatic interaction, then occluded the DTs with crystals up to a depth of 150 µm. The occlusion within DTs was resistant to abrasive and acidic challenges. The occlusion media performed better than commercial desensitizers Duraphat and Gluma. Moreover, this strategy possessed sufficient biocompatible and excellent performance in vivo. The application of occlusion media would shed light on in the management of DH.


Assuntos
Sensibilidade da Dentina , Fluoretos , Humanos , Fluoretos/química , Estrôncio/química , Sensibilidade da Dentina/tratamento farmacológico , Ácido Aspártico/farmacologia , Fosfatos , Dentina , Microscopia Eletrônica de Varredura
6.
Dent Mater ; 40(2): 210-218, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37977993

RESUMO

OBJECTIVES: Apatite minerals can have various anions and cations in their crystal structure in addition to phosphate ion (PO4³â») and calcium ion (Ca2+). The aim of this study is to investigate effects of the borate, fluoride and strontium ions on biomimetic nucleation of calcium phosphate. METHODS: Nano-crystalline hydroxyapatite (H-Ap) was obtained from a supersaturated buffered solution containing 4.12 mM HPO42- and 5.88 mM Ca2+ (H-Ap). Four additives were used in solid solution methods: (i) 0.588 mM F- (F-Ap), (ii) 5.88 mM Sr2+ (Sr-Ap), (iii) 4.12 mM BO33- (BO3-Ap), and (iv) a surface pre-reacted glass ionomer (S-PRG) filler eluate that contained 0.17 mM Sr2+, 0.588 mM F-, 11.1 mM BO33-- (SPRG-Ap). Apatite crystallization was investigated using a solid-state magic-angle spinning NMR spectroscopy and X-ray diffraction (XRD) with the Rietveld analysis. RESULTS: A 2D 1H-31P heteronuclear-correlation NMR showed F- ion incorporation in the apatite structure of the F-Ap and SPRG-Ap. The peaks on the 31P axis of the F-Ap, Sr-Ap, and BO3-Ap were different from that of the H-Ap, and the full width at half maximum increased in the following order: H-Ap∼F-Ap∼BO3-Ap< SPRG-Ap< Sr-Ap, suggesting the incorporation of the F-, Sr2+ and BO33-. The incorporation of F and BO3 was further confirmed by 19F and 11B NMR. The XRD revealed that Sr2+ was preferentially incorporated into the CaII site. SIGNIFICANCE: The F-, Sr2+ and BO33-ions might be involved in modifying the crystallization of apatite precipitation, producing a variety of apatite. S-PRG filler that release these ions may have an effect on remineralization, i.e., the reformation of apatite lost due to caries.


Assuntos
Boratos , Fluoretos , Difração de Raios X , Estrôncio/química , Biomimética , Fosfatos de Cálcio/química , Apatitas/química , Durapatita/química , Espectroscopia de Ressonância Magnética , Íons
7.
Biol Trace Elem Res ; 202(4): 1559-1567, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37491616

RESUMO

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.


Assuntos
Estrôncio , Titânio , Humanos , Titânio/farmacologia , Titânio/química , Estrôncio/farmacologia , Estrôncio/química , Fator A de Crescimento do Endotélio Vascular , Proteína Quinase 3 Ativada por Mitógeno , Sistema de Sinalização das MAP Quinases , Propriedades de Superfície
8.
Int J Dev Biol ; 67(4): 137-146, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37975329

RESUMO

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


Assuntos
Osteogênese , Humanos , Hidroxiapatitas/química , Hidroxiapatitas/farmacologia , Durapatita/química , Durapatita/farmacologia , Estrôncio/farmacologia , Estrôncio/química
9.
Int J Mol Sci ; 24(19)2023 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-37833940

RESUMO

Food and drinks can be contaminated with pollutants such as lead and strontium, which poses a serious danger to human health. For this reason, a number of effective sensors have been developed for the rapid and highly selective detection of such contaminants. TBA, a well-known aptamer developed to selectively target and thereby inhibit the protein of clinical interest α-thrombin, is receiving increasing attention for sensing applications, particularly for the sensing of different cations. Indeed, TBA, in the presence of these cations, folds into the stable G-quadruplex structure. Furthermore, different cations produce small but significant changes in this structure that result in changes in the electrical responses that TBA can produce. In this article, we give an overview of the expected data regarding the use of TBA in the detection of lead and strontium, calculating the expected electrical response using different measurement techniques. Finally, we conclude that TBA should be able to detect strontium with a sensitivity approximately double that achievable for lead.


Assuntos
Aptâmeros de Nucleotídeos , Quadruplex G , Humanos , Aptâmeros de Nucleotídeos/química , Cátions , Trombina/metabolismo , Estrôncio/química
10.
Int J Mol Sci ; 24(19)2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37833975

RESUMO

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


Assuntos
Anti-Infecciosos , Nanoestruturas , Humanos , Cálcio/química , Fosfatos de Cálcio/farmacologia , Fosfatos de Cálcio/química , Regeneração Óssea , Cálcio da Dieta , Estrôncio/farmacologia , Estrôncio/química , Anti-Infecciosos/farmacologia , Difração de Raios X
11.
ACS Biomater Sci Eng ; 9(10): 5761-5771, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37676927

RESUMO

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.


Assuntos
Cálcio , Osteogênese , Camundongos , Animais , Humanos , Cálcio/farmacologia , Fosfatos/farmacologia , Estrôncio/farmacologia , Estrôncio/química , Zinco/farmacologia , Fosfatos de Cálcio/farmacologia , Fosfatos de Cálcio/química , Cimentos Ósseos/farmacologia , Cimentos Ósseos/química
12.
Int J Biol Macromol ; 252: 126524, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37633545

RESUMO

The irregular expression of bone matrix proteins occurring during the mineralization of bone regeneration results in various deformities which poses a major concern of orthopedic reconstruction. The limitations of the existing reconstruction practice paved a way for the development of a metal-organic composite [TQ-Sr-Fe] with Metal ions strontium [Sr] and iron [Fe] and a biomolecule Thymoquinone [TQ] in an attempt to enhance the bone mineralization due to their positive significance in osteoblast differentiation, proliferation and maturation. TQ-Sr-Fe was synthesized by in-situ coprecipitation and subjected to various characterization to determine their nature, compatibility and osteogenic efficiency. The crystallographic and electron microscopy analysis reveals sheet like structure of the composite. The negative cytotoxicity of TQ-Sr-Fe in the MG 63 cell line signified their biocompatibility. Cell adhesion and proliferation rate affirmed osteoconductive and osteoinductive nature of the composites and it was further supported by the gene expression of osteoblastic differentiation. The sequential expression of bone matrix proteins such as OCN, SPARC, COL 1, and Alkaline Phosphatase elevate the calcium deposition of MG-63 osteoblast like cells and initiates mineralization compared to control. Thus, the metal-organic composite TQ-Sr-Fe would make a suitable composite for accelerating mineralization process which would leads to faster bone regeneration.


Assuntos
Fosfatase Alcalina , Matriz Óssea , Fosfatase Alcalina/metabolismo , Matriz Óssea/metabolismo , Osteogênese/genética , Proteínas , Estrôncio/química , Cálcio/metabolismo
13.
Int J Biol Macromol ; 252: 126478, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37625758

RESUMO

The objective of this study is to explore the potential role of alginate (Alg) in the crystallization of metal-substituted hydroxyapatite, with application in orthopaedic reconstruction. The alginate at different concentrations (0.5 and 1.0 wt%) facilitated in situ mineralization of hydroxyapatite (HA) and strontium-substituted HA (SHA, 10 and 30 mol%). The incorporation of the biopolymer and dopant induced notable changes in HA, including reduced crystal size from 31.0 to 16.4 nm and increased lattice volume from 577.3 to 598.0 Å3. The superior affinity of alginate for Sr2+ than for Ca2+ resulted in higher residual alginate in Alg/SHA (13.0 to 19.0 %) compared to Alg/HA (7.1 to 8.2 %). This residual alginate influenced composite properties: surface charge decreased from -26.5 to -45.7 mV, microhardness increased from 0.33 to 0.54 GPa, and dissolution increased from 0.17 to 0.39 %. The in vitro studies revealed that strontium substitution as well as the organization and crystallographic aspects of apatite regulated osteoblastic cell survival, proliferation, differentiation, and biomineralization. The findings suggest that an alginate concentration of 0.5 wt% is optimal for the crystallization of SHA with 10 mol% substitution, and its resulting composite possesses the ideal biomechanical properties to imitate native bone.


Assuntos
Durapatita , Hidroxiapatitas , Hidroxiapatitas/química , Durapatita/química , Estrôncio/química , Alginatos
14.
Biomater Sci ; 11(18): 6299-6310, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37551440

RESUMO

Phosphate-based glass (PBG) is a bioactive agent, composed of a glass network with phosphate as the primary component and can be substituted with various therapeutic ions for functional enhancement. Strontium (Sr) has been shown to stimulate osteogenic activity and inhibit pro-inflammatory responses. Despite this potential, there are limited studies that focus on the proportion of Sr substituted and its impact on the functional activity of resulting Sr-substituted PBG (PSr). In this study, focusing on the cellular biological response we synthesized and investigated the functional activity of PSr by characterizing its properties and comparing the effect of Sr substitution on cellular bioactivity. Moreover, we benchmarked the optimal composition against 45S5 bioactive glass (BG). Our results showed that PSr groups exhibited a glass structure and phosphate network like that of PBG. The release of Sr and P was most stable for PSr6, which showed favorable cell viability. Furthermore, PSr6 elicited excellent early osteogenic marker expression and inhibition of pro-inflammatory cytokine expression, which was significant compared to BG. In addition, compared to BG, PSr6 had markedly higher expression of osteopontin in immunocytochemistry, higher ALP expression in osteogenic media, and denser alizarin red staining in vitro. We also observed a comparable in vivo regenerative response in a 4-week rabbit calvaria defect model. Therefore, based on the results of this study, PSr6 could be identified as the functionally optimized composition with the potential to be applied as a valuable bioactive component of existing biomaterials used for bone regeneration.


Assuntos
Regeneração Óssea , Osteogênese , Animais , Coelhos , Linhagem Celular , Fosfatos , Estrôncio/farmacologia , Estrôncio/química , Vidro/química
15.
J Chromatogr A ; 1706: 464276, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37562105

RESUMO

A novel analytical solution of non-linear chromatography in case of parabolic isotherm for frontal analysis was obtained by combination of Cole-Hopf and Laplace transform. It was used for simulation of strontium capturing on chromatographic column with aim to improve quantitative determination of low-level 90Sr activities. From the experimentally determined breakthrough curves, the retention factor and the number of theoretical plates were calculated using the Glueckauf and Wenzel relations and by fitting the breakthrough curves for the linear isotherm using MatLab. These were used to simulate the breakthrough curves using a parabolic isotherm solution where the non-linear term of the isotherm was taken as a small negative deviation of the retention factor. On the base of theoretical prediction and experimental data, procedure for automated capturing of strontium on chromatographic column with specific dimension and off line "on-column" Cherenkov detection on commercial ultra low-level liquid scintillation counter was developed. It was shown that analytical solution for parabolic isotherm in comparison with solution for linear isotherm gives better prediction of mass of captured Sr on column filled with small amount of Sr resin and SuperLig®620 in case of elevated Sr concentration, even when non-linear effect is not obvious. The solution also makes it possible to predict the mass of resin required for strontium isolation at 100% yield under given conditions. Considering the limited dimensions of the column, and consequently small mass of the resin in them, it resulted in the low efficiency of the columns, which, however, did not affect the yield in real conditions of isolation. The results have shown that the yields achieved after isolation on SuperLig®620 from real samples are 100%. In addition, it is shown that captured 90Sr can be detected through 90Y ingrowth, on column filled with strontium specific resin, with Cherenkov detection efficiency of at least 50%. The efficiency may be enhanced to 60%, depending on parameters which can affect detection efficiency change (type of column, resin type, surrounding solution, etc.). The developed procedures enable quantitative determination of 90Sr in natural water samples with MDAC below 12 mBq l-1 and solid (soil and vegetation) samples with MDAC below 6 Bq kg-1 within 2-3 days. The proposed solution may easily be implemented in radiochemical laboratories where this type of analysis is routinely done within environmental monitoring or other purposes.


Assuntos
Cromatografia , Radioisótopos de Estrôncio , Radioisótopos de Estrôncio/análise , Cromatografia/métodos , Estrôncio/análise , Estrôncio/química , Monitoramento Ambiental
16.
Acta Biomater ; 169: 579-588, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37516416

RESUMO

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+.


Assuntos
Osteoporose , Estrôncio , Humanos , Estrôncio/farmacologia , Estrôncio/química , Osso e Ossos/patologia , Calcificação Fisiológica , Osteoporose/patologia , Colágeno/farmacologia
17.
Biomater Sci ; 11(16): 5590-5604, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37403758

RESUMO

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.


Assuntos
Osteogênese , Tecidos Suporte , Humanos , Tecidos Suporte/química , Glicóis , Fosfatos de Cálcio/química , Minerais , Diferenciação Celular , Estrôncio/química , Impressão Tridimensional
18.
Int J Biol Macromol ; 248: 125927, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37481177

RESUMO

The influence of carbohydrates on the crystallization of metal-substituted hydroxyapatite predicts its relevance to natural bone growth. This study demonstrates the role of carbohydrates in the crystallization of strontium-substituted hydroxyapatite (SHAP). The increasing order of hydroxyl groups, dextrose (monosaccharide) < maltose (disaccharide) < starch (polysaccharide), coordinated with Ca2+/Sr2+ and thus guided SHAP crystallization, with crystal size reduced from 35 to 19 nm, lattice volume increased from 518 to 537 Å3, and residual carbohydrates increased from 1.8 to 20.2 %. The variation in residual carbohydrates is due to their interaction with apatite and/or aqueous insolubility. Compared to pure SHAP, the starch-SHAP with higher residual starch showed increased water uptake from 1.23 ± 0.18 to 4.26 ± 0.21 % and degradation from 0.22 ± 0.06 to 1.53 ± 0.14 %, but decreased microhardness from 0.73 ± 0.12 to 0.38 ± 0.01 GPa and protein affinity from 4.82 ± 0.01 to 0.81 ± 0.01 µg/mg. However, its microhardness value was bone-like, and the reduced protein adsorption was masked by the rich osteogenic behaviour. In vitro cellular response demonstrated that the residual carbohydrate and strontium augmented osteocompatibility, proliferation, differentiation and biomineralization. The result concludes that carbohydrates drive SHAP crystallization, and starch-SHAP replicates natural bone.


Assuntos
Maltose , Engenharia Tecidual , Amido , Cristalização , Hidroxiapatitas/química , Durapatita/química , Estrôncio/química , Glucose
19.
J Phys Chem B ; 127(25): 5588-5600, 2023 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-37327495

RESUMO

Strontium (Sr), an alkali metal with properties similar to calcium, in the form of soluble salts is used to treat osteoporosis. Despite the information accumulated on the role of Sr2+ as a Ca2+ mimetic in biology and medicine, there is no systematic study of how the outcome of the competition between the two dications depends on the physicochemical properties of (i) the metal ions, (ii) the first- and second-shell ligands, and (iii) the protein matrix. Specifically, the key features of a Ca2+-binding protein that enable Sr2+ to displace Ca2+ remain unclear. To address this, we studied the competition between Ca2+ and Sr2+ in protein Ca2+-binding sites using density functional theory combined with the polarizable continuum model. Our findings indicate that Ca2+-sites with multiple strong charge-donating protein ligands, including one or more bidentately bound Asp-/Glu- that are relatively buried and rigid are protected against Sr2+ attack. On the other hand, Ca2+-sites crowded with multiple protein ligands may be prone to Sr2+ displacement if they are solvent-exposed and flexible enough so that an extra backbone ligand from the outer shell can bind to Sr2+. In addition, solvent-exposed Ca2+ sites with only a few weak charge-donating ligands that can rearrange to fit the strontium's coordination requirements are susceptible to Sr2+ displacement. We provide the physical basis of these results and discuss potential novel protein targets of therapeutic Sr2+.


Assuntos
Cálcio , Estrôncio , Estrôncio/química , Ligantes , Cálcio/química , Sítios de Ligação , Solventes
20.
J Mech Behav Biomed Mater ; 144: 105976, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37356210

RESUMO

Strontium borosilicate bioactive glass (SrBG) and calcium aluminate cement (CA) composites have been synthesized. The primary goal of this work is to evaluate how SrBG affects the bioactivity and physico-mechanical characteristics of CA. To fulfill this aim, SrBG was prepared by melt-quenching method and utilized as a substitute for CA by 5, 10, 15, and 20 wt%. To estimate the biological behavior of the prepared specimens, hydrᴏxyapatite layer (HA) establishment on the surface of cement paste was followed; after their immersion in a solution resembles human blood plasma (simulated body fluid solution (SBF)) at a temperature of about37 ± 0.5 °C for 4 weeks. The variations of pH, Ca and P ions concentrations in the SBF solution after soaking were determined. Compressive strength, apparent porosity, and bulk density were also measured. Via Fourier transform IR spectroscopy and X-ray diffraction analyses, the main components had been analyzed. Using scanning electron microscope (SEM) attached to energy dispersive spectroscopy, morphology of the samples was investigated. Additionally, the antimicrobial property was also assessed. The results proved that the hydrᴏxyapatite layer (HA) was developed on the surface of the prepared samples after soaking in the biological solution (SBF). It was also found that increasing SrBG percent in synthesized samples promotes the physico-mechanical characteristics and also the bioactivity performance of CA cement. Finally, these materials also showed good inhibition behavior towards bacterial biᴏfilms, against S. aureus and E. coli. after 48h. This makes these materials excellent candidates for preventing growth of bacteria after their implantation in teeth or bone.


Assuntos
Anti-Infecciosos , Estrôncio , Humanos , Estrôncio/química , Escherichia coli , Staphylococcus aureus , Cimentos Ósseos/química , Anti-Infecciosos/farmacologia , Vidro/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química
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