RESUMEN
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.
Asunto(s)
Estroncio , Pez Cebra , Animales , Estroncio/química , Estroncio/farmacología , Especies Reactivas de Oxígeno/metabolismo , Embrión no Mamífero/efectos de los fármacos , Ensayo de Materiales , Hidroxiapatitas/química , Hidroxiapatitas/farmacología , Nanoestructuras/química , Larva/efectos de los fármacosRESUMEN
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.
Asunto(s)
Regeneración Ósea , Sistemas de Liberación de Medicamentos , Vidrio , Magnesio , Células Madre Mesenquimatosas , Nanopartículas , Estroncio , Humanos , Regeneración Ósea/efectos de los fármacos , Nanopartículas/química , Estroncio/química , Estroncio/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Porosidad , Magnesio/química , Vidrio/química , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Línea Celular , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Proliferación Celular/efectos de los fármacosRESUMEN
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.
Asunto(s)
Antibacterianos , Diferenciación Celular , Gelatina , Hidrogeles , Nanopartículas del Metal , Osteoblastos , Osteogénesis , Impresión Tridimensional , Plata , Estroncio , Ingeniería de Tejidos , Andamios del Tejido , Titanio , Plata/química , Plata/farmacología , Gelatina/química , Estroncio/química , Estroncio/farmacología , Titanio/química , Titanio/farmacología , Ingeniería de Tejidos/métodos , Osteoblastos/efectos de los fármacos , Osteoblastos/citología , Antibacterianos/química , Antibacterianos/farmacología , Andamios del Tejido/química , Hidrogeles/química , Hidrogeles/farmacología , Nanopartículas del Metal/química , Diferenciación Celular/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Animales , Ratones , Huesos/efectos de los fármacosRESUMEN
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 80.95â¯% and 92.45â¯%, 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.
Asunto(s)
Antibacterianos , Antiinflamatorios , Materiales Biocompatibles Revestidos , Escherichia coli , Nanotubos , Prótesis e Implantes , Staphylococcus aureus , Estroncio , Titanio , Titanio/química , Titanio/farmacología , Nanotubos/química , Ratones , Animales , Estroncio/química , Estroncio/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/química , Staphylococcus aureus/efectos de los fármacos , Humanos , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Escherichia coli/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Células RAW 264.7 , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Propiedades de Superficie , Taninos/química , Taninos/farmacología , Osteogénesis/efectos de los fármacos , Poloxámero/química , Poloxámero/farmacología , Proliferación Celular/efectos de los fármacos , Gentamicinas/farmacología , Gentamicinas/química , Tamaño de la PartículaRESUMEN
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.
Asunto(s)
Compuestos de Calcio , Movimiento Celular , Supervivencia Celular , Resinas Epoxi , Materiales de Obturación del Conducto Radicular , Silicatos , Células Madre , Animales , Silicatos/farmacología , Movimiento Celular/efectos de los fármacos , Materiales de Obturación del Conducto Radicular/farmacología , Materiales de Obturación del Conducto Radicular/toxicidad , Ratas , Compuestos de Calcio/farmacología , Resinas Epoxi/farmacología , Resinas Epoxi/toxicidad , Supervivencia Celular/efectos de los fármacos , Células Madre/efectos de los fármacos , Técnicas In Vitro , Ensayo de Materiales , Células Cultivadas , Cerámica/farmacología , Estroncio/farmacología , Papila Dental/citología , Papila Dental/efectos de los fármacos , Ápice del Diente/efectos de los fármacos , Ápice del Diente/citologíaRESUMEN
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.
Asunto(s)
Condrogénesis , Dendrímeros , Diclofenaco , Inflamación , Nanopartículas , Estroncio , Condrogénesis/efectos de los fármacos , Estroncio/química , Estroncio/farmacología , Animales , Diclofenaco/farmacología , Diclofenaco/química , Dendrímeros/química , Dendrímeros/farmacología , Nanopartículas/química , Inflamación/tratamiento farmacológico , Conejos , Ratones , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Hidrogeles/química , Hidrogeles/farmacología , Propiedades de Superficie , Gelatina/química , Cartílago/efectos de los fármacos , Cartílago/fisiología , Liberación de Fármacos , Ingeniería de Tejidos , Portadores de Fármacos/químicaRESUMEN
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.
Asunto(s)
Materiales Biocompatibles , Estroncio , Estroncio/química , Estroncio/farmacología , Humanos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Animales , Metales/químicaRESUMEN
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 (Sr2+), 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 Sr2+ 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.
Asunto(s)
Matriz Extracelular , Microesferas , Nanofibras , Osteoporosis , Estroncio , Estroncio/química , Estroncio/farmacología , Nanofibras/química , Osteoporosis/tratamiento farmacológico , Humanos , Matriz Extracelular/química , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/metabolismo , Animales , Osteogénesis/efectos de los fármacos , Andamios del Tejido/química , Diferenciación Celular/efectos de los fármacos , Ingeniería de Tejidos , Proliferación Celular/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Regeneración/efectos de los fármacosRESUMEN
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, Zn2Sr(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.
Asunto(s)
Regeneración Ósea , Ácido Gálico , Gelatina , Hidrogeles , Osteogénesis , Ácido Gálico/química , Ácido Gálico/farmacología , Regeneración Ósea/efectos de los fármacos , Gelatina/química , Hidrogeles/química , Hidrogeles/farmacología , Animales , Osteogénesis/efectos de los fármacos , Fosfatos/química , Fosfatos/farmacología , Estroncio/química , Estroncio/farmacología , Zinc/química , Zinc/farmacología , Ratones , Humanos , Huesos/efectos de los fármacos , Masculino , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacologíaRESUMEN
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 (Sr2+) 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.
Asunto(s)
Aleaciones , Colágeno , Hidrogeles , Oseointegración , Osteogénesis , Impresión Tridimensional , Andamios del Tejido , Titanio , Titanio/química , Animales , Osteogénesis/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Andamios del Tejido/química , Conejos , Oseointegración/efectos de los fármacos , Colágeno/química , Colágeno/farmacología , Porosidad , Aleaciones/química , Aleaciones/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Estroncio/química , Estroncio/farmacología , Ingeniería de Tejidos/métodos , Alginatos/química , Alginatos/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacologíaRESUMEN
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 (Si4+) and strontium ions (Sr2+) 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 Si4+ and Sr2+, 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.
Asunto(s)
Vendajes , Gelatina , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Silicio , Piel , Estroncio , Cicatrización de Heridas , Gelatina/química , Animales , Estroncio/química , Estroncio/farmacología , Cicatrización de Heridas/efectos de los fármacos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Piel/efectos de los fármacos , Porosidad , Ratas , Humanos , Silicio/química , Ratas Sprague-Dawley , Ratones , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Masculino , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacologíaRESUMEN
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.
Asunto(s)
Aspirina , Fosfatos de Calcio , Cobre , Estroncio , Zinc , Estroncio/química , Estroncio/farmacología , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Humanos , Animales , Aspirina/farmacología , Aspirina/química , Cobre/química , Zinc/química , Zinc/farmacología , Cementos Dentales/química , Cementos Dentales/farmacología , Biopelículas/efectos de los fármacos , Ensayo de Materiales , Pez Cebra , Pulpa Dental/citología , Pulpa Dental/efectos de los fármacos , Streptococcus mutans/efectos de los fármacos , Células Madre/efectos de los fármacos , Difracción de Rayos X , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Proliferación Celular/efectos de los fármacosRESUMEN
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, CaHPO4·2H2O (DCPD) and tetracalcium phosphate, Ca4(PO4)2O (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.
Asunto(s)
Regeneración Ósea , Cobalto , Manganeso , Células Madre Mesenquimatosas , Osteogénesis , Estroncio , Estroncio/farmacología , Estroncio/química , Cobalto/química , Humanos , Osteogénesis/efectos de los fármacos , Manganeso/química , Manganeso/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Regeneración Ósea/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/química , Factor A de Crecimiento Endotelial Vascular/metabolismo , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Supervivencia Celular/efectos de los fármacos , AngiogénesisRESUMEN
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.
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Biopelículas , Periimplantitis , Porphyromonas gingivalis , Estroncio , Titanio , Titanio/química , Titanio/farmacología , Biopelículas/efectos de los fármacos , Periimplantitis/microbiología , Periimplantitis/tratamiento farmacológico , Estroncio/farmacología , Porphyromonas gingivalis/efectos de los fármacos , Humanos , Antibacterianos/farmacología , Materiales Biocompatibles Revestidos/farmacología , Materiales Biocompatibles Revestidos/química , Viabilidad Microbiana/efectos de los fármacos , Implantes Dentales/microbiologíaRESUMEN
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.
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Resinas Acrílicas , Antifúngicos , Candida albicans , Vidrio , Ensayo de Materiales , Fosfatos , Estroncio , Propiedades de Superficie , Candida albicans/efectos de los fármacos , Resinas Acrílicas/química , Estroncio/farmacología , Estroncio/química , Antifúngicos/farmacología , Vidrio/química , Fosfatos/farmacología , Polimerizacion , Dureza , Resistencia Flexional , Humanos , Técnicas In VitroRESUMEN
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.
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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 XRESUMEN
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, TiO2 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.
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Proliferación Celular , Nanotubos , Osteogénesis , Estroncio , Propiedades de Superficie , Titanio , Zinc , Titanio/química , Titanio/farmacología , Estroncio/química , Estroncio/farmacología , Nanotubos/química , Zinc/química , Zinc/farmacología , Osteogénesis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Humanos , Fosfatasa Alcalina/metabolismo , Células Madre/citología , Células Madre/metabolismo , Células Madre/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Células CultivadasRESUMEN
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 (Sr2+). 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 Sr2+ 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 Sr2+ 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.
Asunto(s)
Alginatos , Regeneración Ósea , Hidrogeles , Osteogénesis , Impresión Tridimensional , Estroncio , Andamios del Tejido , Estroncio/química , Estroncio/farmacología , Andamios del Tejido/química , Alginatos/química , Alginatos/farmacología , Regeneración Ósea/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Osteogénesis/efectos de los fármacos , Animales , Ingeniería de Tejidos/métodos , Neovascularización Fisiológica/efectos de los fármacos , Humanos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacosRESUMEN
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. SrTiO3 nanotubes (SrNT) were constructed on the surface of Ti implants as "cannon barrel," the "cannonball" (antibiotic) and "propellant" (NH4HCO3) were codeposited into SrNT with assistance of mussel-inspired copolymerization of dopamine and subsequently sealed by a layer of polydopamine. The encapsulated NH4HCO3 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.
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Antibacterianos , Nanotubos , Óxidos , Estroncio , Titanio , Estroncio/química , Estroncio/farmacología , Animales , Titanio/química , Titanio/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Ratas , Óxidos/química , Óxidos/farmacología , Nanotubos/química , Prótesis e Implantes , Oseointegración/efectos de los fármacos , Ratones , Ratas Sprague-Dawley , Indoles/química , Indoles/farmacología , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Osteogénesis/efectos de los fármacos , Propiedades de Superficie , Polímeros/química , Polímeros/farmacología , Biopelículas/efectos de los fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
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.