RESUMEN
The development of synthetic bone substitutes that equal or exceed the efficacy of autologous graft remains challenging. In this study, a rat calvarial defect model was used as a reference to investigate the influence of composition and architecture of 3D-printed cement, with or without bioactives, on tissue regeneration. Printable cement pastes were formulated by combining hyaluronic acid and cement precursors. Cementitious scaffolds were printed with 3 different patterns. After 7 weeks of implantation with or without bone marrow, multiparametric qualitative and quantitative assessments were performed using µCT, SEM, and histology. None of the set-up strategies was as efficient as autologous cancellous bone graft to repair calvarial defects. Nonetheless, the presence of scaffold improved the skull vault closure, particularly when the scaffold was soaked in total bone marrow before implantation. No significant effect of scaffold macro-architecture was observed on tissue mineralization. Magnesium phosphate-based scaffolds (MgP) seemed to induce higher bone formation than their calcium-phosphate-based counterparts. They also displayed a quicker biodegradation and sparse remaining material was found after 7 weeks of implantation. Although further improvements are required to reach clinical settings, this study demonstrated the potential of organo-mineral cements for bone regeneration and highlighted the peculiar properties of MgP-based cements.
Asunto(s)
Regeneración Ósea , Impresión Tridimensional , Cráneo , Andamios del Tejido , Animales , Regeneración Ósea/efectos de los fármacos , Andamios del Tejido/química , Ratas , Cráneo/efectos de los fármacos , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacología , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Masculino , Cementos para Huesos/farmacología , Cementos para Huesos/química , Fosfatos/química , Osteogénesis/efectos de los fármacos , Microtomografía por Rayos X , Compuestos de MagnesioRESUMEN
Doping of brushite cements with metal ions can entail many positive effects on biological and physicochemical properties. Cu2+ ions are known to exhibit antibacterial properties and can additionally have different positive effects on cells as trace elements, whereas high Cu2+ concentrations are cytotoxic. For therapeutical applications of bone cement, a combination of good biocompatibility and sufficient mechanical properties is required. Therefore, the aim of this study was to investigate different physicochemical and biological aspects, relevant for application, of a brushite cement with Cu2+-doped ß-tricalcium phosphate, monocalcium phosphate monohydrate and phytic acid as setting retarder. Additionally, the ion release was compared with a cement with citric acid as setting retarder. The investigated cements showed good injectability coefficients, as well as compressive strength values sufficient for application. Furthermore, no antibacterial effects were detected irrespective of the Cu2+ concentration or the bacterial strain. The cell experiments with eluate samples showed that the viability of MC3T3-E1 cells tended to decrease with increasing Cu2+ concentration in the cement. It is suggested that these biological responses are caused by the difference in the Cu2+ release from the hardened cement depending on the solvent medium. Furthermore, the cements showed a steady release of Cu2+ ions to a lesser extent in comparison with a cement with citric acid as setting retarder, where a burst release of Cu2+ was observed. In conclusion, despite the anticipated antibacterial effect of Cu2+-doped cements was lacking and mammalian cell viability was slightly affected, Cu2+-concentrations maintained the physicochemical properties as well as the compressive strength of cements and the slow ion release from cements produced with phytic acid is considered advantageous compared to citric acid-based formulations.
Asunto(s)
Cementos para Huesos , Fosfatos de Calcio , Cobre , Ensayo de Materiales , Ratones , Animales , Cobre/química , Cementos para Huesos/química , Cementos para Huesos/farmacología , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Fuerza Compresiva , Supervivencia Celular/efectos de los fármacos , Línea Celular , Células 3T3 , Ácido Cítrico/químicaRESUMEN
Bone adhesives, as alternatives to traditional bone fracture treatment methods, have great benefits in achieving effective fixation and healing of fractured bones. However, current available bone adhesives have limitations in terms of weak mechanical properties, low adhesion strength, and inappropriate degradability, hindering their clinical applications. The development of bone adhesives with strong mechanical properties, adhesion strength, and appropriate degradability remains a great challenge. In this study, polyacrylic acid was incorporated with tetracalcium phosphate and O-phospho-L-serine to form a new bone adhesive via coordination and ionic interactions to achieve exceptional mechanical properties, adhesion strength, and degradability. The bone adhesive could achieve an initial adhesion strength of approximately 3.26 MPa and 0.86 MPa on titanium alloys and bones after 15 min of curing, respectively, and it increased to 5.59 MPa and 2.73 MPa, after 24 h of incubation in water or simulated body fluid (SBF). The compressive strength of the adhesive increased from 10.06 MPa to 72.64 MPa over two weeks, which provided sufficient support for the fractured bone. Importantly, the adhesive started to degrade after 6 to 8 weeks of incubation in SBF, which is beneficial to cell ingrowth and the bone healing process. In addition, the bone adhesives exhibited favorable mineralization capability, biocompatibility, and osteogenic activity. In vivo experiments showed that it has a better bone-healing effect compared with the traditional polymethyl methacrylate bone cement. These results demonstrate that the bone adhesive has great potential in the treatment of bone fractures.
Asunto(s)
Resinas Acrílicas , Cementos para Huesos , Resinas Acrílicas/química , Cementos para Huesos/química , Cementos para Huesos/farmacología , Animales , Ensayo de Materiales , Ratones , Propiedades de Superficie , Titanio/químicaRESUMEN
Decellularized extracellular matrix (dECM) hydrogels are engineered constructs that are widely-used in the field of regenerative medicine. However, the development of ECM-based hydrogels for bone tissue engineering requires enhancement in its osteogenic properties. For this purpose, we initially employed bone-derived dECM hydrogel (dECM-Hy) in combination with calcium phosphate cement (CPC) paste to improve the biological and structural properties of the dECM hydrogel. A decellularization protocol for bovine bone was developed to prepare dECM-Hy, and the mechanically-tuned dECM/CPC-Hy was built based on both rheological and mechanical characteristics. The dECM/CPC-Hy displayed a double swelling ratio and compressive strength. An interconnected structure with distinct hydroxyapatite crystals was evident in dECM/CPC-Hy. The expression levels of Alp, Runx2 and Ocn genes were upregulated in dECM/CPC-Hy compared to the dECM-Hy. A 14-day follow-up of the rats receiving subcutaneous implanted dECM-Hy, dECM/CPC-Hy and mesenchymal stem cells (MSCs)-embedded (dECM/CPC/MSCs-Hy) showed no toxicity, inflammatory factor expression or pathological changes. Radiography and computed tomography (CT) of the calvarial defects revealed new bone formation and elevated number of osteoblasts-osteocytes and osteons in dECM/CPC-Hy and dECM/CPC/MSCs-Hy compared to the control groups. These findings indicate that the dECM/CPC-Hy has substantial potential for bone tissue engineering.
Asunto(s)
Cementos para Huesos , Regeneración Ósea , Fosfatos de Calcio , Células Madre Mesenquimatosas , Animales , Fosfatos de Calcio/química , Regeneración Ósea/efectos de los fármacos , Bovinos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratas , Cementos para Huesos/química , Cementos para Huesos/farmacología , Matriz Extracelular Descelularizada/química , Matriz Extracelular Descelularizada/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Osteogénesis/efectos de los fármacos , Ratas Sprague-Dawley , Ingeniería de Tejidos , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Matriz Extracelular/química , Matriz Extracelular/metabolismoRESUMEN
The morphological dynamics of microbial cell proliferation on an antimicrobial surface at an early growth stage was studied with Escherichia coli on the surface of a gel supplied with AgNbO3 antimicrobial particles. We demonstrated an inhibitory surface concentration, analogous to minimum inhibitory concentration, beyond which the growth of colonies and formation of biofilm are inhibited. In contrast, at lower concentrations of particles, after a lag time the cells circumvent the antimicrobial activity of the particles and grow with a rate similar to the case in the absence of particles. The lag time depends on the surface concentration of the particles and amounts to 2 h at a concentration of ½ minimum inhibitory concentration. The applicability of these findings, in terms of estimating inhibitory surface concentration, was tested in the case of antimicrobial polymethyl methacrylate (PMMA) bone cement.
Asunto(s)
Escherichia coli , Pruebas de Sensibilidad Microbiana , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Polimetil Metacrilato/química , Antiinfecciosos/farmacología , Propiedades de Superficie , Antibacterianos/farmacología , Niobio/farmacología , Niobio/química , Cementos para Huesos/farmacologíaRESUMEN
It's imperative to create a more ideal biological scaffold for bone defect repair. Calcium phosphate bone cements (CPC) could be used as a scaffold. Some ingredients and osteogenic factors could be added to improve its poor mechanical properties and biological activity. As a macromolecule extracted from traditional Chinese medicine, Hedysarum polysaccharides (HPS) would significantly promote the osteogenic activity of bone biomaterials. Zirconium oxide and starch were added to the solid phase and citric acid was added to the liquid phase to optimize CPC. HPS was loaded onto the scaffold as an osteogenic factor, and the prepared CPS + HPS was characterized. Further, the cytocompatibility of CPS + HPS was assessed according to activity, differentiation, and calcification in neonatal rat calvarial osteoblasts, and the biosafety of CPS + HPS was evaluated according to acute toxicity, pyrogen, sensitization, and hemolysis. The success of CPS + HPS in repairing bone defects was evaluated by using a rabbit femur implantation experiment. After optimization, CPS-20-CA-5 containing 10% starch and 5% citric acid displayed the highest mechanical strength of 28.96 ± 0.03 MPa. HPS-50 was demonstrated to exert the best osteogenic effect. The combination of CPS + HPS achieved HPS-loaded CPC. Material characterization, cytocompatibility, biosafety, and femoral implantation experiments indicated that CPS + HPS possessed better pressure resistance and improved osteogenic ability in bone defect repair.CPS + HPS demonstrated effective pressure resistance and superior osteogenic ability, which may be of great significance for bone defects and bone tissue engineering to promote bone regeneration and repair.
Asunto(s)
Cementos para Huesos , Regeneración Ósea , Fosfatos de Calcio , Osteogénesis , Polisacáridos , Andamios del Tejido , Animales , Fosfatos de Calcio/química , Cementos para Huesos/química , Cementos para Huesos/farmacología , Conejos , Polisacáridos/química , Ratas , Andamios del Tejido/química , Osteogénesis/efectos de los fármacos , Regeneración Ósea/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Ensayo de Materiales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ratas Sprague-Dawley , Masculino , Circonio/química , Ingeniería de Tejidos/métodos , Fémur/patologíaRESUMEN
Artificial bone substitutes for bone repair and reconstruction still face enormous challenges. Previous studies have shown that calcium magnesium phosphate cements (CMPCs) possess an excellent bioactive surface, but its clinical application is restricted due to short setting time. This study aimed to develop new CMPC/carboxymethyl chitosan (CMCS) comg of mixed powders of active MgO, calcined MgO and calcium dihydrogen phosphate monohydrate. With this novel strategy, it can adjust the setting time and improve the compressive strength. The results confirmed that CMPC/CMCS composite bone cements were successfully developed with a controllable setting time (18-70 min) and high compressive strength (87 MPa). In addition, the composite bone cements could gradually degrade in PBS with weight loss up to 32% at 28 d. They also promoted the proliferation of pre-osteoblasts, and induced osteogenic differentiation. The findings indicate that CMPC/CMCS composite bone cements hold great promise as a new type of bone repair material in further and in-depth studies.
Asunto(s)
Materiales Biocompatibles , Cementos para Huesos , Fosfatos de Calcio , Diferenciación Celular , Proliferación Celular , Quitosano , Fuerza Compresiva , Compuestos de Magnesio , Ensayo de Materiales , Osteoblastos , Osteogénesis , Quitosano/química , Quitosano/análogos & derivados , Cementos para Huesos/química , Cementos para Huesos/farmacología , Osteogénesis/efectos de los fármacos , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Diferenciación Celular/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Ratones , Osteoblastos/efectos de los fármacos , Osteoblastos/citología , Compuestos de Magnesio/química , Compuestos de Magnesio/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacología , FosfatosAsunto(s)
Antibacterianos , Cementos para Huesos , Pie Diabético , Cicatrización de Heridas , Quinasas Asociadas a rho , Pie Diabético/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Humanos , Antibacterianos/uso terapéutico , Cementos para Huesos/uso terapéutico , Cementos para Huesos/farmacología , Quinasas Asociadas a rho/metabolismo , Masculino , FemeninoRESUMEN
Many kinds of human tumors, including breast carcinomas, frequently metastasize to the bone, making it prone to pathologic fractures. Surgical management of bone metastases ranges from the resection of metastases to bone repair. Current surgical methods for the repair of bone defects include the use of polymethyl methacrylate (PMMA)-based bone cements. A promising alternative material are bioactive glass (BG) particles that in addition to providing physical stability can also induce bone regeneration. Moreover, BGs doped with Fe2O3may also have a negative impact on tumor cells. Here, we tested the hypothesis that BGs can affect metastatic human breast cancer cells. To this end, we assessed the effects of different BG compositions with and without Fe2O3on metastatic human MDA-MB-231 breast cancer cellsin vitro. We found that all BGs tested impaired the viability and proliferation of breast cancer cells in a concentration-dependent manner. The anti-proliferative effects inversely correlated with BG particle size, and were in general less pronounced in mesenchymal stromal cells (MSCs) that served as a control. Moreover, Fe2O3-doped BGs were more potent inhibitors of tumor cell proliferation and metabolic activity than Fe2O3-free BG. Our data therefore indicate that BGs can affect human breast cancer cells more strongly than MSCs, and suggest that the presence of Fe2O3can potentiate anti-proliferative and anti-metabolic effects of BGs. Fe2O3-doped BGs thus have the potential to be used for the surgical management of metastatic bone lesions, and may in addition to their regenerative properties also allow the local control of bone metastases.
Asunto(s)
Neoplasias Óseas , Neoplasias de la Mama , Proliferación Celular , Supervivencia Celular , Cerámica , Vidrio , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Proliferación Celular/efectos de los fármacos , Vidrio/química , Femenino , Línea Celular Tumoral , Cerámica/química , Cerámica/farmacología , Neoplasias Óseas/secundario , Neoplasias Óseas/metabolismo , Supervivencia Celular/efectos de los fármacos , Ensayo de Materiales , Hierro/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Células Madre Mesenquimatosas , Compuestos Férricos/química , Polimetil Metacrilato/química , Tamaño de la Partícula , Cementos para Huesos/química , Cementos para Huesos/farmacologíaRESUMEN
We investigated the possibility of loading PMMA bone cement with antimicrobial nanostructured AgNbO3 particles to counter biofilm formation at the cement-tissue interface. We found that a formulation containing (1-4)% AgNbO3 showed high antibacterial activity against Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa while not showing any toxicity against THP1 human cell lines. In addition, loading the particles did not impact the mechanical properties of the cement. The results thus obtained illustrate the potential of the approach to replace the current technique of mixing cement with conventional antibiotics, which is associated with shortcomings such as efficacy loss from antibiotic depletion.
Asunto(s)
Antibacterianos , Cementos para Huesos , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Polimetil Metacrilato , Pseudomonas aeruginosa , Staphylococcus aureus , Cementos para Huesos/química , Cementos para Huesos/farmacología , Polimetil Metacrilato/química , Polimetil Metacrilato/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Staphylococcus aureus/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Biopelículas/efectos de los fármacos , Nanopartículas/químicaRESUMEN
Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.
Asunto(s)
Cementos para Huesos , Péptido Relacionado con Gen de Calcitonina , Fosfatos de Calcio , Osteogénesis , Porcinos Enanos , Animales , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Cementos para Huesos/farmacología , Cementos para Huesos/química , Ratones , Porcinos , Péptido Relacionado con Gen de Calcitonina/metabolismo , Osteogénesis/efectos de los fármacos , Regeneración Ósea/efectos de los fármacos , Columna Vertebral/cirugía , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Línea Celular , Magnesio/farmacología , Magnesio/químicaAsunto(s)
Antibacterianos , Cementos para Huesos , Pie Diabético , Cicatrización de Heridas , Quinasas Asociadas a rho , Cicatrización de Heridas/efectos de los fármacos , Pie Diabético/tratamiento farmacológico , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Quinasas Asociadas a rho/metabolismo , Cementos para Huesos/uso terapéutico , Cementos para Huesos/farmacología , Masculino , Femenino , Persona de Mediana EdadRESUMEN
The present work reports the adsorption, release, antibacterial properties, and in vitro cytotoxicity of sodium fusidate (SF) associated with a carbonated calcium phosphate bone cement. The adsorption study of SF on cement powder compared to stoichiometric hydroxyapatite and nanocrystalline carbonated apatite was investigated to understand the interaction between this antibiotic and the calcium phosphate phases involved in the cement formulation and setting reaction. The adsorption data revealed a fast kinetic process. However, the evolution of the amount of adsorbed SF was well described by a Freundlich-type isotherm characterized by a low adsorption capacity of the materials toward the SF molecule. The in vitro release results indicated a prolonged and controlled SF release for up to 34 days. The SF amounts eluted daily were at a therapeutic level (0.5-2 mg/L) and close to the antibiotic minimum inhibitory concentration (0.1-0.9 mg/L). Furthermore, the release data fitting and modeling suggested that the drug release occurred mainly by a diffusion mechanism. The antibacterial activity showed the effectiveness of SF released from the formulated cements against Staphylococcus aureus. Furthermore, the biological in vitro study demonstrated that the tested cements didn't show any cytotoxicity towards human peripheral blood mononuclear cells and did not significantly induce inflammation markers like IL-8.
Asunto(s)
Antibacterianos , Cementos para Huesos , Fosfatos de Calcio , Liberación de Fármacos , Ácido Fusídico , Staphylococcus aureus , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Antibacterianos/toxicidad , Humanos , Staphylococcus aureus/efectos de los fármacos , Fosfatos de Calcio/química , Cementos para Huesos/química , Cementos para Huesos/farmacología , Adsorción , Ácido Fusídico/farmacología , Ácido Fusídico/química , Ácido Fusídico/administración & dosificación , Supervivencia Celular/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Leucocitos Mononucleares/efectos de los fármacos , CinéticaRESUMEN
Bone cement is widely used in clinical with optimistic filling and mechanical properties. However, the setting time of bone cement is difficult to accurately control, and the existing bone cements exhibit limited therapeutic functionalities. In response to these challenges, we designed and synthesized Nd-doped whitlockite (Nd-WH), endowing bone cement with photothermal-responsive and fluorescence imaging capabilities. The doping amount and photothermal properties of Nd-doped whitlockite were studied, and the composite bone cement was prepared. The results showed that the setting time of bone cement could be regulated by near infrared irradiation, and the multiple functions of promoting osteogenic differentiation, antibacterial and anti-tumor could be realized by adjusting the power and irradiation time of near infrared. By incorporating Nd-doped whitlockite and bone cement, we developed an all-in-one strategy to achieve setting time control, enhanced osteogenic ability, tumor cell clearance, bacterial clearance, and bone tissue regeneration. The optimized physical and mechanical properties of composite bone cement ensure adaptability and plasticity. In vitro and in vivo experiments validated the effectiveness of this bone cement platform for bone repair, tumor cell clearance and bacterial clearance. The universal methods to regulate the setting time and function of bone cement by photothermal effect has potential in orthopedic surgery and is expected to be a breakthrough in the field of bone defect repair. Further research and clinical validation are needed to ensure its safety, efficacy and sustainability. STATEMENT OF SIGNIFICANCE: Bone cement is a valuable clinical material. However, the setting time of bone cement is difficult to control, and the therapeutic function of existing bone cement is limited. Various studies have shown that the bone repair capacity of bone cements can be enhanced by synergistic stimulatory effects in vivo and ex vivo. Unfortunately, most of the existing photothermal conversion materials are non-degradable and poorly biocompatible. This study provides a bone-like photothermal conversion material with photothermal response and fluorescence imaging properties, and constructed a platform for integrated regulation of the setting time of bone cement and diversification of its functions. Therefore, it helps to design multi-functional bone repair materials that are more convenient and effective in clinical operation.
Asunto(s)
Cementos para Huesos , Rayos Infrarrojos , Compuestos de Magnesio , Fosfatos , Cementos para Huesos/química , Cementos para Huesos/farmacología , Animales , Fosfatos/química , Fosfatos/farmacología , Compuestos de Magnesio/química , Compuestos de Magnesio/farmacología , Regeneración Ósea/efectos de los fármacos , Ratones , Osteogénesis/efectos de los fármacos , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/químicaRESUMEN
Considering the shortcomings of known medical hemostatic materials such as bone wax for bleeding bone management, it is essential to develop alternative bone materials capable of efficient hemostasis and bone regeneration and adaptable to clinical surgical needs. Thus, in the current work, a calcium sulfate hemihydrate and starch-based composite paste was developed and optimized. Firstly, it was found that the use of hydroxypropyl distarch phosphate (HDP) coupled with pregelatinization could generate an injectable, malleable and self-hardening paste with impressive anti-collapse ability in a dynamic aqueous environment, suggesting its potential applicability in both open and minimally invasive clinical practice. The as-hardened matrix exhibited a compressive strength of up to 61.68 ± 5.13 MPa compared to calcium sulfate cement with a compressive strength of 15.16 ± 2.42 MPa, making it a promising candidate for the temporary mechanical stabilization of bone defects. Secondly, the as-prepared paste revealed superior hemostasis and bone regenerative capabilities compared to calcium sulfate cement and bone wax, with greatly enhanced bleeding management and bone healing outcomes when subjected to testing in in vitro and in vivo models. In summary, our results confirmed that calcium sulfate bone cement reinforced with the selected starch can act as a reliable platform for bleeding bone treatment, overcoming the limitations of traditional bone hemostatic agents.
Asunto(s)
Cementos para Huesos , Sulfato de Calcio , Cementos para Huesos/química , Cementos para Huesos/farmacología , Sulfato de Calcio/química , Sulfato de Calcio/farmacología , Animales , Regeneración Ósea/efectos de los fármacos , Hemorragia/tratamiento farmacológico , Almidón/química , Almidón/análogos & derivados , Almidón/farmacología , Ratones , Hemostáticos/farmacología , Hemostáticos/química , Hemostáticos/administración & dosificación , Fuerza Compresiva , Fosfatos/química , Masculino , Gelatina/química , Ratas , ConejosRESUMEN
Antibiotic-loaded calcium phosphate cement (CPC) has emerged as a promising biomaterial for drug delivery in orthopedics. However, there are problems such as the burst release of antibiotics, low cumulative release ratio, inappropriate release cycle, inferior mechanical strength, and poor anti-collapse properties. In this research, montmorillonite-gentamicin (MMT-GS) was fabricated by solution intercalation method and served as the drug release pathways in CPC to avoid burst release of GS, achieving promoted cumulative release ratios and a release cycle matched the time of inflammatory response. The results indicated that the highest cumulative release ratio and release concentration of GS in CPC/MMT-GS was 94.1 ± 2.8â¯% and 1183.05⯵g/mL, and the release cycle was up to 504â¯h. In addition, the hierarchical GS delivery system was divided into three stages, and the kinetics followed the Korsmeyer-Peppas model, the zero-order model, and the diffusion-dissolution model, respectively. Meanwhile, the compressive strength of CPC/MMT-GS was up to 51.33 ± 3.62â¯MPa. Antibacterial results demonstrated that CPC/MMT-GS exhibited excellent in vitro long-lasting antibacterial properties to E. coli and S. aureus. Furthermore, CPC/MMT-GS promoted osteoblast proliferation and exhibited excellent in vivo histocompatibility. Therefore, CPC/MMT-GS has favorable application prospects in the treatment of bone defects with bacterial infections and inflammatory reactions.
Asunto(s)
Antibacterianos , Bentonita , Cementos para Huesos , Fosfatos de Calcio , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Escherichia coli , Gentamicinas , Staphylococcus aureus , Bentonita/química , Antibacterianos/farmacología , Antibacterianos/química , Gentamicinas/farmacología , Gentamicinas/química , Gentamicinas/administración & dosificación , Gentamicinas/farmacocinética , Fosfatos de Calcio/química , Cementos para Huesos/química , Cementos para Huesos/farmacología , Animales , Escherichia coli/efectos de los fármacos , Ratones , Staphylococcus aureus/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Tamaño de la PartículaRESUMEN
Median sternotomy surgery stands as one of the prevailing strategies in cardiac surgery. In this study, the cutting-edge bone adhesive is designed, inspired by the impressive adhesive properties found in mussels and sandcastle worms. This work has created an osteogenic nanocomposite coacervate adhesive by integrating a cellulose-polyphosphodopamide interpenetrating network, quaternized chitosan, and zinc, gallium-doped hydroxyapatite nanoparticles. This adhesive is characterized by robust catechol-metal coordination which effectively adheres to both hard and soft tissues with a maximum adhesive strength of 900 ± 38 kPa on the sheep sternum bone, surpassing that of commercial bone adhesives. The release of zinc and gallium cations from nanocomposite adhesives and quaternized chitosan matrix imparts remarkable antibacterial properties and promotes rapid blood coagulation, in vitro and ex vivo. It is also proved that this nanocomposite adhesive exhibits significant in vitro bioactivity, stable degradability, biocompatibility, and osteogenic ability. Furthermore, the capacity of nanocomposite coacervate to adhere to bone tissue and support osteogenesis contributes to the successful healing of a sternum bone defect in a rabbit model in vivo. In summary, these nanocomposite coacervate adhesives with promising characteristics are expected to provide solutions to clinical issues faced during median sternotomy surgery.
Asunto(s)
Nanocompuestos , Osteogénesis , Esternotomía , Animales , Nanocompuestos/química , Esternotomía/efectos adversos , Conejos , Osteogénesis/efectos de los fármacos , Ovinos , Quitosano/química , Quitosano/farmacología , Hemorragia/prevención & control , Antibacterianos/química , Antibacterianos/farmacología , Adhesivos Tisulares/química , Adhesivos Tisulares/farmacología , Durapatita/química , Cementos para Huesos/química , Cementos para Huesos/farmacología , Adhesivos/química , Adhesivos/farmacologíaRESUMEN
Degenerative spinal pathology is a widespread medical issue, and spine fusion surgeries are frequently performed. In this study, we fabricated an injectable bioactive click chemistry polymer cement for use in spinal fusion and bone regrowth. Taking advantages of the bioorthogonal click reaction, this cement can be crosslinked by itself eliminating the addition of a toxic initiator or catalyst, nor any external energy sources like UV light or heat. Furthermore, nano-hydroxyapatite (nHA) and microspheres carrying recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human vascular endothelial growth factor (rhVEGF) were used to make the cement bioactive for vascular induction and osteointegration. After implantation into a rabbit posterolateral spinal fusion (PLF) model, the cement showed excellent induction of new bone formation and bridging bone, achieving results comparable to autograft control. This is largely due to the osteogenic properties of nano-hydroxyapatite (nHA) and the released rhBMP-2 and rhVEGF growth factors. Since the availability of autograft sources is limited in clinical settings, this injectable bioactive click chemistry cement may be a promising alternative for spine fusion applications in addressing various spinal conditions.
Asunto(s)
Cementos para Huesos , Proteína Morfogenética Ósea 2 , Química Clic , Fumaratos , Poliésteres , Polipropilenos , Fusión Vertebral , Factor A de Crecimiento Endotelial Vascular , Animales , Conejos , Cementos para Huesos/química , Cementos para Huesos/farmacología , Proteína Morfogenética Ósea 2/farmacología , Proteína Morfogenética Ósea 2/administración & dosificación , Polipropilenos/química , Poliésteres/química , Humanos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/farmacología , Fumaratos/química , Durapatita/química , Durapatita/farmacología , Proteínas Recombinantes/farmacología , Inyecciones , Materiales Biocompatibles/química , Factor de Crecimiento Transformador betaRESUMEN
Although calcium phosphate has been extensively utilized in orthopedic applications such as spine, limbs, dentistry, and maxillofacial surgery, the lack of osteoinductive properties often hinders its effectiveness in treating bone defects resulting from pathological micro-environment such as tumor surgery, osteoporosis, osteomyelitis, and diabetic. Therefore, a novel bone cement based on magnesium-doped bioactive glass was developed in this study. The moderate release of magnesium ions improved the mechanical properties by controlling the crystal size of hydroxyapatite. Through detailed discussion of element content and heat treatment temperature, it was found that 2Mg-BG-800 was suitable for the construction of bone cement. 2Mg-BG-BC exhibited favorable initial (15 min) and final (30 min) setting time, compressive strength (29.45 MPa), compressive modulus (1851.49 MPa), injectability, and shape-adaptability. Furthermore, Mg-BG-BC demonstrated the ability to enhance the osteogenic differentiation of BMSCs, and induce macrophage polarization towards the M2 phenotype, suggesting its potential for osteoporotic fracture regeneration.
Asunto(s)
Cementos para Huesos , Vidrio , Magnesio , Osteogénesis , Cementos para Huesos/química , Cementos para Huesos/farmacología , Magnesio/química , Magnesio/farmacología , Osteogénesis/efectos de los fármacos , Animales , Vidrio/química , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/inmunología , Diferenciación Celular/efectos de los fármacos , Ratones , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ensayo de Materiales , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Fuerza CompresivaRESUMEN
Although calciummagnesium phosphate cements (CMPCs) have been widely applied to treating critical-size bone defects, their repair efficiency is unsatisfactory owing to their weak surface bioactivity and uncontrolled ion release. In this study, we lyophilized alginate sodium (AS) as a coating onto HAp/K-struvite (H@KSv) to develop AS/HAp/K-struvite (AH@KSv), which promotes bone regeneration. The compressive strength and hydrophilicity of AH@KSv significantly improved, leading to enhanced cell adhesion in vitro. Importantly, the SA coating enables continuous ions release of Mg2+ and Ca2+, finally leading to enhanced osteogenesis in vitro/vivo and different patterns of new bone ingrowth in vivo. Furthermore, these composites increased the expression levels of biomarkers of the TRPM7/PI3K/Akt signaling pathway via an equilibrium effect of Mg2+ to Ca2+. In conclusion, our study provides novel insights into the mechanisms of Mg-based biomaterials for bone regeneration.