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1.
Biomed Mater ; 16(5)2021 08 19.
Article En | MEDLINE | ID: mdl-34410226

Poly(methyl methacrylate) (PMMA) has been widely used in orthopedic applications, but bone ingrowth and toxic monomer release are drawback of this material. Particle reinforcement with osteoconductive substitute, such as calcium sulfate (CaSO4), is one of the solutions used to modify PMMA bone cement. The current study investigated the mechanical, chemical and biological properties of CaSO4-augmented bone cement. Mechanical strength was measured by a material testing machine. The concentration of methyl methacrylate (MMA) monomer from the various formulations of PMMA mixed with CaSO4was measured by ultra-performance liquid chromatography (UPLC). CCK-8 assay and ALP assay were performed to evaluate cytotoxicity of released MMA monomer and cell differentiation. The attachment of cells to CaSO4-augmented bone cement discs was observed by confocal and scanning electron microscopy, and surface topography was also evaluated by atomic force microscopy. The results revealed that increased CaSO4weight ratios led to compromised mechanical strength and increased MMA monomer release. Cell density and cell differentiation on CaSO4-augmented bone cement discs were decreased at CaSO4weight ratios above 10%. In addition, the presence of micropores on the surface and surface roughness were both increased for PMMA composite discs containing higher levels of CaSO4. These results demonstrated that fewer MC3T3-E1 cells on the surface of CaSO4-PMMA composites was correlated to increased MMA monomer release, micropore number and surface roughness. In summary, the augmentation of a higher proportion of CaSO4(>10 wt. %) to PMMA did not promote the biological properties of traditional PMMA bone cement.


Bone Cements , Calcium Sulfate , Cell Adhesion/drug effects , Polymethyl Methacrylate , Animals , Bone Cements/chemistry , Bone Cements/pharmacology , Bone Cements/toxicity , Calcium Sulfate/chemistry , Calcium Sulfate/pharmacology , Calcium Sulfate/toxicity , Cell Line , Cell Proliferation/drug effects , Cell Survival/drug effects , Mice , Osteoblasts/drug effects , Polymethyl Methacrylate/chemistry , Polymethyl Methacrylate/pharmacology , Polymethyl Methacrylate/toxicity , Surface Properties
2.
Biomed Mater ; 16(1): 015009, 2020 12 16.
Article En | MEDLINE | ID: mdl-32693390

Calcium sulfate (CS) bone cements have been used as bone substitutes for a long time, but their clinical use is currently limited due to their rapid degradation rate and brittleness. This work aimed to study the effect of α-tricalcium phosphate (α-TCP) and silk fibroin nanofibers (SFF) on CS bone cements. The bone cements were prepared from α-CS hemihydrate (α-CSH), calcium sulfate dihydrate (CSD; as a setting accelerator) and varying α-TCP contents (0%, 5%, 10%, 15%, 20% and 25%), with SFF solution or deionized water as the solidification solution at the same liquid/solid ratio. Scanning electron microscopy, particle size distribution, x-ray diffraction and Fourier transform infrared spectroscopy were used to measure the composition and characterize the properties of the materials. The compressive strength, setting time and weight loss rate of samples were also tested. Cytotoxicity was evaluated by a Cell Counting Kit-8 assay. The results suggest that the tuning of α-TCP and SFF has an important role in determining the compressive strength and degradation rate of CS bone cements, and the properties could be changed by varying the content of α-TCP. Moreover, cell experiments showed no toxicity of the samples towards MC3T3 cells. Thus, the materials prepared from α-CSH, CSD, α-TCP and SFF in this work could provide the basis for research into CS-based bone repair materials.


Bone Cements/chemistry , Calcium Phosphates/chemistry , Calcium Sulfate/chemistry , Fibroins/chemistry , 3T3 Cells , Absorbable Implants/adverse effects , Animals , Biomedical Engineering , Bone Cements/toxicity , Bone Substitutes/chemistry , Bone Substitutes/toxicity , Calcium Phosphates/toxicity , Calcium Sulfate/toxicity , Cell Proliferation/drug effects , Compressive Strength , Fibroins/toxicity , Humans , Materials Testing , Mice , Microscopy, Electron, Scanning , Nanofibers/chemistry , Nanofibers/toxicity , Nanofibers/ultrastructure , Particle Size , Spectroscopy, Fourier Transform Infrared , Surface Properties , X-Ray Diffraction
3.
Article En | MEDLINE | ID: mdl-32265039

Dental technicians may be chronically exposed to methyl methacrylate (MMA), used in the production of dental prostheses. We have studied whether occupational exposure to MMA affects genotoxicity biomarkers such as 8-OHdG formation, comet assay, and buccal micronucleus frequency. MMA exposure was assessed via ambient air analysis. Although no significant differences between exposed and non-exposed individuals were seen with respect to blood genotoxicity measurements, we found a higher level of buccal-cell anomalies in the exposed group.


Bone Cements/toxicity , Dental Technicians , Methylmethacrylate/toxicity , Micronuclei, Chromosome-Defective/drug effects , Mouth Mucosa/drug effects , 8-Hydroxy-2'-Deoxyguanosine/blood , Adult , Case-Control Studies , Comet Assay , DNA Damage , Female , Humans , Male , Micronucleus Tests , Mouth Mucosa/cytology , Occupational Exposure/analysis
4.
BMC Musculoskelet Disord ; 20(1): 539, 2019 Nov 13.
Article En | MEDLINE | ID: mdl-31722711

BACKGROUND: The objective of this study was to evaluate the impact of a single- vs. double-layer cementing technique on morphological cementation and the generation of microscopic cement layers or loose cement fragments in unicompartmental knee arthroplasty (UKA). METHODS: UKAs were implanted in 12 cadaver knees. The specimens were divided into two groups of comparable bone mineral density. Six UKAs were implanted using a single-layer cementing technique (group A) and six UKAs were implanted using a double-layer cementing technique (group B). Morphological cementation was assessed on nine cuts through the implant-cement-bone interface in the frontal plane. Loose bone cement fragments and the microscopically quality of layer formation were evaluated. RESULTS: Contact between bone and prosthesis was observed in 45.4% of interfaces in group A and 27.8% in group B (p = 0.126). The significant increase of areas without visible cement interlocking in the anteroposterior direction in group A (p = 0.005) was not evident in group B (p = 0.262). Penetration around the peg tended to occur more frequently in group B (67.5% vs. 90.6% p = 0.091). Scanning electron microscopy identified no evidence of fissure formations within the bilaminar cement mantle. Free bone cement fragments were documented in 66.7% in both groups with no difference concerning mass (p = 1.0). CONCLUSIONS: This in-vitro study showed a tendency towards a more homogenous cementation of tibial UKAs using a double-layer cementing technique, although most of the differences did not reach the level of significance. However, theoretical downsides of the double-layer cementing technique such as an increased formation of free bone fragments or a microscopically fissure formation within the cement layer could not be detected either.


Arthroplasty, Replacement, Knee/methods , Bone Cements/pharmacology , Knee Joint/surgery , Tibia/surgery , Aged , Aged, 80 and over , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/instrumentation , Bone Cements/toxicity , Bone Density , Cadaver , Female , Humans , Knee Joint/diagnostic imaging , Knee Prosthesis , Male , Middle Aged , Prosthesis Design , Tibia/diagnostic imaging , Tomography, X-Ray Computed
5.
Braz Oral Res ; 33: e042, 2019.
Article En | MEDLINE | ID: mdl-31508725

This study evaluated the cytotoxicity and biocompatibility of a new bioceramic endodontic sealer (i.e., Sealer Plus BC) in comparison with those of MTA Fillapex and AH Plus. L929 fibroblasts were cultured and Alamar Blue was used to evaluate cell viability of diluted extracts (1:50, 1:100, and 1:200) from each sealer at 24 h. Polyethylene tubes that were filled with material or empty (as a control) were implanted in the subcutaneous tissue of rats. The rats were killed after 7 and 30 d (n = 8), and the tubes were removed for histological analysis. Parametric data was analyzed using a one-way ANOVA test, and nonparametric data was analyzed via the Kruskal-Wallis test followed by the Dunn test (p < 0.05). A reduction in cell viability was observed in the extracts that were more diluted for Sealer Plus BC when compared to that of Control and AH Plus (p < 0.05). However, the 1:50 dilution of the Sealer Plus BC was similar to that of the Control (p > 0.05). Conversely, more diluted extracts of MTA Fillapex (1:200) and AH Plus (1:100 and 1:200) were similar to the Control (p > 0.05). Histological analysis performed at 7 d did not indicate any significant difference between tissue response for all materials, and the fibrous capsule was thick (p > 0.05). At 30 d, Sealer Plus BC was similar to the Control (p > 0.05) and MTA Fillapex and AH Plus exhibited greater inflammation than the Control (p < 0.05). The fibrous capsule was thin for the Control and for most specimens of Sealer Plus BC and AH Plus. Thus, Sealer Plus BC is biocompatible when compared to MTA Fillapex and AH Plus, and it is less cytotoxic when less-diluted extracts are used.


Bone Cements/chemistry , Calcium Hydroxide/chemistry , Ceramics/chemistry , Root Canal Filling Materials/chemistry , Aluminum Compounds/chemistry , Animals , Biocompatible Materials , Bone Cements/pharmacology , Bone Cements/toxicity , Calcium Compounds/chemistry , Calcium Hydroxide/pharmacology , Calcium Hydroxide/toxicity , Cell Survival/drug effects , Cells, Cultured/drug effects , Drug Combinations , Epoxy Resins/chemistry , Fibroblasts/drug effects , In Vitro Techniques , Inflammation , Male , Materials Testing , Oxides/chemistry , Rats, Wistar , Root Canal Filling Materials/toxicity , Silicates/chemistry , Subcutaneous Tissue/pathology
6.
J Biomed Mater Res A ; 107(12): 2835-2847, 2019 12.
Article En | MEDLINE | ID: mdl-31433892

Poly(methyl methacrylate) (PMMA) bone cement is the most widely used grouting material in the joint arthroplasties and vertebroplasties. The present investigation has been carried out to scavenge the radicals and monomer by addition of an antioxidant to minimize the toxicity of bone cement (BC). The in silico studies were employed to determine the potent natural antioxidant at physiological conditions. The antioxidant methionine demonstrated a strong binding affinity with free radicals and methyl methacrylate (MMA) monomer than cysteine. The designated amount of methionine was optimized by various assay methods and >2% methionine shows strong scavenging capacity in BC. Moreover, the antioxidant-loaded BC (ABC) demonstrated similar handling, physicochemical and mechanical properties to pristine bone cement. Significantly, the developed formulation shows superior biological characteristics such as cell proliferation (2 ± 1 BC and 6 ± 1 ABC), adhesion (0.32 ± 0.02 BC and 0.54 ± 0.01 ABC), and cell viability (81 ± 2% BC and 93 ± 1% ABC) toward human osteoblast-like cells (MG-63). Therefore, the novel antioxidant bone cement is a potential candidate for various orthopedic applications to eliminate the adverse effects, related to residual toxic radical and monomer in bone cement.


Antioxidants/pharmacology , Bone Cements/pharmacology , Methionine/pharmacology , Polymethyl Methacrylate/pharmacology , Antioxidants/chemistry , Bone Cements/chemistry , Bone Cements/toxicity , Cell Line , Cell Proliferation/drug effects , Cell Survival/drug effects , Humans , Materials Testing , Methionine/chemistry , Osteoblasts/cytology , Osteoblasts/drug effects , Polymethyl Methacrylate/chemistry , Polymethyl Methacrylate/toxicity
7.
J Mater Sci Mater Med ; 30(5): 54, 2019 Apr 30.
Article En | MEDLINE | ID: mdl-31041537

The in vitro cytotoxicity of both the multiwalled carbon nanotubes (MWCNT) in suspension with culture medium and the tetracalcium phosphate/monetite cement with addition of 0.8 wt% of MWCNTs on fibroblasts and osteoblasts were studied. The cytotoxicity was evaluated by MTS test (formazan) and live/dead staining. No cytotoxicity of MWCNT extract was measured contrary to about 60% reduction in proliferation of fibroblasts in MWCNT suspension as compared with negative control. The several contact cytotoxicity of MWCNT composite cement surfaces on seeded cells was demonstrated by MTS test and live/dead staining of damaged fibroblasts and dead osteoblasts after 72 h of culture. The detailed microstructure analysis showed a significant refinement of the surface texture due to the formation of thin needle-like hydroxyapatite particles on MWCNTs and this effect could be responsible for cytotoxicity of composites.


Bone Cements/chemistry , Bone Cements/toxicity , Calcium Phosphates/chemistry , Calcium Phosphates/toxicity , Nanotubes, Carbon/chemistry , Nanotubes, Carbon/toxicity , Animals , Biocompatible Materials , Cell Line , Cell Survival/drug effects , Materials Testing , Mice
8.
Bone ; 123: 86-91, 2019 06.
Article En | MEDLINE | ID: mdl-30904629

Cytokines and growth factors mediate inflammatory osteolysis in response to particles released from bone implants. However, the mechanism by which this process develops is not entirely clear. Blood vessels and related factors may be required to deliver immune cells and soluble factors to the injury site. Therefore, in the current study we investigated if, vascular endothelial growth factor (VEGF), which is required for angiogenesis, mediates polymethylmethacrylate (PMMA) particles-induced osteolysis. Using bone marrow derived macrophages (BMMs) and ST2 stromal cell line, we show that PMMA particles increase VEGF expression. Further, using a murine calvarial osteolysis model, we found that PMMA injection over calvaria induce significant increase in VEGF expression as well as new vessel formation, represented by von Willebrand factor (vWF) staining. Co-treatment using a VEGF-neutralizing antibody abrogated expression of vWF, indicating decreased angiogenesis. Finally, VEGF neutralizing antibody reduced expression of Tumor necrosis factor (TNF) and decreased osteoclastogenesis induced by PMMA particles in calvariae. This work highlights the significance of angiogenesis, specifically VEGF, as key driver of PMMA particle-induced inflammatory osteolysis, inhibition of which attenuates this response.


Drug Delivery Systems/methods , Osteolysis/chemically induced , Osteolysis/prevention & control , Polymethyl Methacrylate/toxicity , Skull/drug effects , Vascular Endothelial Growth Factor A/biosynthesis , Animals , Bone Cements/toxicity , Cells, Cultured , Female , Male , Mice , Mice, Inbred C57BL , Microspheres , Osteolysis/metabolism , Random Allocation , Skull/metabolism , Vascular Endothelial Growth Factor A/agonists , Vascular Endothelial Growth Factor A/antagonists & inhibitors
9.
J Mech Behav Biomed Mater ; 94: 42-50, 2019 06.
Article En | MEDLINE | ID: mdl-30856478

In recent years, the magnesium phosphate cements showed impressive advantages for their setting property, mechanical strength, and resorption rate in laboratory investigation. While it remained a big challenge to develop the magnesium phosphate cements with ideal self-setting properties, sufficient mechanical strength, excellent biocompatibility, and osteoinductivity for clinical application. In our work, we prepared the magnesium calcium phosphate cement (MCPC) using the MgO, KH2P2O4, and Ca(H2PO4)2 particles with the citric acid added. The citric acid was adopted to modify the setting time and compressive strength of the MCPC, which were investigated by the X-ray diffractometer and scanning electron microscopy. The cytocompatibility and osteoinductivity of the modified cements were evaluated by the MC3T3-E1 cells proliferation and morphology, alkaline phosphatase assay, alizarin red staining and western blot assay. The results demonstrated that the citric acid modified MCPC was featured of satisfactory setting time, ideal mechanical strength, good cytocompatibility and osteoinductivity, indicating its potential application for bone regeneration.


Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Citric Acid/chemistry , Magnesium/chemistry , Materials Testing , Osteogenesis/drug effects , 3T3 Cells , Animals , Bone Cements/chemistry , Bone Cements/pharmacology , Bone Cements/toxicity , Calcium Phosphates/toxicity , Cell Proliferation/drug effects , Compressive Strength , Mice , Physical Phenomena
10.
J Mech Behav Biomed Mater ; 91: 229-236, 2019 03.
Article En | MEDLINE | ID: mdl-30597376

Inorganic phosphate cements have become prevalent as bone filling materials in clinical applications, owing to beneficial properties such as self-setting, biodegradability and osteoconductivity. However, the further development of phosphate cements with higher strength and improved cytocompatibility is expected. In this paper, we reported the preparation of a novel magnesium phosphate based cement (MPBC), which has similar compositions with magnesium phosphate cement (MPC) but Ca(H2PO4)2·H2O and citric acid were additionally added to modulate the performance. The physicochemical and biological properties of MPBC were investigated, the influences of the added Ca(H2PO4)2·H2O and citric acid on the performances of MPBC were analyzed, and the differences of performance between MPBC and MPC were discussed. Experimental results show that the setting time and compressive strength of MPBC were effectively enhanced by the addition of citric acid. In vitro biological degradation indicates that about 15 wt% of MPBC was reduced in 4 weeks. Compared with MPC, MPBC has weaker alkalinity and less dissolution of phosphate, leading to better suitability for cell proliferation and adhesion. These results suggest that as a bone filling material, MPBC shows better performance than MPC in many key indicators and has promising application prospects.


Bone Cements/chemistry , Calcium Phosphates/chemistry , Citric Acid/chemistry , Magnesium Compounds/chemistry , Materials Testing , Mechanical Phenomena , Phosphates/chemistry , Animals , Bone Cements/toxicity , Compressive Strength , Hydrogen-Ion Concentration , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Mice
11.
Braz. oral res. (Online) ; 33: e042, 2019. tab, graf
Article En | LILACS | ID: biblio-1001597

Abstract: This study evaluated the cytotoxicity and biocompatibility of a new bioceramic endodontic sealer (i.e., Sealer Plus BC) in comparison with those of MTA Fillapex and AH Plus. L929 fibroblasts were cultured and Alamar Blue was used to evaluate cell viability of diluted extracts (1:50, 1:100, and 1:200) from each sealer at 24 h. Polyethylene tubes that were filled with material or empty (as a control) were implanted in the subcutaneous tissue of rats. The rats were killed after 7 and 30 d (n = 8), and the tubes were removed for histological analysis. Parametric data was analyzed using a one-way ANOVA test, and nonparametric data was analyzed via the Kruskal-Wallis test followed by the Dunn test (p < 0.05). A reduction in cell viability was observed in the extracts that were more diluted for Sealer Plus BC when compared to that of Control and AH Plus (p < 0.05). However, the 1:50 dilution of the Sealer Plus BC was similar to that of the Control (p > 0.05). Conversely, more diluted extracts of MTA Fillapex (1:200) and AH Plus (1:100 and 1:200) were similar to the Control (p > 0.05). Histological analysis performed at 7 d did not indicate any significant difference between tissue response for all materials, and the fibrous capsule was thick (p > 0.05). At 30 d, Sealer Plus BC was similar to the Control (p > 0.05) and MTA Fillapex and AH Plus exhibited greater inflammation than the Control (p < 0.05). The fibrous capsule was thin for the Control and for most specimens of Sealer Plus BC and AH Plus. Thus, Sealer Plus BC is biocompatible when compared to MTA Fillapex and AH Plus, and it is less cytotoxic when less-diluted extracts are used.


Animals , Male , Root Canal Filling Materials/chemistry , Bone Cements/chemistry , Calcium Hydroxide/chemistry , Ceramics/chemistry , Oxides/chemistry , Root Canal Filling Materials/toxicity , Biocompatible Materials , Bone Cements/toxicity , Bone Cements/pharmacology , In Vitro Techniques , Materials Testing , Calcium Hydroxide/toxicity , Calcium Hydroxide/pharmacology , Cell Survival/drug effects , Cells, Cultured/drug effects , Rats, Wistar , Silicates/chemistry , Calcium Compounds/blood , Aluminum Compounds/chemistry , Subcutaneous Tissue/pathology , Drug Combinations , Epoxy Resins/chemistry , Fibroblasts/drug effects , Inflammation
12.
PLoS One ; 13(12): e0207753, 2018.
Article En | MEDLINE | ID: mdl-30543660

INTRODUCTION: Antibiotic-loaded poly(methyl methacrylate) bone cements (ALBCs) are widely used in total joint replacement (TJR), for local delivery of antibiotics to provide prophylaxis against prosthetic joint infections (PJI). One of the shortcomings of the current generation of ALBCs is that the antibiotic release profile is characterized by a burst over the first few hours followed by a sharp decrease in rate for the following several days (often below minimum inhibitory concentration (MIC)), and, finally, exhaustion (after, typically, ~ 20 d). This profile means that the ALBCs provide only short-term antimicrobial action against bacterial strains involved PJI. RATIONALE: The purpose of the present study was to develop an improved antibiotic delivery system for an ALBC. This system involved using a layer-by-layer technique to load the antibiotic (gentamicin sulphate) (GEN) on silica nanoparticles, which are then blended with the powder of the cement. Then, the powder was mixed with the liquid of the cement (NP-GEN cement). For controls, two GEN-loaded brands were used (Cemex Genta and Palacos R+G). Gentamicin release and a host of other relevant properties were determined for all the cements studied. RESULTS: Compared to control cement specimens, improved GEN release, longer antimicrobial activity (against clinically-relevant bacterial strains), and comparable setting time, cytocompatibility, compressive strength (both prior to and after aging in PBS at 37 oC for 30 d), 4-point bend strength and modulus, fracture toughness, and PBS uptake. CONCLUSIONS: NP-GEN cement may have a role in preventing or treating PJI.


Anti-Infective Agents/administration & dosage , Anti-Infective Agents/pharmacokinetics , Bone Cements , Drug Delivery Systems , Gentamicins/administration & dosage , Anti-Infective Agents/toxicity , Bone Cements/chemistry , Bone Cements/toxicity , Cell Line , Cell Survival/drug effects , Compressive Strength , Gentamicins/pharmacokinetics , Gentamicins/toxicity , Humans , Materials Testing , Microbial Sensitivity Tests , Nanoparticles/chemistry , Nanotechnology , Osteoblasts/cytology , Osteoblasts/drug effects , Osteoblasts/metabolism , Polymethyl Methacrylate/chemistry , Polymethyl Methacrylate/toxicity , Prosthesis-Related Infections/prevention & control , Rheology , Silicon Dioxide
13.
J Biomed Mater Res B Appl Biomater ; 106(3): 1245-1257, 2018 04.
Article En | MEDLINE | ID: mdl-28580716

In most minimally-invasive procedures used to address severe pain arising from compression fractures of the vertebral bodies, such as percutaneous vertebroplasty (PVP), a poly(methyl methacrylate) (PMMA) bone cement is used. Shortcomings of this type of cement, such as high exotherm temperature and lack of bioactivity, are well known. We prepared different formulations of a composite bone cement, whose solid constituents consisted of PMMA beads and particles of a bioactive glass (BG), where 0-20%(w/w) of the calcium component was substituted by strontium. The difference between the formulations was in the relative amounts of the solid phase constituents and in the Sr-content of BG. We determined the influence of the mixture of solid phase constituents of the cement formulation on a collection of properties, such as maximum exotherm temperature (Tmax ), setting time (tset ), and injectability (I). The selection of the PMMA beads was crucial to obtain cement composite formulations capable to be efficiently injected. Results allowed to select nine solid phase mixtures to be further tested. Then, we determined the influence of the composition of these composite bone cements on Tmax , tset , I, and cell proliferation. The results showed that the performance of various of the selected composite cements was better than that of PMMA cement reference, with lower Tmax , lower tset , and higher I. We found that incorporation of Sr-substituted BGs into these materials bestows bioactivity properties associated with the role of Sr in bone formation, leading to some composite cement formulations that may be suitable for use in PVP. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1245-1257, 2018.


Bone Cements , Composite Resins , Polymethyl Methacrylate/chemistry , Strontium/chemistry , Biocompatible Materials , Bone Cements/toxicity , Cell Survival/drug effects , Composite Resins/toxicity , Compressive Strength , Glass , Humans , Injections , Materials Testing , Particle Size , Powders , Rheology , Strontium/toxicity , Vertebroplasty , Viscosity
14.
Biomed Mater ; 13(2): 025023, 2018 02 08.
Article En | MEDLINE | ID: mdl-28972203

Calcium phosphate cement has been widely investigated as a bone graft substitute due to its excellent self-setting ability, biocompatibility, osteoconductivity and moldability. In addition, mesoporous materials have been studied as potential materials for application in medical devices due to their large surface area, which is capable of loading numerous biological molecules, besides being bioactive. In this study, bone ß-TCP-MCPM-based injectable cement with mesoporous silica particles was synthesized and characterized in terms of its mechanical properties, microstructure, porosity, injectability, in vitro bioactivity and degradability; together with toxicity effects in CHO-K1 cell culture. The results showed that the ß-TCP-MCPM cement is bioactive after soaking in simulated body fluid solution, and mesoporous silica particles provided better physicochemical properties compared with silica-free cement. Toxicity assays showed low CHO-K1 cell viability after treatment with more concentrated extracts (200 mg ml-1). However, this behavior did not compromise the reproductive capacity and did not promote significant DNA damage in those cells. In conclusion, the ß-TCP-MCPM cement associated with mesoporous silica might be considered as a potential bone substitute for the repair and regeneration of bone defects.


Bone Cements/chemistry , Bone Regeneration/drug effects , Bone Substitutes/chemistry , Calcium Phosphates/chemistry , Silicon Dioxide/chemistry , Animals , Body Fluids , Bone Cements/toxicity , CHO Cells , Comet Assay , Cricetinae , Cricetulus , DNA Damage , Injections , Materials Testing , Micronucleus Tests , Porosity , Regeneration , Stress, Mechanical
15.
Biomed Mater ; 12(1): 015022, 2017 02 03.
Article En | MEDLINE | ID: mdl-28157719

A new bioactive calcium sulfate-based formulation (named 'BioCaS') has been developed for bone filler applications. This is a self-setting injectable cement where the preset form comprises bassanite obtained from the uniform submicron-sized precursor crystals of gypsum, modified with hydrogen orthophosphate ions. The results of the safety and efficacy evaluation of BioCaS cement, done as per the International Standards and guidelines, are presented in this paper. The study plan consisted of in vitro screening tests of cytotoxicity and haemolysis and in vivo biocompatibility evaluation, including an acute systemic toxicity test (in mice), an intracutaneous reactivity test (in rabbits), a pyrogen test (in rabbits) and a maximization sensitization test (in guinea pigs). The efficacy of the material in healing bone defects was investigated by implanting it in artificially created defects in rabbit femora, with clinically established hydroxyapatite porous ceramic as the control, followed by histological analysis at 12, 26 and 52 weeks. Set BioCaS cement consisted of hydrogen orthophosphate incorporating low-dimensional gypsum crystal lattices, the bioactivity of which has been identified by immersion in simulated body fluid. BioCaS was proved to be non-cytotoxic and non-haemolytic in the screening tests. In the live/dead assay, human osteoblast-like human osteosarcoma cells adhered well and spread on the surface of the material, attaining typical morphology and affirming the bone cell compatibility of the material. In the biocompatibility evaluation there were no acute systemic effects and the material proved non-pyrogenic. There was no intracutaneous erythemic or oedematous reactivity and no hypersensitivity observed in the Magnusson-Kligman method. The material satisfied the biocompatibility requirements. Bone implantation study revealed BioCaS to be osteoconductive and its efficacy of healing the experimental bone defects in rabbit femora is on a par with that of hydroxyapatite ceramic. The material resorbed at a pace matching that of new bone formation. This property of osteotransductivity will help the defect to heal and gain strength faster.


Bone Cements/chemistry , Calcium Sulfate/chemistry , Animals , Biocompatible Materials/chemistry , Bone Cements/toxicity , Calcium Sulfate/toxicity , Cell Line , Cell Survival/drug effects , Fracture Healing , Guinea Pigs , Hemolysis/drug effects , Humans , Hypersensitivity, Delayed/chemically induced , Irritants/chemistry , Irritants/toxicity , Materials Testing , Mice , Microscopy, Electron, Scanning , Osseointegration , Pyrogens/chemistry , Pyrogens/toxicity , Rabbits
16.
Biomed Mater ; 12(1): 015016, 2017 01 17.
Article En | MEDLINE | ID: mdl-28094246

To follow the design strategy of traditional biphasic calcium phosphate (BCP) ceramic, in the present study, strontium-doped biphasic calcium phosphate bone cement (Sr-BCPC) composites comprising Sr-ß-tricalcium phosphate (TCP)/Sr-hydroxyapatite (HAP) had been prepared for the first time using Sr x -ß-TCP/tetracalcium phosphate (TTCP) as a cement powder and diluted phosphoric acid as a cement liquid. The phase composition, setting time, compressive strength, washout resistance, in vitro degradation rate, microstructure evolutions, hydration dynamics and cytotoxicity of Sr-BCPC at various Sr contents were intensively investigated. It was found that the final cement product was composed of entangled Sr-HAP nano-needles and cobblestone-like Sr-ß-TCP sub-micron particles, and the weight percentages in the final cement product after hydration in simulated body fluid for 24 h were in the ranges of 60 wt%-70 wt% Sr-HAP and 30 wt%-40 wt% Sr-ß-TCP, respectively. Sr and the concentration of Sr exhibit significant effects on the phase compositions, compressive strength, setting time, in vitro degradation rate and cytotoxicity of the biphasic bone cement. In particular, the degradation rate increased considerably with the increase of the Sr-ß-TCP phase. It is anticipated that the introduction of the 'biphasic' design into calcium phosphate bone cements is an effective strategy to improve their degradation properties.


Bone Cements/chemistry , Hydroxyapatites/chemistry , Strontium/chemistry , 3T3 Cells , Animals , Bone Cements/toxicity , Calcium Phosphates/chemistry , Compressive Strength , Drug Design , Hydroxyapatites/toxicity , Materials Testing , Mice , Microscopy, Electron, Scanning , X-Ray Diffraction
17.
Mater Sci Eng C Mater Biol Appl ; 62: 274-82, 2016 May.
Article En | MEDLINE | ID: mdl-26952424

In this study, two different extraction approaches were compared in order to evaluate the cytotoxicity of 7 different acrylic bone cements, mainly developed for spinal applications, to osteoblastic cells. Firstly, a static extraction was carried out continuously over 24h, a method widely used in literature. Secondly, a quasi-dynamic extraction method that allowed the investigation of time-dependent cytotoxic effects of curing acrylic bone cements to cells was introduced. In both cases the extraction of the cements was started at a very early stage of the polymerization process to simulate the conditions during clinical application. Data obtained by the quasi-dynamic extraction method suggest that the cytotoxicity of the setting materials mainly originates from the release of toxic components during the first hour of the polymerization reaction. It was also shown that a static extraction over 24h generally represents this initial stage of the curing process. Furthermore, compared to the static extraction, time-dependent cytotoxicity profiles could be detected using the quasi-dynamic extraction method. Specifically, a modification of commercial OsteopalV with castor oil as a plasticizer as well as a customized cement formulation showed clear differences in cytotoxic behavior compared to the other materials during the setting process. In addition, it was observed that unreacted monomer released from the castor oil modified cement was not the main component affecting the toxicity of the material extracts. The quasi-dynamic extraction method is a useful tool to get deeper insight into the cytotoxic potential of curing acrylic bone cements under relevant biological conditions, allowing systematic optimization of materials under development.


Bone Cements/chemistry , Solid Phase Extraction/methods , Biocompatible Materials/chemistry , Biocompatible Materials/toxicity , Bone Cements/toxicity , Cell Line , Cell Survival/drug effects , Humans , Materials Testing , Polymethyl Methacrylate/chemistry
18.
Mater Sci Eng C Mater Biol Appl ; 53: 95-103, 2015 Aug.
Article En | MEDLINE | ID: mdl-26042695

In this work, composite bone cements, based on a commercial polymethylmethacrylate matrix (Palamed®) loaded with ferrimagnetic bioactive glass-ceramic particles (SC45), were produced and characterized in vitro. The ferrimagnetic bioactive glass-ceramic belongs to the system SiO2-Na2O-CaO-P2O5-FeO-Fe2O3 and contains magnetite (Fe3O4) crystals into a residual amorphous bioactive phase. Three different formulations (containing 10, 15 and 20 wt.% of glass-ceramic particles respectively) have been investigated. These materials are intended to be applied as bone fillers for the hyperthermic treatment of bone tumors. The morphological, compositional, calorimetric and mechanical properties of each formulation have been already discussed in a previous paper. The in vitro properties of the composite bone cements described in the present paper are related to iron ion leaching test (by graphite furnace atomic absorption spectrometer), bioactivity (i.e. the ability to stimulate the formation of a hydroxyapatite - HAp - layer on their surface after soaking in simulated body fluid SBF) and cytocompatibility toward human osteosarcoma cells (ATCC CRL-1427, Mg63). Morphological and chemical characterizations by scanning electron microscopy and energy dispersion spectrometry have been performed on the composite samples after each test. The iron release was negligible and all the tested samples showed the growth of HAp on their surface after 28 days of immersion in a simulated body fluid (SBF). Cells showed good viability, morphology, adhesion, density and the ability to develop bridge-like structures on all investigated samples. A synergistic effect between bioactivity and cell mineralization was also evidenced.


Biocompatible Materials/chemistry , Bone Cements/chemistry , Ceramics/chemistry , Ferrosoferric Oxide/chemistry , Polymethyl Methacrylate/chemistry , Biocompatible Materials/toxicity , Bone Cements/toxicity , Cell Adhesion/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Ceramics/toxicity , Durapatite , Ferrosoferric Oxide/toxicity , Humans , Materials Testing , Polymethyl Methacrylate/toxicity
19.
Biomed Mater ; 10(2): 025009, 2015 Apr 17.
Article En | MEDLINE | ID: mdl-25886478

New insight on the conversion of amorphous calcium phosphate (ACP) to nano-sized alpha tricalcium phosphate (α-TCP) provides a faster pathway to calcium phosphate bone cements. In this work, synthesized ACP powders were treated with either water or ethanol, dried, crystallized between 700 and 800 °C, and then cooled at different cooling rates. Particle size was measured in a scanning electron microscope, but crystallite size calculated by Rietveld analysis. Phase composition and bonding in the crystallized powder was assessed by x-ray diffraction and Fourier-transform infrared spectroscopy. Results showed that 50 nm sized α-TCP formed after crystallization of lyophilized powders. Water treated ACP retained an unstable state that may allow ordering to nanoapatite, and further transition to ß-TCP after crystallization and subsequent decomposition. Powders treated with ethanol, favoured the formation of pure α-TCP. Faster cooling limited the growth of ß-TCP. Both the initial contact with water and the cooling rate after crystallization dictated ß-TCP formation. Nano-sized α-TCP reacted faster with water to an apatite bone cement than conventionally prepared α-TCP. Water treated and freeze-dried powders showed faster apatite cement formation compared to ethanol treated powders. Good biocompatibility was found in pure α-TCP nanoparticles made from ethanol treatment and with a larger crystallite size. This is the first report of pure α-TCP nanoparticles with a reactivity that has not required additional milling to cause cementation.


Bone Cements/chemistry , Calcium Phosphates/chemistry , Nanoparticles/chemistry , Apatites/chemistry , Bone Cements/toxicity , Calcium Phosphates/toxicity , Cells, Cultured , Crystallization , Hot Temperature , Humans , Materials Testing , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Microscopy, Electron, Scanning , Nanoparticles/toxicity , Nanoparticles/ultrastructure , Particle Size , Powder Diffraction , Powders , Spectroscopy, Fourier Transform Infrared
20.
Med Sci Monit ; 21: 1162-72, 2015 Apr 23.
Article En | MEDLINE | ID: mdl-25904398

BACKGROUND: We studied the biological safety, biomechanics, and tissue compatibility of calcium phosphate cement and Polymethyl Methacrylate composite bone cement mixed in different ratios. MATERIAL/METHODS: CPC and PMMA were mixed in different ratios (3:1, 2:1, 1:1, 1:2, 1:5, 1:10, 1:15, and 1:20). PMMA solvent is a general solvent containing a dissolved preparation of the composite bone cement specific to a given specimen to determine biological safety, biomechanics, and tissue compatibility. RESULTS: The CPC/PMMA (33%) group, CPC/PMMA (50%) group, CPC/PMMA (67%) group, and CPC/PMMA (75%) group were more in line with the composite bone cement without cytotoxicity requirements. The compressive strength of the CPC/PMMA (67%) group and CPC/PMMA (75%) group was 20 Mpa-30 Mpa, while that of the CPC/PMMA (4.8%) group, CPC/PMMA (6.25%) group, CPC/PMMA (9.1%) group, CPC/PMMA (16.7%) group, CPC/PMMA (33%) group, and CPC/PMMA (50%) group was 40 Mpa-70 Mpa. Curing time was longer in the CPC group (more than 11 min) and shorter in the PMMA group (less than 2 min). The results of weight loss rate showed that there were no significant differences between the CPC/PMMA group (4.8%, 6.25%, 9.1%, 16.7%, 33%) and PMMA control group (p>0.05). With the decrease of CPC content, the rate of weight loss gradually decreased. CONCLUSIONS: The CPC/PMMA (50%) group, CPC/PMMA (67%) group, and CPC/PMMA (75%) group provide greater variability and selectivity for the composite bone cement in obtaining better application.


Bone Cements/chemistry , Calcium Phosphates/chemistry , Polymethyl Methacrylate/chemistry , 3T3 Cells , Animals , Biomechanical Phenomena , Bone Cements/toxicity , Calcium Phosphates/toxicity , Compressive Strength , Humans , Materials Testing , Mice , Microscopy, Electron, Scanning , Osteoblasts/drug effects , Polymethyl Methacrylate/toxicity , Radiography , Rats , Rats, Sprague-Dawley , Tensile Strength , Tibial Fractures/diagnostic imaging , Tibial Fractures/pathology , Tibial Fractures/therapy , Tissue Engineering , X-Ray Diffraction
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