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Bioactive bone cement: the effect of amounts of glass powder and histologic changes with time.

A study was conducted to examine the influence of the amount of glass powder added to a bioactive bone cement of our formula on its mechanical and biologic properties. Serial changes in the cement with time were also examined. The bioactive bone cement consisted of CaO-SiO2-P2O5-CaF2 glass powder and bisphenol-a-glycidyl methacrylate resin. Glass powder was added to the cement in 30, 50, 70, and 80% weight ratios. The compressive strengths of the resulting cements (171-239 MPa) were more than double that of polymethylmethacrylate cement (68 MPa). Histologic examination of rat tibiae bearing artificial defects packed with each bioactive cement showed direct bone contact 4 weeks after surgery. The cement with a higher percentage of glass powder showed better direct formation of bone around its periphery with a thicker reactive layer. Under scanning electron microscopic observation, the reactive layer showed increased levels of calcium and phosphorus. Examination of histologic changes up to 26 weeks showed progressive bone formation around the cement and no sign of biodegradation.

Animals↗

Mediation of bone ingrowth in porous hydroxyapatite bone graft substitutes.

Previous investigations have shown that both the early biological response and the mechanical properties of a porous hydroxyapatite bone graft substitute are highly sensitive to its pore structure. The objective of this study was to evaluate whether the pore structure continued to influence bone integration in the medium to long term. Two screened batches of porous hydroxyapatite (PHA) designated as batch A and batch B, with porosities of approximately 60 and 80%, respectively, were selected for this study and implanted for periods of 5, 13, and 26 weeks into the lower femur of New Zealand White rabbits. Histomorphometric analysis of the absolute volume of bone ingrowth within batch A and B implants from 5 to 26 weeks showed that the absolute volume of bone ingrowth was consistently lower in batch A (10-21%), compared to batch B implants (24-31%). However, when the volume of bone ingrowth was normalised for the available pore space, this difference was reduced (23-47% and 32-42% for batches A and B, respectively). These observations suggest that differences in the volume of bone ingrowth initially depended on pore interconnectivity rather than pore size, whereas the volume or morphology of the PHA influenced the volume and morphology of bone ingrowth at later time points. Compression testing showed that bone ingrowth had a strong reinforcing effect on PHA bone graft substitutes, and a strong correlation was identified between mechanical properties and the absolute volume of ingrowth for both batches A and B. Furthermore, at 13 and 26 weeks, there was no significant variation in the ultimate compressive strength of integrated batch A and B implants. This similarity in ultimate mechanical properties indicated that the absolute volume of ingrowth may be mediated by the PHA structure through its impact on the dynamics of the local biomechanical environment. The results of push-out testing showed that fixation of PHA bone graft substitutes was independent of density within the range studied, with no significant difference in the interfacial shear stress between batches A and B at each time point throughout the study.

Animals↗

Preparation of epoxy-SiO2 hybrid sol-gel material for bone cement.

An organic-inorganic hybrid material, epoxy-SiO(2), was prepared by incorporating epoxy structure units covalently into a SiO(2) glass network via the sol-gel approach. The precursor was obtained by the reaction of diglycidyl ether of bisphenol A (DGEBA) with 3-aminopropyl trimethoxysilane (APTS). The precursor was then hydrolyzed and co-condensated with tetraethyl orthosilicate (TEOS) in tetrahydrofuran (THF) at room temperature to yield epoxy-SiO(2) hybrid sol-gel material having a 50 wt % SiO(2) content. Thermal properties of the hybrid material were characterized by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The hybrid sol-gel material epoxy-SiO(2) was the solid, powder component of bone cement. The liquid component contains bis-phenol-A glycidyl methacrylate (Bis-GMA), triethyleneglycol dimethacrylate (TEGDMA), and methyl methacrylate (MMA) with 25, 55, and 20 vol %, respectively. We discuss the comparison between the new epoxy-SiO(2) bone cement and the commercial Simplex P bone cement. Mechanical properties such as Young's modulus, compressive strength, hardness, and impact strength of the new epoxy-SiO(2) bone cement exceeded those of Simplex P bone cement. The tensile and bending strengths of the new epoxy-SiO(2) bone cement were approximately the same as those of Simplex P bone cement. In order to evaluate the biocompatibility of the new bone cement, an MTT test and optical microscopy were conducted in cell culture. Results indicated that the new epoxy-SiO(2) bone cement exhibits very low cytotoxicity compared with Simplex P bone cement.

Animals↗

Water-borne, in situ crosslinked biomaterials from phase-segregated precursors.

A novel process for the preparation of water-borne biomaterials for hard tissue repair from injectable precursors is described, where the precursors form crosslinked materials in situ under physiological conditions. The precursors react by means of a Michael-type addition reaction that makes use of addition donors such as pentaerythritol tetrakis 3'-mercaptopropionate (QT) and addition acceptors such as poly(ethylene glycol) diacrylate 570 MW (PEGDA), pentaerythritol triacrylate (TA), and poly(propylene glycol) diacrylate 900 MW (PPODA). These crosslinked materials (at 75 wt% solid), prepared from water dispersions or reverse emulsions, showed ultimate strengths in compression of 1.8 +/- 0.2 and 6.7 +/- 0.5 MPa and ultimate deformations of 35 +/- 2+/- and 37 +/- 2%, respectively. Scanning electron microscopy (SEM) shows that the morphology of the precursors templated the morphology of the final materials. The current study indicates that it is possible to obtain injectable high-modulus materials that have appropriate mechanical properties and gelation kinetics for tissue augmentation and stabilization applications such as mechanical stabilization of the intervertebral disc annulus.

Acrylates↗

A novel porous Ti6Al4V: characterization and cell attachment.

For the first time, a highly porous strong Ti6Al4V was produced by using a "polymeric sponge replication" method. A polymeric sponge, impregnated with a Ti6Al4V slurry prepared from Ti6Al4V powders and binders, was subjected to drying and pyrolyzing to remove the polymeric sponge and binders. After sintering at a high temperature and under high vacuum, a porous Ti6Al4V was produced. Optical microscopical observation, environmental scanning electron microscopy observation (with energy-dispersive micro X-ray analysis), mechanical tests, and metallurgical analyses were performed on the obtained porous Ti6Al4V with regard to the porous structure (both macropores and micropores), mechanical properties, chemical composition, phase compositions, and cell attachment behavior. The porous Ti6Al4V made by this method had a three-dimensional trabecular porous structure with interconnected pores mainly ranging from 400 to 700 microm and a total porosity of about 90%. The compressive strength was 10.3 +/- 3.3 MPa and the elastic constant 0.8 +/- 0.3 GPa. MC3T3-E1 cells attached and spread well in the inner surface of pores. Being similar to cancellous bone with regard to both interconnected porous structure and mechanical properties, the resulting porous Ti6Al4V is expected to be a promising biomaterial for biomedical applications.

3T3 Cells↗

Effects of porosity and pore size on in vitro degradation of three-dimensional porous poly(D,L-lactide-co-glycolide) scaffolds for tissue engineering.

In vitro degradation of seven three-dimensional porous scaffolds composed of PLGA85/15, a very useful poly(D,L-lactide-co-glycolide), was performed in phosphate-buffered saline solution at 37 degrees C up to 26 weeks, and effects of porosity (80-95%) and pore size (50-450 mum) on the degradation of the scaffolds were investigated. A series of quantities were measured during the degradation processes: molecular weight and its distribution of PLGA; compressive strength and modulus; and weight, dimension, and porosity of scaffolds. In all of cases with different pore morphologies, the degradation processes obeyed a three-stage model. Scaffolds with a higher porosity or a smaller pore size degraded more slowly than and thus outlasted those with a lower porosity or a larger pore size. The effects are both attributed to a wall effect and a surface area effect because the scaffolds with lower porosities or larger pores possess thicker pore walls and smaller surface area, which depress the diffusion of acidic degradation products and thus results in a stronger acid-catalyzed hydrolysis. This work suggests that, in designing a tissue-engineering scaffold composed of PLGA and adjusting its degradation rate, the effects of pore morphologies should be taken into consideration in addition to those of chemical composition and condensed state of raw materials.

Biocompatible Materials↗

Factors affecting the structure and properties of an injectable self-setting calcium phosphate foam.

One of the main challenges in the investigation on calcium phosphate cements (CPC) lies in the introduction of macroporosity, without loosing the self-setting ability and injectability, characteristic of the cement-type materials. The benefits of macroporosity are related to the enhancement of bone regeneration mechanisms, such as angiogenesis and tissue ingrowth. In this work, the feasibility to obtain self-setting injectable macroporous hydroxyapatite foams by the incorporation of a protein-based foaming agent to a CPC is demonstrated. Albumen is combined with an alpha-tricalcium phosphate [Ca3(PO4)2, alpha-TCP] paste, which hydrolyzes to a calcium deficient hydroxyapatite during the setting reaction. A systematic study is presented, where the effect of different processing parameters is analyzed in terms of porosity, setting properties, injectability, and compressive strength. Self-setting foams with porosities up to 70%, which maintain their porous structure after injection, are obtained. These injectable foams can be used both for direct in vivo applications and for the fabrication of low temperature tissue engineering scaffolds.

Albumins↗

Fabrication and in vitro characterization of porous biodegradable composites based on phosphate glasses and oligolactide-containing polymer networks.

Degradable porous composite materials for use as temporary bone replacement or tissue engineering scaffolds were produced using a methacrylate-modified oligolactide polymer network and phosphate invert glasses in the system P2O5-CaO-MgO-Na2O-(TiO2). Porous glasses with an open interconnective porosity were produced by a salt sintering process. Compressive strengths were significantly enhanced by polymer coating of the inner surface of the porous glasses or by fabrication of glass powder-reinforced porous polymer specimens. In vitro degradation in simulated body fluid showed a degradation pattern of the composites which could be modulated by the composition and resulting solubility of the incorporated glass phase. Cytocompatibility of the composites was investigated in a FDA/EtBr viability assay using an MC3T3-E1 osteoblast-like cell line and showed good biocompatibility of the materials in vitro.

3T3 Cells↗

Comparative study of bone cements prepared with either HA or alpha-TCP and functionalized methacrylates.

The properties of bone cements prepared with both hydroxyapatite (HA) and alpha-tricalcium phosphate (alpha-TCP) and methacrylates containing acidic or basic groups are the main interest of this article. The presence of methacrylic acid or diethyl amino ethyl methacrylate as comonomers in the bone cement and both ceramic types as filler were found not to affect the amount of residual monomer, which was generally less than 4.5 wt%. In contrast, setting times, maximum temperature, and glass transition temperature were found to be composition dependent. For samples with acidic comonomer, a faster setting time, a higher maximum temperature, and higher glass transition temperatures were observed compared to those with the basic comonomer. The presence of the fillers slightly increased the setting time but did not affect the other parameters. The mechanical properties of the filled bone cements depended mainly on composition and type of testing. Both HA or alpha-TCP filled systems fulfilled the minimum compressive strength required for bone cement application, although a significantly lower value was observed for the alkaline comonomer systems. The minimum bending strength was not satisfied by any of these formulations. The tensile and shear strength of these composites ranged from 20 to 37.9 and from 18 to 27 MPa, respectively. In all cases it was higher for bone cements containing methacrylic acid. The results of this study suggest that the properties of dry unfilled bone cements prepared with MAA are comparable to CMW 3 in mechanical terms but inferior in their setting properties.

Bone Cements↗

A radiopaque polymeric matrix for acrylic bone cements.

As part of the search for an alternative to inorganic radiopaque agents, this work studies the possibility of modifying bone cement formulations by incorporating a radiopaque monomer, that is, 4-iodophenol methacrylate (IPMA), in the liquid phase. The monomer was synthesized in the laboratory, and cements were prepared by the standard method. The influence on the different cement characteristics of various monomer concentrations was studied. It was seen that the setting time decreased as the percentage of monomer increased. The radiopacity attained in the 15 vol.% IPMA formulations was about the same as that for a cement containing 10 wt.% barium sulphate. Dynamic and static mechanical properties were measured. The materials did not show significant differences in the glass transition temperature. However, static mechanical properties showed enhanced compressive strength, tensile strength, and elastic modulus with respect to conventional cements formulated with barium sulphate. Histological studies showed a good response of muscular tissue to implanted specimens.

Barium Sulfate↗

The physicochemical properties of the solidification of calcium phosphate cement.

In this article, the physicochemical properties of the solidification of calcium phosphate cement (CPC) were investigated, and the components of the solidified body and the characteristics involved in the application were measured. The setting process of CPC was moderate and slightly exothermic, the heat liberation rate was slow, and the temperature increased little. At the initial stage of the hydration, the compressive strength rose linearly with time, and reached the maximum value after 4 hours. The volume was slightly shrunken by 1% during the setting process, and the total heavy metal content was below 2 ppm. The porosity of the solidified body was about 30%, which was mainly the gel pore with size below 0.1 microm. The final product of hydration was low crystalline hydroxyapatite (HAP). Its real density was 2.859 g/cm(3), which was lower than the theoretical value. This may be due to the existence of lattice defects, which will lead to a slight rise in solubility when leached in physiological saline.

Adhesives↗

Fabrication and mechanical and tissue ingrowth properties of unidirectionally porous hydroxyapatite/collagen composite.

This study investigated the effects of the three-dimensional (3-D) pore structure of a porous hydroxyapatite/collagen (HAp/Col) composite on their mechanical properties and in vivo tissue ingrowth. The unique 3-D pore structure, comprising unidirectionally interconnected pores, was fabricated by the unidirectional growth of ice crystals by using a cooling stage and a subsequent freeze-drying process. The unidirectional pores had a spindle-shaped cross section, and their size gradually increased from the bottom to the upper face. The porous composite showed an elastic property and anisotropic compressive strength for the pore directions. While the strength and modulus parallel to the pore axis were 1.3- and twofold higher than those of the porous composite with spherical pores formed randomly, the strength and modulus perpendicular to the pore axis showed the lowest values. The subcutaneous implantations revealed that when compared with the random pores, the unidirectional pores promote the ingrowth of the surrounding tissues into the pores.

Absorbable Implants↗

Gamma-radiation-induced changes in structure and properties of tetracalcium phosphate and its derived calcium phosphate cement.

The purpose of the present study was to investigate the gamma-radiation effect on the structure and properties of the single-phase tetracalcium phosphate (TTCP) powder and its derived calcium phosphate cement (CPC). Experimental results show that low-dosed (0-30 kGy) CPC has a setting time of 10-12 min, while high-dosed (40-120 kGy) CPC has a setting time of 8-10 min. The low dose gamma-radiation does not significantly change porosity volume fraction or compressive strength of the CPC. The pH values of all CPC samples fell in a relatively narrow band, with a band width of 8.5-9.1 (in terms of pH value). With a dose of 10 or 20 kGy gamma-radiation, the TTCP-apatite conversion ratio does not change much. With 30 kGy the conversion ratio significantly increases and reaches a maximum value. With further increases in dose, the conversion ratio quickly declines. With increasing gamma-ray dose, the CPC morphology becomes more porous/loose and apatite particles become larger in size. When exposed to a high dose (120 kGy) of gamma-radiation, TTCP structure is radiation-damaged, and gamma-ray-induced formation of apatite is confirmed by transmission electron microscopic/selected-area diffraction/lattice imaging analyses.

Bone Cements↗

Experimental lumbar spine fusion with novel tantalum-coated carbon fiber implant.

Implants of carbon fiber composite have been widely used in orthopedic and spinal surgeries. However, studies using carbon fiber-reinforced cages demonstrate frequent appearance of fibrous layer interposed between the implant and the surrounding bone. The aim of the present study was to test the possibility of coating a biocompatible metal layer on top of the carbon fiber material, to improve its biological performance. Tantalum was chosen because of its bone compatibility, based on our previous studies. A novel spinal fusion cage was fabricated by applying a thin tantalum coating on the surface of carbon-carbon composite material through chemical vapor deposition. Mechanical and biological performance was tested in vitro and in vivo. Compress strength was found to be 4.9 kN (SD, 0.2). Fatigue test with 500,000 cycles was passed. In vitro radiological evaluation demonstrated good compatibility with X-ray and CT scan examinations. In vivo test employed eight pigs weighing 50 kg each. Instrumented lumbar spine fusion of L3/4 and L4/5 with these cages was performed on each pig. After 3 months, excellent bone integration property was demonstrated by direct contact of the cage with the host bone and newly formed bone. No inflammatory cells were found around the implant. Cages packed with two different graft materials (autograft and COLLOSS) achieved the same new bone formation. The present study proved that coating tantalum on top of the carbon-based implant is feasible, and good bone integration could be achieved.

Animals↗

Self-setting properties of a beta-dicalcium silicate reinforced calcium phosphate cement.

Beta-dicalcium silicate was used to reinforce the injectable calcium phosphate cement (iCPC) for the first time in this study. The influence of the content of beta-dicalcium silicate on the mechanical properties, setting time, rheological properties, injectability, phase evolution, microstructure, and biodegradability of iCPC was systematically investigated. The results demonstrated that the addition of 8 wt % beta-dicalcium silicate obviously enhanced the compressive strength of the CPC from 26.5 to 47.5 MPa, and did not significantly influence the biodegradability, setting time, injectability, phase evolution, and microstructure of the CPC. The beta-dicalcium silicate-reinforced iCPC with relatively high mechanical property should have potential prospects for the wider applications in surgery such as orthopedics, oral, and maxillofacial surgery.

Bone Cements↗

The effect of systemically administered PDGF-BB on the rodent skeleton.

Platelet-derived growth factor (PDGF), an osteoblast mitogen, has been demonstrated to accelerate fracture healing and periodontal bone repair when applied locally in vivo. To explore whether PDGF could stimulate bone formation in intact bone, we administered it systemically to rats rendered acutely estrogen-deficient. Because PDGF may stimulate bone resorption in vitro, PDGF was administered with and without an antiresorptive agent (alendronate). All treatments were given by intravenous injection 3 times a week for 6 weeks. Spinal bone mineral density (BMD) decreased by 5% in the vehicle-treated ovariectomized (OVX) rats by the end of the study as determined by DXA. Treatment with PDGF prevented this bone loss and significantly (p < 0.05) increased the bone density in the spine (9%) and whole skeleton (5.8%). Combined treatment with PDGF and alendronate resulted in a greater increase at the spine (18%) and whole skeleton (12.8%) than either agent alone. Histomorphometric analysis demonstrated that treatment with PDGF increased the osteoblast number and osteoblast perimeter without consistent changes in osteoclast estimates. Biomechanical testing demonstrated that PDGF administration increased the vertebral body compressive strength and femoral shaft torsional stiffness and resulted in a trend for enhanced femoral head shearing strength. Coadministration of alendronate further increased these indices of bone strength. PDGF administration also caused premature closure of the growth plate, decreased body fat, and resulted in extraskeletal collagen deposition. We therefore demonstrate, for the first time, that systemic administration of PDGF can increase bone density and strength throughout the skeleton.

Absorptiometry, Photon↗

Locomotion of bluefish.

1. Pressure previously measured on the body surface of swimming bluefish were resolved into their backward vectorial components to allow calculation of profile drag. It was 0.18 kg at a speed of 1.8 m/sec. Tangential drag was calculated as if for a thin plate of an area equal to that of the fish. It was 0.08 kg at 1.8 m/sec. Net drag, 0.26 kg, was the sum of profile and tangential drag. 2. Thrust and drag also were calculated from the changes of acceleration measured during steady swimming, assuming that thrust took place only during the acceleration phase, whereas drag occurred during both acceleration and deceleration. This drag was 0.08 kg at a speed of 1.1 m/sec. It is compatible with the drag of 0.26 at 1.8 m/sec calculated from profile and tangential drag provided drag varies as the square of velocity. 3. The force required to produced maximal acceleration was measured during a scare. It was calculated to be 6.9 kg at a peak acceleration of 3 g. 4. The compression strength of th vertebrae was found to be approximately 20 kg per cm2, or roughly three times the force encountered during maximal acceleration. This safety factor of 3 would be reduced when the back was curved, or if opposing groups of muscles were under tension. 5. The finding that a bluefish can accelerate at 3 g and that the vertebral column is strongg enough to withstand this force indicates that the muscles and body structure of a bluefish would be able to withstand the force of gravity if the fish were otherwise equipped for terrestrial life. This fish may have evolved these strengths simultaneously with land animals. It is speculated that other fish may have evolved some degree of strength to overcome inertia and drag during aquatic locomotion, and this evolution may have been a prelude to terrestrial locomotion.

Acceleration↗

Heterotopic osteogenesis in porous ceramics induced by marrow cells.

When untreated porous calcium phosphate ceramics were transplanted into subcutaneous (s.c.) or intramuscular (i.m.) sites, fibrovascular tissue grew in the pore region without evidence of bone formation. However, when these same ceramics were combined with syngeneic marrow cells, osteogenesis was observed inside the pore region of the implanted ceramic. The osteogenesis began on the surface of the pore region at approximately 3 weeks postimplantation by a process of intramembranous bone formation, with the de novo bone tissue observed directly interfacing with the ceramic surface. Infrequently, small isolated areas showed cartilage formation with no noticeable endochondral ossification. At 4 weeks postimplantation of the ceramic with marrow cells, the osteogenesis in the ceramic accompanied an observed increase in compressive strength, rigidity, and energy absorption of the ceramic. These results suggest that a combination of porous ceramics and marrow cells may be useful for clinical problems requiring osseous reconstruction.

Animals↗