Alejandro López

Polyhedral oligomeric silsesquioxane (POSS)–poly(ethylene glycol) (PEG) hybrids as injectable biomaterials

One of the major issues with the currently available injectable biomaterials for hard tissue replacement is the mismatch between their mechanical properties and those of the surrounding bone. Hybrid bone cements that combine the benefits of tough polymeric and bioactive ceramic materials could become a good alternative. In this work, polyhedral oligomeric silsesquioxane (POSS) was copolymerized with poly(ethylene glycol) (PEG) to form injectable in situ cross-linkable hybrid cements. The hybrids were characterized in terms of their mechanical, rheological, handling and in vitro bioactive properties. The results indicated that hybridization improves the mechanical and bioactive properties of POSS and PEG. The Young moduli of the hybrids were lower than those of commercial cements and more similar to those of cancellous bone. Furthermore, the strength of the hybrids was similar to that of commercial cements. Calcium deficient hydroxyapatite grew on the surface of the hybrids after 28 days in PBS, indicating bioactivity. The study showed that PEG-POSS-based hybrid materials are a promising alternative to commercial bone cements.

The compressive modulus and strength of saturated calcium sulphate dihydrate cements: Implications for testing standards

Calcium sulphate-based bone cement is a bone filler with proven biological advantages including biodegradability, biocompatibility and osteoconductivity. Mechanical properties of such brittle ceramic cements are frequently determined using the testing standard designed for ductile acrylic cements. The aims of the study were (1) to validate the suitability of this common testing protocol using saturated calcium sulphate dihydrate (CSD), and (2) to compare the strength and effective modulus of non-saturated and saturated CSD, in order to determine the changes in the mechanical behavior of CSD upon saturation. Unconfined compression tests to failure were performed on 190 cylindrical CSD samples. The samples were divided into four groups having different saturation levels (saturated, non-saturated) and end conditions (capped and non-capped). Two effective moduli were calculated per sample, based on the deformations measured using the machine platens and a sample-mounted extensometer. The effective moduli of non-saturated groups were found to be independent of the end conditions. The saturated and capped group showed no difference in the effective moduli derived from different measurement methods, while the saturated and non-capped group showed a significant difference between the machine platen- and extensometer-derived moduli. Strength and modulus values were significantly lower for saturated samples. It was assumed that the existence of water in saturated CSD alters the mechanical response of the material due to the changes in chemical and physical behaviors. These factors are considered to play important roles to decrease the shear strength of CSD. It was proposed that the reduction in CSD shear strength evokes local deformation at the platen-sample boundary, affecting the strength and effective moduli derived from the experiments. The results of this study highlighted the importance of appropriate and consistent testing methods when determining the mechanical properties of saturated ceramic cements.

Numerical description and experimental validation of a rheology model for non-Newtonian fluid flow in cancellous bone.

Fluids present or used in biology, medicine and (biomedical) engineering are often significantly non-Newtonian. Furthermore, they are chemically complex and can interact with the porous matrix through which they flow. The porous structures themselves display complex morphological inhomogeneities on a wide range of length scales. In vertebroplasty, a shear-thinning fluid, e.g. poly(methyl methacrylate) (PMMA), is injected into the cavities of vertebral trabecular bone for the stabilization of fractures and metastatic lesions. The main objective of this study was therefore to provide a protocol for numerically investigating the rheological properties of PMMA-based bone cements to predict its spreading behavior while flowing through vertebral trabecular bone. A numerical upscaling scheme based on a dimensionless formulation of the Navier-Stokes equation is proposed in order to relate the pore-scale rheological properties of the PMMA that were experimentally estimated using a plate rheometer, to the continuum-scale. On the pore length scale, a viscosity change on the order of one magnitude was observed whilst the shear-thinning properties caused a viscosity change on the order of only 10% on the continuum length scale and in a flow regime that is relevant for vertebroplasty. An experimental validation, performed on human cadaveric vertebrae (n=9), showed a significant improvement of the cement spreading prediction accuracy with a non-Newtonian formulation. A root mean square cement surface prediction error of 1.53mm (assuming a Newtonian fluid) and 1.37mm (assuming a shear-thinning fluid) was found. Our findings highlight the importance of incorporating the non-Newtonian fluids properties in computational models of porous media at the appropriate length scale.

The effect of unsaturated fatty acid and triglyceride oil addition on the mechanical and antibacterial properties of acrylic bone cements

Acrylic bone cements have an elastic modulus several times higher than the surrounding trabecular bone. This has been hypothesized to contribute to certain clinical complications. There are indications that the addition of specific fatty acids and triglyceride oils may reduce the elastic modulus of these types of cements. Some of these additives also appear to have inherent antibiotic properties, although this has never been evaluated in bone cements. In this study, several types of fatty acids and triglyceride oils were evaluated for use in acrylic bone cements. Their mechanical properties were evaluated under uniaxial compression testing and selected cements were then further characterized in terms of microstructure, handling and antibacterial properties using scanning electron microscopy, polymerization temperature measurements, agar diffusion tests and bactericidal activity assays of cement extracts. It was found that any of the evaluated fatty acids or triglyceride oils could be used to tailor the stiffness of acrylic bone cements, although at varying concentrations, which also depended on the type of commercial base cement used. In particular, the addition of very small amounts of linoleic acid (<2.0 wt%) resulted in Young’s moduli and compressive strengths in the range of human trabecular bone, while maintaining a similar setting time. Further, the addition of 12.6 wt% ricinoleic acid to Osteopal V cement was found to have a significant antibacterial effect, inhibiting growth of Staphylococcus aureus in an agar diffusion test as well as demonstrating 100% bactericidal activity against the same strain.

Compressive mechanical properties and cytocompatibility of bone-compliant, linoleic acid-modified bone cement in a bovine model

Adjacent vertebral fractures are a common complication experienced by osteoporosis patients shortly after vertebroplasty. Whether these fractures are due to the bone cement properties, the cement filling characteristics or to the natural course of the disease is still unclear. However, some data suggests that such fractures might occur because of an imbalance in the load distribution due to a mismatch between the elastic modulus (E) of the bone-cement composite, and that of the vertebral cancellous bone. In this study, the properties of bone-compliant linoleic acid-modified bone cements were assessed using a bovine vertebroplasty model. Two groups of specimens (cement-only and bone-cement composites), and four subgroups comprising bone cements with elastic moduli in the range of 870-3500MPa were tested to failure in uniaxial compression. In addition, monomer release as well as time and concentration-dependent cytocompatibility was assessed through the cement extracts using a Saos-2 cell model. Composites augmented with bone-compliant cements exhibited a reduction in E despite their relatively high bone volume fraction (BVF). Moreover, a significant positive correlation between the BVF and the E for the composites augmented with 870MPa modulus cements was found. This was attributed to the increased relative contribution of the bone to the mechanical properties of the composites with a decrease in E of the bone cement. The use of linoleic acid reduced monomer conversion resulting in six times more monomer released after 24h. However, the cytocompatibility of the bone-compliant cements was comparable to that of the unmodified cements after the extracts were diluted four times. This study represents an important step towards introducing viable bone-compliant bone cements into vertebroplasty practice.

Calcium phosphate cements with strontium halides as radiopacifiers.

High radiopacity is required to monitor the delivery and positioning of injectable implants. Inorganic nonsoluble radiopacifiers are typically used in nondegradable bone cements; however, their usefulness in resorbable cements is limited due to their low solubility. Strontium halides, except strontium fluoride, are ionic water-soluble compounds that possess potential as radiopacifiers. In this study, we compare the radiopacity, mechanical properties, composition, and cytotoxicity of radiopaque brushite cements prepared with strontium fluoride (SrF2 ), strontium chloride (SrCl2 ·6H2 O), strontium bromide (SrBr2 ), or strontium iodide (SrI2 ). Brushite cements containing 10 wt % SrCl2 ·6H2 O, SrBr2 , or SrI2 exhibited equal to or higher radiopacity than commercial radiopaque cements. Furthermore, the brushite crystal lattice in cements that contained the ionic radiopacifiers was larger than in unmodified cements and in cements that contained SrF2 , indicating strontium substitution. Despite the fact that the strontium halides increased the solubility of the cements and affected their mechanical properties, calcium phosphate cements containing SrCl2 ·6H2 O, SrBr2 , and SrI2 showed no significant differences in Saos-2 cell viability and proliferation with respect to the control. Strontium halides: SrCl2 ·6H2 O, SrBr2 , and SrI2 may be potential candidates as radiopacifiers in resorbable biomaterials although their in vivo biocompatibility, when incorporated into injectable implants, is yet to be assessed.

Novel injectable biomaterials for bone augmentation based on isosorbide dimethacrylic monomers

Drawbacks with the commonly used PMMA-based bone cements, such as an excessive elastic modulus and potentially toxic residual monomer content, motivate the development of alternative cements. In this work an attempt to prepare an injectable biomaterial based on isosorbide-alicyclic diol derived from renewable resources was presented. Two novel dimethacrylic monomers ISDGMA - 2,5-bis(2-hydroxy-3-methacryloyloxypropoxy)-1,4:3,6-dianhydro-sorbitol and ISETDMA - dimethacrylate of ethoxylated isosorbide were synthesized and used to prepare a series of low-viscosity compositions comprising bioactive nano-sized hydroxyapatite in the form of a two-paste system. Formulations exhibited a non-Newtonian shear-thinning behavior, setting times between 2.6 min and 5.3 min at 37°C and maximum curing temperatures of 65°C. Due to the hydrophilic nature of ISDGMA, cured compositions could absorb up to 13.6% water and as a result the Youngs modulus decreased from 1,429 MPa down to 470 MPa. Both, poly(ISDGMA) and poly(ISETDMA) were subjected to a MTT study on mice fibroblasts (BALB/3T3) and gave relative cell viabilities above 70% of control. A selected model bone cement was additionally investigated using human osteosarcoma cells (SaOS-2) in an MTS test, which exhibited concentration-dependent cell viability. The preliminary results, presented in this work reveal the potential of two novel dimethacrylic monomers in the preparation of an injectable biomaterial for bone augmentation, which could overcome some of the drawbacks typical for conventional acrylic bone cement.

Synthesis and characterization of injectable composites of poly[D,L‐lactide‐co‐(ε‐caprolactone)] reinforced with β‐TCP and CaCO3 for intervertebral disk augmentation

Degeneration of the intervertebral disk constitutes one of the major causes of low back pain in adults aged 20-50 years old. In this study, injectable, in situ setting, degradable composites aimed for intervertebral disk replacement were prepared. β-TCP and calcium carbonate particles were mixed into acrylic-terminated oligo[D,L-lactide-co-(ε-caprolactone)], which were crosslinked at room temperature. The structure of the oligomers was confirmed by 1H-NMR spectroscopy. The composites were examined via SEM, and the mechanical properties of the crosslinked networks were determined. The porous β-TCP particles showed good mechanical anchorage to the matrix due to polymer penetration into the pores. In vitro degradation tests showed that the composites containing β-TCP slowly degraded, whereas the composites containing CaCO3 exhibited apatite formation capacity. It was concluded that the surface area, morphology, and solubility of the fillers might be used to control the degradation properties. The incorporation of fillers also increased both the elastic modulus and the maximum compression strength of the composites, properties that were similar to those of the physiological disk. These materials have potential for long-term intervertebral disk replacement and regenerative scaffolds because of their low degradation rates, bioactivity, and mechanical properties.

Direct and interactive effects of three variables on properties of PMMA bone cement for vertebral body augmentation

PMMA bone cements are widely used for vertebral body augmentation procedures vertebroplasty and balloon kyphoplasty. Although there are studies in the literature on the direct effects of relevant variables on the properties of these cements, there are none on the interactive effects. In the present work, such a study was performed on both types of effects, with the variables being the concentration of initiator (benzoyl peroxide), the concentration of crosslinker (ethylene glycol dimethacrylate), and the liquid-to-powder ratio used in preparing the cement; and the properties being the compressive strength, the compressive modulus, the doughing time, the setting time, and the maximum polymerization temperature. Two additional properties obtained from the viscosity-versus-time curves, namely the time at the onset of curing, and the critical curing rate were also studied. Significant interactive effects between the amount of crosslinker and the amount of radical initiator were found to affect the doughing time and the critical curing rate. These effects were explained in terms of the reaction kinetics. It was concluded that interactive effects may exist and should be taken into account when designing bone cement formulations.

Biomechanics of low-modulus and standard acrylic bone cements in simulated vertebroplasty: A human ex vivo study

The high stiffness of bone cements used in vertebroplasty has been hypothesised to contribute to the propensity of adjacent vertebral fractures after treatment. Therefore, new low-modulus cements have been developed; however, there are currently no studies assessing the biomechanical aspects of vertebroplasty with these cements in an ex vivo non-prophylactic model. In this study, we induced wedge fractures through eccentric uniaxial compression to single whole-vertebrae, before and after augmentation with either standard or low-modulus cement. Compressive strength and stiffness of individual vertebrae were measured, on 19 samples from metastatic spines and 20 samples from elderly, osteopenic spines. While both cement types increased the strength of both the metastatic (+34% and +63% for standard and low-modulus cement, respectively) and the elderly vertebrae (+303% and +113%, respectively), none of them restored the initial stiffness of metastatic specimens (-51% and -46%, respectively). Furthermore, low-modulus cement gave a lower total stiffness (-13%) of elderly specimens whereas standard cement increased it above initial levels (+17%). Results show that vertebroplasty with low-modulus cement could provide restoration of the initial stiffness while increasing the strength of fractured elderly vertebrae and hence represent a treatment modality which is closer to pre-augmented behaviour. Also, this study indicates that stiffness-modified cement needs to be optimised for patient/pathology specific treatment.