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Biomedical subjects

William Bonfield

Publications and source records attributed to William Bonfield.

At least 19 recordsLinked to original sources
PubMed2006

The response of osteoblasts to nanocrystalline silicon-substituted hydroxyapatite thin films.

Magnetron co-sputtering has been employed to fabricate thin nanocrystalline coatings of silicon-substituted hydroxyapatite (SiHA) of different Si compositions: 0.8 wt%, 2.2 wt%, and 4.9 wt%. A human osteoblast-like (HOB) cell model was used to study the long-term interaction between the HOB cells and coatings in vitro. Results showed that the number of cells growing on all coated titanium (Ti) samples were statistically significantly higher than on uncoated Ti. In addition, HOB cells growing on all SiHA surfaces displayed enhanced cell spreading, with extensive extracellular matrix synthesis. DNA staining revealed normal phenotype nuclear morphology for HOB cells, with several dense chromosomes surrounded by a periphery of intact nuclear membrane. Furthermore, immunofluorescent staining indicated that cells showed improved adhesion on the coated surfaces with increasing Si content, developing mature cytoskeletons with numerous distinct and well-defined actin stress fibres in the cell membranes. Results also demonstrated that the bone mineralisation process was greatest in the presence of the highest Si level (4.9 wt%). However, at very early culturing time point, cells did not attach so readily on the surface of this coating due to rapid dissolution. Thus, this work suggests that a Si content of 2.2 wt% may be the optimum loading to improve the bioactive property of HA thin films.

Cell Adhesion↗
PubMed2006

The structure of the bond between bone and porous silicon-substituted hydroxyapatite bioceramic implants.

The significance of micrometer-sized strut porosity in promoting bone ingrowth into porous hydroxyapatite (HA) scaffolds has only recently been noted. In this study, silicon-substituted HA (0.8 wt % Si-HA) with approximately 8.5% of the total porosity present as microporosity within the struts of the implant was prepared for high-resolution transmission electron microscopy (HR-TEM) via both ultramicrotomy and focused ion beam milling. Between the struts of the porous Si-HA, pores with varying shapes and sizes (1-10 microm in diameter) were characterized. Within the struts, the Si-HA contained features such as grain boundaries and triple-junction grain boundaries. Bone ingrowth and dissolution from a Si-HA implant were studied using HR-TEM after 6 weeks in vivo. Minor local dissolution occurred within several pores within the struts. Organized, mineralized collagen fibrils had grown into the strut porosity at the interface between the porous Si-HA implant and the surface of the surrounding bone. In comparison, deeper within the implant, disorganized and poorly mineralized fibers were observed within the strut porosity. These findings provide valuable insight into the development of bone around porous Si-HA implants.

Animals↗
PubMed2006

Silicon addition to hydroxyapatite increases nanoscale electrostatic, van der Waals, and adhesive interactions.

The normal intersurface forces between nanosized probe tips functionalized with COO(-)-terminated alkanethiol self-assembling monolayers and dense, polycrystalline silicon-substituted synthetic hydroxyapatite (SiHA) and phase pure hydroxyapatite (HA) were measured via a nanomechanical technique called chemically specific high-resolution force spectroscopy. A significantly larger van der Waals interaction was observed for the SiHA compared to HA; Hamaker constants (A) were found to be A(SiHA) = 35 +/- 27 zJ and A(HA) = 13 +/- 12 zJ. Using the Derjaguin-Landau-Verwey-Overbeek approximation, which assumes linear additivity of the electrostatic double layer and van der Waals components, and the nonlinear Poisson-Boltzmann surface charge model for electrostatic double-layer forces, the surface charge per unit area, sigma (C/m(2)), was calculated as a function of position for specific nanosized areas within individual grains. SiHA was observed to be more negatively charged than HA with sigma(SiHA) = -0.024 +/- 0.013 C/m(2), two times greater than sigma(HA) = -0.011 +/- 0.006 C/m(2). Additionally, SiHA was found to have increased surface adhesion (0.7 +/- 0.3 nN) compared to HA (0.5 +/- 0.3 nN). The characterization of the nanoscale variations in surface forces of SiHA and HA will enable an improved understanding of the initial stages of bone-biomaterial bonding.

Biocompatible Materials↗
PubMed2006

Predicting the tensile strength of compacted multi-component mixtures of pharmaceutical powders.

PURPOSE: Pharmaceutical tablets are generally produced by compacting a mixture of several ingredients, including active drugs and excipients. It is of practical importance if the properties of such tablets can be predicted on the basis of the ones for constituent components. The purpose of this work is to develop a theoretical model which can predict the tensile strength of compacted multi-component pharmaceutical mixtures. METHODS: The model was derived on the basis of the Ryshkewitch-Duckworth equation that was originally proposed for porous materials. The required input parameters for the model are the relative density or solid fraction (ratio of the volume of solid materials to the total volume of the tablets) of the multi-component tablets and parameters associated with the constituent single-component powders, which are readily accessible. The tensile strength of tablets made of various powder blends at different relative density was also measured using diametrical compression. RESULTS: It has been shown that the tensile strength of the multi-component powder compacts is primarily a function of the solid fraction. Excellent agreement between prediction and experimental data for tablets of binary, ternary and four-component blends of some widely used pharmaceutical excipients was obtained. CONCLUSION: It has been demonstrated that the proposed model can well predict the tensile strength of multi-component pharmaceutical tablets. Thus, the model will be a useful design tool for formulation engineers in the pharmaceutical industry.

Algorithms↗
PubMed2005

Crystal imperfection studies of pure and silicon substituted hydroxyapatite using Raman and XRD.

Hydroxyapatite (HA) is important in biomedical applications because of its chemical similarity to the mineral content of bone and its consequent bioactivity. Silicon substitution into the hydroxyapatite crystal lattice was found to enhance its bioactivity both in vitro and in vivo [1, 2]. However, the mechanism for the enhancement is still not well understood. In this paper, the crystal imperfections introduced by silicon substitution were studied using XRD and Raman spectroscopy. It was found that silicon substitution did not introduce microstrain, but deceased the crystal size in the hk0 direction. Three new vibration modes and peak broadening were observed in Raman spectra following silicon incorporation. The imperfections introduced by silicon substitution may play a role in enhancing bioactivity. A phenomenological relationship between the width of the PO4 v1 peak and crystal size was established.

Crystallization↗
PubMed2005

Nanoscale variation in surface charge of synthetic hydroxyapatite detected by chemically and spatially specific high-resolution force spectroscopy.

The normal intersurface forces between nanosized probe tips functionalized with COO-- and NH3+-terminated alkanethiol self-assembling monolayers and dense polycrystalline phase pure synthetic hydroxyapatite (HA) were measured via a powerful nanomechanical technique called chemically specific high-resolution force spectroscopy. The data taken on approach of the probe tip to the HA surface was compared to the nonlinear Poisson-Boltzmann-based electrostatic double layer theory to predict the surface charge per unit area of the HA, sigmaHA (C/m2), as a function of ionic strength, position within a variety of grains, and across grain boundaries. The average sigmaHA was found to be approximately -0.02 C/m2 and to vary from -0.0037 to -0.072 C/m2 with nanoscale position in relation to grain boundaries and crystal planes up to -0.19 C/m2/microm. Positional measurement of nanoscale surface properties holds great promise in elucidating the molecular origins of physicochemical processes occurring at the biomaterial interface.

Biocompatible Materials↗
PubMed2005

Ultrastructural observation of single-crystal apatite fibres.

Hydroxyapatite (HAp) has been widely used as a biomaterial for substituting human hard tissues such as bone. By altering the morphology of HAp crystals, novel properties may be produced by controlling the orientation of the crystal planes. Apatite fibres were successfully synthesized by precipitation from aqueous solutions containing Ca(NO(3))(2), (NH(4))(2)HPO(4), urea and HNO(3). The products were composed of carbonate-containing apatite fibres with preferred orientation along the {h00} planes. Examination of individual fibres using transmission electron microscopy showed that the as-synthesized apatite fibres were highly strained single crystals with the c-axis orientation parallel to the long axis of the fibre. The crushed fibres consisted of domains that were preferentially oriented with the c-axis parallel to the long axis of the fibres. When the apatite fibres were heated to 800, 1000 and 1200 degrees C for 1h, the domains were removed and grain boundaries, dislocations and voids were formed.

Biocompatible Materials↗
PubMed2005

A simple predictive model for the tensile strength of binary tablets.

The tensile strength of tablets of single-component powders, such as microcrystalline cellulose (MCC), hydroxypropylmethyl cellulose (HPMC) and starch, and binary mixtures of these powder were measured at various relative densities. It was found that the tensile strength of tablets of powder blends was primarily dependent upon relative density but was independent of the tablet dimensions and compaction kinematics. It was found that the logarithm of tensile strength was proportional to the relative density. A simple model, based upon Ryshkewitch-Duckworth equation that was originally proposed for porous materials, has been developed in order to predict the relationship between the tensile strength and relative density of binary tablets based on the properties of the constituent single-component powders. The validity of the model has been verified with experimental results for various binary mixtures. It has demonstrated that the proposed model can well predict the tensile strength of binary mixtures based upon the properties of single-component powders, such as true density, and the concentrations.

Cellulose↗
PubMed2004

Osteoblast-like cell response to bioactive composites-surface-topography and composition effects.

Two bioactive composites, containing 40 vol % filler in high-density polyethylene (HDPE), were investigated to examine the effects of different filler compositions and different surface patterning. The first composite, known as HAPEX, consists of hydroxyapatite within HDPE, and the second composite, known as AWPEX, consists of glass-ceramic apatite-wollastonite in HDPE. Surface topography effects at 5-50 and 100-150 microm were explored, with cell morphology analyzed with the use of scanning electron microscopy and confocal laser scanning microscopy (CLSM). Biochemical assays of adenosine triphosphate and alkaline phosphatase were used to analyze osteoblast-like cell proliferation and differentiation. For both composites, cell alignment was seen along grooves, pillars, and wells, with preferential cell attachment to ceramic particles within the polymer matrices. HAPEX showed significantly increased cell proliferation over AWPEX (P < 0.005). However, greater cell differentiation occurred for AWPEX over HAPEX (P < 0.005). Polishing significantly increased osteoblast-like cell response over as-cut samples, but surface-topography changes above 50 microm had no consistent effect. Smaller-scale features also showed no significant trend in terms of cell proliferation, but did show significant differences in cell differentiation (P < 0.05). CLSM imaging of actin and vinculin localization within cells showed the greatest change in comparison to polished surface controls for cells cultured on samples with surface features below 50 microm. The fact that similar observations were made for both HAPEX and AWPEX indicated that, for these experiments, the effects of surface topography more strongly influenced cell response than chemical composition.

Adenosine Triphosphate↗
PubMed2004

Ultrastructural comparison of dissolution and apatite precipitation on hydroxyapatite and silicon-substituted hydroxyapatite in vitro and in vivo.

Recent histological studies have demonstrated that the substitution of silicate ions into hydroxyapatite (HA) significantly increases the rate of bone apposition to HA implants. The enhanced bioactivity of silicon-substituted HA (Si-HA) over pure HA has been attributed to the effect of silicate ions in accelerating dissolution. In the present study, high-resolution transmission electron microscopy (HR-TEM) was employed to compare dissolution of HA and Si-HA in an acellular simulated body fluid (SBF) to dissolution in an in vivo model. HR-TEM observations confirmed a difference in morphology of apatite precipitates in vivo and in SBF: apatite deposits were platelike in vivo and nodular in SBF. Compositional mapping suggested that preferential dissolution of silicon from the implant promotes the nucleation of carbonate apatite around the implant. The in vivo findings illustrated an absence of dissolution at the bone-HA or Si-HA interface, whereas dissolution was extensive from within the implant. The amount of dissolution in acellular SBF was similar to dissolution from within the implant, although the site at which the dissolution nucleates was different: dissolution predominates at the crystallite surfaces in SBF, whereas grain boundary dissolution predominates in vivo. These findings suggest that proteins in the in vivo milieu modify the processes of dissolution from the implant.

Biocompatible Materials↗
PubMed2004

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↗
PubMed2004

Ultrastructural comparison of hydroxyapatite and silicon-substituted hydroxyapatite for biomedical applications.

Silicon-substituted hydroxyapatite (Si-HA) has been shown to lead to significantly increased rates of bone apposition when compared with phase-pure hydroxyapatite (HA) bioceramic implants (Patel N, et al. J Mater Sci Mater Med 2002;13:1199-1206). However, uncertainty remains about the mechanism by which Si increases the in vivo bioactivity. In this study, defect structures in Si-HA were observed and characterized for the first time using high-resolution transmission electron microscopy. Using tilting experiments and the g. b = 0 criterion for invisibility, the Burgers vectors of dislocations in phase-pure HA and 0.8 wt % Si-HA were characterized to be screw and mixed in character. Dislocations were observed in both pure HA and 0.8 wt % Si-HA with no significant difference in dislocation density between HA and Si-HA. However, our findings suggest that an increased number of triple junctions in Si-HA may have a significant role in increasing the solubility of the material and the subsequent rate at which bone apposes Si-HA ceramics.

Biocompatible Materials↗
PubMed2004

Effect of sintered silicate-substituted hydroxyapatite on remodelling processes at the bone-implant interface.

Phase pure, sintered granules of hydroxyapatite (HA) and silicon-substituted hydroxyapatite (Si-HA) were implanted for 6 and 12 weeks in an ovine model. Samples containing the bone-implant interface were prepared for ultramicrotomy and transmission electron microscopy (TEM) using an anhydrous sample preparation procedure. The results demonstrate that the morphology of apatite deposits and the sequence of events at the interfaces of bone with pure HA and with Si-HA implants, were different. Organised collagen fibrils were first found at the bone/Si-HA interface after 6 weeks, whereas they were found only after 12 weeks around the pure HA implant. Many more nodular aggregates comprised of plate-like apatite crystallites were observed in the vicinity of Si-HA than around the pure HA after 12 weeks in vivo. These findings suggest that the incorporation of silicate ions into HA promotes processes of bone remodelling at the bone/HA interface. TEM observations suggested that the trabecular bone weaves over the Si-HA and that the collagen fibrils form a mechanical interlock with the Si-HA ceramic implants. High-resolution lattice imaging illustrated apatite crystallites contiguous with the Si-HA ceramic and revealed a direct relationship between the bone mineral and the Si-HA ceramic.

Animals↗
PubMed2002

Novel synthesis and characterization of an AB-type carbonate-substituted hydroxyapatite.

A novel synthesis route has been developed to produce a high-purity mixed AB-type carbonate-substituted hydroxyapatite (CHA) with a carbonate content that is comparable to the type and level observed in bone mineral. This method involves the aqueous precipitation in the presence of carbonate ions in solution of a calcium phosphate apatite with a Ca/P molar ratio greater than the stoichiometric value of 1.67 for hydroxyapatite (HA). The resulting calcium-rich carbonate-apatite is sintered/heat-treated in a carbon dioxide atmosphere to produce a single-phase, crystalline carbonate-substituted hydroxyapatite. In contrast to previous methods for producing B- or AB-type carbonate-substituted hydroxyapatites, no sodium or ammonium ions, which would be present in the reaction mixture from the sodium or ammonium carbonates commonly used as a source of carbonate ions, were present in the final product. The chemical and phase compositions of the carbonate-substituted hydroxyapatite was characterized by X-ray fluorescence and X-ray diffraction, respectively, and the level and nature of the carbonate substitution were studied using C-H-N analysis and Fourier transform infrared spectroscopy, respectively. The carbonate substitution improves the densification of hydroxyapatite and reduces the sintering temperature required to achieve near-full density by approximately 200 degrees C compared to stoichiometric HA. Initial studies have shown that these carbonate-substituted hydroxyapatites have improved mechanical and biologic properties compared to stoichiometric hydroxyapatite.

Bone Substitutes↗
PubMed2002

Characterization of new acrylic bone cements prepared with oleic acid derivatives.

Acrylic bone-cement formulations were prepared with the use of a new tertiary aromatic amine derived from oleic acid, and also by incorporating an acrylic monomer derived from the same acid with the aim of reducing the leaching of toxic residuals and improving mechanical properties. 4-N,N dimethylaminobenzyl oleate (DMAO) was used as an activator in the benzoyl-peroxide radical cold curing of polymethyl methacrylate. Cements that contained DMAO exhibited much lower polymerization exotherm values, ranging between 55 and 62 C, with a setting time around 16--17 min, depending on the amine/BPO molar ratio of the formulation. On curing a commercial bone cement, Palacosreg R with DMAO, a decrease of 20 C in peak temperature and an increase in setting time of 7 min were obtained, the curing parameters remaining well within limits permitted by the standards. In a second stage, partial substitution of MMA by oleyloxyethyl methacrylate (OMA) in the acrylic formulations was performed, the polymerization being initiated with the DMAO/BPO redox system. These formulations exhibited longer setting times and lower peak temperatures with respect to those based on PMMA. The glass transition temperature of the experimental cements were lower than that of PMMA cement because of the presence of long aliphatic chains of both activator and monomer in the cement matrix. Number average molecular weights of the cured cements were in the range of 1.2x10(5). PMMA cements cured with DMAO/BPO revealed a significant (p<0.001) increase in the strain to failure and a significant (p<0.001) decrease in Young's modulus in comparison to Palacosreg R, whereas ultimate tensile strength remained unchanged. When the monomer OMA was incorporated, low concentrations of OMA provided a significant increase in tensile strength and elastic modulus without impairing the strain to failure. The results demonstrate that the experimental cements based on DMAO and OMA have excellent promise for use as orthopaedic and/or dental grouting materials.

Acrylates↗
PubMed2002

Optimizing HAPEX topography influences osteoblast response.

HAPEX (hydroxyapatite-reinforced polyethylene composite) is a second-generation orthopedic biomaterial designed as a bone analog material, which has found clinical success. The use of topography in cell engineering has been shown to affect cell attachment and subsequent response. Thus, by combining bioactivity and enhancing osteoblast response to the implant surface, improved tissue repair and implant life span may be achieved. In this study a primary human osteoblast-like cell model has been used to study the influence of surface topography and chemistry produced by three different production methods. Scanning electron microscopy, fluorescence microscopy, and confocal scanning laser microscopy have been used to study cell adhesion; tritiated thymidine uptake has been used to observe cell proliferation; and the reverse transcriptase-polymerase chain reaction and biochemical methods have been used to study phenotypic expression. Transmission electron microscopy has also been used to look at more long-term morphology. The results show that topography significantly influences cell response, and may be a means of enhancing bone apposition on HAPEX.

Alkaline Phosphatase↗