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Compositional effects on the formation of a calcium phosphate layer and the response of osteoblast-like cells on polymer-bioactive glass composites
Lu, H. H., A. Tang, et al. (2005), Biomaterials 26(32): 6323-34.
Abstract: Biodegradable polymer-ceramic composites are attractive systems for bone tissue engineering applications. These composites have the combined advantages of the component phases, as well as the inherent ease in optimization where desired material properties can be tailored in a well-controlled manner. This study focuses on the optimization of a polylactide-co-glycolide (PLAGA) and 45S5 bioactive glass (BG) composite for bone tissue engineering. The first objective is to examine the effects of composition or overall BG content on the formation of a Ca-P layer on the PLAGA-BG composite. It is expected that with increasing BG content (0%, 10%, 25%, 50% by weight), the required incubation time in a simulated body fluid (SBF) for the composite to form a detectable surface Ca-P layer will decrease. Both the kinetics and the chemistry will be determined using SEM+EDAX, FTIR, and mu-CT methods. Solution phosphorous and calcium concentrations will also be measured. The second objective of the study is to determine the effects of BG content on the maturation of osteoblast-like cells on the PLAGA-BG composite. It is hypothesized that mineralization will increase with increasing BG content, and the composite will support the proliferation and differentiation of osteoblasts. Specifically, cell proliferation, alkaline phosphatase activity and mineralization will be monitored as a function of BG content (0%, 10%, 50% by weight) and culturing time. It was found that the kinetics of Ca-P layer formation and the resulting Ca-P chemistry were dependent on BG content. The response of human osteoblast-like cells to the PLAGA-BG composite was also a function of BG content. The 10% and 25% BG composite supported greater osteoblast growth and differentiation compared to the 50% BG group. The results of this study suggest that there is a threshold BG content which is optimal for osteoblast growth, and the interactions between PLAGA and BG may modulate the kinetics of Ca-P formation and the overall cellular response.

Composition-controlled nanocomposites of apatite and collagen incorporating silicon as an osseopromotive agent
Lynn, A. K., T. Nakamura, et al. (2005), J Biomed Mater Res A 74(3): 447-53.
Abstract: The development of a novel biocomposite of apatite (Ap) and collagen incorporating low-level additions of silicon (Si) as an osseopromotive agent is detailed. Designed to mimic the structural and compositional characteristics of developing bone, this composite is produced via a coprecipitation method, through which the weight percentage of Ap (i.e., the Ap/collagen ratio) can be varied. Coprecipitates produced at Ap contents of 80 wt % (Ap/collagen=4:1), 60 wt % (Ap/collagen=3:2), and 40 wt % (Ap/collagen=2:3) Ap showed markedly different morphologies, ranging from ceramic-like particulates to rope-like macro-fibrils; at all three Ap contents, however, the nanostructural features of the composites remained qualitatively indistinguishable, with equiaxed Ap nanocrystals distributed randomly throughout a matrix of amorphous collagen. Si incorporation was observed to occur preferentially in the collagenous phase-a result with potential impact on local controlled release of Si.

Compound changes and tooth mineralization effects of glass ionomer cements containing bioactive glass (S53P4), an in vivo study
Yli-Urpo, H., M. Narhi, et al. (2005), Biomaterials 26(30): 5934-41.
Abstract: In this study, modifications of glass ionomer cements (GICs) were made by adding bioactive glass (BAG) to GIC to obtain bioactive restorative materials. This study used SEM, EDS and visual analysis to examine the bioactivity and the ability of the study materials to mineralize dentin. Conventional cure and resin-modified light-curing GIC were used. The materials consisted of powder and liquid. Three experimental materials were made by mixing 10-30 wt% of BAG powder with GIC powders. Commercially available GIC without BAG were used as controls. Class III restorations were made in altogether 62 intact beagle dog teeth, and the operation was performed under general anesthesia. The restorations were followed clinically for 1, 3 or 6 weeks. Resin-modified GIC containing BAG showed uniform CaP surface formation on the restorations. Mineral depositions in the close vicinity of the restoration-dentin interface and in deeper parts of dentin tubules were also noticed in resin-modified GIC containing BAG particles. It can be concluded that resin-modified GIC containing BAG have good potential in clinical applications where enhanced mineralization is expected.

Compromised production of extracellular matrix in mice lacking secreted protein, acidic and rich in cysteine (SPARC) leads to a reduced foreign body reaction to implanted biomaterials
Puolakkainen, P., A. D. Bradshaw, et al. (2003), Am J Pathol 162(2): 627-35.
Abstract: SPARC (secreted protein, acidic and rich in cysteine), a matricellular glycoprotein, modulates the interaction of cells with the extracellular matrix (ECM). Recently, accelerated cutaneous wound closure and altered deposition of collagen were reported in SPARC-null mice. Herein we asked whether SPARC might influence the foreign body reaction to biomaterial implants. Polydimethylsiloxane (silicone rubber) disks and cellulose Millipore filters were implanted into wild-type and SPARC-null mice. In wild-type animals, significant levels of SPARC were observed in the cells and the ECM comprising the capsules around the implants. After 4 weeks, SPARC-null mice exhibited a significant decrease in the thickness of the foreign body capsule, as compared to that observed in wild-type mice. A significant reduction in capsular vascular density was also associated with the silicone implants in the SPARC-null animals. Electron microscopy revealed that collagen fibers in the capsules produced by SPARC-null mice were smaller and more uniform in size than those in wild-type animals. Furthermore, staining with picrosirius-red showed that the collagen fibers were less mature in SPARC-null than in wild-type mice. The altered ECM resulting in decreased capsular thickness, indicative of an altered foreign body reaction in SPARC-null mice, implicates SPARC as an important modulator of the encapsulation of implanted biomaterials.

Computational model of device-induced thrombosis and thromboembolism
Goodman, P. D., E. T. Barlow, et al. (2005), Ann Biomed Eng 33(6): 780-97.
Abstract: A numerical model of thrombosis/thromboembolism (T/TE) is presented that predicts the progression of thrombus growth and thromboembolization in low-shear devices (hemodialyzers, oxygenators, etc.). Coupled convection-diffusion-reaction equations were solved to predict velocities, platelet agonist (ADP, thromboxane A2, and thrombin) concentrations, agonist-induced and shear-induced platelet activation, and platelet transport and adhesion to biomaterial surfaces and adherent platelets (hence, thrombus growth). Single-platelet and thrombus embolization were predicted from shear forces and surface adhesion strengths. Values for the platelet-biomaterial reaction constant and the platelet adhesion strength were measured in specific experiments, but all other parameter values were obtained from published sources. The model generated solutions for sequential time steps, while adjusting velocity patterns to accommodate growing surface thrombi. Heparinized human blood was perfused (0.75 ml/min) through 580 microm-ID polyethylene flow cells with flow contractions (280 microm-ID). Thrombus initiation, growth, and embolization were observed with videomicroscopy, while embolization was confirmed by light scattering, and platelet adhesion was determined by scanning electron microscopy. Numerical predictions and experimental observations were similar in indicating: 1) the same three thrombotic locations in the flow cell and the relative order of thrombus development in those locations, 2) equal thrombus growth rates on polyethylene and silicon rubber (in spite of differing overall T/TE), and 3) similar effects of flow rate (1.5 ml/min versus 0.75 ml/min) on platelet adhesion and thrombosis patterns.

Computational studies of shape memory alloy behavior in biomedical applications
Petrini, L., F. Migliavacca, et al. (2005), J Biomech Eng 127(4): 716-25.
Abstract: BACKGROUND: Nowadays, shape memory alloys (SMAs) and in particular Ni-Ti alloys are commonly used in bioengineering applications as they join important qualities as resistance to corrosion, biocompatibility, fatigue resistance, MR compatibility, kink resistance with two unique thermo-mechanical behaviors: the shape memory effect and the pseudoelastic effect. They allow Ni-Ti devices to undergo large mechanically induced deformations and then to recover the original shape by thermal loading or simply by mechanical unloading. METHOD OF APPROACH: A numerical model is developed to catch the most significant SMA macroscopic thermo-mechanical properties and is implemented into a commercial finite element code to simulate the behavior of biomedical devices. RESULTS: The comparison between experimental and numerical response of an intravascular coronary stent allows to verify the model suitability to describe pseudo-elasticity. The numerical study of a spinal vertebrae spacer where the effects of different geometries and material characteristic temperatures are investigated, allows to verify the model suitability to describe shape memory effect. CONCLUSION: the results presented show the importance of computational studies in designing and optimizing new biomedical devices.

Computer simulation of polypeptide adsorption on model biomaterials
Ganazzoli, F. and G. Raffaini (2005), Phys Chem Chem Phys 7(21): 3651-63.
Abstract: When biomaterials are inserted in a biological environment, for instance in a body implant, proteins do quickly adsorb on the exposed surface. Such process is of fundamental importance, since it directs the subsequent cell adhesion. Here we review recent advances in this field obtained with molecular simulations. While coarse-grained models can provide important general results, as it has long been recognized in polymer science, the hierarchical structure of a very complex copolymer such as a protein, together with the nature of the biomaterial surface suggest that atomistic models are better suited to investigate these phenomena. Thus, after briefly mentioning some common features of coarse-grained and atomistic force fields, we first discuss early theoretical and coarse-grained simulation results about protein adsorption, and then we highlight the main results recently obtained by us with atomistic models. In particular, we discuss some conformational and energetic aspects of the adsorption of protein fragments with different secondary structure on surfaces of different wettability, including hydrophobic graphite and hydrophilic poly(vinylalcohol). We also consider other features, such as the simulation of the materials wettability, the hydration of the adsorbed fragments, their kinetics of spreading, and the sequential adsorption of two protein fragments on top of each other, highlighting the results of general interest.

Computerized microscopic image analysis method in tissue-biomaterials interaction
Schreiber, H., H. P. Kinzl, et al. (1990), Biomater Artif Cells Artif Organs 18(5): 637-41.
Abstract: The use of computer-based image analysis belongs to the new methods of biocompatibility testing. When materials were implanted subcutaneously in animals the cells of the connective tissue capsule can give a good standard for the evaluation of biocompatibility. The application of image processing systems allows the automation of a great number of measurings and test - techniques. It is also possible to get quantitative information on cell - and haemocompatibility testing. With the help of the automatic microscopic image analysis the accuracy of morphometric methods increased and scientists time was saved.

Concentrated hydroxyapatite inks for direct-write assembly of 3-D periodic scaffolds
Michna, S., W. Wu, et al. (2005), Biomaterials 26(28): 5632-9.
Abstract: Hydroxyapatite (HA) scaffolds with a 3-D periodic architecture and multiscale porosity have been fabricated by direct-write assembly. Concentrated HA inks with tailored viscoelastic properties were developed to enable the construction of complex 3-D architectures comprised of self-supporting cylindrical rods in a layer-by-layer patterning sequence. By controlling their lattice constant and sintering conditions, 3-D periodic HA scaffolds were produced with a bimodal pore size distribution. Mercury intrusion porosimetry (MIP) was used to determine the characteristic pore size and volume associated with the interconnected pore channels between HA rods and the finer pores within the partially sintered HA rods.

Concentration of biomaterials: virus concentration and viral protein isolation
Hammar, L. (1994), Methods Enzymol 228: 640-58.

Concise review of mechanisms of bacterial adhesion to biomaterial surfaces
An, Y. H. and R. J. Friedman (1998), J Biomed Mater Res 43(3): 338-48.
Abstract: This article reviews the mechanisms of bacterial adhesion to biomaterial surfaces and the factors affecting the adhesion. The process of bacterial adhesion includes an initial physicochemical interaction phase (phase one) and a late molecular and cellular interaction phase (phase two), which is a complicated process affected by many factors, including the characteristics of the bacteria themselves, the target material surface, and the environmental factors, such as the presence of serum proteins or bactericidal substances.

Concise review of mechanisms of bacterial adhesion to biomaterials and of techniques used in estimating bacteria-material interactions
Katsikogianni, M. and Y. F. Missirlis (2004), Eur Cell Mater 8: 37-57; discussion 37-57.
Abstract: This article reviews the mechanisms of bacterial adhesion to biomaterial surfaces, the factors affecting the adhesion, the techniques used in estimating bacteria-material interactions and the models that have been developed in order to predict adhesion. The process of bacterial adhesion includes an initial physicochemical interaction phase and a late molecular and cellular one. It is a complicated process influenced by many factors, including the bacterial properties, the material surface characteristics, the environmental factors, such as the presence of serum proteins and the associated flow conditions. Two categories of techniques used in estimating bacteria-material interactions are described: those that utilize fluid flowing against the adhered bacteria and counting the percentage of bacteria that detach, and those that manipulate single bacteria in various configurations which lend themselves to more specific force application and provide the basis for theoretical analysis of the receptor-ligand interactions. The theories that are reviewed are the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, the thermodynamic approach and the extended DLVO theory. Over the years, significant work has been done to investigate the process of bacterial adhesion to biomaterial surfaces, however a lot of questions still remain unanswered.

Conditioning film and environmental effects on the adherence of Candida spp. to silicone and poly(vinylchloride) biomaterials
Jones, D. S., J. G. McGovern, et al. (2001), J Mater Sci Mater Med 12(5): 399-405.
Abstract: The reported incidence of colonization of oropharyngeal medical devices with Candida spp. has increased in recent years, although few studies that have systematically examined the adherence of yeast cells to such biomaterials, the primary step in the process of colonization. This study, therefore, examined the effects of oropharyngeal atmospheric conditions (5% v/v carbon dioxide) and the presence of a salivary conditioning film on both the surface properties and adherence of Candida albicans, Candida krusei and Candida tropicalis to PVC and silicone. Furthermore, the effects of the salivary conditioning film on the surface properties of these biomaterials are reported. Growth of the three Candida spp. in an atmosphere containing 5% v/v CO2 significantly increased their cell surface hydrophobicity and reduced the zeta potential of C. albicans and C. krusei yet increased the zeta potential of C. tropicalis (p<0.05). Furthermore, growth in 5% v/v CO2 decreased the adherence of C. tropicalis and C. albicans to both PVC and silicone, however, increased adherence of C. krusei (p<0.05). Pre-treatment of the microorganisms with pooled human saliva significantly decreased their cell surface hydrophobicity and increased their adherence to either biomaterial in comparison to yeast cells that had been pre-treated with PBS (p<0.05). Saliva treatment of the microorganisms had no consistent effect on microbial zeta potential. Interestingly, adherence of the three, saliva-treated Candida spp. to saliva-treated silicone and PVC was significantly lower than whenever the microorganisms and biomaterials had been treated with PBS (p<0.05). Treatment of silicone and PVC with saliva significantly altered the surface properties, notably reducing both the advancing and receding contact angles and, additionally, the microrugosity. These effects may contribute to the decreased adherence of saliva-treated microorganisms to these biomaterials. In conclusion, this study has demonstrated the effects of physiological conditions within the oral cavity on the adherence of selected Candida spp. to biomaterials employed as oropharyngeal medical devices. In particular, this study has ominously shown that these materials act as substrates for yeast colonization, highlighting the need for advancements in biomaterial design. Furthermore, it is important that physiological conditions should be employed whenever biocompatibility of oropharyngeal biomaterials is under investigation.

Conference on Orthodontic Advances in Science and Technology (COAST) ''Craniofacial Skeletal Bioengineering'' held at Asilomar Conference Center, Pacific Grove, CA, USA, August 27-30, 2004
King, G. and S. Kapila (2005), Orthod Craniofac Res 8(3): 133.

Conflict resolution and Y2K problems. How biomaterials will face up to the real issues of the future
Williams, D. (1999), Med Device Technol 10(10): 18-20, 22.
Abstract: At the end of this century, the medical device industry has achieved some notable successes, yet achieves so little in terms of significant functional replacement and reconstruction of the body. This is partly because of the materials that are used. This article addresses the main points of concern and highlights the way in which medical devices of the future will be based on different principles and will deploy different tactics in the search for safe and reliable treatments of disease and injury.

Confocal and multi-photon microscopy of dental hard tissues and biomaterials
Watson, T. F., A. Azzopardi, et al. (2000), Am J Dent 13(Spec No): 19D-24D.
Abstract: Confocal microscopy is a technique that can be used both in the clinic and the high-resolution microscopy suite. This form of optical microscopy enables high-resolution images to be made of samples with minimum requirements for specimen preparation. Images may be made of either reflections from the sample surface or, if an immersion medium is used to optically couple the objective lens, then sub-surface images can be produced of reflective or fluorescent structures within semi transparent materials such as cells and dental hard tissues. These images are like optical sections, giving thin (> 0.35 microm) slices up to 200 microm below the surface of a mineralized tissue. The technique generates significant improvements in resolution, lying somewhere between that of conventional light microscopy and TEM/SEM. Instruments that work at video-rate allow high-speed events to be examined, such as in vivo clinical studies, cutting of dental tissues and fracture of adhesive interfaces. New dyes offer many exciting prospects for labeling changes in chemical composition in materials or biological tissues, while new imaging techniques such as multi-photon laser excitation of dyes give the potential of greater depth penetration and improved resolution. As with all new techniques the inexperienced should be aware of some of the artifacts inherent to the system. However, the widespread availability of conventional confocal microscopes should give ample opportunity for dental researchers to capitalize on this new technology.

Confocal micro-Raman observation of nanometer thick oxide layers on metal nanoparticles
Owens, F. J. and B. Reddingius (2005), J Nanosci Nanotechnol 5(5): 836-9.
Abstract: It is shown for the first time that confocal micro-Raman spectroscopy can be used to detect metal oxide nanometer thick layers on metal nanoparticles. The measured frequencies of the observed oxide layers are shifted to lower frequencies and the line widths were asymmetrically broadened compared to Raman spectrum in bulk oxide of the metals. The effects are due to phonon confinement which occurs in materials of nanometer dimensions. Models of phonon confinement are used to estimate the thickness of the oxide layers.

Considerations of species-related hematological differences on the evaluation of biomaterials
Bruck, S. D. (1977), Biomater Med Devices Artif Organs 5(1): 97-113.
Abstract: Species-related hematological differences of experimental animals are important in the proper assessment of biomaterials intended for human use. This area, which has received less than adequate attention in the past, requires the development of new test methodologies with blood of primates and humans, under conditions that better simulate the physiological environment.

Constrained acetabular liners: mechanisms of failure
Yun, A. G., D. Padgett, et al. (2005), J Arthroplasty 20(4): 536-41.
Abstract: Although constrained acetabular liners have been successfully used for the treatment of recurrent hip instability, their usage has led to a growing number of associated complications. Twenty-seven patients (29 hips) who experienced failure of the constrained acetabular construct were retrospectively reviewed to define mechanisms of failure. Of these patients, 8 had a recurrent failure of another constrained liner. The 4 modes of failure were failure of fixation to the pelvis, liner dissociation, biomaterial failure, and femoral head dislocation. As constrained liners are highly subject to mechanical overload, the risk of failure can be minimized by reducing prosthetic impingement and avoiding technical errors.

Construction of a biomimetic zwitterionic interface for monitoring cell proliferation and apoptosis
Du, D., J. Cai, et al. (2005), Langmuir 21(18): 8394-9.
Abstract: A new zwitterionic monolayer film of sulfobetaine was constructed by grafting novelly designed N,N-dimethyl (beta-hydroxyethyloxyethyl) ammonium propanesulfonate (DHAPS) to hydroxyl groups of glass in the presence of hexamethylene diisocyanate (HDI) as a coupling agent and dibutyltin dilaurate (DBTDL) as a catalyst. Experiments of blood adhesion proved that the zwitterionic film possessed excellent hydrophilicity and very good biocompatibility and provided an appropriate biomimetic interface for adhesion and proliferation of cells. Thus, the monitoring of the cell proliferation and apoptotic processes on the zwitterionic surface during an incubation process was achieved, using different techniques, such as electrochemical impedance spectroscopy, scanning electron microscopy, flow cytometric assay, and Trypan blue staining. K562 leukemia cells, as a model, cultured in vitro on the zwitterionic surface kept their viability for 5 days and remained healthy and undifferentiated, indicating that the zwitterionic surface did not have a deleterious effect on cell growth in normal conditions. Thus, this man-made interface would be applicable to the growth of cells and the study of biomaterial-cell interaction and has potential applications in medicine and cytobiology.

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Last Modified: 8 February 2006