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Qualitative prediction of solubilization of highly hydrophobic drugs in block copolymer micelles
Latere Dwan'Isa, J., M. Dinguizli, et al. (2005), J Control Release 101(1-3): 366-8.

Quality control assessment of ePTFE precoating procedure for in vitro endothelial cell seeding
Fernandez, P., A. Deguette, et al. (2005), Biomaterials 26(24): 5042-7.
Abstract: Over the past two decades, in vitro autologous endothelial cell (EC) coverage of expanded polytetrafluoroethylene (ePTFE) graft has been developed and clinically applied with success in infrainguinal bypasses. Before endothelialization, the luminal surface of the graft has to be coated with a currently used fibrinolytically inhibited fibrin glue. The aim of this work is to validate the precoating of the ePTFE (4 mm ID) ringed graft with fibrin. Twenty cm-long grafts were precoated with fibrin glue (2 operators) then fixed for microscopy investigations. Grafts were sliced into 3 regions. Thickness analysis was evaluated by image processing. Three grafts have been tested for endothelialization and observed at days 3, 8. Cell-free coated ePTFE were imaged using high-frequency ultrasound modality. Whatever the examined segment an overall homogeneous covering protein is shown. Fibrin thickness after image processing is 8.5+/-0.25 and 4.1+/-0.4 microm for two operators (P <.001). We have evaluated reproducibility and inter- and intra-variability of the operator, assessed quality controls and quality assurance all along the prosthesis and finally endothelialization and subsequent behaviour under shear stress conditions.

Quantification of a novel h-shaped ultrasonic resonator for separation of biomaterials under terrestrial gravity and microgravity conditions
Bohm, H., L. G. Briarty, et al. (2003), Biotechnol Bioeng 82(1): 74-85.
Abstract: A novel, h-shaped ultrasonic resonator was used to separate biological particulates. The effectiveness of the resonator was demonstrated using suspensions of the cyanobacterium, Spirulina platensis. The key advantages of this approach were improved acoustic field homogeneity, flow characteristics, and overall separation efficiency (sigma = 1 - ratio of concentration in cleared phase to input), monitored using a turbidity sensor. The novel separation concept was also effective under microgravity conditions; gravitational forces influenced overall efficiency. Separation of Spirulina at cleared flow rates of 14 to 58 L/day, as assessed by remote video recording, was evaluated under both microgravity (

Quantification of anion and cation release from a range of ternary phosphate-based glasses with fixed 45 mol% P2O5
Ahmed, I., M. P. Lewis, et al. (2005), J Biomater Appl 20(1): 65-80.
Abstract: This article reports on the use of ion chromatography (IC) to investigate extensively the release profiles of both cations and anions and characterize the relationship between composition and degradation for a ternary-based Na(2)O-CaO-P(2)O(5) glass system developed as biomaterials. Studies are carried out on glasses with the formula 45P(2)O(5)-55(xCaO-Na(2)O) in deionized water, where x = 30, 35, and 40 mol%, using a cumulative release method, where the solution is changed at regular intervals.Degradation behavior is linear with time where the degradation rate shows an initial decrease with increasing CaO content. This rate then increases with a further addition of CaO. Cation release profiles follow similar trends to the degradation rates. Anion release profiles show a decrease for the PO(4) and linear polyphosphate (P(2)O(7) and P(3)O(10)) species with increasing CaO content. This decrease is attributed to the cross-linking of the Ca(2+) ions. In contrast, the cyclic P(3)O(9) anion exhibits the highest amount of anionic release, which demonstrates similar trends to the cations. These release patterns suggest that the cyclic P(3)O(9) species dominate the degradation rates. The proposed mode of degradation is a hydrolysis reaction, with the cyclic metaphosphate undergoing acid/base catalysis. The pH remains constant for the 30 and 35 mol% CaO glasses, and drops to about 5.5 for the 40 mol% composition. By using a response factor, it is possible to semiquantitatively analyze the additional peaks observed in the chromatograms. Suggestions are also put forward as to the identity of some of these unidentified peaks.

Quantification of susceptibility artifacts produced on high-field magnetic resonance images by various biomaterials used for neurosurgical implants. Technical note
Matsuura, H., T. Inoue, et al. (2002), J Neurosurg 97(6): 1472-5.
Abstract: Although various biomaterials such as ceramics or titanium alloy are widely used in neurosurgery, the susceptibility artifacts that appear around these materials cause problems when a magnetic resonance (MR) imager is used to assess lesions after surgery. The purpose of the present study was to quantify the susceptibility artifacts produced by various biomaterials used for neurosurgical implants. Using a 3-tesla MR imaging unit, we obtained MR images of various biomaterials, including six types of ceramics, a cobalt-based alloy (Elgiloy), pure titanium, a titanium alloy, and stainless steel. All implants shared a uniform size and shape. In each image, a linear region of interest was defined across the center of the biomaterial in the transverse direction, and the diameter of the susceptibility artifact was calculated. The ceramics produced a considerably smaller artifact diameter than those produced by other biomaterials. Among the types of ceramics, zirconia was found to produce the smallest artifact diameter. Among the remaining biomaterials, the diameters of the artifacts decreased in order from that associated with stainless steel to those associated with cobalt-based alloys, pure titanium, and titanium alloy. Little difference was observed between the artifact diameters associated with pure titanium and titanium alloy. Ceramics are the most suitable biomaterials for minimizing artifacts in high-field MR imaging.

Quantitative analysis of magnetic resonance imaging susceptibility artifacts caused by neurosurgical biomaterials: comparison of 0.5, 1.5, and 3.0 Tesla magnetic fields
Matsuura, H., T. Inoue, et al. (2005), Neurol Med Chir (Tokyo) 45(8): 395-8; discussion 398-9.
Abstract: Magnetic resonance (MR) imaging is an important diagnostic tool for neurosurgical diseases but susceptibility artifacts caused by biomaterial instrumentation frequently causes difficulty in visualizing postoperative changes. The susceptibility artifacts caused by neurosurgical biomaterials were compared quantitatively by 0.5, 1.5, and 3.0 Tesla MR imaging. MR imaging of uniform size and shape of pieces ceramic (zirconia), pure titanium, titanium alloy, and cobalt-based alloy was performed at 0.5, 1.5, and 3.0 Tesla. A linear region of interest was defined across the center of the biomaterial in the transverse direction, and the susceptibility artifact diameter was calculated. Susceptibility artifacts developed around all biomaterials at all magnetic field strengths. The artifact diameters caused by pure titanium, titanium alloy, and cobalt-based alloy increased in the order of 0.5, 1.5, to 3.0 Tesla magnetic fields. The artifact diameter of ceramic was not influenced by magnetic field strength, and was the smallest of all biomaterials at all magnetic field strengths. The artifacts caused by biomaterials except ceramic increase with the magnetic field strength. Ceramic instrumentation will minimize artifacts in all magnetic fields.

Quantitative analysis of monomer vapor release from two-solution bone cement by using a novel FTIR technique
Merkhan, I. K., J. M. Hasenwinkel, et al. (2005), J Biomed Mater Res B Appl Biomater 74(1): 643-8.
Abstract: Methyl methacrylate monomer can evaporate from bone cement to reach cytotoxic levels of concentrations in the implant bed of total joint prosthesis. Therefore, this study was performed by using a novel Fourier transform infrared spectroscopy method to quantify the release of monomer vapor from experimental two-solution bone cement in vitro during polymerization, to examine the effect of surface area versus cement mass, and to explore the effect of initiation chemistry. The results revealed that monomer vapor release is a surface phenomenon. In addition, initiation chemistry plays a major role in controlling the reaction time, and therefore heat concentration and dissipation, which resulted in a higher absorbance peak as initiation chemicals concentration increased. It was concluded that using the FTIR to monitor MMA vapors is an effective technique to obtain quantitative information about monomer vapor release from bone cements during polymerization and provides insight on the polymerization kinetics of two-solution acrylic bone cement.

Quantitative analysis of the regulation of leukocyte chemosensory migration by a vascular prosthetic biomaterial
Chang, C. C., S. M. Lieberman, et al. (2000), J Mater Sci Mater Med 11(6): 337-44.
Abstract: The need for improved, infection-resistant vascular biomaterials calls for more objective evaluation of the immune pathophysiology of implantable prosthetic materials. In this study we have developed a new strategy to quantitatively characterize population-averaged responses of immune cell migration on vascular prosthetic materials. This approach, incorporating a chemokinetically regulated "biomaterial-gel" sandwich configuration, was applied to quantify both random and directed modes of the chemosensory migration of human neutrophil leukocytes on expanded polytetrafluoroethylene (ePTFE). Our studies show that (a) microporous, synthetic materials like ePTFE suppress the basal rate of random cell migration relative to that reported on non-porous control surfaces; (b) stimulation with chemoattractant (formyl peptide) can significantly elevate rates of random and directed migration on ePTFE; and (c) protein conditioning of ePTFE with albumin or immunoglobulin G can differentially modulate the rates and relative proportion of random and directional components of leukocyte migration response to chemoattractant. This, to our knowledge, is the first objective quantitation of chemokinetically regulated cell migration on implantable prosthetic materials.

Quantitative assessment of the tissue response to implanted biomaterials
Vince, D. G., J. A. Hunt, et al. (1991), Biomaterials 12(8): 731-6.
Abstract: The tissue response to a small number of polymeric biomaterials was studied using monoclonal antibodies specific for certain inflammatory cell types, to develop a reliable and accurate method for the quantitative evaluation of biocompatibility. The sites of antibody binding were identified using an avidin-biotin staining procedure and the sections evaluated using a computer-aided image analysis system. The staining technique successfully demonstrated both polymorphonuclear leucocytes and macrophages in tissue samples containing polymeric biomaterials. The image analysis system facilitated the measurement of up to 30 cell-related parameters and allowed a large number of cells to be analysed.

Quantitative evaluation of the fibrin clot extension on different implant surfaces: an in vitro study
Di Iorio, D., T. Traini, et al. (2005), J Biomed Mater Res B Appl Biomater 74(1): 636-42.
Abstract: The aim of the present study was a quantitative evaluation of the in vitro fibrin clot extension on different implant surfaces. Forty-five disk-shaped commercially pure Grade 2 titanium samples with three different surface topographies (machined, DPS, and Plus) were used in the present study. For the quantitative evaluation of the fibrin clot, 30 specimens were used (10 per group); human whole blood was employed. Venous blood was drawn from three healthy adult volunteers, and 0.2 mL were immediately dropped onto the surface of each specimen. Contact time was 5 min at room temperature; then the samples were rinsed with saline solution and fixed in a buffered solution of glutaraldehyde and paraformaldehyde. Samples were washed again with buffer and dehydrated in an ascending alcohol series. Specimens belonging to all groups were observed under SEM at a magnification of 1000x. From each sample, 50 random micrographs were collected in.tif format with an N x M 1024 x 768 grid of pixels. Quantitative analysis of fibrin clot extension showed the following results: in machined samples fibrin clot extension was 345987.2 +/- 63747.7 pixels(2) (mean +/- SD), in DPS samples fibrin clot extension was 375930.9 +/- 54726.86 pixels(2) (mean +/- SD), and in Plus samples, fibrin clot extension was 612333.6 +/- 46268.42 pixels(2) (mean +/- SD). With ANOVA it was possible to find that there were significant differences among the groups. The Tukey test revealed that the extension of the fibrin clot of Plus samples was statistically higher compared to both machined and DPS samples. The results of this in vitro study indicate that there is a correlation between implant surface morphology and fibrin clot extension. Improvement in surface microtexture complexity seems to determine the formation of a more extensive and three dimensionally complex fibrin scaffold. Further investigations are necessary to explain in more detail the mechanisms that regulate the fibrin clot formation on different implant surfaces.

Quantitative histological analysis of bony ingrowth within the biomaterial Polyactive implanted in different bone locations: an experimental study in rabbits
Bouwmeester, S. J., R. Kuijer, et al. (1998), J Mater Sci Mater Med 9(4): 181-5.
Abstract: The quantity of bone formed in cylinders of a newly developed erodible copolymer, Polyactive (PA60/40) was examined. PA60/40 was implanted in three different bone locations in the rabbit: in the cortex, in bone marrow and in trabecular subchondral bone. Bony ingrowth was assessed after 4, 8, 26 and 52 w after the operation and investigated by histology and image analysis. The ingrowth of bone was observed in PA60/40 placed in the cortex from 4 w onwards. After 8 w, more than 90% of the pores of the biomaterial were filled with dense bone. In bone marrow, initially some bone formation was seen. After 26 w, all newly formed bone was resorbed. Subchondral bone formation was less than in the cortex of the femur, but somewhat comparable to the amount of bone found in healthy trabecular bone. Bone formation appeared not to be affected by the degradation of the biomaterial. It was concluded that Polyactive is a suitable bone graft substitute. Bone formation within PA60/40 is site-dependent and this follows Wolff 's law.

Quantitative in vivo studies of hyperemia in the course of the tissue response to biomaterial implantation
Bouet, T., M. Schmitt, et al. (1990), J Biomed Mater Res 24(11): 1439-61.
Abstract: Hyperemia associated with an inflammatory response has been investigated in rats, by using four different experimental models, i.e., "positive" and "negative" polymer implants from the pharmacopea, operative control, and abscess induced by turpentine oil. 133Xenon clearance, infrared thermography and Laser Doppler Flowmetry (LDF) were used to monitor the subcutaneous local hemodynamic changes from 1 to 40 postoperative days. LDF proved to be a sensitive, reproducible method, able to discriminate positive from negative implants already at the 3rd postoperative day and up to 40 days. This increased local blood flow was also visualized at the site of positive implants at the 14th and 21st postoperative days by means of 133Xe Clearance. Additional information obtained by infrared thermography allowed discrimination between positive implants and control sites but only at the very early stage (1 to 3 days). The significance of the different data collected by the three techniques was correlated with histological events occurring at the different implant sites. LDF may therefore represent a useful technique for noninvasive semiquantitative assessment of tissue response to biomaterials.

Quantitative measurements of contact interactions between solid surfaces--a novel method for characterizing surface properties of biomaterials
Wolf, H., K. Domasch, et al. (1983), Biomaterials 4(4): 289-93.
Abstract: A method developed in colloid chemistry for quantitative measurements of adhesion forces in dispersive systems was adapted for the characterization of surface properties of biomaterials in electrolyte solutions and in the presence of macromolecular adsorption layers. The adhesion force between a reference surface (glass) and different polymers (polyurethanes and cellulose derivatives) was found to be dependent on the immersion time of polymers in electrolyte and on the formation of adsorption layers of serum albumin and fibrinogen. It was concluded that the adhesion forces measured can be considered as a further complex interfacial parameter reflecting such microscopic surface properties of biomaterials, which are responsible for biocompatibility.

Quantitative methods for analysis of integrin binding and focal adhesion formation on biomaterial surfaces
Keselowsky, B. G. and A. J. Garcia (2005), Biomaterials 26(4): 413-8.
Abstract: Integrin binding and focal adhesion assembly are critical to cellular responses to biomaterial surfaces in biomedical and biotechnological applications. While immunostaining techniques to study focal adhesion assembly are well established, a crucial need remains for quantitative methods for analyzing adhesive structures. We present simple yet robust approaches to quantify integrin binding and focal adhesion assembly on biomaterial surfaces. Integrin binding to fibronectin and a RGD-containing synthetic peptide was quantified by sequentially cross-linking integrin-ligand complexes via a water-soluble homo-bifunctional cross-linker, extracting bulk cellular components in detergent, and detecting bound integrins by ELISA. Focal adhesion components (vinculin, talin, alpha-actinin) localized to adhesion plaques were isolated from bulk cytoskeletal and cytoplasmic components by mechanical rupture at a plane close to the basal cell surface and quantified by Western blotting. These approaches represent simple and efficient methodologies to analyze structure-function relationships in cell-material interactions.

Quantitative stereological investigations of porous alumina implant biomaterials
Lemons, J. E. and W. C. Richardson (1976), J Dent Res 55(1): 111-4.
Abstract: We made several conclusions from this study on a candidate porous alumina bioceramic. First, the volume fraction of porosity varied from 64 to 79%, whereas Archimedes density shows 62% porosity. Second, the mean lineal intercept and tangent diameter varied from 0.048 to 0.058 cm and 0.034 to 0.040 cm, respectively, and did not provide a good concept of the minimum pore size neck dimensions for the specimen. Third, the pore-size dimension varied from 0.0185 to 0.1157 cm which indicated a minimum pore neck size large enough for tissue ingrowth and ossification if located in bone. Fourth, the pore structure was totally interconnected with considerable side branching and multi-interconnections. Fifth, the serial sectioning of the porous alumina ceramic biomaterial provides considerable insight into the critical features of the material as a candidate for a surgical implant material and a better understanding of the relationships between two-dimensional and three-dimensional structural components.

Quartz crystal microbalance biosensor study of endothelial cells and their extracellular matrix following cell removal: Evidence for transient cellular stress and viscoelastic changes during detachment and the elastic behavior of the pure matrix
Marx, K. A., T. Zhou, et al. (2005), Anal Biochem 343(1): 23-34.
Abstract: A quartz crystal microbalance (QCM) cell biosensor utilizing living endothelial cells (ECs) or human breast cancer cells (MCF-7) adhering to the gold QCM surface was used to study the relative contributions of the cells and their underlying extracellular matrix (ECM) to the measured QCM Deltaf and DeltaR shifts. The ECM represents a natural biomaterial that is synthesized by the cells to enable their attachment to surfaces. We followed the detachment of the ECs or MCF-7 cells from their ECM using a nonproteolytic method and were able to apportion the total frequency, Deltaf, decrease of the biosensor into contributions from cell attachment and from the intact underlying ECM. We also demonstrated that the Deltaf shift remaining after EC removal corresponds to ECM as determined by light microscopic visualization of the stained protein. During the process of cell detachment, we observed a novel transient increase in viscoelastic behavior expressed as a transient increase in the motional resistance, DeltaR, parameter. Then we showed via a simulation experiment using ECs stained with fluorescent rhodamine-labeled phalloidin, an actin stain, that the transient viscoelastic increase correlated with cellular stress exhibited by the cells during removal with ethylene glycol bis(2-aminoethyl ether)-N,N,N',N'- tetraacetic acid. Prior to cells lifting from their ECM, the attached ECs rearrange their actin microfilaments first into peripheral stress fibers and second into internal aggregates, to maintain cell-cell connectivity, retain their spread morphology, and attempt to adhere more tightly to their underlying ECM. The decrease in DeltaR following its transient rise corresponds to cells finally losing their attachment focal points and lifting from the ECM. We also characterized the normalized f shifts, -Delta(Deltaf)(ECM)/attached cell and -Delta(Deltaf)(cells)/attached cell, as a function of varying the number of adherent cells. Finally, we demonstrate that the underlying native ECM biomaterial, from which all cells have been removed, does not exhibit any significant level of energy dissipation, in contrast to the cells when they are attached to the ECM.

Questionable interpretation of results of ACTIVE Study on matrix coils by Boston Scientific
Sluzewski, M. and W. J. van Rooij (2005), AJNR Am J Neuroradiol 26(8): 2163-4.

Radiation induced MMP expression from rectal cancer is short lived but contributes to in vitro invasion
Speake, W. J., R. A. Dean, et al. (2005), Eur J Surg Oncol 31(8): 869-74.
Abstract: AIMS: Matrix metalloproteinase (MMP) activity is increased after radiation. The aims of this study were to assess the time course of this increase and its effects on malignant cell invasion. METHODS: Colorectal cancer (HCT 116, LoVo, C 170 HM 2, CaCO-2), fibroblast (46-BR.IGI, CCD-18 Co) and fibrosarcoma (HT1080) cell lines were irradiated at 4 gray (4 Gy) and matrix metalloproteinase gene and protein expression examined over a 96 h period by real time polymerase chain reaction and gelatin zymography. Invasion was assessed on Matrigel. Human rectal tumour MMP expression was compared before and after long course radiotherapy. RESULTS: Radiation increased MMP gene expression of tumour cell lines, and resulted in increased MMP protein activity in the HT1080 line. HT1080 and HCT 116 in monoculture and LoVo in co-culture were more invasive after radiation at 48 h in vitro, but long course radiotherapy did not result in a consistent increase in MMP expression from human rectal tumour biopsies. CONCLUSIONS: Radiation results in increased MMP expression for a limited time period. This results in an early increase in cell line invasion. Further clinical research is required to clarify if MMP inhibition given perioperatively following radiotherapy decreases local recurrence rates.

Radiation-induced graft copolymer SBS-g-VP for biomaterial usage
Yang, J. M. and G. H. Hsiue (1996), J Biomed Mater Res 31(2): 281-6.
Abstract: The grafting of 4-vinyl pyridine (VP) to styrene-butadienestyrene triblock copolymer (SBS) by radiation-induced graft copolymerization was studied. The cohesive properties such as cohesive energy (Ecoh), molar volume (V), solubility parameter (delta), molar molecular weight (WM), specific volume (Vg), and density (1/Vg) of SBS-g-VP graft copolymer were calculated according to the group contribution of Fedors. The morphology of SBS-g-VP was studied by optical polarizing microscopy. We also measured the glass transition temperature and the mechanical properties of SBS-g-VP graft copolymer. Contact angle and blood-clotting time experiments were also performed to evaluate the biocompatibility of SBS-g-VP. A second domain was found in the SBS-g-VP graft copolymer, which resulted in different properties between SBS-g-VP and SBS. The blood compatibility of SBS-g-VP as measured by the Lee-White clotting test was better than that of SBS and polystyrene.

Radiographic analysis of the transcrestal sinus floor elevation: short-term observations
Diserens, V., E. Mericske, et al. (2005), Clin Implant Dent Relat Res 7(2): 70-8.
Abstract: BACKGROUND: There are some limitations for implant placement in the posterior maxilla when there is an extended sinus. Various techniques for sinus floor elevation allow an increase in implant length. PURPOSE: The aim of the present radiographic study was to assess the augmented site in the sinus around implants that were installed by means of an osteotome-mediated transcrestal sinus floor elevation. MATERIALS AND METHODS: Thirty-three patients with 44 implants were available. In 39% of the implants the sinus floor elevation was performed exclusively with bone chips. Bone fill material (Bio-Oss, Geistlich Sohne AG, Wolhusen, Switzerland) was additionally used to increase the volume and stability of the lifted area at 61% of the implants. The visibility and morphology of the augmentation were assessed and compared by means of intraoral radiography (long-cone technique). RESULTS: All implants were stable and were considered to be successful when they were reexamined in the context of the present study. The mean residual bone height was 5.78 +/- 1.4 mm. The increase of the implant length as compared to the original bone height resulted in a mean value of 3.87 +/- 2.0 mm. The volume and density of the lifted area were more visible if Bio-Oss was added. A shrinkage and/or condensation of the grafted material was visible at 37% of the implants after a minimum loaded period of 200 days. Equally, a decreased visibility of the original sinus floor was noted at 61% of implants. The formation of a cortical bone layer at the apex of the implants was detected at 35% of implants. CONCLUSIONS: The surgical procedure appears to be a safe method with rare complications. Radiographic assessment of the augmentation procedure proved to be difficult, and measurements are not fully reliable.

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Last Modified: 8 February 2006