bluuebunny/crossref_metadata_2025 huggingface dataset:
Embolization: Critical thrombus height, shear rates, and pulsatility. Patency of blood vessels
Authors: Basmadjian Diran
Published: December 2004

The present article builds on elementary fluid dynamics and previous analyses by the author to delineate approximate boundaries of mural thrombus height HP, maximum shear rate \documentclass{article}\pagestyle{empty}\begin{document}$ \dot \gamma _{{\rm Max}} $\end{document}, and flow pulsatility beyond which thrombi are subject to either very high or very low probabilities of embolization. A thrombus height of ∼0.1 mm emerges as a critical dividing line: Below it, the maximum embolizing shear stress τs is independent of thrombus height and varies only linearly with shear rate. Above it, τs quickly approaches a strong quadratic dependence on both thrombus height and shear rate: \documentclass{article}\pagestyle{empty}\begin{document}$ \tau _{\rm s} \sim (H_{\rm p} \dot \gamma)^2 $\end{document}, significantly increasing the likelihood of an embolizing event. By contrast, convective‐diffusive removal of blood components during the initial stages of thrombus formation varies only weakly with \documentclass{article}\pagestyle{empty}\begin{document}$ \dot \gamma ^{{1 \mathord{\left/ {\vphantom {1 3}} \right. \kern-\nulldelimiterspace} 3}} $\end{document} in all but the smallest vessels. These maximum embolizing stresses are due principally to fluid drag. Acceleration (pulsatile) forces only begin to make their presence felt at \documentclass{article}\pagestyle{empty}\begin{document}$ {\dot \gamma} $\end{document} < 500 s−1 and reach parity with fluid drag at \documentclass{article}\pagestyle{empty}\begin{document}$ {\dot \gamma} $\end{document} ∼ 10 s−1, i.e., at a level where the presence of pulsatility is questionable. The results are used to provide maps of domains with high and low probabilities of an embolytic event and of vessel patency. The maps reveal that relatively modest changes in shear rate and/or vessel lumen can cause shifts from high to low likelihood of vessel patency, opening up possible ways of controlling blockage by manipulation of these variables.
Preadsorption of polymers on glass and silica to reduce fibrinogen adsorption
Authors: Maechling‐Strasser C. , Déjardin Ph. , Galin J. C. , Schmitt A.
Published: December 2004

Glass and silica beads were precoated with various polymers to obtain steric exclusion chromatography (SEC) supports which are nonadsorbant for hydrophilic macromolecules. The efficiency of this treatment was estimated by subsequent radiolabeled fibrinogen adsorption. The result obtained with a block copolymer was better than with various hydrophilic homopolymers. This ABA type block copolymer, where A is a poly(N‐acetylethyleneimine) (PAEI) sequence and B a polyethylene oxide (PEO) sequence was preadsorbed at pH 4.5 and 25°C; the fibrinogen adsorption was reduced to less than 5% of the value observed on untreated solid surfaces. Thus the hemocompatibility of solid supports should be increased by precoating with this block copolymer. Results for nonporous glass beads and porous silica particles were in good correlation.
Synthesis and adsorption of a poly(n‐acetylethyleneimine)‐polyethyleneoxide‐poly (n‐acetylethyleneimine) triblock‐copolymer at a silica/solution interface. influence of its preadsorption on platelet adhesion and fibrinogen adsorption
Authors: Maechling‐Strasser C. , Déjardin Ph. , Galin J. C. , Schmitt A. , Housse‐Ferrari V. , Sébille B. , Mulvihill J. N. , Cazenave J. P.
Published: December 2004

The synthesis of a triblock copolymer poly‐(N‐acetylethyleneimine)‐polyethylenoxide‐poly(N‐acetylethyleneimine) includes two successive steps: the first is the functionalization of a poly(ethyleneglycol) precursor by creating sulfonic esters at its chain ends, the second uses these esters to initiate the cationic polymerization of 2‐methyl‐2‐oxazoline. Homopolymers appear in the raw product; hence successive selective extractions of the copolymer with benzene and dioxane are necessary. The final yield in pure copolymer was 11%. The copolymer was characterized by UV and 1H‐NMR spectrometry and light scattering. Adsorption isotherms were determined on silica, for varying pH and salt concentration. Optimum conditions for coating silica with the polymer were determined. The efficiency of this precoating to reduce the adsorption of fibrinogen was very high (99.2% reduction with respect to bare silica). Steric exclusion chromatography of a variety of proteins gave a satisfactory calibration curve. Platelet accumulation on copolymer precoated glass was reduced to 10–20% of its value on bare glass, a result superior to that obtained by albumin passivation of the same glass surface.
A micromechanical technique for monitoring cell—substrate adhesiveness: Measurements of the strength of red blood cell adhesion to glass and polymer test surfaces
Authors: Bowers V. M. , Fisher L. R. , Francis G. W. , Williams K. L.
Published: December 2004

We report a novel method for rapid comparison of the relative strength of adhesion of cells to different solid surfaces. A vertically oscillating micropipette is brought above an individual cell in such a manner that it makes contact with the cell at the lower limit of its travel. The pressure within the micropipette is gradually reduced until the cell attaches to the micropipette by suction and is lifted from the solid surface. The reduction in pressure required to detach a cell depends on the specific cell‐substrate combination and serves as a relative measure of the strength of cell adhesion. A particular advantage of this approach over conventional methods is the ability to select particular cells from a population. As a test of the reproducibility of the method and its ability to distinguish the strength of adhesion of cells to different solid surfaces, we have used it to measure the adhesiveness of human red blood cells to hydrophilic glass, tissue culture grade polystyrene, polyethylene terephthalate, and polymethyl methacrylate. We find that results for the same surface are highly reproducible and that the method is capable of distinguishing small differences in the adhesiveness of red blood cells to the above surfaces.
Identification of plasma proteins adsorbed to hemodialyzers during clinical use
Authors: Mulzer S. R. , Brash J. L.
Published: December 2004

An investigation has been made of the protein layers formed on hemodialysis membranes during clinical use. Dialyzers having membranes of polymethylmeth‐acrylate (PMMA), Cuprophane, cellulose acetate (CA), and saponified cellulose ester (SCE) were examined. Immediately following dialysis the dialyzers were washed free of blood and the membranes eluted with 2% SDS. The eluates were examined by SDS‐PAGE followed by protein immunoblotting. Antisera to 16 common plasma proteins were used to probe for the presence of these proteins in the eluates. Most of the proteins tested for were found in the different eluates, suggesting that the protein layers are extremely complex. The protein compositions were qualitatively different on the different membranes. Except for HMWK the contact phase clotting factors were present in very small amounts and were largely activated. The clear presence of HMWK and the relatively small amounts of fibrinogen provide support for the occurrence of the Vroman effect. Fibrinogen was found to be degraded and this may be related to the observation that plasminogen was activated to plasmin. Complement C3 was an abundant component of all eluates. It was degraded to small fragments in a way which could not be related to complement activation. Many of the other proteins, particularly those of high molecular weight, were extensively degraded. It is speculated that this heretofore unremarked phenomenon may be due to the action of enzymes released by cell damage.
Thermodynamic study of phase transfer of precipitates on SiC whisker reinforced glass ceramics
Authors: Imai K. , Yuge T. , Ito S. , Kawase T. , Saito S.
Published: December 2004

Physicochemical properties of glass ceramics in weakly buffered, supersaturated, metastable calcium and phosphate solution were studied. Formations of calcium phosphate precipitates were also analyzed thermodynamically. All biomaterials examined here showed primarily dissolution process and subsequent nucleation. Dissolution was enhanced in those which contained Na2O and/or SiC. The dissolution of calcium and phosphate ions from biomaterials and subsequent nucleation of calcium phosphate salts after induction time resulted in a stable equilibrium having solubility characteristics similar to octacalcium phosphate (OCP). The most soluble material, CPSN‐SiC, showed an initial transient equilibrium with amorphous calcium phosphate (ACP). From above results, calcium phosphate ceramics had certain driving force of its own which kept the equilibrium of solution to OCP thermodynamically for 7 days. Despite the favorable solubility equilibrium attained, there still remain problems for clinical application.
The effects of heat treatments and bead size on the corrosion of porous F75 in saline and serum
Authors: Hughes P. J. , Brown S. A. , Payer J. H. , Merritt K.
Published: December 2004

An accelerated anodic corrosion method was used to study the effects of heat treatment and bead size on corrosion and metal ion release of porous coated F75 cylinders in saline and serum. Three heat treatments were used: a standard process for F75 implants (HTA), the standard plus an additional hour in air to produce a thin oxide film (HTA′), and a sintering in high vacuum to produce a chromium‐depleted surface (HTB). Three bead sizes of similar composition were used, with approximate sizes of 215, 300, and 560 μm. The results demonstrated that HTA′ had the lowest corrosion rate and that of HTB was significantly greater than either HTA or HTA′. The corrosion rates of HTA and HTA′ were significantly greater in serum as compared with saline, whereas that of HTB was not affected by the presence of serum, suggesting an interaction between chromium and serum proteins. Bead size had a minimal effect on the corrosion rate of HTA′. For HTA, the small beads had the highest corrosion rate; the lowest was with the medium‐sized beads. Bead size had the most significant effect with HTB, with that of the smaller beads having the higher corrosion rates. The effects of bead size were less consistent in serum, suggesting that protein adsorption may mask some of the surface area effects. It is concluded that the oxide film does reduce corrosion, that proteins do have an influence on the corrosion of F75, and that this method can be a suseful tool for studying the effects of improved heat treatment methods on the corrosion rate of F75 implants.
A fractographic analysis of in vivo poly(methyl methacrylate) bone cement failure mechanisms
Authors: Topoleski L. D. Timmie , Ducheyne Paul , Cukler John M.
Published: December 2004

Cementing with poly(methyl methacrylate) (PMMA) is a common means of fixing total hip prostheses. Bone cement fails mechanically, and subsequent loosening frequently requires correction via revision surgery. An initial step in optimizing bone cement properties is to establish which properties are critical to the material's in vivo performance. The objectives were to discern the critical in vivo failure mechanisms of bone cement. Fracture surfaces of bone cement specimens that failed in vivo were compared with fatigue and rapid fracture surfaces created in vitro. In vivo fracture processes of bone cement were positively identified and explained by the elucidation of PMMA fracture micromechanisms. The ex vivo fracture surfaces are remarkably similar to in vitro fatigue fracture surfaces. The fractographic data document that the primary in vivo failure mechanism of bone cement is fatigue, and the fatigue cracks grow by developing a microcraze shower damage zone. Agglomerates of BaSO4 particles can be implicated in some bone cement failures, large flaws or voids in vivo can lead to a rapid, unstable fracture, pores in the PMMA mass have a clear influence on a propagating crack, and wear of the fracture surfaces occurs, and may produce PMMA debris, exacerbating bone destruction.
Surface passivation by human albumin of plasmaperesis circuits reduces platelet accumulation and thrombus formation. Experimental and clinical studies
Authors: Mulvihill Juliette N. , Faradji Albert , Oberling Francis , Cazenave Jean‐Pierre
Published: December 2004

The contact of flowing blood with an artificial surface leads to adsorption of plasma proteins, followed by platelet adhesion and aggregation and thrombus formation. This phenomenon is enhanced by turbulent flow at joints, bifurcations, and constrictions. In therapeutic plasmapheresis using an IBM blood cell separator, blockage of the extracorporeal circulation system by platelet‐fibrin thrombi imposed a halt in treatment for manual clearance of the circuit for 66 in 149 cases (44%). Thus it was decided to passivate the surface of the extracorporeal circuit by filling the tubing with 4% human serum albumin 15–20 min before the treatment session and then displacing the albumin solution with the patient's blood without creating an air–liquid interface. After introduction of this technique, a blockage was observed for only 11 in 239 cases (5%). In vitro measurements of platelet accumulation on the internal surface of the circulation system were carried out using washed human platelets labeled with 111In‐oxine in the presence of a 40% hematocrit. Preadsorption of the surface with albumin reduced platelet deposition to 4–5% that observed for an equivalent pretreatment with physiological saline.
Use of the acyl azide method for cross‐linking collagen‐rich tissues such as pericardium
Authors: Petite H. , Rault I. , Huc A. , Menasche Ph. , Herbage D.
Published: December 2004

Collagen biomaterials should be cross‐linked in order to prevent biodegradation when they are used as implants. We have compared the cross‐linking efficiencies of glutaraldehyde and acyl azide in pericardium. Glutaraldehyde is used currently, but it elicits a cytotoxic effect which reduces the biocompatibility of cross‐linked tissue. We have attempted to overcome this problem by developing a cross‐linking method that obviates incorporation of foreign agents. Our process involves transformation of free carboxyl groups on collagen into acyl azide groups, which react with free amino groups on adjacent side chains. We have shown that the greatest increase in the thermal stability of collagen, as measured by differential scanning calorimetry, is achieved when tissue swelling is inhibited by the addition of sodium chloride (1 M) during acyl azide formation. Under these conditions, the denaturation temperature (Td) of pericardial collagen treated with acyl azide is raised to 83.4°C and that of tissue treated with glutaraldehyde to 85.1°C. Moreover, acyl‐azide‐treated tissues have the same resistance as glutaraldehydetreated tissues to chemical solubilization by cyanogen bromide and to enzymatic digestion by collagenase.
In vitro biocompatibility of polyetheretherketone and polysulfone composites
Authors: Wenz L. M. , Merritt K. , Brown S. A. , Moet A. , Steffee A. D.
Published: December 2004

Short carbon fiber reinforced composites could potentially replace some of the metal alloys used in orthopedic implants. In particular, polysulfone and, more recently, polyetheretherketone have been considered as the matrix material for carbon fiber reinforced composite implant materials. ASTM standards F813 and F619 for direct contact cell culture evaluation and extraction were employed to determine the in vitro biocompatibility of a carbon fiber composite of polyetheretherketone, PEEK, in comparison to a carbon fiber reinforced polysulfone composite. The cell cultures were assessed qualitatively by microscopy and quantitatively using an enzyme assay to determine cytotoxicity. Overall, the cellular response to the PEEK and polysulfone composites were negligible indicating that further in vivo studies with these materials are appropriate.
Cytotoxicity testing of wound dressings using normal human keratinocytes in culture
Authors: Rosdy Martin , Clauss Louis‐Christian
Published: December 2004

Comparative cytotoxicity testing of 16 wound dressings of different composition show that normal human keratinocytes (NHK) growing on a fibroblastic feeder layer are as sensitive to toxic materials by direct contact as the confluent MRC5 fibroblasts used for standard cell culture cytotoxicity testing, and slightly more sensitive when extracts of the dressings were tested. After direct contact with each of the cell types, we found effects due to 12 dressing samples (75%), but the extracts of only 6 of them induced changes in cell shape or cell death on NHK, and 4 of them on MRC5 cells. In order to assess the compatibility of these dressings with a pure population of epidermal cells, the cell type responsible for reepidermization of healing wounds, we then tested the sensitivity, both to dressing samples and extracts, of normal human keratinocytes (NHK) grown in chemically defined medium and without a feeder layer: The results show epidermal cytocompatibility of 10 dressing extracts, while 6 others induced cytopathic effects. Three of these extracts specifically damaged epidermal cells and inhibited their proliferation. When comparing the sensitivities of NHK (in defined medium) and MRC5 cells, we observed complete correlation for 75% of the dressings by extract testing and in 94% of the cases after direct contact.
Poly(dimethylsiloxane)‐poly(ethylene oxide)‐heparin block copolymers II: Surface characterization and in vitro assessments
Authors: Grainger D. W. , Knutson K. , Kim S. W. , Feijen J.
Published: December 2004

Amphiphilic block copolymers containing poly(dimethylsiloxane), poly(ethylene oxide), as well as heparin‐coated glass beads and tubes were evaluated for the amounts and activities of surface‐immobilized heparin. Because the amphiphilic copolymer system is thermodynanmcally predicted to demonstrate low‐energy phase enrichment on the surfaces of aircast films, studies were also undertaken to understand the in vitro results. Solvent‐cast copolymer films have a heterogeneous microphase‐separated structure according to transmission electron micrographs. Wilhelmy plate contact angle analysis indicates significant surface restructuring occurs upon hydration. Attenuated total reflectance infrared spectroscopy studies of the desiccated and hydrated films at two different sampling depths show compositional heterogeneity as a function of depth, as well as near surface restructuring allowing surface enrichment of the high‐energy segments following contact with water. Significant concentrations of heparin are detected on the surface of these coatings by toluidine blue assays. In addition, a portion of the surface‐bound heparin maintains its original bioactivity as determined by recalification times, thrombin times, and Factor Xa assays. These substrates were also tested for platelet adhesion and activation reactions in vitro using polymer‐coated beads in rabbit platelet‐rich plasma. Heparinized polymers promoted low levels of platelet adhesion and serotonin release. Surface concentrations of heparin from bioactivity assays were then correlated with platelet adhesion and the extent of platelet release to assess the efficacy of this heparin‐immobilized copolymer as a blood‐compatible material or coating.
The influence of hydrogel functional groups on cell behavior
Authors: Smetana K. , Vacík J. , Součková D. , Krčová Z. , Šulc J.
Published: December 2004

This study provides information on the behavior of macrophages on the surface of the subcutaneously implanted hydrogel strips. Hydrogel containing OH,CONH, and (CH3)2Ngroups induced a spreading of macrophages on the implants. The materials containing SO3H groups slightly, and materials containingCOOH groups more intensively, inhibited spreading of the macrophages. The fusion of macrophages into multinucleate cells was inhibited on the surface of materials containing acidic groups (SO3H, COOH) and increased on the hydrogels containing 30 mol% of alkaline (CH3)2N groups in comparison with hydrogels containing OH or CONH groups. The differences of the behavior of macrophages on the surface of individual types of hydrogels are probably independent on the adsorption of plasma fibrnectin onto the hydrogels. The correlation between the macrophages spreading and fusion and surface charge of the hydrogel implant can be hypothetically explained by electrostatic interaction between macrophages cell membrane and implant.
Surface reactions of calcium phosphate ceramics to various solutions
Authors: Hyakuna Katsufumi , Yamamuro Takao , Kotoura Yoshihiko , Oka Masanori , Nakamura Takashi , Kitsugi Toshiaki , Kokubo Tadashi , Kushitani Hideki
Published: December 2004

The surface reactions of calcium phosphate ceramics have been thought to play an important role in bonding with living bone. Hydroxyapatite (HA), tricalcium phosphate (TCP), and two kinds of apatite‐containing glass ceramics were immersed in three types of solutions with different chemical constituents. The first solution was a physiological saline, the second contained phosphate (PO4), and the third was a balanced salt solution consisting of calcium (Ca), magnesium (Mg), and PO4. After serial incubation periods, changes in the solutions were assessed by measurement of total Ca, Mg, and PO4. The ceramic surfaces were studied using scanning electron spectroscopy, infrared reflection spectroscopy, and thin‐film x‐ray diffraction. The surface reactions of the ceramics were greatly affected by the chemical compositions of the surrounding media. In the complete solution with both Ca and PO4, a carbonated apatite layer was formed on the surfaces of HA, TCP, and the glass ceramics. In comparison to HA and TCP, the glass ceramics were characterized as Ca‐releasing materials, the dissolved Ca creating an apatite layer on the surfaces in a few days, in conjunction with PO4stock in the surrounding media. The immersion test with various solutions proved to be a simple and effective method of assessing surface conditions of ceramic materials.
Biocompatibility of a polyether urethane, polypropylene oxide, and a polyether polyester copolymer. A qualitative and quantitative study of three alloplastic tympanic membrane materials in the rat middle ear
Authors: Bakker D. , van Blitterswijk C. A. , Hesseling S. C. , Koerten H. K. , Kuijpers W. , Grote J. J.
Published: December 2004

The biocompatibility of porous implants made of Estane 5714 F1 polyether urethane, polypropylene oxide, and a poly(ethylene oxide hydantoin) and poly(tetramethylene terephthalate) segmented polyether polyester copolymer (HPOE/PBT copolymer), which were selected as candidates for an alloplastic tympanic membrane, was assessed after implantation in rat middle ears for periods of up to 1 year. Implantation of the materials led to tissue reactions initially associated with the wound‐healing process, whereas after 1 month not only the presence of macrophages and foreign‐body giant cells surrounding the implant materials but also implant degradation were characteristic for a foreign‐body reaction. Macrophages and foreign‐body giant cells dominated the picture of the tissue surrounding polypropylene oxide. The altered morphology of these cells, the persistent infiltration of the implantation sites by exudate cells, and the premature death of five rats in the 1‐year group suggest that polypropylene oxide degradation was accompanied by the release of toxic substances. Estane and copolymer degradation did not induce tissue responses reflecting implant toxicity, and tympanic membranes given these alloplasts showed a normal healing pattern. Inclusions in the cytoplasm of macrophages associated with degradation and phagocytosis of all of the polymers under study were found to contain iron, silicon, titanium, and aluminum. Growth of fibrous tissue and bone, the latter into Estane and HPOE/PBT copolymer implants, indicated appropriate implant fixation by tissue, although macrophages and foreign‐body giant cells were present as well. Especially the fixation of copolymer by ingrowth of bone seems promising in terms of the amount of bone in the pores and the electron‐dense bone/copolymer interface. The latter is indicative for bonding osteogenesis. The HPOE/PBT copolymer is a better candidate for alloplastic tympanic membrane than Estane, and the use of polypropylene oxide cannot be recommended.
Student research award in the graduate degree candidate category, 16th annual meeting of the society for biomaterials, Charleston, SC, May 20–23, 1990. Investigation of a hydroxyapatite and calcium sulfate composite supplemented with an osteoinductive factor
Authors: Damien C. J. , Parsons J. R. , Benedict J. J. , Weisman D. S.
Published: December 2004

In the search for a suitable bone graft substitute, a study was conducted using a material that combined a proven osteconductive composite, hydroxyapatite‐calcium sulfate (HA/CS), with an osteoinductive factor, bovine osteogenic factor (OF). The initial study demonstrated the osteoinductive potential of OF in the rabbit muscle model. Once satisfied that the OF was active, it was added to the HA/CS composite and placed in 8‐mm trephine defects in the rabbit cranium. This HA/CS/OF was directly compared to HA/CS augmented with a control protein, rabbit serum albumin (RSA). Animals were sacrificed at 4 and 8 weeks. Results demonstrated increased bone formation with the addition of the OF to the composite with bridging of the defects, in most cases, by 4 weeks. No bridging was seen, at this time period, in the other defects left unfilled or filled with HA/CS/RSA. Osteogenic factor, with the appropriate delivery system, can induce bone formation in the rabbit muscle. It may also increase the rate of bone formation at early time periods in a bony defect site when the delivery system is the osteconductive composite HA/CS.
Tissue reaction to subcutaneous implantation of a collagen sponge. A histological, ultrastructural, and immunological study
Authors: Anselme K. , Bacques C. , Charriere G. , Hartmann D. J. , Herbage D. , Garrone R.
Published: December 2004

The biocompatibility of a subcutaneously implanted bovine collagen sponge (Haemostagen) was studied in rats by analyzing tissue reactions up to 3 months by histological and ultrastructural methods; in addition, the level of serum antibodies to bovine type I collagen (the major implant collagen) was measured by solid‐phase radio‐immunoassay. By 8 h after implantation, the implant was completely filled with polymorphonuclear cells (PMNs). After 8 days, fibroblasts had developed a granulation tissue within the sponge and the PMNs had almost disappeared. The small residue that remained after 1 month consisted of some densely packed collagen fibrils containing giant cells, which had disappeared by 3 months. No antibodies to bovine type I collagen were found in the sera of implanted rats.
Micromechanical spectroscopy of cartilage proteoglycans: Hydration
Authors: Lamure Alain , Harmand Marie‐Françoise , Lacabanne Colette
Published: December 2004

Proteoglycan subunits extracted from calf cartilage have been studied with a high resolving power mechanical spectroscopy: the Thermostimulated Creep (TSC). The influence of hydration on TSC spectra shows the existence of two types of bound water: the weakly bound water increases the inertia of proteoglycan and stiffens their structure; the strongly bound water is responsible to a compensation law indicating the existence of a resonance phenomenon at the physiological temperature. Because of the looseness of bonds in weakly bound water, an increase of the local pressure may induce, in vivo, a release of water in tissues. This hypothesis explains perfectly the role of a water pump of proteoglycans in cartilage.
Development and testing of a human collagen graft material
Authors: Quteish D. , Singh G. , Dolby A. E.
Published: December 2004

Human Type I collagen was extracted from placenta using pepsin and salt fractionation. The collagen was characterized by SDS‐PAG electrophoresis dispersed in acidic medium, freeze‐dried, and crosslinked in a 0.25% glutaraldehyde solution pH 4.5 for 2 days. After washing for 7 days and freeze drying the resultant collagen sponge was tested with regard to mechanical, physical, enzymatic degradation properties and biological responses. The modulus of elasticity was found to be 289 ± 10 g/mm2 and the sponge was in soluble in water, buffered saline, or tissue culture medium over a period of 6 weeks with swelling occurring at less than 5% of volume. The sponge had a high fluid binding capacity, amounting to 56 ± 5 mL tissue culture medium per gram of dry weight. Bacterial collagenase produced slow degradation of the sponge with colmplete disappearance by 24 h only when concentrations (200 units enzyme per mg of the collagen sponge) were used. Cytotoxicity studies using human gingival and periodontal ligament fibroblasts revealed less than 5% apparent cytotoxicity or proliferation. Subcutaneous implantation was folllowed by resorption and vascularization over a period of 6–8 weeks. It was concluded that the collagen sponge prepared from human Type I collagen has potential as a graft material in oral surgical procedures.
Small‐caliber polyurethane and polytetrafluoroethylene grafts: A comparative study in a canine aortoiliac model
Authors: Brothers Thomas E. , Stanley James C. , Burkel William E. , Graham Linda M.
Published: December 2004

In vivo stability of a new small‐caliber polyurethane graft (n8) was assessed in a canine aortoiliac model and compared to that of a conventional expended polytetrafluoroethylene (ePTFE) graft (n8). Six months following implantation, marked aneurysmal dilatation to 230 ± 80% (x ± SD) of the original diameter occurred in polyurethane grafts, while dilatation to 110 ± 8% of the original diameter occurred in ePTFE grafts (p < 0.005). Interval patency was 75% for each graft type. Luminal thrombus affected 59% of polyurethane graft surfaces compared to 22% of ePTFE graft surfaces (p < 0.01). Qualitative examination of representative sections of polyurethane conduits demonstrated thick inner capsules with numerous small islands of graft material surrounded by macrophages and bands of mature fibrous tissue, in contrast to the thinner neointima and limited anastomotic pannus ingrowth observed in ePTFE grafts.
Porcine aortic valve bioprostheses: A morphologic comparison of the effects of fixation pressure
Authors: Hilbert Stephen L. , Barrick Mary K. , Ferrans Victor J.
Published: December 2004

It has been suggested that the mechanical durability of glutaraldehyde‐treated porcine aortic valve (PAV) bioprostheses (BPs) may be increased if collagen crimp approximating that observed in native valvular tissue is maintained during preimplantation processing. Among the factors affecting PAV fixation, the magnitude of the pressure applied to the aortic valve during fixation influences the extent of collagen crimp. Polarized light microscopy is useful for both the qualitative assessment of collagen morphology and the quantitative measurement of collagen crimp in BPs. The purpose of this study was to determine the feasibility of using this optical method to detect quantitative differences in PAV collagen crimp following zero‐, low‐, and high‐pressure fixation. The results of this study demonstrate the following: (1) coupling polarized light microscopy and morphometric measurements provides a quantitative method for the evalution of the relationship between fixation pressure and collagen crimp in PAVs; (2) a significant association between increasing fixation pressure and absence of collagen crimp was observed in cords and the midcusp region; (3) collagen crimp length in the cords is affected by fixation pressure; (4) the alteration of collagen crimp by low‐ and high‐pressure fixation does not uniformly affect all regions of the cusp; and, (5) collagen crimp was consistently present in all cusp regions in zero‐pressure fixed PAVs.
The behavior of alloplastic tympanic membranes in Staphlococcus aureus‐induced middle ear infection. II. Morphological study of epithelial reactions
Authors: Bakker D. , van Blitterswijk C. A. , Hesseling S. C. , Daems W. Th. , Grote J. J.
Published: December 2004

Epithelial reactions to Silastic, Estane polyether urethane, polypropylene oxide, and a poly(ethylene oxide hydantoin) and poly(tetramethylene terephthalate) segmented polyether polyester copolymer were investigated after implantation in tympanic membranes and submucosa of noninfected and Staphylococcus aureus‐infected rat middle ears. Porous implants made of Estane and polypropylene oxide were completely covered by tympanic‐membrane connective tissue, epidermis, and epithelium in 2 weeks and those made of copolymer in between 2 and 4 weeks postoperatively. Silastic implants, which were dense, were not enveloped by tympanic‐membrane tissue but rejected. Starting in the 6th postoperative month the proliferative activity and structure of both the tympanic membrane epithelium and epidermis became normal except for the presence of iron‐containing secretory epithelium near polypropylene oxide. After initial swelling caused by the surgical trauma, neither the proliferative activity nor the composition of the epithelium covering submucosal implants was affected by the presence of any of the biomaterials. Infection of middle ears bearing implants induced epithelial reactions similar to those associated with infected middle ears without an implant.
Histological and ultrastructural appearance of the hydroxyapatite–bone interface
Authors: De Lange G. L. , De Putter C. , De Wijs F. L. J. A.
Published: December 2004

This article describes the histological and ultrastructural appearance of the interface created in the implantation bed, between bone tissue and implants made of dense sintered hydroxyapatite (HA). Biopsies from dog subjects included: (a) loaded permucosal dental implants for tooth substitution, (b) subperiosteally placed implants for alveolar bone correction, (c) endosseously placed dental root implants to retain ridge form following extraction. The light and electron microscopical results show extensive bone apposition on the osseous sides of the implant surfaces. There is an intimate, direct bone contact without any visible interruption. The bone is of normal lamellar type and continuously connected with the trabecular bone. Bone has grown into the finest surface irregularities of the implant. Collagen fibers of the calcified bone matrix are observed within a distance less than 500 Å from the implant surface. The thin (20–100 Å) electron dense layer at the bone‐implant interface resembled the lamina limitans of organic bone matrix, also seen at the inner walls of the osteocytes lacunes. Deposition of bone gives rise to a biologically stable bone‐implant interface, without disturbance of the physiological bone turnover. This is seen as very favorable for desired long term fixation of implant to bone.
Ectopic induction of cartilage and bone by water‐soluble proteins from bovine bone using a polyanhydride delivery vehicle
Authors: Lucas Paul A. , Laurencin Cato , Syftestad Glenn T. , Domb Abraham , Goldberg Victor M. , Caplan Arnold I. , Langer Robert
Published: December 2004

Controlled release delivery vehicles for water‐soluble osteogenic proteins from demineralized bovine bone matrix were constructed using polyanhydride polymers. The water‐soluble proteins were isolated from a 4 M guanidine hydrochloride extract of bone matrix. The water‐soluble proteins possessed Chondrogenic Stimulating Activity (CSA) when tested in stage 24 chick limb bud cell cultures, but were incapable of inducing cartilage or bone in vivo when implanted intramuscularly into mice by themselves. The polyanhydride polymers alone were also incapable of inducting ectopic cartilage or bone. However, when the water‐soluble proteins were incorporated into the polymeric delivery vehicle, the combination was capable of inducing cartilage and bone up to 50% of the time. These results demonstrate that it is possible to use polyanhydride polymers as controlled‐release delivery vehicles for soluble bioactive factors that interact with a local cell population.
Release and detection of dental corrosion products in vivo: Development of an experimental model in rabbits
Authors: Reuling Norbert , Wisser W. , Jung A. , Denschlag H. O.
Published: December 2004

An experimental animal model was developed to investigate the release of metal ions from nonprecious dental alloys. Cast specimens of five NiCr‐alloys and CoCr‐alloys were implanted intramuscularly in rabbits for periods of 2, 4, 8, and 12 weeks. The concentrations of nickel, chromium, cobalt, and molybdenum in the implantloaded muscles were determined by electrothermal atomic absorption spectrometry (AAS) and neutron activation analysis (NAA). Reference muscle samples of each animal were analyzed to determine the individual control values. Significant increases in the tissue concentrations of these metals occurred in the immediate vicinity of the implants. Concentration gradients of the corrosion products were found between the implant contact tissue and the implant periphery (p < 0.001). Tissue concentrations of nickel and chromium correlated (r < 0.7). Microprobe analysis before and after implantation of the alloy specimens indicated an even corrosive loss of the alloy surfaces and changes in the surface element distributions. Advantages and limitations of this animal model are discussed, as well as its application in future studies.
In vitro degradation of glycine/DL‐lactic acid copolymers
Authors: Helder J. , Dijkstra P. J. , Feijen J.
Published: December 2004

The in vitro degradation of glycine‐DL‐lactic acid copolymers was studied as a function of the composition. These polydepsipeptides were prepared by ring‐opening copolymerization of 6‐methyl‐2,5‐morpholinedione and DL‐lactide. The degradation of discs of the copolymers was performed in a phosphate buffer at pH 7.4 and 37°C. The decrease in molecular weight and weight was determined until complete weight loss had occurred. Poly(DL‐lactide) was used as a reference material. All (co)‐polymers show an immediate decrease in molecular weight, whereas the weight remains almost unchanged during a longer period of time. Decrease in weight started earlier as the glycine content of the copolymer increased. The lactic acid content of the residual material increased during the weight loss showing a higher solubility of polymer fragments with a relatively high content of glycine residues. From the hydrolysis constants it was concluded that the degradation was best described by hydrolysis of ester bonds via a bulk erosion process, autocatalyzed by the generated carboxylic acid end groups. The rate constants varied from 4–7 × 10−2 (day−1) for all (co)polymers. All (co)polymers show an increase in the molecular weight distribution upon weight loss.
Hard tissue replacement (HTR) polymer as an implant material
Authors: Amler M. H. , LeGeros R. Z.
Published: December 2004

This study aimed to evaluate the effectiveness of a synthetic implant material Hard Tissue Replacement polymer (HTR) for: (1) compatibility with bone and soft tissues, (2) capacity to physically attach to bone and soft tissues, and (3) capacity for bone induction and metaplasia. HTR was implanted for a 3‐week test period in femur bones, connective tissue, and skeletal muscle of 15 Sprague‐Dawley descent rats for histological examination and implanted in bone in 6 rats for infrared absorption analyses to determine the presence of new bone. Compatibility (defined as absence of significant inflammation) was present in 13/14 (93%) bone sites, 7/9 (78%) connective tissue, and 4/4 (100%) muscle sites. Physical attachment of HTR occurred in 10/14 (71%) bone sites, 4/9 (44%) connective tissue, and 1/7 (14%) muscle sites. Density of new bone appeared to be greater with HTR than in controls. However, no metaplastic bone was formed in nonbony sites indicating that this material is nonosteogenic. These preliminary findings demonstrated the effectiveness of HTR as an implant material.
Blood compatibility of PEO grafted polyurethane and HEMA/styrene block copolymer surfaces
Authors: Nojiri Chisato , Okano Teruo , Jacobs Harvey A. , Park Ki Dong , Mohammad S. Fazal , Olsen Don B. , Kim Sung Wan
Published: December 2004

HEMA/styrene (HEMA/STY) block copolymers and poly(ethylene oxide) 4,000 M.W. (PEO4K) grafted Biomer (B‐PEO4K) surfaces have been synthesized, characterized, and evaluated as blood‐contacting materials. These surfaces have demonstrated improved blood compatibility, compared to Biomer, in in vitro and ex vivo experiments. Biomer vascular grafts (6 mm I.D. 7 cm in length) were fabricated by a dip coating process. The luminal surface was modified either with PEO grafting, HEMA/STY coating, or Biomer coating (control). These surface‐modified grafts were implanted in the abdominal aortas of dogs and evaluated for graft patency and protein adsorption.

Surface protein layer thickness was measured by transmission electron microscopy (TEM). B‐PEO4K and Biomer showed thick multilayers of adsorbed proteins (1000–2000 Å) after 3 weeks to 1 month implantation. In contrast, HEMA/STY only showed a monolayer protein thickness (<200 Å), even after 3 months.

Visualization of adsorbed plasma proteins (albumin, IgG, and fibrinogen) was performed with scanning electron microscopy (SEM)/TEM using an immunogold double antibody technique. The pattern of protein distribution showed high concentrations of fibrinogen and IgG, and less albumin adsorbed onto Biomer and B‐PEO4K. In contrast, HEMA/STY showed a patchy protein distribution pattern with high concentrations of albumin and IgG, and relatively less fibrinogen.

Adsorbed monolayer patterns showed improved compatibility over multilayered proteins. The Biomer and B‐PEO4K grafts occluded within 1 month, while HEMA/STY grafts were patent for over 3 months. The thin and stable adsorbed protein layer on HEMA/STY surfaces may be associated with the microdomain structures of the surface, and will play an important role in long‐term in vivo blood compatibility. This manuscript will evaluate the long‐term in vivo performance of these polymers, analyze the extent of protein adsorption onto the surfaces, and correlate protein layer thickness to the thrombogenicity of the polymer surfaces.
Biochemical changes and cytotoxicity associated with the degradation of polymeric glutaraldehyde derived crosslinks
Authors: Huang‐Lee Lynn L. H. , Cheung David T. , Nimni Marcel E.
Published: December 2004

The reversibility of glutaraldehyde crosslinks has been suggested as a reason for failure of long‐term bioprosthetic implants. The stability of such crosslinks was investigated in tendons and model compounds. Small but cytotoxic levels of glutaraldehyde were still released from crosslinked tendons even after these tendons were extensively rinsed for up to 6 months. The toxic effect was evidenced by the death of fibroblasts surrounding a midsection piece of rinsed crosslinked tendon, while the end section pieces did not show toxic effects. The formation and stability of glutaraldehyde modified [14]‐L‐lysine derivatives were investigated. The polymerization of glutaraldehyde with amino compounds was initially fast but continued to proceed slowly for months. Degradation of high‐molecular‐weight soluble polymers was detected by gel filtration chromatography. Low‐molecular‐weight soluble materials were also released from insoluble products which were formed when high concentrations of glutaraldehyde and radioactive lysine were reacted. These chemical and biological studies suggest that local cytotoxicity of glutaraldehyde crosslinked bioprostheses may be due to unstable glutaraldehyde polymers that persist in the interstices of crosslinked tissues.
Titanium‐coated micromachined grooves of different dimensions affect epithelial and connective‐tissue cells differently in vivo
Authors: Chehroudi B. , Gould T. R. L. , Brunette D. M.
Published: December 2004

A desirable feature of an implant surface which penetrates epithelium would be that the surface impedes epithelial downgrowth. Previous experiments have shown that the micromachined, horizontally oriented grooves on the percutaneous implant surface can impede epithelial downgrowth (Chehroudi et al., J. Biomed. Mater. Res., 22, 459 (1988) and 23, 1067 (1989)). However, little is known of the effect of varying groove parameters such as depth, spacing, and orientation on epithelial downgrowth and attachment of epithelial (E)‐cells and fibroblasts (F) to percutaneous implants in vivo. Grooves were produced with a 30‐μm pitch and depths of 22 μm, 10 μm, or 3 μm. In addition, 10‐μm‐ and 3‐μm‐deep grooves were made with pitches of 39 μm and 7 μm, respectively. Implants with grooves oriented either horizontally or vertically to the long axis of the implant as well as smooth control surfaces were coated with 50 nm of titanium and placed in the parietal area of rats for a period of 7 days. Close attachment of E‐cells was found on the smooth, 10‐μm‐ and 3‐μm‐deep, horizontally or vertically aligned grooved surfaces; in contrast, E‐cells bridged over the 22‐μm‐deep, horizontally oriented grooves. F formed a capsule on the smooth surface as well as the 10‐μm‐ and 3‐μm‐deep horizontally oriented grooves, but F inserted obliquely into the 22‐μm‐deep, horizontally aligned grooved surface. Histomorphometric measurements indicated that the epithelial downgrowth was greatest on the vertically oriented grooved and smooth surfaces and was shortest on the 22‐μm‐deep and 10‐μm‐deep horizontally aligned grooved surfaces. These differences indicate that epithelial downgrowth was accelerated on the vertically oriented grooved surfaces and inhibited on the horizontally oriented grooved surfaces. Moreover, the mechanism of inhibition of the epithelial downgrowth may differ among these surfaces. E‐cells bridged over the 22‐μm‐deep grooves and their migration appeared to be inhibited by the F that inserted into the implant surface. In the shallower horizontal grooves, however, epithelial downgrowth was probably inhibited by contact guidance because there was no evidence of F inserting obliquely into the implant surface.
Macromolecular release from collagen monolithic devices
Authors: Gilbert Donna L. , Kim Sung Wan
Published: December 2004

Collagen monolithic devices varying in crosslinking density, collagen structure, and crosslinker were fabricated. In vitro release rates of a model macromolecule, inulin, were found to be linear with t1/2 and were affected by crosslinking density, nature of crosslinker, and collagen structure. The biodegradation of the collagen matrix was also examined. Proteolytic enzymes did not degrade the collagen devices; the degradation rate with collagenase was dependent on collagen structure, crosslinker, crosslinking density, and enzyme concentration. In vivo biocompatibility, degradation, and 14C‐inulin release rates were evaluated subcutaneously in rats. After 3 weeks, none of the collagen discs induced any severe cellular response. Dacron® induced a stronger fibroblast response but fewer inflammatory cells as compared to the collgen discs. No significant degradation of the collagen discs occurred within 3 weeks. In vivo release of 14C‐inulin from collagen monolithic devices was diffusion controlled.