bluuebunny/crossref_metadata_2025 huggingface dataset:
Difference in tumor incidence and other tissue responses to polyetherurethanes and polydimethylsiloxane in long‐term subcutaneous implantation into rats
Authors: Nakamura A. , Kawasaki Y. , Takada K. , Aida Y. , Kurokama Y. , Kojima S. , Shintani H. , Matsui M. , Nohmi T. , Matsuoka A. , Sofuni T. , Kurihara M. , Miyata N. , Uchima T. , Fujimaki M.
Published: May 2005

The long‐term (1‐ and 2‐year) adverse tissue responses including tumor formation by subcutaneous implanation of polyurethanes (PUS) and silicone (Sil) films intorats were compared. The weight‐averaged molecular weights (Mw) of the PUS prepared from 4,4′‐diphenylmethanediisocyanate, poly (tetramethyleneglycol) of M, = 1000 and 1,4‐butanediol are 220,000 (U‐4), 124,000 (U‐6), and 55,600 (U‐8). The 50:50 mixed film of U‐6 and silicone (U‐b/sil) was prepared by rollmixing of the noncured silicone and the U‐6 solution followed by evaporation of the solvent and heat‐curing at 70°C. The tissue responses around implants were classified into four groups as follows: (A) tumor, (B) atypical cell proliferation accompanied by preneoplastic changes, (C) cell proliferation without preneoplastic changes, (D) no obvious responses. In both implantation periods, the PUS gave higher incidents of the adverse responses including tumor formation in comparison to Sil. No significant molecular weightdependent trend was found in a 1‐year study using U‐4, 6, and 8. Significant PU‐dose‐dependent trends were found in a 2‐year study: the total active incidence (A + B + C), U‐6(22/29) > U‐6/si1(11/29) > sil(7/28); tumor incidence (A), U‐6(11/29) > U‐6/si1(2/29) = si1(2/28). No detectable amounts of 4,4′‐methylenedianiline (MDA) were found in the PUS. The methanol extracts from the PUS were negative in the mutagenicity tests. These indicate no relationship between the tumor formation by the PU films and the mutagenicities of the chemicals (mainly oligomers) leached from the PUs.
Postadsorptive transition in fibrinogen adsorbed to polyurethanes: Changes in antibody binding and sodium dodecy1 sulfate elutability
Authors: Chinn Joseph A. , Posso Sylvia E. , Horbett Thomas A. , Ratner Buddy D.
Published: May 2005

Residence time‐dependent changes in fibrinogen after adsorption to six different polyurethanes were examined by measuring polyclonal antifibrinogen binding to the adsorbed protein. The amount of adsorbed fibrinogen that could be eluted by sodium dodecyl sulfate (SDS) was also measured. Baboon fibrinogen was first adsorbed from dilute plasma to the polymers, which were then stored in either buffer or buffered albumin solution prior to testing. Subsequently, the amount of antifibrinogen bound by the adsorbed fibrinogen was measured using a direct enzyme linked immunosorbent assay (ELISA). Alternatively, the surface with the adsorbed fibrinogen was soaked in a 3% SDS solution, and the amount of retained 125I‐radiolabeled fibrinogen was measured. With increasing residence time, decreases in both antibody binding and the SDS elutability of the adsorbed fibrinogen occurred, but the rate of change was dependent on the polyurethane to which the fibrinogen was adsorbed. In addition, the antibody binding per unit of adsorbed fibrinogen, when measured immediately after the adsorption step, varied by approximately a factor of 3 among the various polyurethanes. When the protein‐coated surfaces were stored in buffered albumin solution rather than buffer, the decrease in the reactivity of fibrinogen with residence time did not occur on some of the surfaces. This study shows that the chemical properties of the adsorbing surface influence the rate at which adsorbed fibrinogen undergoes change. The significance of the polymer‐dependent changes in adsorbed fibrinogen with respect to blood reactions with polymers is discussed.
Biocompatibility studies on plasm polymerized interface materials encompassing both hydrophobic and hydrophilic surfaces
Authors: Johnson Steven D. , Anderson James M. , Marchant Roger E.
Published: May 2005

The biocompatibility of radiofrequency plasma polymerized films (<100 nm thick) deposited on biomedical polymer supports has been characterized by in vitro and in vivo methods. The polymer interface materials covered a wide range of elemental composition and surface properties, and were prepared from N‐vinyl‐2‐ pyrrolidone, γ‐butyrolactone, n‐hexane, and hexamethyldisilazane (PPHMDSZ). The biocompatibility studies showed that the interface materials were noncytotoxic to mouse and human fibroblasts, as shown by morphologic evaluation, and by determination of extracellular LDH; and they did not stimulate interleukin‐1‐like production from human monocytes, as indicated by a thymocyte proliferation assay. The human fibroblast proliferation assay showed that three of the polymers supported cell growth at levels comparable to, or greater than, polymer controls, while the hydrophobic PPHMDSZ inhibited both cell attachment and proliferation. The response to subcutaneous implantation for all test materials was indicative of biocompatibility, with rapid resolution of the acute phase response and normal wound healing. The wide range of composition and surface properties for the plasma polymerized films evaluated in this study suggest that this general class of materials is likely to exhibit excellent biocompatibility.
In vitro and in vivo digestion of collagen covalently immobilized onto the silicone surface
Authors: Okada Toshiyuki , Ikada Yoshito
Published: May 2005

In order to study the in vivo digestion of immobilized collagen and gelatin, these proteins labeled with 125I or fluorescein isothiocyanate (FITC) were covalently immobilized onto silicone surfaces, which were grafted with acrylic acid to introduce carboxyl groups, and implanted subcutaneously in rats and mice. When the proteins were labeled with FITC, the amount of proteins immobilized decreased with the increase of the number of FITC molecules conjugated with the protein molecule. In the wet state, FITC conjugated with the proteins was less stable than 125I. Approximately half of the amount of the immobilized proteins was digested in vivo within the first week and until 5 weeks after implantation the proteins were gradually digested. At that time, the amount of the proteins remaining on the silicone surface ranged from 0.6 to 1.0 μg/cm2, which was several times larger than the amount of an assumed monolayer adsorption of proteins. Even after 15 weeks, the amount of proteins remaining on the silicone was almost the same as after 5 weeks. No significant difference in digestion was observed between collagen and gelatin, regardless of the labeling agent. Because of less stability and easier handling of FITC and higher stability and more difficult handling of 125I, FITC seems more suitable for short‐term and 125I for long‐term studies. © 1992 John Wiley & Sons, Inc.
Changes in fibrinogen adsorbed to segmented polyurethanes and hydroxyethylmethacrylate‐ethylmethacrylate copolymers
Authors: Slack S. M. , Horbett T. A.
Published: May 2005

Fibrinogen adsorption from blood to biomaterials may regulate platelet adhesion and thrombus formation because of fibrinogen's central role in the coagulation cascade and its ability to bind specifically to the platelet membrane glycoprotein (GP) IIb‐IIIa. Adsorption of fibrinogen from blood plasma to many materials exhibits a maximum with respect to plasma dilution and exposure time (the Vroman effect). In this study fibrinogen adsorption to several polymers was examined to ascertain the influence of controlled changes in surface chemistry on the Vroman effect. The materials included hydroxyethylmethacrylate‐ethylmethacrylate (HEMA/EMA) copolymers, Biomer, and a series of segmented polyurethanes (PEUs), two of which contained fluorinated chain extenders. Each material exhibited maximal adsorption of fibrinogen at intermediate plasma concentrations. Little effect of soft‐segment type or molecular weight was observed and no significant differences in fibrinogen adsorption to the fluorinated PEUs were seen. Changes in the strength of fibrinogen attachment to these materials with time after adsorption were also assessed. Fibrinogen adsorbed for 1 min was displaced more readily by blood plasma than that adsorbed for 1 h, regardless of the material. The more hydrophobic polymers exhibited greater retention of adsorbed fibrinogen. In addition, the fraction of fibrinogen retained by polyethylene depended on the amount of fibrinogen adsorbed to the surface, being greatest when the surface loading was the least. These studies indicate that spreading or transition of adsorbed fibrinogen molecules from a weakly to tightly bound state is a general consequence of protein adsorption to solid surfaces. © 1992 John Wiley & Sons, Inc.
111Indium labeling of microorganisms to facilitate the investigation of bacterial adhesion
Authors: Ardehali R. , Mohammad S. F.
Published: May 2005

The ability of bacteria to adhere to polymeric interfaces has attracted considerable attention in recent years. Metabolic labeling of microorganisms with 35S‐methionine or other β‐emitters is commonly utilized for quantification of bacterial adhesion to biopolymers. Since the use of these isotopes is cumbersome, the possibility of labeling the microorganisms with 111Indium, a strong γ‐emitter, was explored. This report demonstrates that bacteria can be easily labeled with 111Indium. Staphylococcus aureus, Staphylococcus epidermiids, and Pseudomonas aeruginosa were labeled with either 111Indium‐oxine or 35S‐methionine; and labeling efficiency, retention of incorporated labels, and growth kinetics of labeled bacteria were compared under identical experimental conditions. Bacteria labeled with 111In‐oxine incorporated approximately 90% of radioactivity within 10 min, whereas 35S‐methionine incorporation required many hours of incubation. Both the incorporated isotopes were gradually released by rapidly growing bacteria into the suspension medium. Of the total incorporated labels, approximately 20% 111In and 15% 35S were released in the surrounding medium every 24 h. No release of incorporated labels occurred when cells were fixed with 2.5% buffered glutaraldehyde. Growth kinetics and scanning or transmission electron microscopic analysis showed no detectable differences among control (nonlabeled), 111In‐, or 35S‐labeled bacteria. Labeling of bacteria with 111In‐oxine does not interfere with bacterial adherence. These observations suggest that 111In incorporation provides a simple and rapid method of labeling of microorganisms. Compared to currently available techniques, the use of 111In‐labeled bacteria will facilitate the quantitation of adherent bacteria to interfaces. © 1993 John Wiley & Sons, Inc.
Plasma protein adsorption to hemodialysis membranes: Studies in an in vitro model
Authors: Parzer Sabina , Balcke Peter , Mannhalter Christine
Published: May 2005

Upon interaction of whole blood with foreign materials, heterogeneous protein films are deposited onto the artificial surface (eg, hemodialysis membranes). The composition of these protein films subsequently affects various processes, eg, thrombogenesis or activation of the complement system. We developed an in vitro model with which we can identify and study proteins interacting with capillaries during hemodialysis. Using this model we studied the cuprophane dialyzer GFS 120 (CP) and the polymethylmetacrylate membrane Filtryzer B2‐1.2 (PMMA). Heparinized whole blood from healthy young volunteers was dialyzed on an extracorporeal dialysis machine. After the dialysis procedure the adsorbed material was eluted from the hemodialysis membranes by different eluants and subsequently analyzed by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and immunoblotting. A number of proteins could be identified in the eluates of both membrane types. Interestingly, platelet glycoproteins could only be found in PMMA eluates. Albumin, IgG, and antithrombin III were mainly present in the cuprophane eluates. Fibrinogen was demonstrable in all eluates, but in relatively low amounts, and the protein was significantly degraded. Degradation products of antithrombin III and complement factor 3 could also be identified. The process causing the degradation has not yet been identified, but may be due to proteases released from damaged cells. © 1993 John Wiley & Sons, Inc.
Human umbilical vein endothelial cell culture on heparin‐like microcarriers
Authors: Najab‐Benhayoun M. , Serne H. , Jozefowicz M. , Fischer A. M. , Brisson C. , Sultan Y.
Published: May 2005

Biospecific functional polymers, i. e., polymers randomly substituted with specific chemical functional groups, were designed to interact with living systems. Interactions between polystyrene sodium sulfonate (PSSO3Na) and insulin secreting RINm5F cells have been previously described.

For the sake of comparison, interactions of PSSO3Na with human umbilical vein endothelial cells (HUVEC) were studied. In this case, the interaction is indirect, i.e., mediated by a binding protein, fibronectin (Fn). This was evidenced by HUVEC culture on Fn precoated PSSO3Na microcarriers. The interactions between PSSO3Na and HUVEC result in a biologically normal proliferation of cells and synthesis and secretion of Von Willebrand Factor (VWF). These results show that different biospecific interactions may occur between cells in culture, binding proteins and polymers randomly substituted with suitable functional groups. HUVEC, when cultured on heparin‐like microcarriers, behave differently from other cells like RINm5F, whose interaction with the same polymers is not mediated by binding proteins. © 1993 John Wiley & Sons, Inc.
Phase studies of a urethane model compound and polyether macroglycols by infrared spectroscopy and the relationship between eutectic composition of soft segment and blood compatibility
Authors: Isama Kazuo , Kojima Shigeo , Nakamura Akitada
Published: May 2005

The binary mixtures of a urethane model compound, diethyl 4,4′‐methylenebis(N‐phenylcarbamate) (MDU), and various polyether macroglycols have been investigated mainly by infrared (IR) spectroscopy. The mixtures of macroglycol and MDU showed two CO bands (free CO at higher wave number, hydrogen bonded CO at lower wave number), and the intensity of free CO increased while that of hydrogen bonded CO decreased linearly with increasing molar ratio of macroglycol/MDU. The slope of the increase or decrease suddenly changed at the specific molar ratio around the eutectic composition. The eutectic molar composition for PTMO1000/MDU was determined as 1.15 or 1.1 by differential scanning calorimetry (DSC) or infrared (IR) studies while that for PTMO3000/MDU as 0.345 or 0.55 by DSC or IR, respectively. The eutectic compositions for other sets were determined by IR studies as follows: PEO1000/MDU, 0.4; PEO3000/MDU, 0.16; PPO1000/MDU, 1.4; PPO3000/MDU, 0.45. The number of ethylene oxide, tetramethylene oxide, and propylene oxide units to form a eutectic with MDU calculated from these values were 15–20, 10–11, and 23–24, respectively. The similar DSC or IR changes were observed in the various kinds of polyurethanes such as MDI/BD, MDI/MDI/PTMO/BD, and MDI/PTMO polymers. The relationship between the eutectic compositions of soft segments (MDI/macroglycol) and the ideal Mn of the macroglycols in blood compatibility of segmented polyurethanes are discussed. © 1993 John Wiley & Sons, Inc.
Interactions of complement fraction C1q, fibronectin, and immunoglobulin G with polyacrylic microparticles used as solid‐phase in immunoassay
Authors: Cliquet F. , Cuillière M. L. , Montagne P. , Duheille J.
Published: May 2005

A microparticle‐enhanced nephelometric immunoassay was recently described, where polyacrylic, hydrophilic, and polyfunctional microparticles are used as the solid phase. It is a one‐step immunoassay based on the nephelometric quantification of microparticle agglutination. In such assays, the measurement of analytes at low concentration may be impaired by the need of using undiluted biological samples. This leads to work with high concentrations of several proteins liable to interfere with the agglutination process. In this paper, we report on a study performed with human serum and purified proteins, which were assayed by classical analytical methods. This work identified three major components of human serum specifically involved in yielding polyacrylic microparticle instability: complement fraction C1q, fibronectin, and immunoglobulins G. In this order of importance, they all showed a marked ability to be adsorbed on the microparticle's surface. Pretreatment of human serum with microparticles decreased the concentrations in C1q (82%), fibronectin (16%), and immunoglobulin G (4%) very unequally. However, it allowed the elimination of microparticle instability, consequently providing the possible use of such polyacrylic microparticles in a one‐step nephelometric immunoassay of analytes at low concentration in biological samples, without washes or phase separation. © 1993 John Wiley & Sons, Inc.
Salicylic acid prevents the adherence of bacteria and yeast to silastic catheters
Authors: Farber Bruce F. , Wolff Arlene G.
Published: May 2005

During the pathogenesis of catheter‐related urinary tract infection, bacteria attach to the catheter and migrate along a biofilm into the bladder. We studied the effect of coating silastic catheters with salicylic acid on bacterial and yeast adherence. An agar roll technique, bioluminescent assay, and radiolabeling study all produced consistent results. There was a dose related inhibition of adherence with Pseudomonas aeruginosa, Enterobacter aerogenes, Klebsiella pneumoniae, Candida albicans, and Enterococcus faecalis. Inhibition of over 90% was noted with Enterobacter and Pseudomonas. Similar results were obtained in broth and synthetic urine. A dose related reduction in adherence was seen with all gram‐negative rods and yeast as measured by a radiolabeling assay. TDMAC was used to bind the salicylic acid to the catheters with > 95% inhibition of the gram‐negative rods. These studies suggest the potential role of coating catheters with salicylic acid to reduce bacterial adherence and urinary tract infection. © 1993 John Wiley & Sons, Inc.
Histomorphometric assessment of the mechanisms for rapid ingrowth of bone to HA/TCP coated implants
Authors: Burr David B. , Mori Satoshi , Boyd Robert D. , Sun T. C. , Blaha J. David , Lane Leon , Parr Jack
Published: May 2005

The purpose of this work is to use dynamic histomorphometry to evaluate the basic biological mechanisms by which hydroxyapatite/tricalcium phosphate (HA/TCP) implant coatings accelerate bone formation rates. Twenty‐five rabbits had an HA/TCP coated cylindrical titanium fiber metal mesh implant surgically placed in the subchondral bone of the proximal tibia and a noncoated implant placed in the contralateral tibia. Twenty‐two of these animals had HA/TCP coated cylindrical solid titanium implants placed in the distal femur and an uncoated implant placed in te contraleteral femur. The animals were double labeled with vital stains, and sacrificed at 3, 6, 16, or 26 weeks after surgery. Histomorphometric analyses were done of the bone implant interfaces. Both static and dynamic histomorphometric parameters indicate that HA/TCP coatings stimulate faster bone ingrowth to coated fiber metal implants through the early production of woven bone and by subsequent rapid lamellar bone formation rates. Coated fiber metal implants demonstrated significantly more bone ingrowth than noncoated implants through 16 weeks postimplatatin, but not by 26 weeks, In solid implants, the differences between coated and noncoated implants are less pronouned and not statistically significant, although there is a trend toward increased bone appostion to the surface of the implants over the first 16 weeks following implantation. The clinical significance of these results is that coated implants may allow earlier return to normal weightbearing. © 1993 John Wiley & Sons, Inc.
Collagen types I and III at the implant/tissue interface
Authors: von Recum A. F. , Opitz H. , Wu E.
Published: May 2005

Collagen composition in tissue capsules around implants has been reported to deffer histologically from collagen in subcutaneous connective tissue. In the present study, an immune histochemical analysis of collagen types I and III was undertaken in tissue capsules of various implant materials. The materials in cluded polyvinyl chloride/polyacrylonitrile copolymer, poly(ethylene terephthalate), polysiloxane, titanium, and hydroxyapatite, which had been implanted into the dorsal subcutaneous space of rabbits for various time periods from 28 and to 90 days. The results indicate that collagen type III stained in all capsules independent of the evaluated materials, implantation periods, and material surface roughness. Collagen type I stained only in titanium implant capsules and dominated there over collagen type III. The staining sensitivity was highly specific and reproducible. The presence of collagen type III can be expected because it is the collagen of connective tissue healing. Collagen type I appears to be a response to chemical or electrochemical titanium surface properties but not to surface roughness. The quantitative relationship between the two collagen types may indicate capsule tissue stability and therefore serve as another biocompatibility measure. © 1993 John Wiley & Sons, Inc.
Detection of remnant proteolytic activities in unimplanted glutaraldehyde‐treated bovine pericardium and explanted cardiac bioprostheses
Authors: Simionescu Dan , Simionescu Agneta , Deac Radu
Published: May 2005

The presence and activity of proteolytic enzymes has been investigated in vitro on slouble and insoluble preparations obtained from both unimplanted and implanted glutaraldehyde‐treated bovine parietal pericardium. Using detection by colorimetric techniques, soluble preparations were shown to hydrolyze enzyme substrates that are characteristic for trypsinlike proteases, cathepsin‐like proteases, and collagenase. As detected by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis in gradient gels and gel filtration on Sepharose CL‐6B, insoluble (pellet) preparations degraded denatured type I collagen in a time‐dependent pattern, producing low‐molecular‐weight fragments. These activities were partially inhibited by phenylmethylsulfonyl fluoride, N‐ethyl maleimide, soybean trypsin inhibitor, parachloromercurybenzoic acid, or ethylenediaminetetraacetic acid, suggesting the presence of a heterogeneous enzymatic mixture. Insoluble preparations incubated with pure pericardial dermatan sulfate proteoglycan detached the glycosaminoglycan chains from their core protein carrier, producing a digestion pattern similar to Cathepsin C. These findings demonstrate the presence of active proteases in glutaraldehydefixed bovine pericardium per se and in explanted pericardial bioprosthetic cardiac valves, an additional factor that might contribute to intrinsic extracelluar matrix degeneration in pericardial bioprosthetic devices. © 1993 John Wiley & Sons, Inc.
New ideas in biomaterials science—a path to engineered biomaterials
Authors: Ratner Buddy D.
Published: May 2005

Our existing biomaterials, although demonstrating generally satisfactory clinical performance, were developed based upon a trial‐and‐error optimization approach rather than being engineered to produce the desired interfacial reaction. Most biomaterials exhibit a nonspecific biological reaction, with sluggish kinetics and a broad spectrum of active processes simultaneously occurring. This article describes materials science, nanotechnology, and molecular biology techniques that may permit the synthesis of precisely engineered surfaces. Such surfaces might demonstrate rapid, precise reactions with proteins and cells. This opens the question, “what type of specific surface bioreactions do we want?” New thoughts on biocompatibility are presented that may be helpful in the design of specific surfaces yielding precise, defined biological responses. © 1993 John Wiley & Sons, Inc.
Behavior of primary bone cells on characterized polystyrene surfaces
Authors: Callen B. W. , Sodhi R. N. S. , Shelton R. M. , Davies J. E.
Published: May 2005

Primary bone cells, isolated from the periosteally stripped calvariae of neonate rats, were cultured on 60Co γ‐irradiation‐sterilized bacteriologic‐grade polystyrene that had been either surface treated with concentrated sulfuric acid or received further γ‐irradiation treatments facilitated cell colonization of the polystyrene compared to those surfaces not treated in the laboratory. x‐Ray photoelectron spectroscopy (XPS) showed that the two treatments introduced different chemical groups onto the polymer surface and that cell adhesion was related to γ‐irradiation in a dose‐dependent manner. These results show that simple biologic assays, such as cell colonization, are not able to distinguish between differences in surface chemistry demonstrated by such a routinely employed surface analysis technique. Thus, there is a need to develop more sensitive biologic assays that provide functional information of a precision that can be correlated with subtle changes in substratum surface chemistry. Further, we argue that because cells isolated by tissue digestion using proteolytic enzymes respond more readily to changes in the surface chemistry of the substratum they colonize, compared to explanted cells; biologic assays designed for biomaterials testing must take into account changes effected in cell adhesion behavior by isolation procedures. © 1993 John Wiley & Sons, Inc.
Delivery of growth factor to wounds using a genetically engineered biological bandage
Authors: Leyen Sheila Andreatta‐Van , Smith Daniel J. , Bulgrin Jeffrey P. , Schafer Irwin A. , Eckert Richard L.
Published: May 2005

Increasing the rate of wound healing of acute wounds and promoting the closure of chronic ulcers is an important goal in wound therapy. Growth factors have been shown to facilitate this process; however, the systems described for growth factor delivery are not ideal. In the present report we demonstrate the feasibility of a new method of delivering growth factors to the wound site using a genetically engineered biological bandage. The bandage consysts of keratinocytes (SCC‐13 cells) that are engineered by gene transfer to produce high levels of bovine growth hormone (bGH). bGH was selected for these studies because it can be easily distinguished from rat and human growth hormone in wound fluids and culture medium. The bGH‐producing cells are contained and maintained in serum‐free medium inside an envelope composed of a low protein binding, 0.2 μm pore size, polysulfone membrane. The genetically engineered cells cannot escape from the bandage, but the bGH is freely released into the surrounding culture medium. When placed onto a full‐thickness, surgically generated wound on rats, the cells within the bandage continue to produce and release bGH into the wound for at least 3 days. This system is a safe and reliable way of providing real‐time delivery of any desired biomolecule into the wound site. © 1993 John Wiley & Sons, Inc.
Prevention of thrombus formation on biomaterials exposed to blood using different antiplatelet drugs: Experimental study in dogs
Authors: Escudero M. C. , Alvarez L. , de Haro J. , Millán I. , Jorge E. , Castillo‐Olivares J. L.
Published: May 2005

An ex vivo shunt, established in dogs between both femoral arteries and right atrium, has been used to quantify the platelet deposition on six prosthetic materials used in the construction of cardiovascular prostheses: highly porous knitted Dacron (intervascular HP 800, 1400 mL/cm2/min/120 mm Hg), low‐porosity woven Dacron (intervascular LP 200, 200 mL/cm2/min/120 mm Hg), double velour knitted Dacron, Avcothane 51 elastomere, and the mesothelial and epipericardial surfaces of bovine pericardium. In the search for a method to prevent platelet thrombi formation on these materials, we studied four groups of dogs: group 1 (control), group 2 (5 mg/kg body weight (BW)/day acetylsalicylic acid), group 3 (20 mg/kg BW/day acetylsalicylic acid), and group 4 (5 mg/kg BW/day acetylsalicylic acid plus 5 mg/kg BW/day dipyridamole). Platelets were labeled with 111In‐oxine. The least thrombogenic material was Avcothane 51 elastomere. The only effective treatment for reduction of platelet deposition on the six materials was 5 mg/kg BW/day of acetylsalicylic acid. The dose used in group 3 only decreased the deposition of platelets on three of the six materials studied. The treatment employed in group 4 did not significantly reduce the deposition of platelets on any of the materials when compared with the control group. © 1994 John Wiley & Sons, Inc.
The role of hydrated silica, titania, and alumina in inducing apatite on implants
Authors: Li Panjian , Ohtsuki Chikara , Kokubo Tadashi , Nakanishi Kazuki , Soga Naohiro , de Groot Klaas
Published: May 2005

Pure soluble silica prepared by a sol‐gel method induced bone‐like hydroxyapatite formation onto its surface when the silica was immersed in a simulated body fluid (SBF), whereas silica glass and quartz did not. This finding directly supports the hypothesis that hydrated silica plays an important role in biologically active hydroxyapatite formation on the surfaces of bioactive glasses and glass‐ceramics, which leads to bone‐bonding. Gel‐derived titania is also a hydroxyapatite inducer because of its abundant TiOH groups. These results provide further insight into the unique osseointegration of titanium and its alloys. It is suspected that gel‐derived titania develops an apatite layer by taking calcium and phosphate from the body fluid, thus producing bonebonding. Although sufficient AlOH groups may remain in the alumina gel, they do not serve to initiate apatite generation when immersed in SBF. This phenomenon explains the fact that an intermediate fibrous tissue is usually found to separate the alumina implant from bone. One may infer that both abundant OH groups and negatively charged surfaces of gel‐derived silica and titania are important for hydroxyapatite induction. Material which possesses and / or develops both a negatively charged surface and abundant OH groups in a physiologically‐related fluid is most likely to be an efficient apatite inducer. Such materials are suitable candidates to serve as bone‐bonding biomaterials. © 1994 John Wiley & Sons, Inc.
Theoretical analysis of in vivo macrophage adhesion and foreign body gaint cell formation on polydimethylsiloxane, low density polyethylene, and polyetherurethanes
Authors: Kao Weiyuan John , Zhao Qing H. , Hiltner Anne , Anderson James M.
Published: May 2005

Quantitative description of foreign body giant cell (FBGC) formation on implanted polymer surfaces as a function of time can conceivably correlate cell adhesion with polymer properties and possibly predict the behavior of the polymer in vivo. In the present study, the formation of FBGCs on various biomedical polymers was quantified by two parameters: the density of adherent macrophages present initially that participate in FBGC formation (d0) and the rate constant for cell fusion (k); both kinetic parameters were used to calculate the time‐dependent FBGC density (dfc).

The materials used were: three Pellethane poly(etherurethanes) (PEUs) varying in weight percent of hard segment, one poly(etherurethane urea) (PEUU), and NHLBI‐DTB primary reference materials: low density polyethylene (LDPE), silica‐free polydimethylsiloxane (PDMS). The results indicated that up to 5 weeks of implantation, FBGCs were formed from the fusion of one population of adherent macrophages present by 3 days post‐implantation. Furthermore, only a small fraction (<8%) of this initial adherent macrophage population participated in FBGC formation. Based on the results of previous studies and the current study, it was concluded that increase in PEU hard segment weight percent, surface hardness and hydrophobicity increased total protein adsorption and effectively increased d0 and dfc. No further correlations between the material properties of all polymers and the cell kinetics can be made at this time. However, this study demonstrated that macrophage adhesion and FBGC formation can be quantified with the cell fusion model, and are modulated by various polymer properties. © 1994 John Wiley & Sons, Inc.
Histological changes of implanted collagen material during bone induction
Authors: Horisaka Yasuyuki , Okamoto Yasuo , Matsumoto Naoyuki , Yoshimura Yoshiyuki , Hirano Atsuko , Nishida Mikio , Kawada Jun , Yamashita Kikuji , Takagi Tomomichi
Published: May 2005

Studies were made on the fate of implanted material during bone induction. Mixtures of 1 mg of crude bone morphogenetic protein (BMP), or bovine serum albumin as a control, and 1.5 mg of bovine collagen, were pressed into discs and implanted under the fascia of the rectus abdominus muscle of rats. The tissues with implants were fixed 7, 10, and 14 days later and examined histologically. On day 7 after implantation, the implant was surrounded and invaded by alkaline phosphatasepositive cells. New bone and cartilage were seen at the periphery of the implant. In the regions of calcified cartilage and bone, these osteogenic matrices were intermixed with the implant. The mineral deposits were seen by electron microscopy not only on the osteogenic matrices but also on the implanted collagen. On day 14, the bone had spread to the center of the implant. No osteogenesis or chondrogenesis was seen in control implants. It was concluded that the calcification occurred on the implanted collagen during bone induction, and that it was related to successive bone formation and remodeling. © 1994 John Wiley & Sons, Inc.
Comparison of 316LVM and MP35N alloys as charge injection electrodes
Authors: Cogan Stuart F. , Jones George S. , Hills Doris V. , Walter James S. , Riedy Lisa W.
Published: May 2005

An In vitro comparison of the corrosion response of 316LVM stainless steel and MP35N (a CoNiCrMo alloy) electrodes under conditions appropriate to applications in functional electrical stimulation (FES) was made. Electrodes of both alloys were subjected to a cathodic 40 μC/cm2 charge injection protocol and the potential transient response was recorded over a 96 h period. The transient responses were compared with potentiodynamic polarization data used to establish the quasiequilibrium response of the alloys in the carbonate and phosphate‐buffered saline electrolyte used in the study. The MP35N electrodes exhibited extensive pitting corrosion during charge injection, whereas little corrosion was observed on 316LVM electrodes. An explanation for the susceptibility of MP35N to corrosion during charge injection is found in the potentiodynamic polarization data, which reveal a breakdown potential (critical pitting potential) of 0.45 V (SCE) for MP35N compared with 1.05 V (SCE) for 316LVM. Factors that may influence corrosion response during charge injection from alloys exhibiting active–passive behavior are discussed. © 1994 John Wiley & Sons, Inc.
Adsorption and activation of zymogens at solid–liquid interfaces. I. Chymotrypsinogen on alkylamino modified silica derivates
Authors: Yen Hung‐Ren Homer , Oscarsson Sven , Ulbrich Karel , Kopeček Jindřich
Published: May 2005

Silica beads were modified with alkylamino groups of different lengths (C2, C4, C6, C8, and C10) and hydrophobicity. The relationship between surface structure and adsorption of chymotrypsinogen followed by its activation with trypsin at the solid‐liquid interface was studied. From the adsorption isotherms, it follows that underivatized silica adsorbed chymotrypsinogen (CTG) well. The adsorption of CTG on alkylamino modified silicas appeared to correlate with the hydrophobicity of the latter. The longer the alkyl chains were, the higher was the amount of adsorbed CTG. The activation of adsorbed CTG with trypsin at the solid—liquid interface was a slower process when compared with the activation conducted in solution. Parallel experiments were performed with chymotrypsin (CT). The adsorption behavior was similar to that of CTG. The activity of adsorbed CT was inversely proportional to the hydrophobicity of the beads. These results correlated well with the desorption of CT after repeated washings. Repeated addition of substrate (Gly‐Gly‐Phe‐NAp) to the CT covered beads resulted in the CT desorption. The higher the hydrophobicity of the beads was, the lower was the desorption of CT. © 1994 John Wiley & Sons, Inc.
Subcutaneous, catheter‐related inflammation in a rabbit model correlates with peripheral vein phlebitis in human volunteers
Authors: Carruth William A. , Byron M. Parke , Solomon Donald D. , White Wain L. , Stoddard Gregory J. , Marosok Randy D. , Sherertz Robert J.
Published: May 2005

In the development of a polyurethane vascular catheter with anti‐infective properties, it became desirable to develop a measure of tissue inflammation. This was investigated in a rabbit model by implanting uncoated catheters and catheters coated with heparin (HEP), chlorhexidine (CH), or CH/HEP in the subcutaneous space with or without 104 Staphylococcus aureus. At intervals of 2, 4 and 7 days after implantation, animals were sacrificed; tissue blocks containing catheters were removed and preserved with formaldehyde; and sections were stained with hematoxylin and eosin. Using a histologic index, 240 sections (10 for each experimental condition) were evaluated by two investigators blinded to experimental conditions. Uncoated catheters or catheters coated with CH alone had a lower histologic index (less inflammation) than catheters coated with HEP alone or CH/HEP (P <.05). When catheters were inoculated with S. aureus, those coated with CH, with or without HEP, had a lower histologic index than uncoated catheters (P <.05). Next, 30 volunteers had a control catheter inserted in a vein in one forearm and a catheter coated with either CH alone or CH/HEP in a vein in the other forearm. After 96 h of observation there was a greater risk of phlebitis associated with CH/HEP catheters than control catheters (P <.05), and no difference in the risk of phlebitis between CH catheters and control catheters (P = 0.43). Thus, the amount of inflammation around the catheter in the subcutaneous space of rabbit correlated with the risk of peripheral vein phlebitis. © 1994 John Wiley & Sons, Inc.
In vitro study of the intrinsic toxicity of synthetic surfaces to cells
Authors: Ertel Sylvie I. , Ratner Buddy D. , Kaul Amarjeev , Schway Michael B. , Horbett Thomas A.
Published: May 2005

A trypan blue inclusion assay was used to measure cell death on poly(dimethyl siloxane) (PDMS), polyethylene (PE), poly(methyl methacrylate) (PMMA), polyurethanes, glass, and glow‐discharge‐treated polystyrene or poly(ethylene terephthalate). Cell lines used were bovine aortic endothelial, 3T3, mouse peritoneal macrophage, and BHK cells. In the absence of proteins in the media, PDMS, PE, PMMA, and some polyurethanes were consistently found to induce cell death. This toxic effect disappeared if the cells were seeded in serum‐containing medium or if concentrated solutions of proteins (albumin, IgG, or fibronectin) were preadsorbed on the materials. The substrate toxicity appeared to be due to the physical properties of the substrate and not to the release of toxic leachables. © 1994 John Wiley & Sons, Inc.
Fixation of bioprosthetic tissues with monofunctional and multifunctional polyepoxy compounds
Authors: Tu Roger , Shen Shih‐Hwa , Lin David , Hata Cary , Thyagarajan Kalathi , Noishiki Yasuharu , Quijano Rodolfo C.
Published: May 2005

Collagen from a native tissue is fixed with a polyepoxy compound (PC) for use as a new biologic prosthetic material. Prior studies have shown that this biomaterial has comparable properties with collagen fixed with glutaraldehyde (GA), and thus has great promise for biomedical applications. A prior kinetic study indicated that the reaction between the functional groups of collagen and the multifunctional epoxy EX‐313 is a 2.5th‐order reaction. The purpose of this study was to understand the mechanism of the amino acid‐PC reactions in a fixation process. Bovine arteries were fixed with a monofunctional PC (EX‐313) and a multifunctional PC (EX‐313) as a function of fixation time. A sequential fixation with a second fixative was used to identify the available remaining reactive sites from a prior fixation. The denaturation temperature (Td) was measured on each sample. Because the denaturation temperature is a direct indication of crosslinking of individual amino acids with the fixative, the increase in Td of a subsequent fixation may be indicative of the available remaining amino acids. The fixation index was measured on each sample to reflect the increase of fixation completion in a sequential fixation process. The fixation index and crosslink data also revealed that the reactive amino acids for EX‐131 and EX‐131 may not be exactly the same. The data in this study suggest that a monofunctional fixative can pre‐react with the amino acids of collagen to effectively block further fixation of collagen with a second fixative. This amino acid masking may be associated with collagen branching. Collagen branching and its effect on denaturation temperature are described. © 1994 John Wiley & Sons, Inc.
Correlation between corneal epithelial cell outgrowth and monoclonal antibody binding to the cell binding domain of adsorbed fibronectin
Authors: Pettit Dean K. , Hoffman Allan S. , Horbett Thomas A.
Published: May 2005

The ability of corneal epithelial cells to attach, spread, and migrate on synthetic surfaces is largely determined by the characteristics of the adsorbed protein layer. In previous studies we have described an in vitro model for quantitating epithelial cell outgrowth from explanted corneal buttons onto synthetic materials (Pettit et al., Invest. Ophthalmol. Vis. Sci., 31, 2269 [1990]). We have also described the role of fibronectin (fn) adsorption and binding strength on epithelial cell outgrowth (Pettit et al., J. Biomed. Mater. Res., 26, 1259 [1992]). In the current study we have used a monoclonal antibody against the RGD cell binding domain of fn (mAb 3E3) to further characterize the role of adsorbed fn in promoting epithelial cell outgrowth. Ten materials of diverse chemical and physical properties were adsorbed with fn (0.1 mg/ml) or mixtures of fn and albumin (concentrations totaling 0.1 mg/ml) and tested for antibody recognition of the cell binding domain. The surface density of bound anti‐cell binding domain antibody varied from a low of 0.66 ± 0.11 for fluorinated ethylene propylene copolymer (FEP) to a high of 1.90 ± 0.26 for tissue culture polystyrene dish substrates (units are OD at 450 nm measured in the ELISA technique normalized to polyethylene). A general increase in cell outgrowth areas was noted, with increases in recognizable cell binding domain. However, several exceptions to this trend were noted as well (e. g., low cell outgrowth but high antibody recognizability for glass). These results suggest that, although the number of cell binding domains exposed on adsorbed fn molecules may influence cell outgrowth, other characteristics of the adsorbed protein, such as the binding strength to the underlying substrate, may be equally important in characterizing epithelial cell‐substrate interactions. © 1994 John Wiley & Sons, Inc.
Interspecies differences in systemic drug availability following subscutaneous pulsatile administration in cattle, sheep, dogs, and rats
Authors: Leppert Paula S. , Cammack Leilani , Cargill Robyn , Coffman Lori , Cortese Margot , Engle Karen , Krupco Colette , Fix Joseph A.
Published: May 2005

Rats, dogs, sheep, and cattle were implanted subcutaneously with stainless‐steel tissue cages. Bolus injections of cefoxitin and ivermectin were administered to the interiors of the tissue cages 11, 32, and 60 days after implantation to simulate pulsatile drug release from an implanted device. Plasma drug levels were determined for 6 h for cefoxitin and up to 8 days for ivermectin. Tissue cages were retrieved 3 and 6 months after implantation for macroscopic and microscopic examination. In dogs and rats, plasma levels of both drugs following administrations to the tissue cages were significantly lower than those following subcutaneous injection, suggesting that the tissue growth around and in the cages posed a barrier to systemic drug availability in those species. In cattle and sheep, the tissue cages and associated tissue did not inhibit systemic availability of either drug as compared with routine subcutaneous administration. © 1994 John Wiley & Sons, Inc.
Interpenetrating polymer network (IPN) as a permanent joint between the elements of a new type of artificial cornea
Authors: Chirila Traian V. , Vijayasekaran Sarojini , Horne Robert , Chen Yi‐Chi , Dalton Paul D. , Constable Ian J. , Crawford Geoffrey J.
Published: May 2005

The combination at the interface between two chemically identical polymers was investigated by light and electron (scanning, transmission) microscopy. The polymers constitute elements of a new type of artificial cornea in which the peripheral skirt is made from spongy poly(2‐hydroxyethyl methacrylate) (PHEMA) and the central optical zone from homogeneous, transparent PHEMA. Their two‐phase combination along the boundary fulfill formally the requirements for an interpenetrating polymer network (IPN). The procedure for the manufacture of prosthesis was described in detail. Thin and ultrathin sections excised from the interface region were investigated using microscopic techniques. Light microscopy allowed the measurement of the diffusion path length of transparent PHEMA into sponge, which was approximately 0.5 mm. Transmission electron microscopy revealed a cellular‐like morphology as well as larger segregated zones, which indicated network interpenetration on a molecular level and also a relatively poor miscibility of the two polymers despite their identical chemical structure. The latter was interpreted as a result of the submicroscopic restraints imposed by polymer I (sponge) upon polymer II. This study provides evidence that the interface combination of the prosthetic elements should be regarded as a gradient homo‐IPN. This system offers a union between elements much stronger than those previously reported in artificial corneas. © 1994 John Wiley & Sons, Inc.
Description of the mathematical law that defines the relaxation of bovine pericardium subjected to stress
Authors: Sestafe J. V. Garcia , GarcíA Paez J. M. , san Martín A. Carrera , Jorge‐Herrero E. , Navidad R. , Candela I. , Castillo‐Olivares J. L.
Published: May 2005

A material subjected to traction stress increases in length; if we maintain the elongation constant, the stress varies over a period of time. This phenomenon has been referred to as relaxation. The purpose of this study was to define a mathematical law that relates the variation in stress to time when elongation remains constant in bovine pericardium. The mathematical function obtained after assaying 34 samples to the point of relaxation, subjected to initial stresses ranging from 0.17‐10.07 MPa, responds to the following equation:y= −0.0252 + 0.953 α ‐ (0.0165 + 0.015 α)lnt, where γ is the stress withstood at an instant in time,t, after initial stress α. A normogram, validated by assays of up to 6,340 min duration (4.40 days), is presented for graphic calculation, permitting the computation of the loss of stress due to relaxation of this biomaterial, with initial stresses ranging from 1‐10 MPa. © 1994 John Wiley & Sons, Inc.