bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo characterization of the inflammatory properties of poly(tetrafluoroethylene) particulates
Authors: Kossovsky Nir , Millett David , Juma Saad , Little Nancy , Briggs Preston C. , Raz Schlomo , Berg Eric
Published: December 2004

Suburothelial injections of particulate poly(tetrafluoroethylene) (PTFE) is becoming a widely accepted treatment for a number of urological disorders. Because little is known about the long‐term histologic morphology of the injection site, this animal study was performed. Three populations, each consisting of two mongrel dogs, five New Zealand White rabbits, and 10 BALB/c mice, were injected with poly(tetrafluoroethylene) particulate in a glycerine carrier (Polytef Paste) and were followed for a period of 1 week, 3 months, 6 months, and 1 year. Mice received one subcutaneous dorsal injection each, rabbits received two subareolar injections each, and dogs received three subareolar injections each in addition to two periurethral injections. Histologic examination of the biopsy sites revealed a persistent chronic inflammatory reaction with progressive growth of the involved tissue volume. In addition to giant cells and macrophages, lymphocytes became apparent at 3 months and constituted up to 40% of the cellular infiltrate by 1 year. Plasma cells were also noted at the 1‐year period in the rabbit model. The progressive growth of the inflammatory pseudotumors evoked by injected PTFE may compromise the long‐term safety of certain urological procedures involving particulate PTFE.
Synthesis and nonthrombogenicity of polyetherurethaneurea film grafted with poly(sodium vinyl sulfonate)
Authors: Ito Yoshihiro , Iguchi Yuichiro , Kashiwagi Takashi , Imanishi Yukio
Published: December 2004

Synthesis of nonthrombogenic materials without using biologically active substances was explored. Poly(sodium vinyl sulfonate) is a water‐soluble synthetic polymer and activates antithrombin III to exert nonthrombogenicity that was dependent on the molecular weight. Polyetherurethaneurea film was plasmatreated and graft‐polymerized with sodium vinyl sulfonate. The graft film showed excellent in vitro and ex vivo nonthrombogenicity by suppressing interactions with plasma proteins and platelets as well as by inactivating bloodclotting factors.
Physical and blood‐contacting properties of polyurethanes based on a sulfonic acid‐containing diol chain extender
Authors: Okkema A. Z. , Visser S. A. , Cooper S. I.
Published: December 2004

Polyurethanes chain extended with N,N‐bis (2‐hydroxyethyl)‐2‐aminoethanefulfonic acid (BES) were synthesized. The effect of the sulfonic acid group on the polymers' bulk, surface, and bloodcontacting properties was evaluated by comparing the BES‐based polymers with polyurethanes based on N‐ethyldiethanolamine (EDEA). In addition, the effect of soft‐segment polarity was addressed by comparing polyurethanes based on polyetetramethylene oxide (PTMO) (MW = 1000) with polymers based on polyethylene oxide (PEO) (MW = 1000). The EDEA control samples had physical properties similar to a viscous fluid. The presence of the sulfonic acid group dramatically enhanced the degree of microphase separation and the mechanical strength of all the polymers. The more polar PEO soft segment resulted in polymers which were more phase mixed than the PTMO‐based polyurethanes. Surface characterization studies revealed that in vacuum, all the surfaces were enriched in the polyether soft‐segment phase. After 24‐h equilibration in water, all the surfaces had similar surface polarities independent of the SO3H content. The canine ex vivo blood‐contacting results showed that the sulfonic acid group in the PTMO‐based polymers significantly reduced the number and activation of the adherent platelets. Fibrinogen deposition, however, increased with increasing sulfonic acid content. In contrast, platelet and fibrinogen deposition on the sulfonic acidcontaining PEO‐based polymers was greatly enhanced.
Asymmetric membrane filters for the removal of leukocytes from blood
Authors: Bruil A. , Van Aken W. G. , Beugeling T. , Feijen J. , Steneker I. , Huisman J. G. , Prins H. K.
Published: December 2004

As part of a study on the mechanisms of leukocyte filtration, the influence of pore size distribution on filter efficiency was investigated. Conventional leukocyte filters are not suitable for model studies, as these filters are composed of tightly packed synthetic fibers, with a poorly defined porous structure. Therefore, open cellular polyurethane membranes with pore size distributions varying from approximately 15 to 65 μm were prepared. Filtration experiments with stacked packages of these membranes showed that leukocytes are best removed (>99%) by filters with a pore size distribution of 11–19 μm. These pore sizes approach the size of leukocytes (6–12 μm). However, due to fast clogging, blood flow through these filters is rapidly reduced, which results in a low filter capacity. With an asymmetric membrane filter, in which the pore size decreases from about 65 to 15 μm in the direction of blood flow, both moderate removal of leukocytes (>80%) and maintenance of flow (∼0.2 mL/s) are obtained. This results in efficient leukocyte removal. From cell analysis of both filtrate and filter, it is concluded that adhesion rather than sieving is the major filtration mechanism. Thus, further optimization of the filter may be achieved by surface modification.
Water‐curable and biodegradable prepolymers
Authors: Kobayashi Hisatoshi , Hyon Suong‐Hyu , Ikada Yoshito
Published: December 2004

In an attempt to develop biodegradable polymers which can be shaped in situ and adhere to living tissues, we synthesized esterurethane prepolymers which can be cured upon contact with water in living tissues. First, D,L‐lactide polymerization or D,L‐lactide‐ϵ‐caprolactone (50:50) co‐polymerization was carried out using ethylene glycol or poly(ethylene glycol) as initiator to obtain hydroxyl‐terminated biodegradable polyesters. They were then reacted with an excess of diisocyanate such as hexamethylene diisocyanate, toluylene diisocyanate, and diphenylmethane diisocyanate to introduce a reactive isocyanate group to both of the end groups of the polyesters. The isocyanate‐terminated prepolymers could be cured in the presence of water and the cured polymers were degraded by hydrolysis both in vitro and in vivo. It was found that the presence of appropriate amounts of hydrophilic units in the main chain was essential for giving a high curing rate and a high degradation rate for the biodegradable urethane prepolymers. The tissue responses to the cured polymers were not severe.
Lysine‐enhanced glutaraldehyde crosslinking of collagenous biomaterials
Authors: Simionescu Agneta , Simionescu Dan , Deac Radu
Published: December 2004

Crosslinking of collagenous biomaterials currently employs the use of glutaraldehyde. The putative enhancement of glutaraldehyde crosslinking by lysine was investigated in three model systems: bovine pericardium, collagen membranes, and bovine serum albumin. Repetitive sequential treatment of bovine pericardium with glutaraldehyde and lysine and finally with formaldehyde produced a matrix which, by the two criteria used (shrinkage temperature and urea/SDS soluble collagen), was shown to be more highly crosslinked than pericardium fixed in glutaraldehyde alone. Essentially the same results were obtained when membranes prepared from pepsin‐soluble pericardial collagen were subjected to sequential glutaraldehyde and lysine treatments, reaching shrinkage temperatures of more than 90°C. Heart valves prepared from lysineenhanced glutaraldehyde crosslinke bovine pericardium were tested in vitro in an accelerated fatigue tester and have been shown to behave satisfactorily after 300 million cycles. These additional crosslinks proved to be stable in saline at 37°C. Studies on bovine serum albumin attempted to get an insight into the mechanisms of lysine enhancement of glutaraldehyde crosslinking by treating sequentially albumin with glutaraldehyde and lysine and analysis of the products by gel filtration and SDS‐PAGE. These studies suggest that free amino groups exposed by proteins are initially reacted with glutaraldehyde and the bridged by the diamino compound (lysine) producing more extensive intermolecular crosslinking than glutaraldehyde alone.
Acoustic emission during fatigue of porous‐coated Ti‐6Al‐4V implant alloy
Authors: Kohn David H. , Ducheyne Paul , Awerbuch Jonathan
Published: December 2004

Acoustic emission (AE) events and event intensities (e.g., event amplitude, counts, duration, and energy counts) were recorded and analyzed during fatigue loading of uncoated and porous‐coated Ti‐6A1‐4V AE source location, spatial filtering, event, and event intensity distributions were used to detect, monitor, analyze, and predict failures. AE provides the ability to spatially and temporally locate multiple fatigue cracks, in real time. Fatigue of porous‐coated Ti‐6A1‐4V is governed by a sequential, multimode fracture process of: transverse fracture in the porous coating; sphere/sphere and sphere/substrate debonding; substrate fatigue crack initiation; slow and rapid substrate fatigue crack propagation. Because of the porosity of the coating, the different stages of fracture within the coating occur in a discontinuous fashion, There‐fore, the AE events generated are intermittent and the onset of each mode of fracture in the porous coating can be detected by increases in AE event rate. Changes in AE event rate also correspond to changes in crack extension rate, and may therefore be used to predict failure. AE offers two distinct advantages over conventional optical and microscopic methods of analyzing fatigue cracks–it is more sensitive and it can determine the time history of damage progression. The magnitude of the AE event intensities increased with increasing stress. Failure mechanisms are best differentiated by analyzing AE event amplitudes. Intergranular fracture and microvoid coalescence generated the highest AE event amplitudes (100 dB), whereas, plastic flow and friction generated the lowest AE event amplitudes (55–65 dB). Fractures in the porous coating were characterized by AE event amplitudes of less than 80 dB.
Effect of sulfonation of segmented polyurethanes on the transient adsorption of fibrinogen from plasma: Possible correlation with anticoagulant behavior
Authors: Santerre J. P. , ten Hove P. , VanderKamp N. H. , Brash J. L.
Published: December 2004

The influence of polyurethane sulfonation on fibrinogen adsorption from plasma and on plasma coagulation has been investigated. Sulfonated polyurethanes were synthesized using a two‐step solution polymerization in which a diamino disulfonic acid was used as chain extender, thus incorporating sulfonate groups into the hard segments. Polymer molecular weights were determined by size exclusion chromatography and weight average values were in the range of 50,000 to 200,000. Equilibrium water uptake of solid polymer specimens was substantial and was found to increase with increasing sulfonate content. Titration of sulfonate groups allowed an estimate of the retention of free sulfonate in the polymers which ranged from 50 to 85%. Loss of free sulfonate is attributed to reaction of isocyanate with sulfonate groups during chain extension. Both surface chemistry and hydrophilicity were assessed using a combination of ESCA and water contact angle measurements. The ESCA data indicate enrichment of soft segment in the surface. Contact angles show increasing hydrophilicity with increasing sulfur content. Fibrinogen adsorption from plasma to the sulfonated polyurethane surfaces was studied using radioiodine labeling. Fibrinogen surface concentration was found to increase strongly as sulfonate content increased. Fibrinogen adsorption behavior is quite different from that of conventional unsulfonated polyurethanes in the sense that the adsorption levels are much higher and there is little displacement of initially adsorbed fibrinogen (Vroman effect). The data are interpreted i n terms of two mechanisms: fibrinogen uptake (i.e., absorption) into a polymer–plasma “gel” hypothesized to exist at the surface of these materials, and adsorption in the usual sense. Thrombin times of human plasma in which polymer particles were suspended were prolonged and were found to increase with increasing sulfonate content of the polymers, suggesting that sulfonate groups confer a measure of anti‐coagulant activity on these materials.
High‐strength hydrogels based on N‐vinyl pyrrolidinone and 4‐t‐butyl‐2‐hydroxycyclohexylmethacrylate
Authors: Friends G. D. , Künzler J. F. , Ozark R. M.
Published: December 2004

A nonionic, high‐water‐content, highstrength hydrogel based on N‐vinyl pyrrolidinone (NVP) and a novel hydrophilic‐bulky monomer, 4‐t‐butyl‐2‐ hydroxycyclohexylmethacrylate (TBCM), was developed. The TBCM was prepared in three relatively simple, high‐yield steps. The copolymerization of NVP with varying concentrations of TBCM resulted in transparent hydrogel films possessing a wide range in mechanical and physical properties. A copolymer composition of 91.7 parts NVP, 8.0 parts TBCM, and 0.3 parts ethylene glycol dimethacrylate (EGDMA) gave a transparent, flexible film possessing a water content of 86%, a modulus of 130 g/mm2, and a tear strength of 3.4 g/mm. In contrast, a copolymer composition of 49.7 parts NVP, 50 parts TBCM, and 0.3 parts EGDMA gave a transparent, hard hydrogel film possessing a water content of 26% and a modulus of 86,000 g/mm2. All of the high‐water co‐polymer compositions developed resulted in lysozyme uptake typical of nonionic high‐water‐content hydrogels and oxygen permeability levels greater than 50 (cm3 O2(STP) · cm)/(s · cm2 · mm Hg) × l0−11.
A finite element analysis of the push‐out test: Influence of test conditions
Authors: Dhert W. J. A. , Verheyen C. C. P. M. , Braak L. H. , De Wijn J. R. , Klein C. P. A. T. , de Groot K. , Rozing P. M.
Published: December 2004

The commonly used method for quantitative evaluation of the strength of a bone‐implant interface is the push‐out test. In order to give an impulse to standardization and to gain more insight in the biomechanics of the push‐out test, a finite element analysis of this test was performed. This study focused on the influence of test conditions on the push‐out results. The influence of the following four parameters on the interface stress distribution was tested: (a) clearance of the hole in the support jig, (b) Young's modulus of the implant; (c) cortical thickness; and (d) implant diameter. The distance between the implant and the support jig turned out to be very critical for the occurrence of peak stresses in the interface. Variations of the Young's modulus of the implants resulted in a wide range of interface shear stresses. Variation of the cortical thickness showed a reciprocal relationship between cortical thickness and interface shear stress. However, the interface stress distribution remained uniform under the specific test circumstances. These findings also hold for variations in implant diameter. The present investigation shows that the clearance of the hole in the support jig, and the Young's modulus of the implant are parameters which most strongly influence the interface stress distribution. The clearance of the hole in the support jig is the most critical parameter, but also the parameter that can be controlled most easily. Lack of standardization with regard to these parameters can lead to uninterpretable test results. It is recommended that the clearance of the hole in the support jig is at least 0.7 mm and that push‐out results are only compared with each other when materials with similar Young's modulus are concerned.
Compositional dependence of calcium phosphate layer formation in fluoride bioglasses®
Authors: Kim Cheol Y. , Clark A. E. , Hench L. L.
Published: December 2004

Bioglasses® form a double layer composed of apatite and a silica‐rich layer when placed in a simulated physiological solution as well as in living tissue [A. E. Clark, C.G. Pantano, and L. L. Hench, „Auger spectroscopic analysis of bioglass corrosion films,”︁ J. Am. Ceram. SOC., 59(1−2), 37−39 (1976).]. In the present work, the mechanisms of the calcium phosphate layer and the silica‐rich layer formation of fluoride Bioglassesm i n Tris‐buffer solution are studied as a function of the SiOz content. Fourier Transform Infrared Reflection Spectroscopy (FTIRS) is used to investigate the mechanism of formation of calcium phosphate and silica‐rich layers on the glass surface. Ion concentration in reacted solution and elemental depth profiles are obtained by Induced Coupled Plasma Atomic Emission Spectrometry (ICP) and Auger Elect on Spectroscopy (AES), respectGely. SiO bonds with one nonbridging oxygen and SiOSi bonds form at the early stage of reaction. Strong phosphorus ion uptake occurs when an amorphous calcium phosphate layer crystallizes. Glasses with high silica content (conventional glass) form the silica‐rich layer first followed by a calcium phosphate layer on top. However, glasses with low silica content (invert glass) form both layers simultaneously. The rate of apatite formation decreases with increasing SiOz content, especially in the region of conventional glass compositions. Ion release rates decreases as Si02 content increases, with a significant change occurring at the compositional boundary between invert and conventional glasses. © 1992 John Wiley & Sons, Inc.
PEO enhancement of platelet deposition, fibrinogen deposition, and complement C3 activation
Authors: Chaikof Elliot L. , Merrill Edward W. , Callow Allan D. , Connolly Raymond J. , Verdon Sylvie L. , Ramberg Karen
Published: December 2004

Whereas it has been commonly thought that adding polyethylene oxide PEO to a surface would diminish the capacity of the surface to cause deposition of platelets and of fibrinogen, and to activate complement C3, we present data showing exactly the opposite. These unexpected results are obtained with low molecular weight (2000) PEO, and are not found with higher molecular weight (20,000) PEO.
Calcification of implanted vascular tissues associated with elastin in an experimental animal model
Authors: Paule W. J. , Bernick S. , Strates B. , Nimmi M. E.
Published: December 2004

We have previously studied the process of calcification in bioprosthetic porcine heart valves crosslinked with glutaraldehyde. Observations using light microscopy had indicated that calcification of elastic fibers occurs in implanted heart valves, in addition to calcification associated with collagen fibers. To determine the contribution of elastin to the process of calcification, small pieces of rabbit aorta were crosslinked with 0.2% glutaraldehyde, rinsed in buffer, and implanted subcutaneously in young adult male rats. Cross‐linked jugular vein implants were included as controls. After an implantation period of 1 month or longer, we observed many areas of calcification in the aortic media associated with elastin and fewer such areas associated with collagen. The elastin‐rich aortic tissues accumulated more calcium than venous tissues. Calcium deposits appeared similar in both allogeneic and xenogeneic implants. Calcified areas viewed under the electron microscope included intercellular nonfibrous material. Calcified areas involved predominantly the outer layers of elastic fibers. Calcific deposits included needle‐ like crystals of hydroxyapatite but often consisted of an amorphous flocculant material surrounded by crystals. The close spatial relationship of hydroxyapatite crystals and elastic membranes seen in this study may be relevant to the initiation of dystrophic calcification in glutaraldehyde cross‐linked aortic grafts. © 1992 John Wiley & Sons, Inc.
Introducing a selectively biodegradable filament wound arterial prosthesis: A short‐term implantation study
Authors: Cohn Daniel , Elchai Zohar , Gershon Baruch , Karck Mathias , Lazarovici Galila , Sela Jona , Chandra Mukul , Marom Gad , Uretzky Gideon
Published: December 2004

This article introduces a new compliant and selectively biodegradable filament wound vascular graft and reports the findings of a shorterm implantation study. A basic feature of filament winding is its ability to tailor and better control the mechanical properties of the prosthesis, so that a closer match with the anisotropic properties of native arteries is achieved. The elastomeric vascular grafts comprise poly(ether urethane urea) fibers (Lycra) embedded in a twocomponent matrix consisting of poly(ether urethane) (Pelle‐ thane) and a highly flexible poly(ethy1ene glycol)/poly(lactic acid) biodegradable segmented copolymer (PELA). Typical tensile modulus values fall in the few megapascals (MPa) range, this being comparable to that of natural arteries. The wound graft exhibits excellent handling and suturability characteristics as well as enhanced burst strength. Furthermore, due to its biodegradable constituent, the prosthesis combines minimal intraoperative blood loss and high healing porosity. The graft displays initially negligible in vitro water permeation, which increases gradually with time. In this short‐term study, the prostheses were implanted in the canine carotid, and their biological performance was compared to that of expanded Gore‐Tex. The luminal surface of the wound grafts was coated with a thin layer of pseudointima, strongly adhered to the prosthesis surface. Contrasting with the very stiff Gore‐Tex grafts, the filament wound prostheses retained their high compliance, being highly pulsatile upon explantation. Histological studies fully corroborated these findings, underscoring the healing properties of these new filament wound vascular prostheses. © 1992 John Wiley & Sons, Inc.
Human neutrophil response to short‐term exposure to F‐75 cobalt‐based alloy
Authors: Yang Jun , Shanbhag Arun , Lilien Jack , Black Jonathan
Published: December 2004

The effect of biomaterials on the activation of human neutrophils was studied. Human neutrophils were incubated with F‐75 cobalt‐based alloy or polystyrene microspheres of a nonphagocytosable size with two times total neutrophil plane surface area. Scanning and transmission electron microscope (SEM, TEM), energy dispersive x‐ray microanalysis (EDX), and graphite furnace atomic absorption spectroscopy (GFAAS) were used to analyze changes in cellular morphology and metal content. This report presents evidence that human PMNs display morphological changes related to foreign material challenge, including activation on F‐75 bead surfaces, pinocytosis of corrosion products, formation of intracellular vacuoles, degranulation, etc. Moreover, when PMNs were present, the corrosion release rate of F‐75 increased as much as three times over cell‐free controls. © 1992 John Wiley & Sons, Inc.
Neocartilage formation in vitro and in vivo using cells cultured on synthetic biodegradable polymers
Authors: Freed L. E. , Marquis J. C. , Nohria A. , Emmanual J. , Mikos A. G. , Langer R.
Published: December 2004

Cartilaginous implants for potential use in reconstructive or orthopedic surgery were created using chondrocytes grown on synthetic, biodegradable polymer scaffolds. Chondrocytes isolated from bovine or human articular or costal cartilage were cultured on fibrous polyglycolic acid (PGA) and porous poly(L)lactic acid (PLLA) and used in parallel in vitro and in vivo studies. Samples were taken at timed intervals for assessment of cell number and cartilage matrix (sulfated glycosaminoglycan [S‐GAG], collagen). The chondrocytes secreted cartilage matrix to fill the void spaces in the polymer scaffolds that were simultaneously biodegrading. In vitro, chondrocytes grown on PGA for 6 weeks reached a cell density of 5.2 × 107 cells/g, which was 8.3‐fold higher than at day 1, and equalled the cellularity of normal bovine articular cartilage. In vitro, the cell growth rate was approximately twice as high on PGA as it was on PLLA; cells grown on PGA produced S‐GAG at a high steady rate, while cells grown on PLLA produced only minimal amounts of S‐GAG. These differences could be attributed to polymer geometry and biodegradation rate. In vivo, chondrocytes grown on both PGA and PLLA for 1–6 months maintained the three‐dimensional (3‐D) shapes of the original polymer scaffolds, appeared glistening white macroscopically, contained S‐GAG and type II collagen, and closely resembled cartilage histologically. These studies demonstrate the feasibility of culturing isolated chondrocytes on biodegradable polymer scaffolds to regenerate 3‐D neocartilage. © 1993 John Wiley & Sons, Inc.
The effect of calcium phosphate ceramic composition and structure on in vitro behavior. I. Dissolution
Authors: Ducheyne Paul , Radin Shulamith , King Linda
Published: December 2004

Synthetic calcium phosphate ceramic (CPC) surfaces can be transformed to a biological apatite through a sequence of reactions which include dissolution, precipitation, and ion exchange. By virtue of the reactions being material‐dependent, it is important to determine parametric rate effects. In this study we focused on the effect of stoichiometry and crystal structure of CPCs on the dissolution kinetics. Monophse, biphase, and multiphase CPCs with a Ca/P ratio equal to or greater than 1.5 were studied. The experiments were performed in a calcium‐ and phosphate‐free Tris buffer solution at pH 7.3. The dissolution behavior of the CPCs studied was found to vary over a wide range. The dissolution rate of the monophase CPCs increased in the order of stoichiometric hydroxyapatite, calcium deficient hydroxyapatite, oxyhydroxyapatite, β‐tricalcium phosphate, α‐tricalcium phosphate, and tetracalcium phosphate. Dissolution of biphase and multiphase CPCs increased prorated the concentration of more soluble component. © 1993 John Wiley & Sons Inc.
Measurement of intracellular hydrogen peroxide induced by biomaterials implanted in a rodent air pouch
Authors: Krause Tyrone J. , Robertson Fredika M. , Greco Ralph S.
Published: December 2004

Biomaterials elicit an inflammatory response that is undoubtedly a factor in their heading and in the complications associated with their use. Herein, we report the modification of a rat air pouch in which we measured the production of intracellular hydrogen peroxide by inflammatory cells adherent to the surfaces of silicone elastomer (SE) and expanded polytetrafluoroethylene (ePTFE). We used the fluorescent probe dichlorofluorescein diacetate (DCFH‐DA) to measure the intracellular production of hydrogen peroxide 2 and 7 days after implantation. After 2 days, host cells adherent to ePTFE produced almost 3.5 times more hydrogen peroxide than did cells adherent to SE (P < .001). By 7 days, the H2O2 production on cells adherent to ePTFE had decreased while that on cells adherent to SE was unchanged. These data indicate that the air pouch is a good alternative to other in vivo models for studies of the biological reactions induced by biomaterials. © 1993 John Wiley & Sons, Inc.
A new type of biomaterial for artificial skin: Dehydrothermally cross‐linked composites of fibrillar and denatured collagens
Authors: Koide M. , Osaki K. , Konishi J. , Oyamada K. , Katakura T. , Takahashi A. , Yoshizato K.
Published: December 2004

A new type of biomaterial for artificial skin was developed as a form of sponge by combining fibrillar collagen (F‐collagen) with gelatin. The sponge was physically and metabolically stabilized by introducing dehydrothermal cross links. To get the final product, various conditions in the preparation of sponges were evaluated by in vitro cellular responses and in vivo tissue reactions. Fibroblasts placed on a sponge of gelatin attached themselves to it, migrated well into the sponge, and remained inside it for at least 7 days. However, sponges of gelatin showed structural instability for hydrolytic degradation by the cells. Most fibroblasts appeared not to penetrate into the interior of a sponge of F‐collagen but to remain on its surface when fibroblasts were placed on the sponge, suggesting poor attraction of F‐collagen revealed an intense infiltration of neutrophils into the sponge, indicating F‐collagen as an inducer of the inflammatory reaction. These aggravating characters of F‐collagen sponges were greatly improved by blending gelatin with F‐collagen. The new type of collagen‐based biomaterials developed in the present study is expected to become a useful matrix substance for artificial skin. © 1993 John Wiley & Sons, Inc.
Thrombin and albumin adsorption to PVA and heparin–PVA hydrogels. 2: Competition and displacement
Authors: Smith Barbara A. H. , Sefton Michael V.
Published: December 2004

Thrombin adsorption to polyvinyl alcohol (PVA) was different from its adsorption to polyethylene (PE)—not so much in amount, but in its affinity. Thrombin was more easily displaced from polyethylene and its adsorption was more readily prevented by prior or simultaneous exposure to albumin. From PVA (or heparin–PVA), only ∼ 30% of the adsorbed protein could be removed by a series of eluents, including even harsh ones such as 2.5M NaOH and 6M guanidine;>85% could be removed from PE. Thrombin adsorption to PVA was not affected by the presence of BSA in solution or at the surface, but was virtually prevented on PE by preexposure to or adsorption with BSA. Heparin‐PVA was not much different than PVA in most of these experiments, but did exhibit a “Vroman effect”. In the absence of fibringen or antithrombin III, there was a maximum in thrombin adsorption from plasma at a plasma concentration of 1%. The behavior on this surface was dependent on both exposure time and protein concentration. These studies highlight the complexity of the interaction between plasma proteins and polymer surfaces (particularly hydrogel surfaces) and the difficulty of obtaining a clear picture of what happens when a single protein interacts with a polymer in the presence of other proteins. © 1993 John Wiley & Sons, Inc.
Enzyme–biomaterial interactions: Effect of biosystems on degradation of polyurethanes
Authors: Santerre J. P. , Labow R. S. , Adams G. A.
Published: December 2004

Enzyme‐induced liberation of hard‐segment‐containing components from polyurethanes was evaluated using two 14C‐labeled polyurethanes. A polyester ureaurethane and polyether urea‐urethane were synthesized from toluene‐2,4‐diisocyanate (TDI)/ polycaprolactone diol (PCL) or TDI/polyethylene glycol (PEO) with 14C‐labeled ethylene diamine. Both materials were characterized using electron spectroscopy for chemical analysis (ESCA), differential scanning calorimetry (DSC), size exclusion chromotography, and material chemistry by Fourier transform infrared (FTIR) spectroscopy. Biodegradation assays were carried out using cholesterol esterase (CE), collagenase (CO), cathepsin B (CB), and xanthine oxidase (XO) at the pH optimum conditions for each enzyme at 37°C. Biodegradation was analyzed by monitoring the release of radiolabel, by weight change, and by surface analysis using scanning electron microscopy. The polyester urea‐urethane was shown to be susceptible to enzymatic degradation above the effect of the buffer control solution by the CE but not by the other enzyme systems as monitored by radiolabel released. In the initial period of incubation, the rate of degradation was increased for all systems, including buffer controls; however, the rates dropped off rapidly by day 28. The change in weight data for the polyester urea‐urethane and polyether urea‐urethane showed no enzyme‐dependent biodegradation above the buffer controls. However, in sodium acetate buffer at pH = 5, the polymers showed a significant weight loss relative to other buffers. In conclusion, this study showed that the biological component responsible for the onset of the biodegradation process is more likely the result of a multitude of biologically mediated compounds acting synergistically, with the process being enhanceds by physical parameters such as material dissolution. In addition characterization of surface and bulk chemistry as well as material structure evaluation have been shown to be essential to interpret degradation data. © 1993 John Wiley & Sons, Inc.
Organoapatites: Materials for artificial bone. III. Biological testing
Authors: Stupp Samuel I. , Hanson Jacqueline A. , Eurell Jo Ann , Ciegler Glenn W. , Johnson Ann
Published: December 2004

This article reports on the in vivo testing of new artificial bone materials we have termed “organoapatites.” These materials consist of mineral networks in which organic polymers are intimately dispersed by nucleation and growth of apatite crystals from a mother liquor containing the organic substances. Organoapatites were tested as implants in adult canine cortical bone for periods in the range from 12–35 weeks and fluorochromes were used in the model to investigate the kinetics of bone growth or repair. The analysis of histological samples was carried out using histomorphometric methods as well as fluorescence microscopy. Results showed excellent apposition of poly(amino acid) organoapatites with mineralized bone and fibrous encapsulation when a synthetic polyelectrolyte was the only organic component. This observation suggests that the molecularly dispersed organic dopant amounting to only 2–3% by weight of the microstructure can play a critical role in the tissue response to the implant. Relative to apatite controls, organoapatites were also found to have greater resistance to fragmentation in vivo and those containing amino acid units revealed interfacial bioerosion accompanined by regeneration of mineralized tissue. Design of organoapatite compositions and microstructures may therefore be useful in achieving the specific rate of biological response which is clinically desired. © 1993 John Wiley & Sons, Inc.
Collagen fibers as a temporary scaffold for replacement of ACL in goats
Authors: Chvapil Milos , Speer Donald P. , Holubec Hana , Chvapil Thomas A. , King David H.
Published: December 2004

ACL substitutes made of braided or plied purified collagen fibers and cross‐linked with hexamethylenediisocyanate were implanted into a total of 14 adult goats to achieve resorption within 8 to 10 months. Two types of collagen fiber prostheses differing in degree of collegen purification were tested. The implants were harvested 2 to 11 months postimplantation, tested for mechanical strength, and evaluated by morphological methods. In the first group (n = 5), the less purified and less crosslinked collagen fiber ACL implant induced fast connective tissue ingrowth. At 6 months postimplantation, 40 to 60% of the collagen implant was resorbed. No studies on breaking strength were done in this group. In the second group, highly purified and more crosslinked ACL implants were less infiltrated by cells and were resorbed only by 10 to 20%. Still, the breaking strength was decreased to 10% of the original implant strength. In the second group, the fixation of the ACL implant in the bone tunnel with a bone wedge was insufficient (n = 6); however, additional fixation with metal screws was successful (n = 3). We conclude that cross‐linked collagen fibers alone cannot be used as a safe ACL substitute as they quickly lose mechanical strength despite limited biodegradation. © 1993 John Wiley & Sons, Inc.
Interaction of heparin with polyallylamine‐immobilized surfaces
Authors: Ma Xinghang , Mohammad Syed Fazal , Kim Sung Wan
Published: December 2004

A new method to bind ionically and remove heparin from solution and dilute serum is described. Utilizing cellulose diacetate (CA) as the polymer substrate, a cationic polymer chain—poly(allylamine)‐PALA—was immobilized directly onto the CA surface and onto the surface using poly(ethylene glycol) (PEG) spacer groups. The ionic interaction between the anionic heparin molecule and the cationic PALA polymer is specific and effective to remove haparin from the bulk solution. The binding properties of heparin onto the PALA and PEG‐PALA surfaces were examined. The effects of PEG spacers on heparin binding onto the PALA‐immobilized surface were investigated by varying the MW of PEG spacers. PALA (MW 8500)‐immobilized surfaces exhibited enhanced heparin binding. The maximum heparin binding was observed in the region of PEG MW 2000–4000. For the high‐molecular‐weight PALA (MW 50,000)‐immobilized surfaces, heparin binding was independent of the molecular weight of PEG. PEG spacers were also evaluated for their ability to prevent or decrease protein (albumin) adsorption. It was observed that at high albumin concentrations, the adsorption of proteins decreased with increasing chain length of PEG, up to MW 3400. These observations suggest that low‐molecular‐weight PALA (MW 8500)‐immobilized CA surfaces with PEG spacers (MW 3400) may provide increased heparin binding capacity and decreased protein adsorption. © 1993 John Wiley & Sons, Inc.
Protein adsorption to poly(ether urethane ureas) modified with acrylate and methacrylate polymer and copolymer additives
Authors: Brunstedt Michael R. , Ziats Nicholas P. , Robertson Steven P. , Hiltner Anne , Anderson James M. , Lodoen Gary A. , Payet C. R.
Published: December 2004

To understand better blood interactions with poly(ether urethane urea) (PEUU) materials, a radioimmunoassay and whole or diluted human plasma were used to characterize the presence of fibrinogen, immunoglobulin G, factor VIII/von Willebrand factor, Hageman factor on (factor XII), and albumin on a PEUU formulation and on PEUU formulation modified with the amphiphilic additive Methacrol 2138F (co[diisopropylaminoethyl methacrylate (DIPAM)/decyl methacrylate] [3/1]), or with hydrophobic acrylate or methacrylate polymer or copolymer additives. The protein adsorption assay showed that PEUU films loaded or coated with Methacrol 2138F (Methacrol) or homopoly‐DIPAM (h‐DIPAM) adsorbed significantly lower amounts of the studied proteins than did either the base PEUU formulations or the PEUUs loaded with th more hydrophobic acrylate or methacrylate polymer additives. Experiments with Methacrol‐loaded PEUUs, where the loading of Methacrol was varied from 0.25 wt% to 20.0 wt% showed that the adsorption of each of the characterized proteins did not vary significantly throughout the Methacrol loading range, and that all Methacrol‐loaded PEUU formulations adsorbed significantly lower amounts of the studied proteins than did the unloaded PEUU. Phase separation within the additive loaded PEUUs was characterized by scanning electron microscopy (SEM). The solubility parameters of the additives, as well as of the base PEUU, were calculated and used to interpret differences in phase separation of the additive modified PEUUs. The analysis showed that additives of lower solubility parameter phase‐separated into fewer large microdroplets within the PEUU matrix. SEM analysis also showed that additive microdroplets were not present on the air side surface of loaded PEUUs. To explain the differences in protein adsorption to the air side of additive loaded PEUUs when compared to the base PEUU, it was assumed that the additives near this region of the solvent swollen PEUU matrix may have migrated to, at or near the PEUU–air interface during film formation, creating an additive enriched PEUU surface region. Once at this surface region, it was suggested that dynamic surface reorientation in response to an aqueous medium ensured that the additives were able significantly to influence protein adsorption behavior only if they interacted with aqueous media more favorably than the PEUU. © 1993 John Wiley & Sons, Inc.
Extracellular matrix analogs as carriers for growth factors: In vitro fibroblast behavior
Authors: Roy France , DeBlois Chantal , Doillon Charles J.
Published: December 2004

Repair of connective tissue involves interactions between growth factors (GFs) and extracellular matrix (ECM) molecules. On the other hand, biological biomaterials could be used to carry and deliver GFs to stimulate wound healing. In the present study, fibroblasts were cultivated in a serum‐free culture medium onto collagen (type I), hyaluronic acid, chondroitin sulfate, fibronectin, or fibrin. FGF, EGF, or PDGF was incorporated within those substrates. Using immuno‐ and radiolabeling assays, the distribution of GFs within the ECM analogs was relatively uniform and GFs retained in substrates were dependent on the substrates. Fibroblast replication was determined by the incorporation of [3H]‐thymidine and compared to control groups. On collagen or chondroitin sulfate, the incorporation of GFs did not significantly improve cell proliferation. On hyaluronic acid, the incorporation of FGF and PDGF enhanced cell replication at 48 h. The incorporation of PDGF in fibronectin enhanced cell replication. On fibrin, the incorporation of PDGF, EGF, and FGF significantly enhanced cell replication. However, cell replication on FGF‐incorporated fibrin was higher by 48 h than that on fibrin in the presence of FGF‐supplemented culture medium. Fibrin sustains the biological activity of GFs, FGF in particular, and can be a carrier for GF that stimulates cell replication. © 1993 John Wiley & Sons, Inc.
Effect of crosslinking agent content, monomer functionality, and repeat unit chemistry on properties of unfilled resins
Authors: Beatty M. W. , Swartz M. L. , Moore B. K. , Phillips R. W. , Roberts T. A.
Published: December 2004

Seven mechanical/physical properties were used to evaluate 10 unfilled resins: eight aromatic dimethacrylates and two urethane dimethacrylates. Physical property tests included compressive strength, Young's modulus in compression, uniaxial tensile strength, intrinsic yield point, toothbrush abrasion, Knoop hardness, and water sorption. Controlled changes were made in the following four material parameters: amount of crosslinking diluent present in the uncured monomer, functionality of the monomer, repeat unit chemistry of the monomer (urethane vs. aromatic structure) and mode of activation (chemical vs. visible light). Polymers containing a high concentration of crosslinking agent (50 wt%) were found to be tougher and to possess lower hardness than materials containing lesser amounts of crosslinking agent. This was attributed to the flexible nature of the triethylene glycol dimethacrylate crosslinking molecule. Exposure to water plasticized the highly crosslinked materials to the degree that the yield point and elastic modulus were effectively lowered. Most of the tested properties were unaffected by differences in functionality except resistance to toothbrush abrasion, which was enhanced for polymers derived from high functionality monomers. The urethane‐based polymers sorbed substantially more water than the aromatic‐based materials, which presumably resulted in lower values for surface hardness. However, the urethane resins were very tough, and excellent resistance to toothbrush abrasion was observed. Property differences caused by differences in activation mode were small, although the visible light materials did sorb more water. © 1993 John Wiley & Sons, Inc.
Fluoroalkylethyl silane coating as a moisture barrier for dental ceramics
Authors: Rosenstiel S. F. , Denry I. L. , Zhu W. , Gupta P. K. , van der Sluys R. A.
Published: December 2004

The performance of dental ceramics is reduced in wet environments due to stress‐corrosion limiting restoration lifetime. As analysis suggests that fracture is typically initiated from the internal surface, placement of a thin coating before a restoration is cemented to place may prevent fracture if it acts as a moisture barrier. Of coating we tested, a fluoroalkylethyl silane (du Pont MPD‐7680) showed promise. This study aimed to test a range of concentrations on glass and to determine any strength improvement on dental ceramics. Glass slides (n = 8–9) were indented (29‐N load) stored 24 h, etched, coated with 100, 50, and 25% fluorosilane in isopropyl alcohol, and air‐cured for 24 h. The slides were fractured on a biaxial fixture in water at 0.5 mm/min and maximum stresses calculated. Uncoated controls were tested in water and liquid N2 to determine the inert strength without stress‐corrosion. Results showed increasing mean strength from uncoated (53.6 MPa) to 100% (68.0 MPa) which compared to the 80.4 MPa inert strength. ANOVA showed P < .05. Subsequently the experiment was repeated on discs of three dental ceramics (n = 7–10): feldspathic (Ceramco), glass‐ceramic (Dicor MGC), high‐leucite (Optec) with the 100% solution only. Mean strength was significantly (P < .01) enhanced in the feldspathic (56.2 MPa, untreated, 70.7 MPa, treated) but not the high‐leucite (83.1, 83.0) or the glass‐ceramic (283.9, 271.4). Fluoroalkylethyl silane coating reduced stres‐corrosion in glass and feldspathic porcelain. It may be a practical approach to reducing fracture of ceramic restorations. © 1993 John Wiley & Sons, Inc.
Microencapsulated human hepatoma (HepG2) cells: In vitro growth and protein release
Authors: Uludag Hasan , Sefton Michael V.
Published: December 2004

The feasibility of a microencapsulation process ultimately for cell transplantation was investigated by encapsulating human hepatoma (HepG2) cells in hydroxyethyl methacrylate–methyl methacrylate (HEMA–MMA) membranes through an interfacial precipitation process. Changes in viability and metabolic activity as well as protein secretion by the encapsulated cells were studied in vitro. When encapsulated at either low or high density (1 or 5 × 106 cells/mL, respectively), HepG2 cells retained their active metabolic state and/or proliferated during the initial 1‐week period, after which a significant drop in cell viability was obtained. Encapsulati of a biological attachment substrate, Matrigel, along with the cells, however, resulted in rapid proliferation in both low and high density capsules with prolonged maintenance of an active metabolic state. The secretion of four model proteins (α1‐acid glycoprotein, α1‐antitrypsin, haptaglobin and fibrinogen) was demonstrated during the 2‐week study period for the Matrigel encapsulated cells. Furthermore, the encapsulated cells remained responsive to interleukin 6 (IL6), a physiological stimulator of plasma protein secretion, as determined by the elevated secretion of haptaglobin in response to IL6 treatment. We conclude that HEMA–MMA capsules, in the presence of an attachment substrate, provide a suitable environment for the growth and expression of differentiated functions of encapsulated hepatoma cells. © 1993 John Wiley & Sons, Inc.
A novel recovery system for cultured cells using plasma‐treated polystyrene dishes grafted with poly(N‐isopropylacrylamide)
Authors: Okano Teruo , Yamada Noriko , Sakai Hideaki , Sakurai Yasuhisa
Published: December 2004

Poly(N‐isopropyl acrylamide) (PIPA Am) demonstrated a fully expanded chain conformation below 32°C and a collapsed, compact conformation at high temperatures. This unique temperature responsive polymer was grafted onto surfaces of commercial polystyrene dishes and used as temperature switches for creating hydrophilic surfaces below 32°C and hydrophobic surfaces above 32°C. Cells attachment and the growth of bovine endothelial cells and rat hepatocytes on PIPA Am‐grafted surfaces at 37°C demonstrated similar behavior to the commercialized culture dishes. Both cell types were observed to detach from the PIPA Am‐grafted surface simply by reducing the temperature below the polymer transition temperature (collapse). Cells recovered by this method maintained substrate adhesivity, growth, and secretion activities nearly identical to those found in primary cultured cells in contrast to the compromised function found in cultured cells damaged by trypsinization. These results provide strong evidence that PIPA Am‐grafted surfaces, as thermal switches are very effective for reversing cell attachment and detachment without cell damage. Properties of cell culture surfaces can be readily transformed by this technique reversibly into hydrophilic and hydrophobic coatings of PIPA Am‐grafted polymers. © 1993 John Wiley & Sons, Inc.