bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain tissue reaction to permselective polymer capsules
Authors: Winn Shelley R. , Aebischer Patrick , Galletti Pierre M.
Published: December 2004

The brain tissue reaction to permselective polymer capsules implanted in rats was evaluated for 1 to 54 weeks. The polymer capsules were well tolerated in all animals and no recognizable neurological or behavioral deficits were associated with the implants. Necrosis at the brain/polymer interface, as assessed with Nissl stain, was not observed. Foreign body giant cells were consistently absent. Immunocytochemically identified reactive neuroglial cells showed a remarkably low‐grade tissue response to the synthetic material be yond the first 2 weeks of observation. Immunolabeled cortical neurons revealed conserved columnar arrays around the implants. Transmission electron microscopy showed a minimal degree of collagen deposition compared to implants in peripheral sites, and normal synapses within a few micrometers from the brain/polymer interface, supporting the prospect of biocompatible, immunoisolated xenografts in the central nervous system.
Effect of substrate condition and substituted phenols and methacrylates on toluene diisocyanate/dentin bond strengths
Authors: Stackhouse James A. , Kristol David S. , Von Hagen Stanley , Rao Gururajan
Published: December 2004

One aim of this in vitro investigation was to determine the effect of substituting four phenols and two methacrylates with vinyl functions on the dentin bond strengths of several new experimental dentin bonding agents. Another objective was to determine the effect of postextraction age and dentin level within the tooth on tensile bond strengths of these toluene diisocyanate‐derived adhesives. Extracted third molars were divided into postextraction age groups and sectioned into three slices ∼400 m̈m thick. The four substituted phenols were: eugenol, o‐methoxyphenol, o‐chlorophenol, and p‐cresol. Substituted methacrylates with vinyl ligands were 2‐hydroxyethyl methacrylate (HEMA) and 6‐hydroxyhexyl methacrylate (HHMA). Results showed that adhesives made with o‐chlorophenol, p‐cresol, and methoxyphenol with HEMA were the best, while those made with eugenol and HHMA were the worst. The post extraction age of the tooth and the dentin depth had no consistent effect on most adhesive bond strengths which were generally around 10.3 MPa (1500 psi).
Compressed poly(vinyl alcohol)‐polycaprolactone admixture as a model to evaluate erodible implants for sustained drug delivery
Authors: Wang Paul Y.
Published: December 2004

An implant may release a drug either by diffusion concurrent with dissolution of the polymeric implant material without depolymerization (Type A) or by bioerosion involving depolymerization (Type B). The Type A material may induce immune response, while the erosion of Type B polymer releases fragments which could cause toxicity problems. It is proposed that a combination of the two types of polymers may attenuate the intensity of immune response and toxicity, because the presence of one in an implant of the same weight reduces the amount of the other. However, it is important to determine first, if sustained delivery may be achieved by such an implant. In this study, partially hydrolyzed poly(vinyl acetate) (PVA) and polycaprolactone (PCL) were chosen as the model Type A, and B polymers, respectively, to evaluate this objective in vitro. Pellet discs were prepared to assess the effects of compression, proportion of PVA to PCL, acetyl content of PVA, PCL hydrolysis catalyst and drug loading, using methylene blue (MB) as a model drug. Results showed that sustained delivery could be effected, but PCL erosion did not occur as planned. Therefore, PCL served only as a passive component of the implant, while PVA was eroded with the release of MB. Consequently, it was inferred that a polymer may not be required as a passive component, which suggested the use of other compounds of known biocompatibility. Tests with insulin in a compressed solid admixture with cholesterol showed that reduction of hyperglycemia in diabetic Wistar rat could be effected reproducibly for at least 2 weeks. Thus, the present study, originally planned to test a proposed concept, indicates that many nonpolymeric materials of known biocompatibility may be suitable for drug delivery implants as well.
Platelet shape change and cytoskeletal reorganization on polyurethaneureas
Authors: Goodman S. L. , Grasel T. G. , Cooper S. L. , Albrecht R. M.
Published: December 2004

Understanding how platelet activation responses are affected by polymers having varied surface physicochemical properties can lead to improved materials for vascular applications. The in vitro responses of human platelets were studied upon adherence to four polyurethaneureas with different soft segments, as well as to Biomer, and to Formvar. Platelets were observed by video‐enhanced light microscopy (VLM) as they adhered to polymer films. Platelets were subsequently prepared for high‐voltage transmission electron microscopy (HVEM) to view the cytoskeleton and other ultrastructural features. Scanning electron microscopy (SEM) was then used to characterize cell surface morphology and to survey platelet populations. Shape change and cytoskeletal reorganization differed on the various surfaces. The extent of shape change and cytoskeletal reorganization was related to polyurethane surface energetic properties. While the most extensive shape change was observed on the hydrophilic and polar Formvar surface, the least shape change was observed on a polyethylene oxide soft segment polyurethane with similar surface‐water energetic properties. Therefore properties other than surface‐water energetics must be involved in determining platelet responses to different classes of polymers. HVEM also showed that cytoskeletal reorganization proceeded to completion only on Formvar. Polyurethane adherent platelets, although appearing fully spread by SEM or VLM, never exhibited complete cytoskeletal reorganization.
Transient adsorption of fibrinogen on foreign surfaces: Similar behavior in plasma and whole blood
Authors: Brash J. L. , ten Hove P.
Published: December 2004

The adsorption of fibrinogen from both human whole blood and plasma to a number of “foreign” surfaces is reported. Adsorption was measured as a function of plasma or blood dilution using radioiodine labeling. We showed previously that adsorption of fibrinogen from plasma exhibits a maximum at a plasma dilution of about 100:1, and have attributed this behavior to competition from other plasma proteins. (The same phenomenon is manifest as a time transient in fibrinogen adsorption.) In the present work we show that exactly the same trends are observed in whole blood. For each of the four surfaces, glass, siliconized glass, collagencoated glass and polyethylene, the adsorption of fibrinogen as a function of dilution is the same in whole blood as in plasma. Each of these surfaces shows a unique dependence of fibrinogen adsorption on plasma or blood dilution. On cuprophane and a hydrophilic polyether urethane there is essentially no adsorption of fibrinogen from blood or plasma. For the hydrophilic polyurethane this result may be artifactual, but the absence of fibrinogen binding to cuprophane in blood or plasma is real since fibrinogen is found to be adsorbed in monolayer amounts from buffer.
Titanium‐coated dacron® velour: A study of interfacial connective tissue formation
Authors: Yan John Y. J. , Cooke Francis W. , Vaskelis Paul S. , von Recum Andreas F.
Published: December 2004

Polyethylene terephthalate in textile form (Dacron®) has been used extensively as a surgical implant material for applications such as vascular grafts and percutaneous access devices. It is moderately histocompatible eliciting a chronic inflammatory reaction predominnately in tissue which has grown into the pores of the fabric. Titanium implants on the other hand, induce only the slightest inflammatory response and connective tissue adhesion to the titanium oxide surface is excellent. It was, therefore, hypothesized that a titanium coating on Dacron® fabric might improve its histocompatibility while leaving its desirable mechanical properties unaffected. To test this idea, Dacron® velour specimens were coated with titanium by vacuum deposition and were implanted together with uncoated controls in rabbits subcutis. After various implantation times, the specimens were recovered and the associated tissue was examined histologically. Qualitative and semiquantitative analysis revealed that tissue ingrowth quantity and quality was highly variable, not only between test and control specimens, but also between animals and even between specimens within the same animal. This indicated that there may be a number of factors influencing tissue ingrowth that were not adequately controlled in this study. The titanium coating which was undoubtedly highly oxidized had a profound qualitative and quantitative effect on fibroblast activity (ground substance formation) and fibroblast adhesion to the Dacron® fibers. The results obtained after these short‐term implantation periods indicate that titanium coating affects the quality of the interfacing tissue and may actually improve long‐term histocompatibility. Long‐term studies will have to confirm these preliminary data.
Platelet adhesion onto protein‐coated and uncoated polyetherurethaneurea having tertiary amino groups in the substituents and its derivatives
Authors: Ito Yoshihiro , Sisido Masahiko , Imanishi Yukio
Published: December 2004

Interactions of platelet with novel polyetherurethaneurea and its heparinized derivative were investigated. Platelet adhesion onto the material and release of serotonin or adenosine phosphate from platelet‐rich plasma (PRP) were suppressed by an introduction of amino groups to polyetherurethaneurea, by quaternization of the polymer. When the material was precoated with one of major plasma proteins and the protein‐coated materials were taken to contact with washed platelet suspension (WP), the dependence of platelet adhesion and activation on the properties of polymers was different from that observed for PRP interaction. Platelet adhesion and activation were promoted according to the nature of coating proteins in the order albumin < γ‐globulin < fibrinogen and with increasing degree of denaturation of coating proteins. When the polymer materials were coated with proteins by immersing in aqueous solution containing two kinds of plasma proteins, adhesion behaviors of platelet were similar to those observed for PRP—uncoated material interaction. These experimental facts indicate that the selectivity of platelet for proteincoated material cannot be assessed by the interaction of WP with materials coated with a single kind of protein. It was concluded that material surface to which albumin is selectively adsorbed without denaturation does not stimulate adhering platelets for release reactions.
Attachment and growth of fibroblast cells on polypeptide derivatives
Authors: Kang Inn‐Kyu , Ito Yoshihiro , Sisido Masahiko , Imanishi Yukio
Published: December 2004

Attachment and growth of mouse fibroblast cells on polypeptide derivatives with different wettabilities were studied in the presence or absence of serum proteins. In the presence of serum, a peak level of cell attachment was observed for substrates with a contact angle of around 70°. However, no relationship was found between cell attachment and water contact angle of the substrate in the absence of serum. Ca2+‐dependent cell attachment was observed on hydrophobic polypeptides in the absence of serum proteins. This suggests that Ca2+‐dependent membrane proteins function as mediators for cell attachment to hydrophobic polypeptides. In the presence of serum proteins, it was found that cell attachment is affected by the metabolism, Ca2+, and the cytoskeleton of the cell. Cell growth rate on hydrophilic polypeptide substrates was higher than that on intermediate or hydrophobic polypeptide substrates. This demonstrates that the strong interaction between cells and substrates will be unfavorable for a dewebbing process during mitosis.
Brain biocompatibility of a biodegradable, controlled‐release polymer in rats
Authors: Tamargo Rafael J. , Epstein Jonathan I. , Reinhard Carla S. , Chasin Mark , Brem Henry
Published: December 2004

We report the biocompatibility in the rat brain of a controlled‐release, biodegradable polymer, the polyanhydride poly‐[bis(p‐carboxyphenoxy)propane‐sebacic acid] copolymer (PCPP‐SA) in a 20:80 formulation. The biodegradable polyanhydride can be used for drug delivery directly into the brain, circumventing the difficulties posed by the blood—brain barrier and avoiding the consequences of having to administer toxic doses systemically to reach therapeutic doses in the central nervous system. The tissue reaction in the presence of PCPP‐SA was compared to that seen with other standard neurosurgical implants. Fifty‐six adult Sprague‐Dawley rats were assigned to one of seven groups and underwent bilateral frontal lobe implantation of PCPP‐SA (42 hemispheres), Surgicel (oxidized regenerated cellulose) (35 hemispheres), or Gelfoam (absorbable gelatin sponge) (35 hemispheres). None of the animals showed any behavioral changes or neurological deficits suggestive of either systemic or localized toxicity from the biodegradable polyanhydride, all surviving to the scheduled data of sacrifice. PCPP‐SA evoked a well localized inflammatory reaction, comparable to that of Surgicel, which resolved as the PCPP‐SA polymer degraded over five weeks. The biodegradable polyanhydride has been shown in this study to be nontoxic and biocompatible in the rat brain, when compared to standard neurosurgical implants.
The interaction of cultured cells with membranes composed of random and block copolypeptides
Authors: Minoura Norihiko , Aiba Sei‐ichi , Fujiwara Yukihiko , Koshizaki Naoto , Imai Yohji
Published: December 2004

Random copolypeptides and block copolypeptides were synthesized, and an interaction between these polypeptide membranes and the cells was studied by a cell culture method (cell line, Ca. 9.22). In random copolypeptides composed of γ‐methyl L‐glutamate and γ‐benzyl L‐glutamate, cell attachment and cell growth depended on the monomer composition, and showed a maximum at around 70 mole % of benzyl glutamate. Block copolypeptide composed of L‐methionine and oxyethylene exhibited low cell attachment and cell growth even at 10 mole % of oxyethylene content, compared to L‐methionine homopolymer. ESCA study of the membrane suggested this result to be due to concentration of the poly(oxyethylene) block chain of the polymer on the surface of the membrane. Block copolypeptide composed of N5‐(3‐hydroxypropyl) L‐glutamine and L‐leucine exhibited low cell attachment and cell growth, while the corresponding random copolypeptide exhibited high cell attachment and cell growth. This difference is attributable to the microheterophase structure with the hydrophilic domains embedded in the hydrophobic matrix in the block copolypeptide membrane.
Enhanced patency of small‐diameter tubings after surface immobilization of heparin fragments. A study in the dog
Authors: Arnander Claes
Published: December 2004

The luminal surfaces of polyethylene and polyurethane tubings of 1 mm inner diameter and 1 m in length were coated with heparin by end point attachment and thereafter sterilized in ethylene oxide. The tubings were inserted as arterio‐venous shunts from the aorta to the superior caval vein via a carotid artery and a jugular vein. Patency was assessed with an ultrasound doppler flow meter and flow measurements. All nonheparinized shunts occluded within 10 days with a mean elapsed time from the insertion of the tubing is the last positive doppler registration being 3.5 days. The corresponding patency time for heparinized shunts was 25.9 days. The occlusion of the heparinized tubings was due to the incorporation of the ends of the tubings in the walls of aorta and caval vein, whereas the nonheparinized tubings occluded as a result of clot formation. It is concluded that surface immobilization of heparin with sequences capable of activating antithrombin may be beneficial in the development of small‐diameter vascular protheses.
The spatial resolution of protein adsorption on surfaces of heterogeneous metallic biomaterials
Authors: Williams R. L. , Williams D. F.
Published: December 2004

This study was designed to examine the heterogeneity of the adsorption of proteins onto metallic materials. The materials studied included pure Ag, Au, and Ti and sintered Ag 10% Ti and Ag 10% Ta. The distribution of the protein adsorption was studied using I‐125 labeled albumin detected by microautoradiography. The surface morphology of the specimens was examined in the scanning electron microscope prior to exposure to the protein solution. A heterogeneous distribution in albumin adsorption was observed over the Ag surface. Similar regions were observed over parts of the mixed metal specimens, but superimposed on this pattern were distinct regions of very low protein adsorption which appeared to correlate closely with the regions of Ti or Ta observed in the scanning electron microscope. A uniform distribution of adsorbed albumin was observed on the Au and Ti, with Au giving a much denser microautoradiograph than Ti. This work demonstrates that variations in the protein adsorption to heterogeneous materials can be observed on a microscopic scale.
Influence of antibiotic impregnation on the fatigue life of simplex P and palacos R acrylic bone cements, with and without centrifugation
Authors: Davies Jeffrey P. , O'Connor Daniel O. , Burke Dennis W. , Harris William H.
Published: December 2004

The fatigue properties of Simplex P and Palacos R bone cements were compared to their antibiotic impregnated counterparts AKZ

Supported in part by EM Laboratories, 5 Skyline Drive, Hawthorne, NY 10532; and The William H. Harris Foundation.

and Palacos R with gentamycin

AKZ bone cement is the trade name used by Howmedica Inc. of Rutherford, NJ to describe Simplex P mixed with 0.5 g of erythromycin and 0.24 g of colistin methane sulphonate Both the Simplex P and AKZ cements were obtained from Howmedica. Palacos R and Palacos R with gentamycin (0.5 g/40 g.) were supplied by E. Merck Laboratories.

The effect of porosity reduction by centrifugation of all four cement types was also assessed. Fifteen specimens of each cement type were prepared according to manufacturer's instructions and 15 additional specimens of each cement type were prepared by mixing the powder with chilled monomer (0°C) and then centrifuging the cement immediately after mixing. Fifteen fully reversed tension‐compression fatigue tests were performed at 15 MPa in stress control for each cement preparation in vitro while simulating the in vivo state (37°C and 100% humidity). The number of cycles to failure were recorded. There was no significant difference in the fatigue life of Palacos R and Simplex P when both cements were prepared in the standard fashion. The addition of 1/2 g of gentamycin to Palacos R did not significantly alter its fatigue properties. The addition of 0.5 g of erythromycin and 0.24 g of colistin did not decrease the fatigue life of Simplex P. Centrifugation significantly improved the fatigue properties of Simplex P and AKZ. The fatigue lives of Palacos R and Palacos R with gentamycin were not improved by centrifugation. The fatigue life of centrifuged Simplex P was significantly greater than the fatigue life of Palacos R and of Palacos R with gentamycin, whether the Palacos R based cements were centrifuged or not.
In vitro platelet interactions with a heparin–polyvinyl alcohol hydrogel
Authors: Cholakis Cynthia H. , Sefton Michael V.
Published: December 2004

No difference in in vitro platelet reactivity was found between an immobilized heparin containing hydrogel (heparin–PVA) and the hydrogel without heparin (PVA), in a variety of experimental assays. There was no significant difference between the heparin–PVA and PVA coated polyethylene tubing in the number of 51Cr‐labeled platelets, the extent of 14C serotonin release by the adherent platelets or in the degree of platelet count decrease after 1 h exposure to citrated canine whole blood in a Chandler loop system. Furthermore, adhesion and release values were lower than those observed with the uncoated polyethylene tubing (e.g., 9.3 ± 4.3 plt/103 μ2 on PVA; 18.3 ± 4.6 plt/103 μ2 on polyethylene). There was also no significant difference between heparin–PVA and PVA in bead column retention values with canine blood and with the previously reported washed human platelet adhesion/release values. Thus there appears to be no effect of the immobilized heparin by itself on the in vitro interactions of PVA with platelets, with the reactivity towards platelets dominated by that of the underlying substrate (i.e., PVA).
The bovine pericardial xenograft: III. Effect of uniaxial and sequential biaxial stress during fixation on the tensile viscoelastic properties of bovine pericardium
Authors: Lee J. Michael , Ku Michael , Haberer Sean A.
Published: December 2004

Our previous two articles have shown that glutaraldehyde‐fixed bovine pericardium is nearly isotropic, whether fixed without constraints, with tethering, or with pressure. In this study, we have used uniaxial stress during fixation to produce bovine pericardial material with marked tensile anisotropy. Rectangular and cruciate pericardial samples have been mechanically examined after one of four treatments: (i) fixation under 88‐kPa uniaxial stress, (ii) fixation under 176‐kPa uniaxial stress, (iii) 3 h of 176‐kPa uniaxial stress in saline followed by 24‐h fixation under the same stress, (iv) fixation under 176‐kPa uniaxial stress followed by a second fixation under 176‐kPa stress in a direction normal to the first. Strips of material were cut at 0°, 30°, 60°, and 90° to direction of the initial stress, and tested for response to cyclic loading, stress relaxation, plastic deformation, and fracture properties. Fixation under uniaxial stress produced anistropy similar to that seen in porcine aortic valve leaflets; however, the overall extensibility of the material depended on the applied stress and the aspect ratio of the stressed sample. While loading in saline produced no change, the sequential biaxial stressing produced a reduction in anisotropy, suggesting exposure of additional crosslinking sites. Uniaxial stress during fixation may be a useful method for construction of anisotropic heart valve leaflets.
Plasma protein adsorbed biomedical polymers: Activation of human monocytes and induction of interleukin 1
Authors: Bonfield Tracey L. , Colton Erica , Anderson James M.
Published: December 2004

These studies involved the evaluation of human monocyte/macrophage activation by biomedical polymers coated with human blood proteins. The biomedical polymers were polyethylene, polydimethylsiloxane, woven Dacron fabric, expanded polytetrafluoroethylene, Biomer®, and tissue culture treated polystyrene as the control. They were adsorbed with human blood proteins: albumin, fibrinogen, fibronectin, hemoglobin, and gamma globulin. The protein adsorbed polymers were evaluated for their potential to activate the monocyte/macrophage cellular population in vitro as assessed by the induction of the monocyte/macrophage inflammatory mediator, Interleukin 1 (Il1). Suppression of IL1 was observed when protein adsorbed polymers were compared to the appropriate protein adsorbed control. Protein adsorbed polymers, when compared to polymers without protein adsorption, stimulated IL1 production. The data presented in this manuscript show the level of induction and secretion of IL1 was dependent on the biomedical polymer and the protein adsorbed, as well as the requirement of lipopolysaccharide. These results show differential interactions occur between the proteins, monocytes/macrophages, and biomedical polymers which alter activation and induction of IL1.
IR spectral changes of bovine serum albumin upon surface adsorption
Authors: Lenk Thomas J. , Ratner Buddy D. , Gendreau R. Michael , Chittur Krishnan K.
Published: December 2004

The adsorption of bovine serum albumin from flowing solutions onto germanium and three polyetherurethanes varying in soft segment content was studied by a Fourier transform infrared/attenuated total reflectance technique. Spectral differences observed in the amide I, II, and III regions upon adsorption to all four surfaces were consistent with a loss of helix and gain of β‐structure. There appeared to be a slight difference between BSA adsorbed to germanium and the PEUs, but no distinction could be made between BSA adsorbed to the different PEUs.
The effect of local controlled release of sodium fluoride on the stimulation of bone growth
Authors: Tencer A. F. , Allen B. L. , Woodard P. L. , Self J. , L'Heureux A. , Calhoun J. H. , Brown K. L.
Published: December 2004

This study was performed to test the feasibility of using a biodegradable delivery system for the local controlled release of sodium fluoride as a mechanism for the stimulation of local bone growth. Sodium fluoride grains were mixed with poly‐DL‐lactic acid (PLA), and the mixture was then dissolved in acetone. After driving off the solvent, sheets of this material were rolled into rods 3.2 mm in diameter and 28.6 mm long. These were inserted into the intramedullary canals of the right femora of adult New Zealand White rabbits. A sham implant, made the same way but containing no fluoride, was inserted into the contralateral left leg. The effects of three different concentrations of sodium fluoride, 0.125 g NaF/g PLA, 0.250 g NaF/g PLA, and 0.500 g NaF/g PLA, were determined after a 4‐week implantation period. In a second set of experiments, the concentration was fixed at 0.500 g NaF/g PLA with implantation durations of 4, 8, and 16 weeks. Expressed in terms of property ratios (experimental/control), bending strengths of the femora were significantly raised in most groups with the notable exception of Group 3 (0.500 g NaF/g PLA, 4 weeks). Cross‐sectional area ratios in the distal femora were increased in all groups compared to right/left values for a normal unoperated group (p < 0.05), with the highest ratio being 1.50 (SD = 0.44) for Group 4 (0.500 g NaF/g PLA, 8 weeks). Only Group 4 animals showed significant (p < 0.05) increases in midshaft area ratio and none had responses proximally. Growth rates, measured by sequential fluorochrome labeling of bone followed the area ratio data and were only significant for the distal femora.
Human erythrocyte adhesion and spreading on protein‐coated polymer surfaces
Authors: Steinberg J. , Neumann A. W. , Absolom D. R. , Zingg W.
Published: December 2004

Protein adsorption is the first event which occurs when polymer surfaces are exposed to blood. The adsorption of proteins modifies the surface properties of the substrates and therefore influences subsequent cell—surface interactions. In an attempt to elucidate the fundamental mechanisms governing cell—proteinated‐surface interactions, the extent of fresh human erythrocyte adhesion and spreading on protein‐coated surfaces was examined. Five human serum proteins (albumin, fibrinogen, immunoglobulin G, fibronectin, and transferrin) were used at bulk concentrations ranging from 0.01 mg/mL to 50 mg/mL. Polymer substrates covering a wide range of wettability were employed. Protein adsorption significantly reduces erythrocyte adhesion and spreading on all test surfaces with minimum adhesion observed on fibrinogen: IgG > albumin > fibronectin > transferrin > fibrinogen. The extent of these effects is dependent on the nature of the adsorbed protein, the protein bulk concentration, and the surface properties of the underlying polymer substrates.
Cytotoxicity of alkyl‐2‐cyanoacrylate adhesives
Authors: Papatheofanis Frank J.
Published: December 2004

The cytotoxicity of methyl‐ and isobutyl‐2‐cyanoacrylate adhesives was determined using a rat polymorphonuclear leukocyte suspension. Cell degranulation increased and migration decreased on addition of the alkyl‐2‐cyanoacrylates to the suspension in a concentration‐dependent manner. When. acetylsalicylic acid or indomethacin, inhibitors of prostaglandin H Synthase, were present, the cytotoxicity observed on addition of the adhesives to the leukocytes decreased up to eightfold in a dose‐dependent manner as detected by trypan blue exclusion. Likewise, glutathione peroxidase and superoxide dismutase lowered such cytotoxicity resulting from the cyanoacrylates up to eight‐ and sevenfold, respectively. The data suggested that the adhesives may have generated prostaglandin and thromboxane biosynthesis, and participated in membranal oxidation and lysis. Such a mechanism may contribute to under standing the thrombotic events associated with the necrosis observed on application of these adhesives to tissues in vivo.
Bioceramics and the origin of life
Authors: Hench Larry L.
Published: December 2004

Creation of life involves establishing an organism that is capable of self‐maintenance, self‐reproduction, and adjustment to a changing environment. A Bioactive Substrate Theory of the origin of life is proposed, where the function of the bioactive substrates was to achieve the irreversible ordering of macromolecules into replicative structures. The ordering was a result of six precytic ordering factors which provide the mechanisms for simultaneous formation of primitive codonic‐bases, anabolic processes and energy‐producing, catabolic processes on bioactive inorganic glassy crystalline assemblages. Time dependent changes in the isoelectric point of the inorganic assemblages enabled the anabolic and catabolic processes to be isolated within the same bilipid membrane. The enormous diversity of inorganic glass‐crystal assemblages associated with volcanic activity resulted in many alternative evolutionary pathways for the precytic structures, eventually producing the major genetic pathways for life observed today. The evidence for bioactive ordering factors is examined including selective adsorption of optically active amino acids on optically active mineral substrates and specific cellular responses to bioactive implant materials. The implications of this theory on the biochemical design of implants, and prevention of disease states in modern man are discussed.
Tissue reaction to intraperitoneal polymer implants: Species difference and effects of corticoid and doxorubicin
Authors: Christenson L. , Aebischer P. , McMillan P. , Galletti P. M.
Published: December 2004

The peritoneal cavity is a convenient site for implantation of encapsulated hormonesecreting tissue. However, host tissue organization around such implants may affect solute exchange and viability of the encapsulated tissue. The reaction to polyvinyl chloride acrylic copolymer capsules implanted in the peritoneal cavity of rats and mice was therefore studied. Some animals received a slow release dexamethasone pellet, others were pretreated with doxorubicin, in an attempt to minimize the tissue reaction. The tissue reaction was significantly thicker in rats than in mice at both 2 and 6 weeks after implantation. In rats, corticoids decreased significantly the thickness of the reactive layer as compared to control at all time points studied, but doxorubicin had no effect. The tissue reaction in mice was not significantly affected by corticoid treatment. In both species the thickness of the tissue reaction did not increase significantly between 2 and 6 weeks. At 3 days the tissue reaction consisted of an interrupted single layer of macrophages in mice, whereas in rats the reaction consisted of two or three layers of macrophages and polymorphonuclear cells. At both 2 and 6 weeks, several cell layers surrounded the implants: a single layer of macrophages lying along the polymer, a variable number of layers of fibroblasts interspresed with collagen fibrils (fewer in mice than in rats, and fewer in corticoid treated rats than control rats) and an outer monolayer of mesothelial cells. We conclude that the intensity of tissue reaction to polymer implants in the peritoneal cavity is species dependent and can be decreased by the administration of corticoids but not doxorubicin.
Oligomers with pendant isocyanate groups as tissue adhesives: II. Adhesion to bone and other tissues
Authors: Brauer G. M. , Lee C. H.
Published: December 2004

The adhesive properties of a series of oligomers prepared from 2‐isocyanatoethyl methacrylates (IEM) and/or m‐iso‐propenyl‐α,α‐dimethylbenzyl isocyanate (TMI) and various acrylates or methacrylates were studied. The bond strength of bone, dentin, or soft tissue specimens joined with these oligomers respectively to bone, dental composite restorative, or denture base resin were determined by tensile adhesion or shear tests. These oligomers are more effective in forming stronger bonds to bone than are other tissue adhesives. Fracture occurs cohesively, usually within the bone. Thermocycling in water for 1 week between 5°C and 55°C did not decrease adhesion indicating that exposure to water or thermal shock produced no deterioration of the bond. Tensile adhesion of bovine or human dentin joined to composite restorative resin by means of the oligomers is similar to that of the best dental bonding agents such as Gluma (glutaraldehyde and 2‐hydroxyethyl methacrylate) or ferric oxalate + Nphenylglycine + dimethylacryloxyethyl‐pyromellitate. These oligomers also strongly bond soft tissues and calfskin and to acrylic resins and composites.
Strengthening of bone—implant interface by the use of granule coatings on alumina ceramics
Authors: Kakutani Yoshiaki , Yamamuro Takao , Nakamura Takashi , Kotoura Yoshihiko
Published: December 2004

Three different granule coatings (a granular alumina ceramic coating, a granular hydroxyapatite coating, and a polished granular hydroxyapatite coating) applied to alumina ceramic substrate were evaluated for their strengthening effects of the bone—implant interface in rabbit tibiae. For a comparison, noncoated alumina ceramics, and dense hydroxyapatite were assessed in the same way. The granular alumina ceramic coating, creating a bioinert, porous surface, was effective due to a strong mechanical bond between the bone and implant. The interface strength was even higher than that of the dense hydroxyapatite. The granular hydroxyapatite coating, creating a bioactive, porous surface, was less effective than the granular alumina ceramic coating because of the brittleness of the hydroxyapatite granules, although it formed a direct and mechanical bond with bone tissue. The polished granular hydroxyapatite coating, creating a bioactive, smooth surface, was least effective because of the brittleness of the hydroxyapatite granules, though it presented an improved interface strength compared with that of the noncoated alumina ceramics due to a direct bond between the bone and hydroxyapatite granules.
Elimination of nickel, cobalt, and chromium following repeated injections of high dose metal salts
Authors: Merritt Katharine , Crowe Timothy D. , Brown Stanley A.
Published: December 2004

A study was conducted to determine the ability of hamsters to eliminate in the urine, or store in the organs, large quantities of metal salts given over a period of several months. In addition, the effect of prior immunization on metal ion clearance was determined. The results indicated that nickel was rapidly eliminated in the urine and that the level in the organs was similar to that of control animals. Cobalt was eliminated more slowly than was nickel. The organ levels of cobalt were similar to those of control animals with a slight elevation in the liver of the injected animals. Chromium was eliminated in the urine very slowly, was red cell associated, and the levels were elevated in all the organs (liver, lung, spleen, kidney) compared to control. Prior immunization with metal salts increased the storage of chromium.
In vitro stimulation of fibroblast activity by factors generated from human monocytes activated by biomedical polymers
Authors: Miller K. M. , Anderson J. M.
Published: December 2004

Biomedical polymers used in constructing implantable artificial devices may affect host responses to the material and ultimately contribute to the success or failure of a device via mechanisms of cell–polymer interactions. Human peripheral blood monocytes (MO) cultured in the presence of several such biomedical polymers released factors that stimulated fibroblast proliferation and/or collagen synthesis. The factors that stimulated fibroblast proliferation were differentially released from monocytes cultured in the presence of Dacron, polyethylene, expanded polytetrafluoroethylene (ePTFE), polydimethylsiloxane, and polystyrene (control). Supernatants obtained from monocytes cultured in the presence of Biomer, a segmented polyetherurethane, were unable to stimulate fibroblast proliferation. However, supernatants from all cultures, including MO‐Biomer cultures, were able to induce collagen production from the same target fibroblasts. These same supernatants also were shown to contain interleukin 1 (IL1) activity. Neutralization of the fibroblast stimulatory potential (FSP) activity with antibodies directed against human IL1 and human PDGF demonstrated that IL1 and not PDGF was responsible for the FSP activity. Results of this study show that by affecting macrophage activation, different biomedical polymers can affect host biocompatibility responses by altering fibroblast proliferation and function.
Injectable cross‐linked collagen with improved flow properties
Authors: Wallace Donald G. , Rhee Woonza , Reihanian Hertsel , Ksander George , Lee Richard , Braun William B. , Weiss Barbara A. , Pharriss Bruce B.
Published: December 2004

Aqueous suspensions of glutaraldehyde cross‐linked fibrillar collagen and non‐cross‐linked fibrillar collagen were examined by rheometry, particle size analysis, and microscopic techniques. Although cross‐linked collagen suspensions were similar to non‐cross‐linked suspensions by microscopic and size analyses, they differed in rheometric properties. Concentric cylinder Couette flow, shear creep, uniaxial creep, and porous bed flow all revealed that cross‐linked collagen was more resistant to deformation and flow than non‐cross‐linked collagen. These results were in agreement with in vivo dermal implantation studies, both in pig and human; i.e., compared to non‐cross‐linked collagen, the cross‐linked formulation was more difficult to inject into tissue and did not spread uniformly, sometimes giving rise to palpable lumps or large masses evident in histological sections. When hyaluronic acid was blended with cross‐linked collagen to achieve a final hyaluronate concentration of 5 mg/mL, there was a significant improvement in ease of injection into tissue. Rheometry on blends of hyaluronate and cross‐linked collagen demonstrated that the blend required lower forces to achieve deformation and flow, compared to cross‐linked collagen alone. Particle size analysis on the blend showed a reduction in fiber aggregate dimensions, compared to crosslinked collagen alone.
Student research award in the hospital intern, resident or clinical fellow category, 15th annual meeting of the society for biomaterials, Lake Buena Vista, Florida, April 28–May 2, 1989. An evaluation of purified reconstituted type 1 collagen fibers
Authors: Law J. K. , Parsons J. R. , Silver F. H. , Weiss A. B.
Published: December 2004

Collagen fibers composed of type I collagen molecules were studied for biocompatibility and mechanical properties. These fibers were crosslinked using two different processes: (1) glutaraldehyde, (2) dehydration followed by exposure to cyanamide (DHT/C); the latter method produces only urea as a by‐product of the crosslinking process and is postulated to be more biocompatible. An in vitro model using rat tendon fibroblasts growing on individual fibers was used to evaluate outgrowth rates, cell/fiber interactions, and cell morphology. These studies showed an advantage with DHT/C crosslinking, relative to glutaraldehyde crosslinking, in promoting fibroblast growth. In vivo intramuscular implantation in rats showed excellent biocompatibility for both kinds of collagen implants. In addition, aligned ingrowth into the implant from the medial collateral ligament when applied in that location was demonstrated. Mechanical testing demonstrated the higher strength of dry fibers; however, upon hydration, there was a marked decrease in stress to failure. This reduction in strength was due principally to an increase in cross section due to swelling. These collagen fibers appear to be very biocompatible even in the presence of low concentrations of glutaraldehyde. They promote fibrous aligned ingrowth in a setting of ligament healing. Thus, they represent a strong candidate as a scaffold ligament or tendon prosthesis if crosslink density can be increased.
In vitro and ex vivo platelet interactions with hydrophilic‐hydrophobic poly(ethylene oxide)‐polystyrene multiblock copolymers
Authors: Grainger D. W. , Nojiri C. , Okano T. , Kim S. W.
Published: December 2004

Hydrophilic‐hydrophobic multiblock copolymers synthesized from telechelic oligomers of poly(ethylene oxide) (PEO) and polystyrene (PS) have been used to study the influence of hydrophilic and hydrophobic balance on interfacial interactions of these surfaces with blood components. In vitro coagulation assays show no inherent ability of these amphiphilic surfaces to affect contact activation or coagulation factors. In vitro platelet adhesion and release reactions from rabbit platelet‐rich plasma were shown to be greatest on Biomer and PS homopolymer surfaces and least on cross‐linked PEO surfaces, with the PEO–PS block copolymers demonstrating intermediate responses. These same substrates were tested in a new low‐flow, low‐shear arterio–artery shunt system in rabbits. Whole blood occlusion times were not a direct function of hydrophilic content as both PEO and PS homopolymers and Biomer showed short occlusion times, while PEO–PS block copolymers prolonged occlusion times considerably, depending on composition. Overall, results suggest that PEO–PS block copolymers promote unique whole blood responses in contrast to homopolymer and Biomer controls which are more complex than direct correlations to bulk hydrophilic and hydrophobic contents.
Surface characterization of the cuticle of dirofilaria immitis
Authors: Bilge Fertac H. , Kadipasaoglu Kamuran A. , McCormick C. Michael , Baier Robert E.
Published: December 2004

The surface reactivity of the dog heartworm (D. immitis) was evaluated by comprehensive contact angle measurements and a platelet retention test. Contact angle data yielded calculated surface energy terms very similar to those previously reported for intact vascular endothelium. The platelet test revealed the native worm surface to be nonreactive, retaining fewer platelets than glass or worms whose surfaces had been modified by extraction with acid and high salt solutions. The cuticular morphology of the heartworm was studied with both light and electron microscopy, the latter coupled with ferritin‐conjugated double‐layer immunolabeling to reveal adsorbed host protein on the cuticle surfaces. Multiple attenuated internal reflection (MAIR) IR spectroscopy confirmed the general composition of this surface layer to be glycoproteinaceous. Morphological and histochemical studies confirmed and extended previous descriptions of nematode cuticle, adding ultrastructural detail on cortical, medial, and basal layers. A trilaminar membrane, apparently corresponding to a mammalian cell membrane (plasmalemma), constituted the external cortical layer as observed in high magnifications. The existence of a glycocalyx of varying thickness was demonstrated in ruthenium red‐stained sections. MAIR IR spectra showed this glycoproteinaceous film to appear, in fully hydrated samples, as a loose biological gel. Ferritin‐antibody conjugate labeling confirmed the presence of adsorbed dog albumin, dog immunoglobulin class G (IgG) and dog complement fraction 3 (C3) in the cuticular surface layer. It is likely, therefore, that D. immitis heartworms demonstrate long‐term thromboresistance at least in part due to their passive low‐surface‐energy overcoating with host proteins.
Effects of a grooved titanium‐coated implant surface on epithelial cell behavior in vitro and in vivo
Authors: Chehroudi B. , Gould T. R. L. , Brunette D. M.
Published: December 2004

The effects of a grooved titanium‐coated substratum on epithelial (E) cell behavior were studied in vitro and in vivo. V‐shaped grooves, 10 m̈m deep, were produced in silicon wafers by micromachining, a process which was developed for the fabrication of microelectornic components. The grooved substrata were replicated in epoxy resin and coated with 50 nm of titanium. More E cells were found attached to the grooved titanium surfaces than to adjacent smooth surfaces. In comparison to the smooth surfaces where clusters of E cells were randomly oriented, on the grooved surfaces, clusters of E cells were markedly oriented along the long axis of grooves. Grooved and smooth titanium‐coated epoxy implants were placed percutaneously in the parietal area of rats. Electron and light microscopic obsrvations indicated that E cells were tightly attached to the implant surfaces and this attachment is through basal lamina‐like and hemidesmosome‐like structures. In the grooved portion of the implant, E cells interdigitated into the grooves and had rounded nuclei. Histomorphometric measurements indicated that there was a shorter length of epithelial attachment, longer length of connective tissue attachment, and less recession in the grooved, compared to the smooth portion of implants after 7 and 10 days. These results indicate that horizontal grooves produced by micro‐machining can significantly impede epithelial downgrowth on titanium‐coated epoxy implants.
Student research award in the undergraduate, master candidate, or health science degree candidate category, 15th annual meeting of the society for biomaterials, Lake Buena Vista, Florida, April 28–may 2, 1989. Toxicity of copper‐based dental alloys in cell culture
Authors: Bumgardner Joel D. , Lucas Linda C. , Tilden Arabella B.
Published: December 2004

The biocompatibility of three commercial copper‐based dental casting alloys—Duracast MS, Goldent, and Trindium—three experimental copper alloys, and a control gold alloy, Modulay, were investigated. Trindium, Duracast MS, experimental alloys 1 and 2 are aluminum bronzes; Goldent is a hybrid aluminum–brass alloy; and experimental alloy #3 is a high zinc brass alloy. ASTM F813–83 Standard Practice for Direct Contact Cell Culture Evaluation of Materials for Medical Devices, a 3‐day direct‐contact cell culture regimen and atomic absorption spectroscopy were utilized for evaluating the biocompatibility of these alloys in both Waymouth's and RPMI 1640 complete media. Cellular proliferation assays, using 3H‐thymidine uptake, were also conducted in Waymouth's media. In this investigation, only the experimental alloy #3 elicited alterations in morphology and viability of the fibroblast monolayer during the ASTM and 3‐day culture tests in either media. Cell cultures exposed to experimental alloy #3 experienced copper concentrations greater than 16.0 ppm in Waymouth's and 10 ppm copper in RPMI 1640 media. Differences in the size of the cytotoxic zone around experimental alloy #3 were also observed, with the larger zone occurring in Waymouth's media. In contrast to the direct cell contact studies, all alloys caused decreases in 3H‐thymidine uptake in Waymouth's media at much reduced metal ion concentrations as compared to the controls. Thus, adverse changes in DNA synthesis occurred at much lower copper and zinc concentrations than changes in morphology and viability. Consequently, the assessment of biocompatibility is dependent on the parameters evaluated, and several parameters must be analyzed before a material may be considered biocompatible.