bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro properties of crosslinked, reconstituted collagen sheets
Authors: Morykwas Michael J.
Published: December 2004

Reconstituted, 100‐μm‐thick collagen sheets were crosslinked with either UV light, chromium, or cysteine for use as a burn covering. The sheets were also exposed to a “surface agent” (hydroxyproline, fibronectin, or soluble basement membrane matrix containing Type IV collagen) as a preliminary step in planned adherence studies. Since some chemicals render the collagen toxic, the modified sheets were tested for cytotoxicity using human keratinocytes and fibroblasts. Autoradiography and 3H‐thymidine incorporation were used to quantitate the proliferative rate of these cells in vitro. There was a universal depression of keratinocyte incorporation of 3H‐thymidine following a 1‐day exposure to any collagen sheet when compared to cells not exposed to any collagen. This effect had lessened by 5 days' exposure to the collagen. Conversely, the fibroblasts showed an enhancement in rate of incorporation after 1‐day exposure, especially for cells exposed to collagen sheets crosslinked by UV light. This effect had also lessened by 5 days' exposure. Autoradiography showed few significant variations for any of the cells exposed for either time period. Chromium leaching was determined, with no values greater than 30% of the allowable maximum set by both the British and American Pharmacopeia.
Sequential polydepsipeptides as biodegradable carriers for drug delivery systems
Authors: Yoshida Masaru , Asano Masaharu , Kumakura Minoru , Katakai Ryoichi , Mashimo Tooru , Yuasa Hisako , Imai Kyoichi , Yamanaka Hidetoshi
Published: December 2004

Sequential polydepsipeptides containing both peptide and ester bonds, poly[(L‐alanyl)n‐γ‐ethyl L‐glutamyl‐L‐lactyl] (n = 0, 1, 2, and 3) (poly[(Ala)n‐Glu(OEt)‐Lac]), were prepared for application as biodegradable carriers for drug delivery systems. The in vivo degradation of these polymers was evaluated by subcutaneous implantation in the backs of male rats, and was strongly influenced by the number (n) of Ala units in poly[(Ala)n‐Glu(OEt)‐Lac]. The resulting poly(Ala‐Ala‐Glu(OEt)‐Lac) gave the highest degradability, in which 100% degradation was observed 24 weeks from the start of implantation. A luteinizing‐hormone‐releasing hormone agonist des‐Gly10‐[D‐Leu6]‐LH‐RH ethylamide (LH‐RH agonist), was incorporated into a sequential poly(Ala‐Ala‐Glu(OEt)‐Lac) carrier by the melt‐pressing technique, which gave fine cylindrical polymer formulations with different structures of drug dispersion, e.g., blend‐type and sandwich‐type formulations. The rate of in vivo release of LH‐RH agonist from a blend‐type formulation showed a linear decrease with time until its release was finished after 6 weeks' implantation. In contrast, in a sandwichtype formulation, the in vivo release rate was apparently maintained constant over a period of 16 weeks (24 ± 14 μg/day).
Postadsorptive transitions in fibrinogen: Influence of polymer properties
Authors: Rapoza Richard J. , Horbett Thomas A.
Published: December 2004

Changes in the fibrinogen molecule after its adsorption to biomaterials may be important in determining blood compatibility. Previously, postadsorptive transitions were detected by measuring the elutability of adsorbed proteins with surfactant solutions. The elutability decreased with increased residence time, suggesting that protein—surface interactions increased with residence time. In this study, we have examined the effects of polymer structure and composition, chain mobility, and hydrophobicity on the postadsorptive transitions of fibrinogen. Glassy, rigid polymers showed high fibrinogen adsorption, regardless of whether the polymer was hydrophilic or hydrophobic. However, the binding strength (as measured by elutability) was much lower on hydrophilic polymers and oxygen‐containing hydrophobic polymers. Short‐term transitions, requiring 2 h or less after adsorption, were observed only on hydrophobic polymers that contained no oxygen. More gradual transitions were observed on hydrophobic polymers containing oxygen, but only after a lag time of 1–4 h.
Modulation of cell adhesion by modification of titanium surfaces with covalently attached self‐assembled monolayers
Authors: Sukenik Chaim N. , Balachander Natarajan , Culp Lloyd A. , Lewandowska Kristine , Merritt Katherine
Published: December 2004

The surface of titanium has been modified by covalent attachment of an organic monolayer anchored by a siloxane network. This coating completely covers the metal and allows controlled modification of surface properties by the exposed chemical end‐groups of the monolayer forming surfactant. The attachment of such a film allows different bulk materials (e.g., glass and titanium) to have identical surface properties and this can be used in regulating cell adhesion responses. This control over surface functionality can modulate the functions of fibronectin in regulating attachment and neurite formation by neuronal cells. The effect on bacterial adherence that is achieved by using such monolayers to vary surface hydrophilicity is also assessed.
Study of the mineral—organic linkage in an apatitic reinforced bone cement
Authors: Dandurand J. , Delpech V. , Lebugle A. , Lamure A. , Lacabanne C.
Published: December 2004

In order to increase mechanical properties of surgical cements, an apatitic filler has been linked to the polymethylmethacrylate (PMMA) matrix. We report here the study of the linkage between the mineral and organic components by a dielectric spectroscopy: Thermally Stimulated Current. First, the mineral—organic interface between apatitic—octocalcic phosphate and hydroxyethylmethacrylate (HEMA) has been investigated. Second, the filler—matrix interface between grafted apatite and PMMA has been examined. It has been shown that the filler is chemically linked to the matrix and stiffens the PMMA bone cement.
In vivo thrombus formation induced by complement activation on polymer surfaces
Authors: Hayashi K. , Fukumura H. , Yamamoto N.
Published: December 2004

To clarify involvement of complement activation in thrombus formation on polymer surfaces, in vitro complement activation was evaluated for polyethylene (PE) tubes radiation‐graft copolymerized with acrylamide (AAm), acrylic acid (AC), 2‐hydroxyethyl methacrylate (HEMA), Nvinylpyrrolidone (NVP), and vinyl alcohol (VOH), and compared to their in vivo antithrombogenicity and cell adherence in canine peripheral veins. The complement‐activating surfaces (NVP and VOH) cause preferential adhesion of leukocytes and were more thrombogenic than the low complement‐activating surfaces (AAm, PE, and HEMA). Infusion of naja haje cobra venom factor depressed leukocyte adhesion, followed by a marked decrease in thrombogenesis, for the strong classical‐pathway‐activating surface (NVP). Although estimation of in vitro activation for AC was inconclusive because of a large effect of adsorption, AC behaved like VOH in vivo. These results suggest that C5a(des Arg) mediated activation of leukocytes may play a role in thrombus formation by complement activation on polymer surfaces.
Rapidly degraded terpolymers of DL‐lactide, glycolide, and ϵ‐caprolactone with increased hydrophilicity by copolymerization with polyethers
Authors: Sawhney Amarpreet S. , Hubbell Jeffrey A.
Published: December 2004

A series of 66 terpolymers of dl‐lactide, glycolide, and ϵ‐caprolactone was synthesized for the purpose of identifying those materials which exhibited rapid degradation in vitro. Polymers having half‐lives from a few weeks to several months were identified. The morphology of each material was scanning calorimetry. A terpolymeric composition of 60% glycolide, 30% dl‐lactide, and 10% ϵ‐caprolactone, which exhibited a half‐life of 17 days, was selected for further investigation. The hydrophilicity of this material was increased by performing the polymerization in the presence of a polyether prepolymer, Pluronic F‐68, with the motivation of concomitantly reducing cell and tissue adhesion. An increase in the hydrophilicty of the material was apparent from contact angle measurements. Copolymerization with the prepolymer also resulted in a stronger and partly crystalline material which was mechanically stable at physiological temperature in water. A slight increase was observed in the half‐life of the polymer relative to the base polymer due to the presence of the prepolymer.
The wear behavior of ion‐implanted Ti‐6Al‐4V against UHMW polyethylene
Authors: McKellop H. A. , Röstlund T. V.
Published: December 2004

Nitrogen‐ion‐implanted Ti‐6Al‐4V against UHMW polythylene was tested on a joint simulator to evaluate the wear behavior under different conditions. It was concluded that the polymer wear rate was not affected by ion implantation. The metallic wear, on the other hand, was substantially reduced by this treatment. It was also found that ion implantation resulted in good protection of the metal surface against third‐body wear by PMMA, while the introduction of C.P. titanium particles in the joint initiated tremendious wear. Although ion implantation improved the wear of titanium alloy against UHMW polyethylene, the durability of the implanted layer needs further study.
Poly(anhydride) administration in high doses in vivo: Studies of biocompatibility and toxicology
Authors: Laurencin C. , Domb A. , Morris C. , Brown V. , Chasin M. , McConnell R. , Lange N. , Langer R.
Published: December 2004

Poly(anhydrides) proposed for use as vehicles for controlled drug delivery were administered subcutaneously in Sprague‐Dawley rats at two dosage levels (800 mg/kg rat and 2400 mg/kg rat) for a period of eight weeks. Biocompatibility was assessed using a number of methods. Thirtysix clinical chemistry and hematology parameters were monitored throughout the study. Blood values were statistically analyzed for any possible effects due to the implanted polymer. After 8 weeks, rats were sacrificed and complete necropsies were performed. Histological evaluations of 33 organ sites including heart, lung, liver, kidney, and brain were performed. In addition, subcutaneous implant sites were excised and examined both grossly and microscopically. Results from evaluations of blood chemistry and hematology data, organ analyses and local implant site analyses overall demonstrated that the poly(anhydride) biomaterial possessed excellent in vivo biocompatibility.
A parametric study of the factors affecting the fatigue strength of porous coated Ti‐6A1‐4V implant alloy
Authors: Kohn David H. , Ducheyne Paul
Published: December 2004

The high cycle fatigue strength of porous coated Ti‐6Al‐4V is approximately 75% less than the fatigue strength of uncoated Ti‐6Al‐4V. This study separates the effects of three parameters thought to be responsible for this reduction: interfacial geometry, microstructure, and surface alternations brought about by sintering. To achieve the goal of one parameter variations, hydrogen‐alloying treatments, which refined the lamellar microstructure of β‐annealed and porous coated Ti‐6Al‐4V, were formulated. The fatigue strength of smooth‐surfaced Ti‐6Al‐4V subjected to hydrogen‐alloying treatments is 643–669 MPa, significantly greater than the fatigue strength of β‐annealed Ti‐6Al‐4V (497 MPa) and also greater than the fatigue strength of preannealed, equiaxed Ti‐6Al‐4V (590 MPa). The fatigue strength of porous coated Ti‐6Al‐4V, however, is independent of microstructure. This leads to the conclusion that the notch effect of the surface porosity does not allow the material to take advantage of the superior fatigue crack initation resistance of a refined α‐grain size. Thus, sinternecks act as initiated microcracks and fatigue of porous coated Ti‐6Al‐4V is propagation controlled.
Impact resistance of highly crosslinked plastic denture teeth
Authors: Suzuki Shiro , Sakoh Mitsuo , Shiba Akihiko
Published: December 2004

The impact resistance of highly crosslinked plastic denture teeth materials such as SR‐Orthosit (R), Crystal‐ND (R), and Mitel‐OM (R) was investigated and compared to that of conventional denture teeth materials. Dentures with upper second molars were placed on a metal model. The thicknesses of the denture teeth were 1.4, 1.0, and 0.4 mm. An impact force was repeatedly applied to the central fossae of the denture teeth with an impact test machine. Impact resistance was defined as the number of impacts sustained by the tooth material prior to fracture. The results showed that the impact resistance of highly crosslinked plastic teeth decreased with decreasing thickness, but was comparable to that of conventional plastic teeth when the teeth were 1.4 mm thick and supported by denture base resin. It is hypothesized that the layer of PMMA denture base resin beneath the denture teeth functions as a shock absorber during impact.
Interactions of proteins in human plasma with modified polystyrene resins
Authors: Boisson‐Vidal C. , Jozefonvicz J. , Brash J. L.
Published: December 2004

Investigations are reported on the composition of protein layers adsorbed from plasma to various modified polystyrene resins. As well as polystyrene itself, polystyrene bearing sulfonate groups in the benzene rings, and polystyrene sulfonate in which the sulfonate groups were converted to amino acid sulfamide, were investigated. Some of these resins were shown in previous work to have anticoagulant properties. To study the adsorption of proteins from plasma, the resins were exposed to citrate anticoagulated human plasma for 3 h. Adsorbed proteins were then eluted sequentially by 1M Tris buffer and 4% SDS solution, and examined by SDS‐PAGE. The gel patterns were similar on all resins except polystyrene. From the MWs of the gel bands, the major protein component appeared to be fibrinogen. Smaller amounts of plasminogen, transferrin, albumin, and IgG were also present. In addition, Ouchterlony immunoassay of the eluates from one resin gave positive identification of complement C3, fibronectin, IgG, and IgM. Many other minor gel bands remain unidentified. A consistent finding for all resins was the presence of plasmin‐type fibrinogen degradation products though the amounts varied with resin type. It is concluded from this (and from experiments showing FDP formation when fibrinogen was adsorbed to the resins, from buffer containing a trace of plasminogen) that the functional groups in these materials promote the adsorption of plasminogen and its activation to a plasmin‐like molecule. It appears from the substantial quantities of fibrinogen adsorbed to these materials after 3 h exposure to plasma that the Vroman effect (giving transient adsorption of fibrinogen) is not operative on these materials. It is hypothesized that specific interactions occur between fibrinogen and sulfonate groups.
Effects of injecting massive amounts of bioactive ceramics in mice
Authors: Kawanabe Keiichi , Yamamuro Takao , Nakamura Takashi , Kotani Seiya
Published: December 2004

The effects of massive administration of bioactive ceramic powder (Bioglass (45S5), Ceravital (KGS), apatite‐wollastnite containing glass ceramics (A‐W GC), and hydroxyapatite (HA)), by intraperitoneal (IP), intramuscular (IM), or subcutaneous (SC) injection in Balb/c mice were examined in this investigation. Alumina, Silica Glass (SG), and A‐W‐A1 (containing the same amount of crystal as A‐W GC and 6.3% Alumina) were used as nonbioactive controls. The particle size of each material injected was smaller than 44 μm. In addition to the above, two more sizes (smaller than 105 μm and smaller than 255 μm) of A‐W GC powder, and a 1 × 1 × 0.2 cm plate of the A‐W GC were also evaluated. When the particle size was smaller than 44 μm, intraperitoneal injections of 5 mg per g of body weight of BG, KGS, A‐W GC, and A‐W‐A1 were lethal to the mice. Ceramics in fine powder form, which are generally believed to have higher bioactivity, are associated with higher mortality except A‐W‐A1. On the other hand, when the particle size of the ceramic was increased, the fatal effects of ceramic powders in mice decreased. Plate form of ceramics implanted I.P. had no systemic effects. Intramuscular or SC injections of bioactive ceramic powder with a particle size smaller than 44 μm had almost no systemic effects. Both the particle size of the ceramic powder and the route of administration influenced the reactivity of the bioactive ceramics in the mice. In conclusion, regardless of particle size, neither SC nor IM injection of large doses of highly bioactive ceramics had an adverse effect on the host (mouse).
Bone‐particle‐impregnated bone cement: An in vivo weight‐bearing study
Authors: Dai K. R. , Liu Y. K. , Park J. B. , Clark C. R. , Nishiyama K. , Zheng Z. K.
Published: December 2004

To evaluate an experimental inorganicbone‐particle‐impregnated bone cement, canine hip prostheses were implanted in dogs using a regular bone cement on one side and the experimental bone cement on the other. In a preliminary feasibility study, bone ingrowth into the resorbed bone‐particle spaces was established 3 months after implantation in three dogs. In a more detailed study, twenty‐eight (28) dogs were divided in four groups to delineate the effects of time on the phenomena of bony ingrowth. One month after implantation, active bone ingrowth into the bone cement was obvious. By 3 months postimplantation, the ingrowth appeared to have traversed the thickness of the bone‐particle‐impregnated cement. By the fifth month, most of the interconnected inorganic bone particles were replaced by new bone. At the end of a year, the ingrown bone was mature and negligible new bone activity was present. Biomechanical pushout tests closely corroborated the histologic observations. The maximum shear strength of the cement/bone interface of the experimental side reached 3.6 times that of the control side at 5 months postimplantation. No further improvements were seen at 12 months postimplantation. A viable bone/cement interface may result in a better orthopedic implant fixation system by combining the advantages of both cement for immediate rigidity and biological ingrowth for longterm stability.
The use of polylactic acid matrix and periosteal grafts for the reconstruction of rabbit knee articular defects
Authors: von Schroeder Herbert P. , Kwan Michael , Amiel David , Coutts Richard D.
Published: December 2004

In order to find a material that would improve cartilage repair, we investigated the use of porous polylactic acid matrix (PLA) with and without periosteal grafts in large articular defects in the medial femoral condyles of 18 New Zealand white rabbit knees. The right knee defect was filled with PLA, the left defect was filled with PLA and a periosteal graft. All animals were killed at 12 weeks. PLA allowed for the de novo growth of neocartilage at the articular surface in all specimens and appeared to serve as a scaffolding for cell migration and matrix formation. Histologically, small amounts of PLA remained under the neocartilage with the majority being replaced by bone. PLA was a suitable carrier for periosteal grafts with a high graft survival rate (89%) and proliferation of a neocartilage which was thicker and more closely resembled articular cartilage than PLA alone knees. Biochemically, there was more type II collagen in the grafted knees (83%) than in the PLA alone knees (65%). Biomechanical tests of the neocartilage included equilibrium displacement, aggregate modulus, and apparent permeability. These tests were not statistically different between PLA alone and grafted knees. Comparison to normal cartilage indicated that the neocartilage was less stiff but had similar permeability. A consistent repair of the articular defects was achieved with and without periosteal grafts resulting in a tissue that closely resembled hyaline articular cartilage.
Effect of soft segment chemistry on the biostability of segmented polyurethanes. I. In vitro oxidation
Authors: Takahara Atsushi , Coury Arthur J. , Hergenrother Robert W. , Cooper Stuart L.
Published: December 2004

A series of segmented polyurethanes (SPUs) containing various polyol soft segments was prepared and their resistance to oxidative degradation was investigated after aging in AgNO3 solution. The SPU with the polyether soft segment showed a large reduction in mechanical strength after exposure to the oxidative environment. Surface cracking was often observed for these specimens. XPS measurements revealed that scission of the ether linkage occurs upon oxidation. The oxidative resistance of SPUs containing aliphatic hydrocarbon soft segments was significantly improved over the poly(tetramethylene oxide) (PTMO) based polyurethane.
Interaction of plasma proteins with heparinized gel particles studied by high‐resolution two‐dimensional gel electrophoresis
Authors: Ho C‐H. , Hlady V. , Nyquist G. , Andrade J. D. , Caldwell K. D.
Published: December 2004

In order to further the understanding of protein‐surface interactions in the coagulation system, we have chosen to study plasma protein adsorption onto heparin immobilized surfaces. Heparin‐binding proteins are abundant in plasma: a search of amino acid sequences revealed that many plasma proteins have possible heparin binding sites. Plasma protein adsorption to the heparinized surfaces is monitored by a novel technique in which the solution depletion of proteins is analytically determined using quantitative two‐dimensional polyacrylamide gel electrophoresis (2‐D PAGE). This method enables simultaneous, quantitative detection of the majority of plasma proteins before, during, and after their adsorption onto high surface area adsorbents. Using computerized densitometry of silverstained 2‐D PAGE gels, the amount of each protein can be determined from the integrated optical density of each protein “spot.” Kinetics of adsorption and adsorption isotherms of four important heparin binding proteins, antithrombin III (ATIII), complement factor C3 (C3), apolipoprotein AI (Apo‐AI) and apolipoprotein AIV (Apo‐AIV) are reported in this paper. From the adsorption isotherms, the apparent binding constants of each protein‐immobilized heparin complex, Ka, were calculated. The surface binding constants were of the same order of magnitude as the respective solution binding constants in the literature. The surface binding constants followed the same order as the respective solution binding constants: Ka (ATIII) > Ka (Apo‐AIV) > Ka (C3) > Ka (Apo‐AI), indicating that protein binding to the immobilized heparin used is not essentially different from solution binding.
Dental implant design–effect on bone remodeling
Authors: Pilliar R. M. , Deporter D. A. , Watson P. A. , Valiquette N.
Published: December 2004

Bone remodeling around three different endossesous dental implant designs placed in dog mandibles was studied using radiography during lengthy periods of function and by histology after animal sacrifice. The three designs investigated were (a) threaded (c.p. titanium), (b) fully porous‐coated (titanium alloy), and (c) partially porous‐coated (titanium alloy). The implants were kept in function for either 32 weeks (fully porous‐coated) or 73 to 77 weeks (partially porous‐coated and threaded). The studies indicated that some crestal bone loss occurred for both the threaded and partially porous‐coated implants while no significant bone loss was seen with fully porous‐coated implants in the absence of plaque‐associated infection. It is suggested that these observed differences are a result of the different stress states that develop in bone surrounding the three designs underlying the importance of implant design on bone remodeling.
Human vascular graft failure and frequency of infection
Authors: Vinard E. , Eloy R. , Descotes J. , Brudon J. R. , Guidicelli H. , Patra P. , Streichenberger R. , David M.
Published: December 2004

Among 212 vascular prostheses collected in a cascular explant retrival programe, 50 exhibited one or more criteria of graft infection i.e., (a) clinical evidence of graft infection, (b) positive bacteriological analyses of the graft, and (c) presence at the blood‐prosthetic interface of characterized microorganisms. Whereas each of these criteria was noted respectively in 25, 26, and 20 cases, there was no complete overlapping among the three criteria, but their combination led us to consider 50 cases of infected vascular grafts among the 212 collected. These results, and the occurrence in two cases among six investigations for viral infection, suggest that extensive bacteriological investigations of cascular explanted should be inculded in an implant retrieval program, and that infection may represent a high risk in graft failure.
Immunomodulating effects of serum‐material interactions
Authors: Omokawa Susumu , Malchesky Paul S. , Goldcamp James B. , Savon Susan R. , Nosé Yukihiko
Published: December 2004

The objective of this study is to evaluate an in vitro model to assess the effects of serum‐material interactions on complement activation, macromolecular adsorption, and lymphocyte response. Minifilters of clinically available materials (PVA, EVAL‐4A, and EVAL‐D) used in extracorporeal therapies were evaluated. The test circuit consisted of a pump, sterile tubing, collection vessels, and the minifilter. A sham circuit similar to the test circuit was constructed, but without the filter. Serum flow rates and volumes processed were scaled down to those of clinical use. Post PVA serum showed the highest degree of complement activation, macromolecular solute adsorption, and lymphocyte suppressive response when incubated with Con‐A, PHA, PWM, and Candida. Post EVAL‐4A sera enhanced the response of lymphocytes to Con‐A and PHA, while Post EVAL‐D sera showed a slight suppression to these mitogens. Blood‐material interactions have been shown to cause blood cellular changes. The in vitro model employed is simple to apply and does not require an animal or patient. The membrane modules used are a mini‐type of clinically available extracorporeal filters, and there is a greater direct relevancy to clinical applications than there would be using specially formulated materials. This system would provide useful preclinical information in evaluating the effects of serum‐material interactions.
In vitro tendon cell growth rates on a synthetic fiber scaffold material and on standard culture plates
Authors: Ricci J. L. , Gona A. G. , Alexander H.
Published: December 2004

Growth rates of rat tendon fibroblasts cultured in a three‐dimensional carbon fiber matrix were compared with those of cells cultured on standard flat culture plates. The carbon fiber has been used as a tissue scaffold for tendon and ligament repair in animal and clinical studies. While cell growth on the culture plates appears to follow a growth curve containing a lag phase, a log phase, and plateau phase of growth, cell growth in the fiber matrix was characterized by a suppressed log phase of growth. SEM and cytotoxicity studies indicated that this effect was not caused by growth‐inhibiting or cytotoxic substances from the carbon fiber. While we cannot rule out the possibility that cell growth was influenced by the surface chemistry of the carbon substrate, evidence from this and other studies suggests that the observed effect was caused by a lack of readily available surface area for cell attachment and growth on the small fibers. Because cell colonies growing on individual fibers are limited (at least in theory) to growing in two directions only, they enjoy limited opportunities for cell migration and growth– in contrast with cell colonies on flat culture plates. These results suggest fundamental differences in the mechanisms controlling cell growth on planar vs. three‐dimensional fiber substrates.
A physicochemical study of the morphology of progesterone‐loaded microspheres fabricated from poly(D,L‐lactide‐co‐glycolide)
Authors: Rosilio V. , Benoit J. P. , Deyme M. , Thies C. , Madelmont G.
Published: December 2004

Progesterone‐loaded microspheres are fabricated by a solvent evaporation process from a poly(D,L‐lactide‐co‐glycolide) (85/15 PLG) and from α‐progesterone. Methylene chloride is used as solvent and polyvinyl alcohol and methylcellulose are used as surfactants. The microspheres are characterized by scanning electron microscopy, differential scanning calorimetry, and x‐ray powder diagrams. Our study shows that the morphology and the thermal behavior of PLG microspheres can vary significantly with progesterone loading and sample thermal history. Below and at 16.5% loading the microspheres exhibit a smooth outer surface. Above 23% loading, the surface becomes rough, embedded by copolymer particles or well‐defined crystals. Pores and cracks can also be observed. Below 35% the progesterone is molecularly dispersed. At 35% and above crystal doMayns of the steroid appear and two crystalline forms are found: α‐ and β‐progesterone. The physical state of progesterone and the nature of its crystal doMayns dispersed in the PLG matrix can change during storage. Also a progressive development of an endothermic peak at the Tg event of the copolymer is observed during storage. No well defined relationship of peak size to progesterone loading can be shown.
Hylan gel composition for percutaneous embolization
Authors: Larsen Nancy E. , Leshchiner Edward A. , Parent Edward G. , Hendrikson‐Aho Julie , Balazs Endre A. , Hilal Sadek K.
Published: December 2004

Viscoelastic, pseudoplastic, radiopaque injectable hylan gel for percutaneous embolization was developed and evaluated by in vitro and in vivo tests. The embolization gel is composed of cross‐linked hylan (hyaluronan, hyaluronate), tantalum, microcrystalline cellulose, hexamethonium chloride, and thrombin. Upon delivery through small‐lumen catheters to the appropriate vascular site, the gel induces formation of a solid blood/gel coagulum. Results from animal studies (rat aorta, rabbit auricular artery) demonstrate that formation of complete and long‐lasting arterial blockage is readily achievable without complications due to blood flow, partial vessel obstruction, uncontrolled polymerization, or movement of the gel or its components (specifically thrombin and hexamethonium chloride) into the circulation. Microscopic evaluation indicates that arterial occlusion initially occurs as a result of the injected gel and formed fibrin; at 7 weeks and beyond, arteries are occluded by injected gel, inflammatory cells and fibrosis (scar tissue).
Osteoblast responses to orthopedic implant materials in vitro
Authors: Puleo David A. , Holleran Lisa A. , Doremus Robert H. , Bizios Rena
Published: December 2004

Responses of neonatal rat calvarial osteoblasts to a variety of orthopedic implant materials were examined in vitro. Attachment, proliferation, and collagen synthesis of a well‐characterized line of osteoblasts with 316L stainless steel, Ti‐6Al‐4V, CoCR‐Mo, PMMA, hydroxyapatite, borosilicate glass, and tissue culture polystyrene were studied. Cell adhesion and growth were similar on nonapatitic materials. In contrast, attachment and growth of osteoblasts were significantly lower and slower, respectively, on hydroxyapatite. Collagen synthesis per cell and relative collagen synthesis, however, were comparable on all the materials tested.
Fibroblast and hepatocyte behavior on synthetic polymer surfaces
Authors: Saltzman W. Mark , Parsons‐Wingerter Patricia , Leong Kam W. , Lin Shin
Published: December 2004

Biodegradable poly(phosphoesters) with varying side group chemistry and copolymers of styrene and methyl vinyl ketone (MVK) with varying degrees of hydrophobicity were used to study the growth and behavior of surface‐attached fibroblasts and hepatocytes. Mouse 3T3 fibroblasts and chicken embryo fibroblasts attached and proliferated on all of the polymers tested. Fewer cells attached to copolymers of styrene and MVK than to glass or tissue culture polystyrene controls; cell attachment to several poly(phosphoester) surfaces was indistinguishable from controls. The mean speed of fibroblast migration was faster on surfaces where fewer cells attached (59 to 84 μm/h on low attachment surfaces compared with 40 to 46 μm/h on high attachment surfaces). When surface‐attached cells were stained with fluorescently labeled phalloidin, only a fraction of the cells on low attachment surfaces were shown to have prominent arrays of actin filament bundles. Chicken hepatocytes also attached to the polymer surfaces. When a suspension containing a large number of cells was placed over the polymer surfaces, approximately 50% of the hepatocytes attached during the first 9 h. Surprisingly, hepatocyte attachment and viability in culture were relatively insensitive to the chemistry of the synthetic polymer substrates. Cell number increased by about a factor of 2 over the first 48 h of culture, then decreased back to ∼50% of initial cell number over the next several days. Cell morphology did depend on the chemical structure of the substrates.
Biological responses to polyethylene oxide modified polyethylene terephthalate surfaces
Authors: Desai Neil P. , Hubbell Jeffrey A.
Published: December 2004

Polyethylene oxide (PEO) of molecular weights 5,000, 10,000, 18,500, and 100,000 g/mol was covalently grafted to surfaces of otherwise cell adhesive polyethylene terephthalate (PET) films. Analysis of these surfaces by measurement of contact angles and ESCA verified the presence of the grafted PEO. Protein adsorption assays of radiolabeled albumin and fibrinogen showed a marked reduction in adsorbed protein for the 18,500 and 100,000 molecular weight PEO coupled surfaces. Cell growth assays using human foreskin fibroblasts in culture showed that the higher‐molecular‐weight PEO surfaces supported cell growth to a much lower extent than the two lower‐molecular‐weight PEOs. Flow of whole blood over these surfaces and visualization of platelet adherence using epifluorescence videomicroscopy showed very low platelet adherence only on the two higher‐molecular‐weight PEO coupled surfaces. Scanning electron microscopy corroborated these results. It was concluded that PEO of molecular weights neighboring 18,500 and higher was effective in reducing protein adsorption and cellular interactions on these surfaces.
TEM immunogold staining of C3 from plasma onto titanium oxides
Authors: McAlarney M. E. , Skalak R. , Kim S. , Neugroschl D. , Machlin E. S.
Published: December 2004

Immunogold staining in conjunction with TEM was used to observe C3 adsorption from plasma in relation to the underlying titanium structure of thermal, anodic, and electropolished oxides. Heat treatments and oxide thickness were found to have no significant effect on the adsorption behavior of C3, while surface oxide type possibly has. Surface concentration of C3 was found to be time‐ and plasma concentration‐dependent. Evidence is given for the possible involvement of C3 in protein exchange, i.e., the Vroman effect. Diluted plasma resulted in a random distribution of gold colloids, whereas clustering occurred with undiluted plasma. Although C3 concentrations present on grain boundaries followed the same trend as that found on the surface, C3 was found to have a higher grain boundary than bulk concentration for 0.1% plasma.
Competitive adsorption of vitronection with albumin, fibrinogen, and fibronectin on polymeric biomaterials
Authors: Fabrizius‐Homan D. J. , Cooper S. L.
Published: December 2004

Vitronectin (VN) was competitively adsorbed with human serum albumin (HSA), fibrinogen (FGN), and fibronectin (FN) from binary component mixtures in order to compare the relative affinities of these proteins for various polymer materials. Competitive adsorption was monitored by incubating radiolabeled protein solutions inside 0.125‐in. i.d. tubing of the polymers, flushing with buffer, and measuring the adherent radioactiviy. Adsorption experiments at equal mass concentrations of the competing proteins revealed that VN comprises at least 75% by weight of the adsorbed protein when competitively adsorbed with HSA and approximately 50% by weight when competitively adsorbed with FGN and FN on all surfaces except a poly(ethylene oxide)‐based polyurethane where it comprised closer to 80 wt%. When VN was competitively adsorbed in the presence of increasing amounts of HSA, FGN, and FN, the amount of VN adsorbed on a weight basis was diminished the most by FGN. HSA had the least inhibitory effect at low bulk concentrations and FN had the weakest effect at higher bulk concentration levels. When HSA, FGN, and FN were competitively adsorbed in the presence of increasing amounts of VN, VN diminished their adsorption on a weight basis in the order: HSA > FN > FGN.
Histologic evaluation of the osseous adaptation to titanium and hydroxyapatite‐coated titanium implants
Authors: Jansen J. A. , van de Waerden J. P. C. M. , Wolke J. G. C. , De Groot K.
Published: December 2004

The aim of this study was to obtain more information about the bone reaction to titanium and hydroxypatite (HA)‐coated titanium implants during the first 3 months after implantation. Therefore, uncoated and coated implants were inserted into the tibia of rabbits for various implantation periods. The histological results demonstrated that although there were no marked differences in bony reaction at the cortical level to the different implant materials, HA‐coating appeared to induce more bone formation in the medullary cavity. It was also noted, that 3 months after insertion loss of coating thickness had occurred.
The bonding behavior of calcite to bone
Authors: Fujita Yoshitsugu , Yamamuro Takao , Nakamura Takashi , Kotani Seiya , Ohtsuki Chikara , Kokubo Tadashi
Published: December 2004

Plates of calcite (CaCO3) were implanted in rabbit tibiae, and their biocompatibility and bonding ability to bone were studied. The plates were also implanted subfascially in rabbit muscle for 8 weeks, and changes on their surfaces in the body were examined. Contact microradiography and Giemsa surface stain demostrated direct bonding between calcite and bone without interpositions. The average failure load of the interface between calcite and bone was 4.11 kg, indicating an adequate strength of bonding. However, a Ca‐P‐rich layer, which formed on the surfaces of other bioactive ceramics in vivo, was not detected by a scanning electron microscope‐electron probe x‐ray microanalyzer. Scanning electron micrographs of the surface of calcite implanted subfascially for 8 weeks showed marked degradation and a rough surface. However, the surface apatite layer was not detected by thin‐film x‐ray diffraction analysis and Fourier transform infrared reflection spectroscopy. Calcite is a biodegradable material that bonds to bone without a surface apatite layer. The mechanical bonding provided by the anchoring effect of the newly formed bone into the surface roughness of calcite is considered to be a major factor in calcite‐bone bonding.
Combined chemical and mechanical effects on free radicals in UHMWPE joints during implantation
Authors: Jahan M. S. , Wang C. , Schwartz G. , Davidson J. A.
Published: December 2004

An electron spin resonance (ESR) technique is employed to determine the free radical distribution in the articulating surfaces of retrieved acetabular cups and knee‐joint plateaus (retrieved after more than 6 years of implantation). Similar measurements made on samples prepared from cyclically stressed and unstressed cups, and on samples following oxidations in nitric acid and intralipid solutions provided sufficient data to gain more knowledge about the combined chemical and mechanical effects on PE free radicals during implantation. In UHMWPE free radicals are primarily initiated by gamma‐ray sterilization; however, during implantation, peroxy (scission type) free radicals are formed and reach a maximum concentration level (equilibrium state) due to oxidation by chemical (hemoglobin and/or synovial fluids) environment of the joints. Subsequently, due to frictional heating and stress in the loading zones, free radical reaction is accelerated and their number is reduced only in those areas. This is consistent with the observations of a temperature rise in acetabular cups duringin vitrofrictional wear stress tests andin vivotelemetry observations, as reported by others. Compared with the previously reported SEM micrographs the low‐free‐radical regions are correlated with high‐wear areas and the high‐free‐radical regions with the low‐wear areas.
A new canine model for evaluating blood prosthetic arterial graft interactions
Authors: Brophy Colleen M. , Ito Ralph K. , Quist William C. , Rosenblatt Michael S. , Contreras Mauricio , Tsoukas Athanassios , Logerfo Frank W.
Published: December 2004

Various models have been proposed to examine blood‐prosthetic materials interactions in terms of the effect of the prosthetic material on platelet structure and function, blood coagulation and fibrinolysis, and tissue infiltrates (cellular or acellular). In addition, these modeles have been used to examine the change in the graft surface over time. Particular difficulties in examining graft‐materials interactions include species differences, short residence time for blood‐materials interactions with commonly employed short grafts, and length of study limitations with ex vivo shunts. In this paper we report a canine, carotid‐aorta subcutaneous prosthetic graft model. The specific advantages of this model are the length of the graft, which allows prolonged contact of blood with the prosthetic surface; the subcutaneous location of the graft, which allows repeated sampling of blood along the graft; and the healing characteristics of canine grafts. We selected the canine model because the healing characteristics are morphologically similar to those in humans in that endothelialization of the prosthetic surface is limited. Other models, such as the pig, are favored for use when examining blood coagulation, platelet, or fibrinolytic studies; however, these models can fully endothelialize prosthetic surfaces.
Evaluation of polyphosphates and polyphosphonates as degradable biomaterials
Authors: Richards M. , Dahiyat B. I. , Arm D. M. , Brown P. R. , Leong K. W.
Published: December 2004

A series of polymers, bisphenol A‐based poly(phosphoesters), were evaluated as degradable biomaterials. Degradation was observed for the four polymers studied under both in vitro and in vivo conditions. The rate of degradation was affected by polymer side‐chain structure and correlated with the swelling behavior. The ethyl side‐chain polymers absorbed more water than their phenyl counterparts. Among the sterilization methods, UV irradiation followed by antibiotic treatment was the most suitable, as steam autoclave and ethylene oxide treatments altered the properties of several of the poly(phosphoesters). Tissue response to the poly(phosphoesters) in rabbits was characterized by minor encapsulation and slight or no lymphocyte, giant cell, or macrophage activity. No evidence of edema or necrosis was found. The elastic moduli of these materials varied from 488 MPa for poly(bisphenol A‐ethylphosphate) (BPA/EOP) to 627 MPa for the more rigid poly(bisphenol A‐phenylphosphonate) (BPA/PP). The ultimate strength, modulus, and energy to failure of BPA/PP were lower than those of similarly compression molded high‐molecular‐weight poly(L‐lactic acid) (PLLA).
Synthesis and bioactivity of copolymers with fragments of heparin
Authors: Mazid M. A. , Moase E. , Scott E. , Hanna H. R. , Unger F. M.
Published: December 2004

A new type of biocompatible copolymer comprising small fragments of heparin, (octa‐ to dodecasaccharides) copolymerized with a synthetic monomeric component, viz. acrylamide, has been prepared. The heparin fragments are produced by enzymatic or chemical means and are copolymerized, directly or after suitable derivatization, with acrylamide as the major polymerizable component. The polymeric material incorporates the heparin segments as pendant moieties such that their essential functional groups and structural features for specific binding with the selective serine protease coagulation factor inhibitor antithrombin III are preserved. An important feature of this copolymer is its biocompatibility which relates specifically to its antithrombotic and antithrombogenic activity derived from those of heparin fragments. The biological activity of heparin fragments and copolymers thereof are determined in terms of APTT and anti‐Xa activity, their antithrombotic potential being expressed as a ratio of anti‐Xa activity to APTT. The copolymers reported have biological activities similar to equivalent amounts of respective heparin fragments, and show higher antithrombotic activity compared to intact heparin or commercially available low‐molecular‐weight heparin (4,000–6,000 Da).
Student research award in the hospital intern, resident or clinical fellow Category, 17th Annual Meeting of the Society for Biomaterials, scottsdale, AZ May 1–5,1991. A new biological membrane for pericardial closure
Authors: Muralidharan S. , Gu Jiang , Laub Glenn W. , Cichon Romuald , Daloisio Connie , McGrath Lynn B.
Published: December 2004

In an attempt to develop a new and better biological membrane for the pericardium, we evaluated the use of glutaraldehyde treated human amniotic membrane (AM) and compared it to polytetraflouroethylene (PTFE) membrane as a pericardial substitute. Four dogs underwent a right thoracotomy. Two 4 × 3‐cm portions of pericardium, 3–4 cm apart, were excised in each animal and both sites replaced with a similar sized patch of 0.8% glutaraldehyde‐treated AM and 0.2‐mm PTFE membrane respectively. The AM was sutured to the pericardial defect with its smooth surface facing the epicardium. After 18 weeks, the materials were evaluated. The AM patches revealed minimal extrapericardial and no epicardial adhesion. The PTFE patches had moderate to severe epicardial adhesions and severe extrapericardial adhesions. Histopathological examination of AM patches revealed that the integrity of the AM was preserved, however, neovascularization and slight lymphocytic infiltration were observed. In the PTFE patches, there were severe inflammatory infiltration and fibroblast proliferation into both surfaces. AM patches by virtue of their low immunogenicity evoke very minimal host to graft reaction. These AM grafts, however, tear easily unless carefully sutured. Improved methods of treatment may improve suturing strength. We conclude that AM performs satisfactorily and is superior to PTFE as a pericardial substitute.
NIR‐spectroscopic investigation of water sorption characteristics of dental resins and composites
Authors: Venz S. , Dickens B.
Published: December 2004

A near infrared (NIR) method using the 5200 cm−1 absorption of water has been employed to examine water absorbed in photopolymerized dental resins and composites in the form of 0.01‐cm‐to 0.15‐cm‐thick specimens. The concentration, c [mol L−1], of absorbed water in specimens of thickness t [cm] was calculated by means of Beer's law, A = ϵct. A is the NIR absorbance and ϵ is the absorptivity of absorbed water. ϵ depends on the environment of the water molecule and it is necessary to estimate ϵ for water in each material. Water sorption was determined gravimetrically and correlated to the absorbance in the NIR spectrum. Once the relationship between ϵ and water content was known for a material, water sorption was determined rapidly on very thin specimens for faster equilibration. Where dissolution of the specimen occurred, the solubility behavior of the specimen was evaluated from a comparison of NIR and gravimetric measurements. The NIR absorptivity, ϵ, of water absorbed in a polymeric medium was found to be inversely related to the degree of hydrophilicity and hydrogen bonding capability of the polymer. The presence of water clusters in a polyethylene oxide methacrylate polymer was inferred from convex‐up curvature in the plot of ϵ vs. water content.