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Integration of the basic, behavioral, and biomaterials sciences with the clinical curriculum
Shreve, W. B., H. Mohammed, et al. (1980), J Dent Educ 44(2): 76-9.
Abstract: An approach to effective integration of the basic, behavioral, and biomaterials sciences with the clinical curriculum is described. Teaching is accomplished by both scientists and clinicians on multidisciplinary teams. The instructional format is based on terminal objectives that are stated in behavioral terms. Examples of the objectives and the manner in which they are fulfilled are presented.

Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiation
Keselowsky, B. G., D. M. Collard, et al. (2005), Proc Natl Acad Sci U S A 102(17): 5953-7.
Abstract: Biomaterial surface chemistry has profound consequences on cellular and host responses, but the underlying molecular mechanisms remain poorly understood. Using self-assembled monolayers as model biomaterial surfaces presenting well defined chemistries, we demonstrate that surface chemistry modulates osteoblastic differentiation and matrix mineralization independently from alterations in cell proliferation. Surfaces were precoated with equal densities of fibronectin (FN), and surface chemistry modulated FN structure to alter integrin adhesion receptor binding. OH- and NH(2)-terminated surfaces up-regulated osteoblast-specific gene expression, alkaline phosphatase enzymatic activity, and matrix mineralization compared with surfaces presenting COOH and CH(3) groups. These surface chemistry-dependent differences in cell differentiation were controlled by binding of specific integrins to adsorbed FN. Function-perturbing antibodies against the central cell binding domain of FN completely inhibited matrix mineralization. Furthermore, blocking antibodies against beta(1) integrin inhibited matrix mineralization on the OH and NH(2) surfaces, whereas function-perturbing antibodies specific for beta(3) integrin increased mineralization on the COOH substrate. These results establish surface-dependent differences in integrin binding as a mechanism regulating differential cellular responses to biomaterial surfaces. This mechanism could be exploited to engineer materials that control integrin binding specificity to elicit desired cellular activities to enhance the integration of biomaterials and improve the performance of biotechnological culture supports.

Integrin expression at the bone/biomaterial interface
Clarke, S. A. and P. A. Revell (2001), J Biomed Mater Res 57(1): 84-91.
Abstract: The aim of this study was to visualize integrin expression by cells in interface tissue in relation to their ligands. Tissue samples were obtained from 25 patients undergoing revision of aseptically loose total joint replacements. Serial sections were immunolabeled for the integrins alpha(2)beta(1), alpha(v)beta(3), alpha(4)beta(1), alpha(L)beta(2) (CD11a), alpha(M)beta(2) (CD11b), and alpha(X)beta(2) (CD11c), and the ligands fibronectin, laminin, vitronectin, intercellular adhesion molecule-1, and vascular adhesion molecule-1. Most cells were found to express alpha(2)beta(1), most macrophages and giant cells expressed CD11b, and the majority of CD11a was found on perivascular T lymphocytes. From the small amount of alpha(4)beta(1) and vascular adhesion molecule-1 expression in the interface tissue and the combination of CD11a, CD11b, and intercellular adhesion molecule-1 expression, it would seem that macrophages use beta(2) integrins to transmigrate.

Interaction between O-carboxymethylchitosan and dipalmitoyl-sn-glycero-3-phosphocholine bilayer
Zhu, A. P., N. Fang, et al. (2005), Biomaterials 26(34): 6873-9.
Abstract: O-carboxylmethylchitosan (OCMCS), a chitosan derivative, has emerged as a strong polymeric biomembrane perturbant. In this study, the interaction between OCMCS and dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was examined with cross-polarization microscopy, differential scanning calorimetry (DSC) and the surface pressure-area isotherms techniques. Cross-polarized light images showed that OCMCS induced the fusion of small DPPC multilamellar vesicles (MLV) to form large lamellar structures. From DSC measurement, the highest degree of fusion was found at the optimum OCMCS concentrations between 0.0625 and 0.2 mg/ml which are orders of magnitude lower than those required for similar reductions with unmodified chitosan as perturbant. At these concentrations, the association of DPPC and OCMCS enhances the fusion of DPPC vesicles. Surface pressure-area isotherms of DPPC monolayer in the presence of OCMCS imply interactions between OCMCS and DPPC in neutral condition. In comparison with chitosan, OCMCS proved to be a more effective membrane perturbant not only in neutral but also in acidic and basic conditions. The physical driving forces for OCMCS-induced perturbation of DPPC bilayer in neutral conditions are mainly hydrogen bonding and hydrophobic interactions. In acidic or basic conditions, the physical driving forces are dominated by the electrostatic interactions. The strong OCMCS-DPPC interaction will potentially increase the effectiveness of OCMCS for gene or drug delivery.

Interaction of blood-cells/-components and tissue cells with body foreign surfaces in a cone plate rheometer under hydrodynamic shear load
Brandt, O. (2005), Clin Hemorheol Microcirc 32(2): 145-9.

Interaction of cells with L-lactide/glycolide copolymers synthesized with the use of tin or zirconium compounds
Czajkowska, B., P. Dobrzynski, et al. (2005), J Biomed Mater Res A 74(4): 591-7.
Abstract: Comparative studies have been carried out on the viability of cells culture and production of collagen on lactide/glycolide copolymers synthesized using zirconium or tin initiators. Cell response of various cell types: fibroblast-like cells, osteoblast-like cells, monocyte/macrophage-like cells has been examined. Cell response depends on the kind of cells and the initiator used during the synthesis of the polymer. In a number of cases the cells grown on materials containing zirconium have been reported to have better survival (for example, Saos2 cells). An enhanced collagen production on these copolymers has been also observed.

Interaction of human serum lipoproteins with biomaterials
Jayakumari, N., M. Chitra, et al. (1989), J Biomed Mater Res 23(11): 1261-70.
Abstract: Human serum was incubated with representative portions of polyvinyl chloride (PVC) blood storage bags and vascular prostheses. The in vitro interaction process with lipoprotein was followed by polyacrylamide gel electrophoresis (PAGE) using sudan black and nitroblue tetrazolium (NBT) in the prestaining procedure. Densitometric scan of all the lipoprotein bands in serum after incubation with PVC bag material when prestained with sudan black showed remarkable increase in intensity. However, in the same experiment when NBT was used for prestaining no increase in the intensity of any of the lipoprotein bands could be observed. Since sudan black is known to bind cholesterol specifically we suggest that a molecular unfolding occurs when lipoprotein interacts with PVC bag material. When similar experiments were carried out with vascular prosthesis there was conspicuous decrease in the intensity of the high-density lipoprotein (HDL) band especially when stained with NBT. This indicates preferential adhesion of HDL during interaction with vascular prosthesis.

Interaction of nonionic PEO-PPO diblock copolymers with lipid bilayers
Firestone, M. A. and S. Seifert (2005), Biomacromolecules 6(5): 2678-87.
Abstract: The relationship between the molecular architecture of a series of poly(ethylene oxide)-b-poly(propylene oxide) (PEO-PPO) diblock copolymers and the nature of their interactions with lipid bilayers has been studied using small- and wide-angle X-ray scattering (SAXS and WAXS) and differential scanning calorimetry (DSC). The number of molecular repeat units in the hydrophobic PPO block has been found to be a critical determinant of the nature of diblock copolymer-lipid bilayer association. For dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-based biomembrane structures, polymers whose PPO chain length approximates that of the acyl chains of the lipid bilayer yield highly ordered, expanded lamellar structures consistent with well-integrated (into the lipid bilayer) PPO blocks. Shorter diblock copolymers produce mixed lamellar and nonlamellar mesophases. The thermotropic phase behavior of the polymer-doped membrane systems is highly influenced by the presence and molecular architecture of the diblock copolymer, as evidenced by shifting of the main phase transition to higher temperatures, broadening of the main transition, and the appearance of other features. Studies of temperature-induced changes in the mesophase structure for compositions prepared with well-integrated PEO-PPO polymers indicate that they undergo reversible changes to a nonlamellar structure as the temperature is lowered. Increasing either the number of repeat units in the PEO block or the polymer concentration promotes a greater degree of structural ordering.

Interaction of poly(styrene sulfonic acid) with the alternative pathway of the serum complement system
Murakami, Y., H. Iwata, et al. (2005), J Biomater Sci Polym Ed 16(3): 381-95.
Abstract: Bioartificial pancreas, in which the islets of Langerhans are enclosed in artificial membrane to be protected from the host immune system, is expected to be a promising medical device to treat patients who suffer from insulin-dependent diabetes. Our strategy for preparation of a bioartificial pancreas involves utilizing a membrane including polymeric materials that can inhibit the complement reaction. In this study, we examined the effects of poly(styrene sulfonic acid) (PSSa) on the alternative pathway of the serum complement system to identify the mechanism(s) involved. PSSa was dissolved in pooled normal human serum (NHS), and the mixtures were incubated at 37 degrees C for 30 min. Complement activities in sera were determined by hemolytic assays. Amounts of complement activation products released were determined by ELISA. Interactions of PSSa with complement components and fragments were examined with electrophoresis and immunoblotting. From these examinations, it appeared that the manner of PSSa effects on the alternative pathway (AP) highly depends on its concentration. PSSa seemingly acted as an activator when its concentration was 0.005 g/dl to 0.05 g/dl, while it acted as an inhibitor when its concentration was more than 0.1 g/dl. In terms of activation or inhibition of the AP, forming complex of PSSa with factor H induced activation, and that with factor D induced inhibition.

Interaction of poly(styrene sulfonic acid) with the classical pathway of the serum complement system
Murakami, Y., H. Iwata, et al. (2005), J Biomater Sci Polym Ed 16(6): 685-97.
Abstract: Bioartificial pancreas, in which the islets of Langerhans (islets) are enclosed in artificial membrane to be protected from the host immune system, is expected to be a promising medical device to treat patients who suffer from insulin-dependent diabetes. Our strategy for the preparation of a bioartificial pancreas involves utilizing a membrane including polymeric materials that can inhibit the complement. When we examined a membrane containing poly(styrene sulfonic acid), long survival of islets enclosed in the membrane was observed in recipients carrying antibodies against islet cells. This fact stimulated us to start examinations of effects of PSSa on the complement system. In this study, we examined effects of PSSa on the classical pathway (CP) of the serum complement system to identify the mechanism(s) involved. The electric static interaction between cationic C1q (pI 9.3) and anionic PSSa induces PSSa-C1q complex formation. The dissociation of C1q(r2s2) complex by PSSa results inactivation of the CP activity. Those results indicate that PSSa was not an activator of the CP, but an inhibitor of CP activation. This study clarifies the mechanism by which PSSa protects islets in a microcapsule from the humoral immunity of the recipient carrying anti-islet antibodies. A microcapsule containing PSSa seems to effectively protect the islet from attacks of the host immune system after transplantation carrying antibodies against islet cells.

Interaction of various pectin formulations with porcine colonic tissues
Liu, L., M. L. Fishman, et al. (2005), Biomaterials 26(29): 5907-16.
Abstract: Pectins of low and high degrees of esterification, as well as pectin derivatives carrying primary amines, were investigate for gel forming ability with mucosal tissues. The combination of scanning electronic microscopy and small deformation dynamic mechanical studies revealed that pectins with higher net electrical charges are more bioadhesive than the less charged ones. Both the negatively charged pectin formulation, P-25, and the positively charged formulation, P-N, were able to synergize with the mucus to produce rheologically strengthened gels. The highly esterified pectin, P-94, also synergized with the mucosal glycoproteins to form a gel structure via coil entanglements. The ex vivo studies further confirmed the microstructures of mucus gel networks with adsorbed pectins. When incubated with porcine intestinal mucus membrane, P-94 gels were found generally bound to the lumen area, P-25 gels were able to penetrate deeply near the wall area, P-N gels interacted with mucins via electrostatic bonding and dispersed into the whole area from the lumen to the wall. Hence, both P-N and P-94, by enhancing the protective barrier properties of mucus systems, may be useful alternatives for the treatment of mucus related irritation and infection. In drug-delivery systems, P-N and P-25 would deliver incorporated drugs mainly by pectin dissolution, while a diffusion mechanism would release drugs from P-94 gels.

Interactions between endothelial cells and a poly(carbonate-silsesquioxane-bridge-urea)urethane
Punshon, G., D. S. Vara, et al. (2005), Biomaterials 26(32): 6271-9.
Abstract: We have recently developed a polymer which contains silsesquioxane in the form of nano-bridges poly(carbonate-silsesquioxane-bridge-urea)urethane (PCBSU) for cardiovascular device applications. The polymer has been characterised and the durability has been confirmed with long-term in vivo tests. The aim of this study was to test the cytocompatibility of the new polymer and to investigate any potential cytotoxic effects. To assess the effect of direct contact with PCBSU sections of polymer material were cut and placed into a 24-well plate. Six discs were seeded with 2 x 10(5) human umbilical vein cells (HUVEC). As a positive control, six wells were seeded with the same number of HUVEC. In a further experiment to assess indirect contact with PCBSU a sample of the polymer was powdered using a Micro-Dismembrator. Cell culture medium was exposed to powdered polymer (1-100 mg/ml) for a period of 7 days. HUVEC seeded as above were then exposed to the treated cell culture medium for 24 and 96 h. Finally, cell proliferation was studied over 16 days by seeding 2 x 10(5) HUVEC on films of PCBSU cast in glass Petri dishes. Cell viability and growth were assessed using Alamar blue, lactate dehydrogenase and Pico green assays and morphology was studied by Toluidine blue staining and scanning electron microscopy. Viable cells were demonstrated to be present after 16 days seeded on PCBSU. Exposing cells to PCBSU-treated cell culture medium resulted in no apparent damage to the cells at concentrations of 1 or 10 mg/ml, and only a slight reduction at 100 mg/ml after 96 h exposure. This study demonstrates that PCBSU can support the growth of endothelial cells for a prolonged period and does not demonstrate any significant toxic effects to cells. Thus it has the potential to be used both as a medical device and as scaffolding in tissue engineering applications.

Interactions between self-assembled polyelectrolyte shells and tumor cells
Ai, H., J. J. Pink, et al. (2005), J Biomed Mater Res A 73(3): 303-12.
Abstract: Layer-by-layer self-assembled polyelectrolyte shells are a new class of micro/nanocapsules with unique physicochemical properties for potential applications in drug/gene delivery. The objective of this study was to investigate the interactions of polyelectrolyte shells (approximately 1 mum in diameter) with MCF-7 breast cancer cells and identify key parameters that affect such interactions. Tailoring of surface properties of polyelectrolyte shells was achieved by choosing different outermost layer materials, including cationic polymers, anionic polymers, and lipid bilayers. Different surface compositions led to a wide range of electrostatic potentials from -46 to +47 mV in phophate-buffered saline buffer. Confocal microscopy studies showed that the polyelectrolyte shells were internalized into the cell cytoplasm, but not into the nuclei. Correlation of cell uptake with shell surface compositions was complicated by the adsorption of serum proteins on the surface of polyelectrolyte shells, particularly polycation-coated shells. To prevent protein adsorption, poly(ethylene glycol) (PEG) grafted poly(ethyleneimine) (PEI) copolymers (1:1, 1:5, 1:10 graft ratios) were synthesized and introduced on the shell surface. Shells coated with PEI-PEG copolymers effectively reduced protein adsorption whereas PEI-PEG copolymers with lower graft ratios achieved higher cell uptake efficiency after 24 h of incubation with MCF-7 cells.

Interactions of acinar cells on biomaterials with various surface properties
Chen, M. H., Y. H. Hsu, et al. (2005), J Biomed Mater Res A 74(2): 254-62.
Abstract: The purpose of this study is to evaluate the interactions of rat parotid acinar cells on biomaterials with different surface properties. The biomaterials used in this study included polyvinyl alcohol (PVA), chitosan, poly (ethylene-co-vinyl alcohol) (EVAL), and polyvinylidene fluoride (PVDF). Cell morphology was observed by photomicroscope. Cell growth and differentiated characteristic function were separately assayed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction activity and amylase activity. Results indicated that behaviors of acinar cells on materials might differ to a great extent depending on the surface hydrophilicity and morphology of the materials. On the relatively hydrophobic materials, the abilities of acinar cells to adhere and proliferate increased simultaneously. In addition, porous PVDF had higher cell growth compared with dense PVDF. Therefore, the hydrophobic PVDF with a porous structure was the best substrate for culturing acinar cells. According to our findings, a tubular PVDF scaffold with dense outer surface to prevent saliva leakage and with porous inner surface for the cell growth was proposed to serve as an artificial salivary gland for future use in the treatment of patients with salivary hypofunction.

Interactions of blood proteins with poly(isobutylcyanoacrylate) nanoparticles decorated with a polysaccharidic brush
Labarre, D., C. Vauthier, et al. (2005), Biomaterials 26(24): 5075-84.
Abstract: The aim of this work was to examine the in vitro interactions of core-shell poly(isobutylcyanoacrylate)-polysaccharide nanoparticles (NP) with blood proteins. The particles were prepared by initiating the emulsion polymerization of isobutylcyanoacrylate (IBCA) in the presence of dextran 71 or 15 kDa, heparin, a blend of dextran 71 and heparin, or dextran sulphate in aqueous medium at pH 1. The mechanisms of polymerisation were redox radical (Rad) or anionic (An), resulting in differences in the spatial arrangement of the polysaccharide chains at the NP surface, i.e. "loops" and "trains" by anionic polymerization, "brush" by radical polymerization. Surface composition of NPs was determined by X-ray photo-electron spectroscopy (XPS) and surface charge by zeta potential measurements. In the presence of citrated blood plasma, efficacy of the steric repulsive effect of the NP dextran shell towards protein adsorption decreased in the order: Dex71-Rad > Dex15-Rad > Dex71-AnDex15-An. Dextran-coated NPs adsorbed ApoA-I and fibrinogen from plasma. Concerning activation of complement in serum, the effect was sharp: Dex71-Rad was a very low activator whereas Dex15-An, Dex15-Rad and Dex71-An were strong activators. In citrated plasma, the steric repulsive effects of Hep-Rad and Dex-Hep-Rad NPs were similar to Dex71-An, and Dex-Sulph-Rad NPs adsorbed twice more proteins than Hep-Rad. Hep-Rad, Dex-Hep-Rad and Dex-Sulph-Rad NPs adsorbed IgG and fibrinogen. Complement was not activated in serum in the presence of Hep-Rad and Dex-Hep-Rad and a slight adsorption of C3 was noted. C3 was completely adsorbed on Dex-Sulph-Rad. The exquisite sensitivity of blood proteins to differences in the nature and outermost structure of the polysaccharides-coated NPs is highlighted by the present results.

Interactions of blood with surfaces: hemocompatibility and thromboresistance of biomaterials
Cazenave, J. P. and J. Mulvihill (1988), Contrib Nephrol 62: 118-27.

Interactions of GRF(1-29)NH2 with plasma proteins and their effects on the release of the peptide from a PLAGA matrix
Mariette, B., J. Coudane, et al. (2005), J Control Release 106(3): 253-62.
Abstract: The administration of the GRF(1-29)NH2 Growth Hormone Releasing Hormone analog is known as relevant of the concept of drug delivery system using a bioresorbable matrix. However, the release of this peptide from poly(dl-lactic acid-co-glycolic acid) matrices is affected by its insolubility at neutral in salted media and in plasma as well. In order to investigate the origin and the nature of the insolubility in these media in more details, the precipitates collected when the peptide was set in contact with saline, isotonic pH=7.4 phosphate buffer and plasma were analyzed by various techniques, namely weighting, gel chromatography, 1D- and 2D-immunoelectrophoresis, and dialysis to discern the soluble from the insoluble or aggregated fractions. It is shown that precipitation in protein-free salted media is due to a salting out phenomenon complemented by the neutralization of the solubilizing electrostatic charges in the isotonic buffer. In contrast, the precipitation in plasma is due to inter polyelectrolyte-type complexation that involved polyanionic proteins having a rather low isoelectric point like albumin, transferin, haptoglobulin and IgG immunoglobulins. When a rather large quantity of GRF(1-29)NH2 was entrapped in bioresorbable pellets working at a percolating regime after subcutaneous implantation in rats, the peptide was slowly released despite the complexation with plasma proteins. However only a very small part of the peptide was found in blood, this small part being still large enough to cause a detectable increase of the circulating growth hormone concentration. Attempts made to increase the solubility of the peptide in plasma were successful when the peptide was combined with arginine, an amino acid known to promote the poor hormonal activity of injected GRF(1-29)NH2 solutions under clinical conditions.

Interactions of Streptococcus mutans glucosyltransferase B with lysozyme in solution and on the surface of hydroxyapatite
Kho, H. S., A. M. Vacca Smith, et al. (2005), Caries Res 39(5): 411-6.
Abstract: Several active enzymes have been identified as components of acquired enamel pellicle. In the present study, the interactions of Streptococcus mutans glucosyltransferase B (GtfB) with lysozyme in solution and on the surface of hydroxyapatite (HA) beads were studied. Experiments were also performed to investigate whether structural differences exist between glucans formed by GtfB enzyme in the presence or absence of lysozyme in solution and on the surface of HA. Hen egg-white lysozyme (HEWL) and saliva were used as the sources of lysozyme; lysozyme-depleted saliva was used as control. Lysozyme activity was significantly reduced when adsorbed onto HA beads compared with that in solution. The GtfB enzyme did not affect the activity of lysozyme in solution or that of adsorbed lysozyme onto HA. The presence of HEWL increased GtfB activity; bovine serum albumin had an even greater enhancing effect. Depletion of lysozyme from whole saliva increased GtfB activity in solution, but not on the surface of saliva-coated HA. The presence of lysozyme affected the amount of glucan formation by GtfB, but not the structure of glucans formed in solution and on the surface. Therefore, the interaction of lysozyme and GtfB enzymes on HA surface may modulate the formation of glucan and dental plaque.

Interactions of vancomycin resistant enterococci with biomaterial surfaces
Su, S. H., J. W. Eaton, et al. (1998), Asaio J 44(6): 770-5.
Abstract: Enterococci are a frequent cause of nosocomial infections and are often found adherent to indwelling catheters. Concern about such device associated infections has increased with the appearance of vancomycin resistant (VR) enterococci. However, the possible influence of vancomycin resistance in the pathogenesis of biomaterial centered infection has not yet been assessed. Using polyethylene terephthalate (PET) disks as model surfaces, the authors evaluated possible differences in the adherence and persistence of vancomycin sensitive (VS) and VR strains of Enterococcus faecium and Enterococcus faecalis on biomaterial surfaces in vitro and in vivo. The results indicate that: 1) as expected, the clearance of free VR and VS organisms after intraperitoneal injection into normal mice is equally efficient. 2) In vitro, VR bacteria are roughly twice as adherent to plasma coated PET surfaces as are VS organisms. 3) However, in vivo persistence of VS organisms preadherent to biomaterial implants is 5- to 10-fold better than that of preadherent VR organisms. The authors now believe that a discrete change in bacterial cell wall composition between VR and VS enterococci may contribute to the substantial differences in bacterial adhesion and survival of adherent organisms.

Interfacial fracture toughness of tissue-biomaterial systems
Wang, X. and C. M. Agrawal (1997), J Biomed Mater Res 38(1): 1-10.
Abstract: Tissue-biomaterial interfacial bonding strength plays a significant role in the success of the biomaterials used for load-bearing orthopedic prostheses. To assess the interfacial bonding strength, this study examined a fracture mechanics approach using a bilayer compact sandwich (BCS) specimen, in which a bilayer coupon comprising the interface between tissue and biomaterial was sandwiched between two holders. First, the theoretical basis for measuring interfacial fracture toughness using the BCS specimen was developed. Next, the effect of finite interlayer thickness on the measurements was addressed and a correction factor was determined using finite element analysis techniques. Accordingly, the theoretical solution was modified to account for the effect of the interlayer thickness. Finally, using a bone to bone-cement interface the BCS technique was empirically verified in terms of overall size, material combination, and interlayer thickness. It is expected that the BCS technique will provide an effective means for researchers to study and analyze tissue-biomaterial interfaces.

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Last Modified: 8 February 2006