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Stability of radiopaque iodine-containing biomaterials
Aldenhof, Y. B., M. A. Kruft, et al. (2002), Biomaterials 23(3): 881-6.
Abstract: Stability tests have been performed on two typical iodine-containing radiopaque poly(methacrylate) copolymers. Material A is a terpolymer of methylmethacrylate (MMA), 2-hydroxyethyl methacrylate (HEMA) and 2-[4-iodobenzoyl]-oxo-ethylmethacrylate (4-IEMA); material B is a copolymer of MMA and 4-IEMA. Cylindrical specimens of material A were implanted subcutaneously and intraperitoneally in Wistar rats. The implants were retrieved after 2 years. Histology showed that the material was well-tolerated. Detailed analysis of the surface of the implants by electron spectroscopy for chemical analysis (ESCA) revealed that the material remained stable. No differences could be detected between the ESCA spectra of the explants, and those of the control specimens, which were from the same synthetic batch and which were stored in dry form during the entire experimental period. Material B was also stable upon irradiation with X-rays in vitro, even at high doses, compared to the clinical situation. Exposure of material B to gamma-radiation, however, was found to lead to structural degradation. This was evident from clear yellowing, and also from the ESCA spectra. The spectra revealed that material B deteriorates during gamma-irradiation through rupture of C-C and or C-O chemical bonds, not via C-I bond disruption. It can be concluded that iodine is tightly bound to these radiopaque biomaterials. This is important with regard to potential applications of these materials as implant biomaterials.

Stability of trypsin immobilized on inorganic orthopedic biomaterials
Holt, L. J. and D. A. Puleo (1996), Artif Cells Blood Substit Immobil Biotechnol 24(6): 613-20.
Abstract: Biochemical surface modification of biomaterials utilizes immobilized biomolecules to induce preferred tissue responses. Although several techniques are available for immobilizing biomolecules on organic substrates, comparatively few are available for use with inorganic materials, such as those used in many orthopedic applications. The present study investigated the stability/elutability of a model enzyme immobilized on Co-Cr-Mo and Ti-6Al-4V alloys using p-nitrophenyl chloroformate (p-NPC). Trypsin-conjugated biomaterials were incubated in cell culture medium at 37 degrees C for up to 96 hr, and the residual immobilized activity was measured. Although all samples initially bound enzymatically active trypsin, significant decreases were observed within the first 2 hr of incubation. Immobilization of trypsin on Co-Cr-Mo treated with 0.65 mg p-NPC/cm2 of nominal surface area gave significantly higher residual activity than on untreated samples at 24-96 hr of incubation and prevented the nearly complete loss of enzymatic activity that was observed with free (not immobilized) enzyme. Derivatization of Ti-6Al-4V with p-NPC was not beneficial to the level of immobilized enzymatic activity after incubation in medium for longer than 6 hr.

Stabilization of collagen using plant polyphenol: role of catechin
Madhan, B., V. Subramanian, et al. (2005), Int J Biol Macromol 37(1-2): 47-53.
Abstract: Collagen, a unique connective tissue protein finds extensive application as biocompatible biomaterial in wound healing, as drug carriers, cosmetics, etc. A work has been undertaken to study the stabilization of type I collagen using the plant polyphenol catechin. Catechin treated collagen fibres showed a shrinkage temperature around 70 degrees C implying that catechin is able to impart thermal stability to collagen. Catechin treated collagen fibres has been found to be stable even after treatment with high concentration of the secondary structural destabilizer, urea. Circular dichroism studies revealed that there is no major alteration in the structure of collagen on treatment with catechin. The study has demonstrated the involvement of hydrogen bonding and hydrophobic interactions as the major forces involved in the stabilization of collagen by the plant polyphenol, catechin.

Stabilization of enzymes by multipoint immobilization of thiolated proteins on new epoxy-thiol supports
Grazu, V., O. Abian, et al. (2005), Biotechnol Bioeng 90(5): 597-605.
Abstract: The controlled and partial modification of epoxy groups of Eupergit C and EP-Sepabeads with sodium sulfide has permitted the preparation of thiol-epoxy supports. Their use allowed not only the specific immobilization of enzymes through their thiol groups via thiol-disulfide interchange, but also enzyme stabilization via multipoint covalent attachment. Penicillin G acylase (PGA) from Escherichia coli and lipase from Rhizomucor miehei were used as model enzymes. Both enzymes lacked exposed cysteine residues, but were introduced via chemical modification under very mild conditions. In the first moments of the immobilization, a certain percentage of immobilized protein could be released from the support by incubation with DTT; this confirms that the first step was via a thiol-disulfide interchange. Moreover, the promotion of some further epoxy-enzyme bonds was confirmed because no enzyme release was detected after some immobilization time by incubation with DTT. In the case of the heterodimeric PGA, it was possible to demonstrate the formation of at least one epoxy bond per enzyme subunit by analyzing with SDS-PAGE the supernatants obtained after boiling the enzyme derivatives in the presence of mercaptoethanol and SDS. Thermal inactivation studies showed that these multipoint enzyme-support attachments promoted an increase in the stability of the immobilized enzymes. In both cases, the stabilization factor was around 12-15-fold comparing optimal derivatives with their just-thiol immobilized counterparts.

Stabilization of glucose oxidase in alginate microspheres with photoreactive diazoresin nanofilm coatings
Srivastava, R., J. Q. Brown, et al. (2005), Biotechnol Bioeng 91(1): 124-31.
Abstract: The nanoassembly and photo-crosslinking of diazo-resin (DAR) coatings on small alginate microspheres for stable enzyme entrapment is described. Multilayer nanofilms of DAR with poly(styrene sulfonate) (PSS) were used in an effort to stabilize the encapsulation of glucose oxidase enzyme for biosensor applications. The activity and physical encapsulation of the trapped enzyme were measured over 24 weeks to compare the effectiveness of nanofilm coatings and crosslinking for stabilization. Uncoated spheres exhibited rapid loss of activity, retaining only 20% of initial activity after one week, and a dramatic reduction in effective activity over 24 weeks, whereas the uncrosslinked and crosslinked {DAR/PSS}-coated spheres retained more than 50% of their initial activity after 4 weeks, which remained stable even after 24 weeks for the two and three bilayer films. Nanofilms comprising more polyelectrolyte layers maintained higher overall activity compared to films of the same composition but fewer layers, and crosslinking the films increased retention of activity over uncrosslinked films after 24 weeks. These findings demonstrate that enzyme immobilization and stabilization can be achieved by using simple modifications to the layer-by-layer self-assembly technique.

Stable encapsulation of active enzyme by application of multilayer nanofilm coatings to alginate microspheres
Srivastava, R., J. Q. Brown, et al. (2005), Macromol Biosci 5(8): 717-27.
Abstract: In an effort to improve the stability for long-term biosensor use, layer-by-layer self-assembly was explored as a potential technique to provide a diffusion barrier to encapsulated glucose oxidase inside alginate microspheres (<5 microm), fabricated using an emulsification technique. The total loss of encapsulated enzyme was reduced to less than 25 and 15% with the application of single PAH/PSS and crosslinked PAH/PAA coatings, respectively, in comparison to at least a 45% loss observed with uncoated and PDDA/PSS-coated microspheres. Furthermore, it was found that enzyme within PAH/PSS- and crosslinked PAH/PAA-coated spheres retained more than 84 and 60% of initial activity, respectively, after three months, whereas uncoated and PDDA/PSS-coated microspheres retained less than 20%.

Stable permanently hydrophilic protein-resistant thin-film coatings on poly(dimethylsiloxane) substrates by electrostatic self-assembly and chemical cross-linking
Makamba, H., Y. Y. Hsieh, et al. (2005), Anal Chem 77(13): 3971-8.
Abstract: Poly(dimethylsiloxane) (PDMS) is a biomaterial that presents serious surface instability characterized by hydrophobicity recovery. Permanently hydrophilic PDMS surfaces were created using electrostatic self-assembly of polyethyleneimine and poly(acrylic acid) on top of a hydrolyzed poly(styrene-alt-maleic anhydride) base layer adsorbed on PDMS. Cross-linking of the polyelectrolyte multilayers (PEMS) by carbodiimide coupling and covalent attachment of poly(ethylene glycol) (PEG) chains to the PEMS produced stable, hydrophilic, protein-resistant coatings, which resisted hydrophobicity recovery in air. Attenuated total reflection Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy revealed that the thin films had excellent chemical stability and resisted hydrophobicity recovery in air over 77 days of measurement. The spectra also showed a dense coverage for PEG dialdehyde and excellent resistance to protein adsorption from undiluted rat serum. Atomic force microscopy revealed dense coverage with PEG dialdehyde and PEG diamine. Contact angle measurements showed that all films were hydrophilic and that the PEG dialdehyde-topped thin film had a virtually constant contact angle (approximately 20 degrees) over the five months of the study. Electrokinetic analysis of the coatings in microchannels always exposed to air also gave good protein separation and constant electroosmotic flow during the five months that the measurements were done. We expect that the stable, hydrophilic, protein-resistant thin-film coatings will be useful for many applications that require long-term surface stability.

Standardized experimental procedures in tissue engineering: cure or curse
Russell, A. J. (2005), Tissue Eng 11(9-10): vii-ix.

Staphylococcus aureus adhesion to bone matrix and bone-associated biomaterials
Hudson, M. C., W. K. Ramp, et al. (1999), FEMS Microbiol Lett 173(2): 279-84.
Abstract: Staphylococcus aureus is a frequent cause of orthopedic infections in humans. The bacterium expresses several adhesins that facilitate bacterial binding to the bone matrix and to bone implant biomaterials coated with host plasma constituents. The relevant S. aureus adhesins are termed microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) and specific MSCRAMMs are involved in bone and joint infections.

States in adherent platelet morphology and the processing of adsorbed protein on biomaterials
Feuerstein, I. A. and J. I. Sheppard (1993), Biomaterials 14(2): 137-47.
Abstract: This study evaluates the range of adherent platelet morphologies and their relationship to preadsorbed protein. Fluorescently labelled protein was used so changes in its distribution could be followed along with morphological states assessed with modulation-contrast microscopy. Our particular concern was with the quantitative relationship between the platelet and the fluorescent image. The findings from this study continue to support the idea that platelets do interact with adsorbed protein so that protein redistribution occurs and that thrombin accelerates this. Evidence is also presented to support platelet shrinkage, membrane vesicle formation and destruction as a result of thrombin. The shrinking of adherent platelets causes areas free of pre-adsorbed protein to be exposed. This process will be important determining the nature of the substrate available to cells contacting surfaces along with other adsorbed protein-related processes, e.g. reversible adsorption and post-adsorptive transitions.

Static indentation of anisotropic biomaterials using axially asymmetric indenters--a computational study
Bischoff, J. E. (2004), J Biomech Eng 126(4): 498-505.
Abstract: Indentation has historically been used by biomechanicians to extract the small strain elastic or viscoelastic properties of biological tissues. Because of the axisymmetry of indenters used in these studies however, analysis of the results requires the assumption of material isotropy and often yields an "effective" elastic modulus. Since most biological tissues such as bone and myocardium are known to be anisotropic, the use of conventional indentation techniques for estimating material properties is therefore limited. The feasibility of using an axially asymmetric indenter to determine material directions and in-plane material properties for anisotropic tissue is explored here using finite element analysis. The load versus displacement curves as would be measured by an indenter depend on the orientation of the indenter cross section relative to the in-plane material axes, thus suggesting a method for determining the underlying material directions. Additionally, the stiffness of the tissue response to indentation is sensitive to the values of the in-plane anisotropic material properties and prestretches, and thus test results can be used to back out relevant constitutive parameters.

Status of selected biomaterials for oral and maxillofacial surgery
Leake, D., H. C. Schwartz, et al. (1979), Biomater Med Devices Artif Organs 7(2): 213-27.

Steady-state diffusion of water through soft-contact-lens materials
Fornasiero, F., F. Krull, et al. (2005), Biomaterials 26(28): 5704-16.
Abstract: Water transport through soft contact lenses (SCL) is important for acceptable performance on the human eye. Chemical-potential gradient-driven diffusion rates of water through SCL materials are measured with an evaporation-cell technique. Water is evaporated from the bottom surface of a lens membrane by impinging air at controlled flow rate and humidity. The resulting weight loss of a water reservoir covering the top surface of the contact-lens material is recorded as a function of time. New results are reported for a conventional hydrogel material (SofLens One Day, hilafilcon A, water content at saturation w10 = 70 weight %) and a silicone hydrogel material (PureVision, balafilcon A, w10 = 36%), with and without surface oxygen plasma treatment. Also, previously reported data for a conventional 2-hydroxyethyl methacrylate (HEMA)-SCL (w10 = 38%) hydrogel are reexamined and compared with those for SofLens One Day and PureVision hydrogels. Measured steady-state water fluxes are largest for SofLens One Day, followed by PureVision and HEMA. In some cases, the measured steady-state water fluxes increase with rising relative air humidity. This increase, due to an apparent mass-transfer resistance at the surface (trapping skinning), is associated with formation of a glassy skin at the air/membrane interface when the relative humidity is below 55-75%. Steady-state water fluxes are interpreted through an extended Maxwell-Stefan diffusion model for a mixture of species starkly different in size. Thermodynamic nonideality is considered through Flory-Rehner polymer-solution theory. Shrinking/swelling is self-consistently modeled by conservation of the total polymer mass. Fitted Maxwell-Stefan diffusivities increase significantly with water concentration in the contact lens.

Stem cell-based composite tissue constructs for regenerative medicine
Rahaman, M. N. and J. J. Mao (2005), Biotechnol Bioeng 91(3): 261-84.
Abstract: A major task of contemporary medicine and dentistry is restoration of human tissues and organs lost to diseases and trauma. A decade-long intense effort in tissue engineering has provided the proof of concept for cell-based replacement of a number of individual tissues such as the skin, cartilage, and bone. Recent work in stem cell-based in vivo restoration of multiple tissue phenotypes by composite tissue constructs such as osteochondral and fibro-osseous grafts has demonstrated probable clues for bioengineered replacement of complex anatomical structures consisting of multiple cell lineages such as the synovial joint condyle, tendon-bone complex, bone-ligament junction, and the periodontium. Of greater significance is a tangible contribution by current attempts to restore the structure and function of multitissue structures using cell-based composite tissue constructs to the understanding of ultimate biological restoration of complex organs such as the kidney or liver. The present review focuses on recent advances in stem cell-based composite tissue constructs and attempts to outline challenges for the manipulation of stem cells in tailored biomaterials in alignment with approaches potentially utilizable in regenerative medicine of human tissues and organs.

Stent-based delivery of ABT-578 via a phosphorylcholine surface coating reduces neointimal formation in the porcine coronary model
Collingwood, R., L. Gibson, et al. (2005), Catheter Cardiovasc Interv 65(2): 227-32.
Abstract: Stent-based delivery of the antiproliferative and immunosuppressive macrocyclic lactone sirolimus reduces neointimal formation and restenosis by cytostatic inhibition of vascular smooth muscle cell proliferation. The objective of this study was to determine the feasibility and efficacy of stent-based delivery of ABT-578, a structurally unique macrocyclic lactone. Stainless steel balloon-expandable stents were coated with thin layer of phosphorylcholine (PC) or PC with ABT-578 (10 microg/mm). Fifteen juvenile domestic pigs underwent placement of oversized bare metal (n = 15), PC (n = 8), and PC with ABT-578 (n = 9) stents in the coronary arteries. At 28 days, histology demonstrated similar mean injury scores for the control, PC-, and ABT-578-coated stents. The mean neointimal area (mm2) was significantly reduced for ABT-578 (1.70 +/- 0.47) as compared with PC (2.82 +/- 1.24) and control (2.89 +/- 1.91) stents (P < or = 0.05). The 40% reduction in neointimal area resulted in significantly less mean percent diameter stenosis for ABT-578 (19.4% +/- 4.0%) as compared with PC (30.3 +/- 12.1 %) and control (29.4% +/- 15.5%) stents (P < or = 0.03). Twelve of the 45 bare metal stent cross-sections (26.7%) exhibited a giant cell reaction, while none of the sections from the ABT-578-eluting stents had a giant cell reaction (P = 0.004). Stent-based delivery of ABT-578 via a PC surface coating inhibits neointimal formation at 28 days in the porcine coronary model. Further study is necessary to determine the dose-response and long-term effects ABT-578-eluting stents in the porcine coronary model.

Stenting: biomaterials in mini-invasive cardiovascular applications
Prunotto, M. and M. Galloni (2005), Anal Bioanal Chem 381(3): 531-3.

Sterile inflammation after transradial catheterization using a hydrophilic sheath: a case report
Ziakas, A., G. Karkavelas, et al. (2005), Int J Cardiol 99(3): 495-6.

Sterilized ibuprofen-loaded poly(D,L-lactide-co-glycolide) microspheres for intra-articular administration: effect of gamma-irradiation and storage
Fernandez-Carballido, A., R. Herrero-Vanrell, et al. (2004), J Microencapsul 21(6): 653-65.
Abstract: The aim of this study was to prepare and characterize a controlled-release system (microspheres) loaded with ibuprofen, for intra-articular administration, to extend its anti-inflammatory effect in the knee joint cavity. Among the bioresorbable polymers employed, poly(D,L-lactic-co-glycolic) acid (PLGA) (13137 Da) was chosen because of its high biocompatiblity. Microspheres were produced by the solvent evaporation process from an O/W emulsion. Labrafil M 1944 CS was included in the formulation as an additive in order to modulate the release rate of the non-steroidal anti-inflammatory drug (NSAID). Once prepared, the microspheres were sobre-sterilized by gamma-irradiation. The effect of the irradiation dose (25 kGy) exposure, at low temperature, on the formulation was evaluated. The sterilization procedure employed did not alter the physicochemical characteristics of the formulation. Dissolution profiles of formulations behaved similarly and overlapped (f2=87.23, f1=4.2) before and after sterilization. Size Exclusion Chromatography (SEC) revealed no significant changes in the polymer molecular weight. Additionally, a stability study of the sterilized formulation was carried out using microsphere storage conditions of 4 degrees C in a vacuum desiccator for 1 year. The results obtained after storing the sterilized microspheres show no significant alterations in the ibuprofen release rate (f2 = 85.06, f1 = 4.32) or in the molecular weight of the PLGA (12957 Da). The employment of low molecular weight PLGA polymers resulted as advantageous, due to the practical absence of degradation after gamma irradiation (25 kGy) exposure at low temperature.

Sternal resection and reconstruction after renal cell carcinoma metastatic to the sternum
Pyle, J. W., J. L. Ash, et al. (2005), J Thorac Cardiovasc Surg 129(5): 1177-8.

Stimulated endothelial cell adhesion and angiogenesis with laminin-5 modification of expanded polytetrafluoroethylene
Kidd, K. R., D. Dal Ponte, et al. (2005), Tissue Eng 11(9-10): 1379-91.
Abstract: Biomedical implants often exhibit poor clinical performance due to the formation of a periimplant avascular fibrous capsule. Surface modification of synthetic materials has been evaluated to accelerate the formation of functional microcirculation in association with implants. The current study used a flow-mediated protein deposition system to modify expanded polytetrafluoroethylene (ePTFE) with a laminin-5-rich conditioned growth medium and with medium from which laminin-5 had been selectively removed. An in vitro model of endothelial cell adherence determined that laminin-5 modification resulted in significantly increased adhesion of human microvessel endothelial cells to ePTFE. In vivo studies evaluating the periimplant vascular response to laminin-5-treated samples indicated that absorption of laminin-5-rich conditioned medium supported accelerated neovascularization of ePTFE implants. A flow system designed to treat porous implant materials facilitates laminin-5 modification of commercially available ePTFE, resulting in increased endothelial cell adhesion in vitro and increased vascularization in vivo.


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