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Surface modification of interconnected porous scaffolds
Liu, X., Y. Won, et al. (2005), J Biomed Mater Res A 74(1): 84-91.
Abstract: Surface properties of scaffolds play an important role in cell adhesion and growth. Biodegradable poly(alpha-hydroxy acids) have been widely used as scaffolding materials for tissue engineering; however, the lack of functional groups is a limitation. In this work, gelatin was successfully immobilized onto the surface of poly(alpha-hydroxy acids) films and porous scaffolds by a new entrapment process. The surface composition and properties were examined using attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectra (XPS), and contact angle measurements. Control over the amount of entrapped gelatin was achieved by varying the solvent composition, the duration of soaking, the concentration of gelatin in solution, and chemical crosslinking. The amount of entrapped gelatin increased with the ratio of dioxane/water in the solvent mixture used. Chemical crosslinking after physical entrapment considerably increased the amount of retained gelatin on the surface of poly(alpha-hydroxy acids). Osteoblasts were cultured on these films and scaffolds. The surface modification significantly improved cell attachment and proliferation. Cell numbers on the surface-modified films and scaffolds were significantly higher than those on controls 4 h and 1 day after cell seeding. The osteoblasts showed higher proliferation on surface-modified scaffolds than on the control during 4 weeks of in vitro cultivation. More collagen fibers and other cell secretions were deposited on the surface-modified scaffolds than on the control scaffolds. This novel surface treatment strategy provides a convenient and universal way to modify the surface properties of three-dimensional scaffolds and thus promote cell adhesion and proliferation for tissue engineering.

Surface modification of polymeric biomaterials by albumin grafting using h-irradiation
Kamath, K. R. and K. Park (1994), J Appl Biomater 5(2): 163-73.
Abstract: Polymeric biomaterial surfaces were modified by albumin grafting to improve their blood compatibility. Albumin molecules were functionalized by introducing double bonds using glycidyl acrylate. The functionalized albumin was covalently attached to various biomaterial surfaces such as polypropylene, polycarbonate, and poly(vinyl chloride) by h-irradiation. Surface-induced platelet adhesion and thrombus formation on the albumin-grafted surfaces was examined using computer-enhanced video microscopy and scanning electron microscopy. The amount of the grafted albumin was dependent on the h-irradiation dose and the concentration of albumin used for adsorption. The grafted albumin molecules remained on the surface even after exposure to blood for prolonged time periods. This approach was used to graft albumin to polymeric materials of an oxygenator. The albumin grafting resulted in a substantial improvement in blood compatibility as compared to control oxygenators. The covalent grafting of functionalized albumin by h-irradiation obviates the need for premodification of chemically inert polymer surfaces. It is useful for albumin grafting to various biomaterial surfaces.

Surface modification of polymeric biomaterials with poly(ethylene oxide), albumin, and heparin for reduced thrombogenicity
Amiji, M. and K. Park (1993), J Biomater Sci Polym Ed 4(3): 217-34.
Abstract: Appropriate surface modification has significantly improved the blood compatibility of polymeric biomaterials. This article reviews methods of surface modification with water-soluble polymers, such as polyethylene oxide (PEO), albumin, and heparin. PEO is a synthetic, neutral, water-soluble polymer, while albumin and heparin are a natural globular protein and an anionic polysaccharide, respectively. When grafted onto the surface, all three macromolecules share a common feature to reduce thrombogenicity of biomaterials. The reduced thrombogenicity is due to the unique hydrodynamic properties of the grafted macromolecules. In aqueous medium, surface-bound water-soluble polymers are expected to be highly flexible and extend into the bulk solution. Biomaterials grafted with either PEO, albumin, or heparin are able to resist plasma protein adsorption and platelet adhesion predominantly by a steric repulsion mechanism.

Surface modification of silicone intraocular implants to inhibit cell proliferation
Yammine, P., G. Pavon-Djavid, et al. (2005), Biomacromolecules 6(5): 2630-7.
Abstract: Photo-cross-linkable polymers bearing cinnamic, sulfonate, and carboxylate groups were synthesized by radical polymerization leading to randomly distributed copolymers. These polymers were used to coat silicone intraocular lenses in order to reduce posterior capsule opacification, also named "secondary cataract". We previously demonstrated that polymers containing both carboxylate and sulfonate groups inhibit cell proliferation, and formulations with the ratio R = COO-/(COO- + SO3-) equal to 0.64 provided the highest inhibitory effect. Ionic polymers with this formulation were synthesized to contain a monomer with pendant siloxane groups in order to get compatibility with the silicone matrix of the intraocular lenses. Anchorage of the ionic polymer at the surface of the silicone implant was achieved by a cycloaddition reaction of the photosensitive groups according to two options. These modified silicone surfaces grafted onto intraocular lenses were shown to inhibit cell proliferation to 60%.

Surface modification of starch based blends using potassium permanganate-nitric acid system and its effect on the adhesion and proliferation of osteoblast-like cells
Pashkuleva, I., A. P. Marques, et al. (2005), J Mater Sci Mater Med 16(1): 81-92.
Abstract: The surface modification of three starch based polymeric biomaterials, using a KMnO4/HNO3 oxidizing system, and the effect of that modification on the osteoblastic cell adhesion has been investigated. The rationale of this work is as follows--starch based polymers have been proposed for use as tissue engineering scaffolds in several publications. It is known that in biodegradable systems it is quite difficult to have both cell adhesion and proliferation. Starch based polymers have shown to perform better than poly-lactic acid based materials but there is still room for improvement. This particular work is aimed at enhancing cell adhesion and proliferation on the surface of several starch based polymer blends that are being proposed as tissue engineering scaffolds.The surface of the polymeric biomaterials was chemically modified using a KMnO4/HNO3 system. This treatment resulted in more hydrophilic surfaces, which was confirmed by contact angle measurements. The effect of the treatment on the bioactivity of the surface modified biomaterials was also studied. The bioactivity tests, performed in simulated body fluid after biomimetic coating, showed that a dense film of calcium phosphate was formed after 30 days. Finally, human osteoblast-like cells were cultured on unmodified (control) and modified materials in order to observe the effect of the presence of higher numbers of polar groups on the adhesion and proliferation of those cells. Two of the modified polymers presented changes in the adhesion behavior and a significant increase in the proliferation rate kinetics when compared to the unmodified controls.

Surface modification of surface sol-gel derived titanium oxide films by self-assembled monolayers (SAMs) and non-specific protein adsorption studies
Advincula, M., X. Fan, et al. (2005), Colloids Surf B Biointerfaces 42(1): 29-43.
Abstract: Biological events occurring at the implant-host interface, including protein adsorption are mainly influenced by surface properties of the implant. Titanium alloys, one of the most widely used implants, has shown good biocompatibility primarily through its surface oxide. In this study, a surface sol-gel process based on the surface reaction of metal alkoxides with a hydroxylated surface was used to prepare ultrathin titanium oxide (TiOx) coatings on silicon wafers. The oxide deposited on the surface was then modified by self-assembled monolayers (SAMs) of silanes with different functional groups. Interesting surface morphology trends and protein adhesion properties of the modified titanium oxide surfaces were observed as studied by non-specific protein binding of serum albumin. The surface properties were investigated systematically using water contact angle, ellipsometry, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM) measurements. Results showed that the surface sol-gel process predominantly formed homogeneous, but rough and porous titanium oxide layers. The protein adsorption was dependent primarily on the silane chemistry, packing of the alkyl chains (extent of van der Waals interaction), morphology (porosity and roughness), and wettability of the sol-gel oxide. Comparison was made with a thermally evaporated TiOx-Ti/Si-wafer substrate (control). This method further extends the functionalization of surface sol-gel derived TiOx layers for possible titanium alloy bioimplant surface modification.

Surface modification of titanium based biomaterials by ion beam
Xianghuai, L., Z. Zhihong, et al. (1996), J Biomater Appl 10(4): 330-7.
Abstract: Ion beam enhanced deposition (IBED) was adopted to synthesize biocompatible titanium oxide film. Structure characteristics of titanium oxide film were investigated by RBS, AES, and XRD. The blood compatibility of the titanium oxide film was studied by measurements of blood clotting time and platelet adhesion. The results show that the anticoagulation property of titanium oxide film is improved significantly. The mechanism of anticoagulation of the titanium oxide film was discussed.

Surface morphology and wear mechanisms of four clinically relevant biomaterials after hip simulator testing
Kurtz, S. M., C. L. Muhlstein, et al. (2000), J Biomed Mater Res 52(3): 447-59.
Abstract: The surfaces of worn components hold clues to the underlying wear mechanisms. Previous evidence suggested that the absolute wear rates of acetabular components in a hip simulator were related to mechanical behavior; we hypothesized that the surface morphology of the liners might also be sensitive to mechanical properties. A noncontact, three-dimensional surface topography measurement system based on white light interferometry was used to quantify the surface morphology of ultra-high molecular weight polyethylene, polytetrafluoroethylene, high-density polyethylene, and polyacetal liners, and their corresponding femoral heads, after 3 million cycles in a multi-directional hip simulator. Comparisons were made with the fatigue soaked and control (as machined) components. Statistically significant power law relationships were observed between the arithmetic mean surface roughness (R(a)) of the worn acetabular liners and the volumetric wear rate in the hip simulator (p < 0.01, r(2) = 0.52). Significant relationships were also observed between R(a) and the elastic and large deformation mechanical behavior of the liner materials, measured directly from the wear-tested liners using the small punch test (p < 0.01, r(2) = 0.54-0.81). The results support the hypothesis that wear mechanisms of acetabular liners during hip simulator testing are related to surface morphology in conjunction with the mechanical behavior of the polymeric materials.

Surface physics methods and in vitro bone-biomaterial interface control
Muster, D., P. Humbert, et al. (1990), Biomaterials 11: 57-62.
Abstract: After a brief review of the main characteristics of some spectroscopic and microscopic methods for surface and interface analysis, preliminary and prospective studies of biocompatible materials (hydroxyapatite, alumina) for implant coating purposes are presented. The results show that the use of complementary techniques allows information on the physical and chemical properties of the coatings both on a microscopic and on an atomic scale to be obtained.

Surface plasmon resonance analysis of dynamic biological interactions with biomaterials
Green, R. J., R. A. Frazier, et al. (2000), Biomaterials 21(18): 1823-35.
Abstract: Surface plasmon resonance (SPR) is an optical technique that is widely gaining recognition as a valuable tool to investigate biological interactions. SPR offers real time in situ analysis of dynamic surface events and, thus, is capable of defining rates of adsorption and desorption for a range of surface interactions. In this review we highlight the diversity of SPR analysis. Examples of a wide range of applications of SPR are presented, concentrating on work relevant to the analysis of biomaterials. Particular emphasis is given to the use of SPR as a complimentary tool, showing the broad range of techniques that are routinely used alongside SPR analysis.

Surface plasmon resonance: a technique for characterizing biomaterial surfaces
Corneillie, S. and E. Schacht (1998), Med Device Technol 9(1): 28-31.
Abstract: Surface plasmon resonance is an optical technique that allows the study of surface phenomena in real time, without preliminary labelling. The technique is useful in biomaterial science to determine affinity constants, concentrations, kinetics, film thickness and dielectric properties of material surfaces. This article examines the technology and some of its applications.

Surface properties of PEO-silicone composites: reducing protein adsorption
Chen, H., M. A. Brook, et al. (2005), J Biomater Sci Polym Ed 16(4): 531-48.
Abstract: Silicone-based polymers with reduced protein adsorption were successfully prepared by incorporating mono- or bifunctional poly(ethylene oxide) (PEO) derivatives, respectively, into PDMS during rubber formation using classic room temperature vulcanization chemistry. Characterization of the films by water contact-angle measurements and XPS showed that the PEO was present on the film surface, with greater amounts of PEO at the interface modified with monofunctional PEO. Scanning electron microscopy showed the PEO domains segregated into regular zigzag patterns on the PEO-modified surfaces. Significant reductions in the adsorption of fibrinogen, albumin and lysozyme were observed on both PEO-modified surfaces, although the monofunctional PEO surfaces performed much better in this regard. The reductions in protein adsorption were comparable for all three proteins on both surfaces, suggesting that molecular mass of the protein is not a significant factor in determining the magnitude of protein deposition. Western blot studies showed that the adsorption of proteins from plasma to the monofunctional PEO-modified surfaces was also significantly reduced and surprisingly selective, with very few bands noted relative to the control surfaces and those modified with bifunctional PEO.

Surface properties of silk fibroin films and their interaction with fibroblasts
Servoli, E., D. Maniglio, et al. (2005), Macromol Biosci 5(12): 1175-83.
Abstract: There is a growing interest in the use of silk as a biomaterial for tissue engineering. Silk threads from Bombyx mori have a fibrous core of fibroin, the protein responsible for biocompatibility and bioactivity, which is surrounded by a family of "gummy" proteins, called sericins, which are almost completely removed during silk degumming. Three different methanol treatments on regenerated fibroin films were used to convert viscous solutions of Silk I to an insoluble crystalline form (Silk II), in an attempt to devise new processing protocols for the creation of a cell guiding fibroin surface. Human fibroblasts (MRC5 line) were used as probes of the cell-biomaterial interaction in the early stages of the process (1 h, 3 h, 6 h and 4 d after seeding). The effect of each treatment on cell adhesion, spreading and distribution was monitored by scanning electron microscopy (SEM) and was correlated to superficial properties (like roughness and crystallinity) and fibroin conformation by means of atomic force microscopy (AFM), used in both topographical and acoustic mode, and attenuated total internal reflection infrared spectroscopy (FTIR-ATR). It was found that traditional methanol treatments where fibroin films were soaked in methanol solution produced roughness patterns that affected only the very early stages of fibroblast adhesion (until 3 h from seeding), while the new treatment proposed could really dialogue with the cells. Its non-homogeneous surface can explain the existence of cells spreading in specific directions and the presence of cell repellent areas even 4 d after seeding.

Surface proteins of coagulase-negative staphylococci: their role in adherence to biomaterials and in opsonization
Fleer, A., C. P. Timmerman, et al. (1990), J Biomater Appl 5(2): 154-65.
Abstract: During the last decade coagulase-negative staphylococci (CN-Staph) have clearly emerged as pathogens in patients equipped with foreign devices. This has fueled the interest in these bacteria considerably and as a result, knowledge of the biology of CN-Staph as well as insight into the pathogenesis of biomaterial-associated infections due to these bacteria are rapidly expanding. Adherence of bacteria to biomaterials is a necessary step in the process of these infections. Evidence is accumulating that surface proteins of CN-Staph are essential in the early phases of adherence to biomaterials. By using monoclonal antibodies in immunoblotting and immune electron micrography we have identified a cell wall protein complex apparently located on the surface of CN-Staph and involved in adherence to biomaterials. Further studies will be oriented at characterization of the protein adhesin(s) and at identification of the surface structures with which the adhesion is associated.

Surface study of biomaterials by electron induced vibrational spectroscopy
Pireaux, J. J. (1992), Clin Mater 11(1-4): 53-60.
Abstract: Besides the identification of elements and chemical groups on a material surface, the determination of its structure, or of the relative orientation of different chemical groups, is probably of utmost importance for biomaterials and their modified surfaces. 'Electron induced vibrational spectroscopy' is a new technique, as far as applications to biomaterials are concerned, and is capable of recording well-resolved vibrational bands from the extreme surface. Basics and the potentials of the technique are presented here for nonspecialists, with illustrations from model polymers, Langmuir-Blodgett films, carbon materials, and ceramics.

Surface techniques to examine the biomaterial-host interface: an introduction to the papers
Chittur, K. K. (1998), Biomaterials 19(4-5): 301-5.

Surface texturing and coating of biomaterial implants: effects on tissue integration and fibrosis
Clubb, F. J., Jr., D. L. Clapper, et al. (1999), Asaio J 45(4): 281-7.
Abstract: To determine whether texturing and coating have additive effects in promoting tissue integration and inhibiting fibrosis, we evaluated smooth silicone rubber (SSR), textured silicone rubber (TSR), porous silicone rubber (PSR), expanded polytetrafluoroethylene (ePTFE), and porous polyurethane (PPU) subcutaneous implants in eight minipigs. Some of the implants were coated with type IV collagen (Col) and/or fibronectin (Fn). At 6 months, we removed the implants and examined them microscopically. Texturing was more important than Col and Fn in reducing fibrosis and inflammation. The PSR yielded the best response, including reduced fibrosis and inflammation, satisfactory adherence, and no dystrophic mineralization.

Surface treatments and roughness properties of Ti-based biomaterials
Bagno, A. and C. Di Bello (2004), J Mater Sci Mater Med 15(9): 935-49.
Abstract: Nowadays, the use of implanted devices is a well-acknowledged practice in the field of orthopaedic and dental surgery. Scientific research and clinical experience suggest that the successful exploitation of these devices mainly depends on osseointegration, considered as both anatomical congruency and load-bearing capacity. Indeed, the osseointegration process is influenced by a wide range of factors: anatomical location, implant size and design, surgical procedure, loading effects, biological fluids, age and sex, and, in particular, surface characteristics. For this reason, several attempts have been aimed at modifying implant surface composition and morphology to optimise implant-to-bone contact and improve integration. Preliminary interactions between implanted materials and biological environment are deemed to be governed by the surface properties; they control the amount and quality of cell adhesion on the surface and, consequently, cell/tissue growth. Thus, surface properties govern new bone tissue formation and implant osseointegration. This paper reviews the state of art in the field of physical, chemical and biochemical treatments commonly used on Ti-based biomaterials for the production of biomedical devices. In particular, roughness characteristics due to physical and chemical techniques are investigated; the development of biologically active surfaces by means of biochemical functionalisation is also considered.

Surface-active biomaterials
Hench, L. L. and J. Wilson (1984), Science 226(4675): 630-6.
Abstract: Since the discovery in 1969 of a man-made surface-active material that would bond to bone, a range of materials with the same ability has been developed. These include glass, glass-ceramic, and ceramic materials which have a range of reaction rates and from which it should be possible to select a surface-active material for a specific application. The available materials and their similarities, differences, and current clinical applications are reviewed.

Surface-enhanced Raman spectra of calf thymus DNA adsorbed on concentrated silver colloid
Ke, W., D. Zhou, et al. (2005), Appl Spectrosc 59(4): 418-23.
Abstract: Raman and surface-enhanced Raman scattering (SERS) spectra of calf thymus DNA were investigated. We have carried out improvements to the silver colloid preparation method of Lee and Meisel in two respects. In one method, the silver sol was boiled with rapid stirring for over two hours. In the second method, the silver sol was concentrated by centrifugation before adding it to the DNA solution. The resulting hydrosol could be stored for 15 months because of its high stabilization. Structural information with respect to the phosphate backbone, deoxyribose, and four bases of DNA could be obtained before and after the DNA solutions were added to the concentrated Ag colloid substrate. The intensities of almost all characteristic bands assigned to various groups of the components of DNA were enhanced to a remarkable degree. The enhancement effect of the DNA solution at neutral pH 7.0 was obviously much better than that at acidic pH 3.4 or at alkaline pH 8.5. Intensity increases of the SERS bands of the DNA solution with time were observed. The SERS signals obtained 16 hours after the interaction of the Ag colloid with the DNA solution were much better than the SERS signals obtained just after the mixed liquid was prepared. This method can be widely used to store the Ag colloid for long times and to obtain the SERS spectra of DNA molecules, and it can further be used to study the adsorption behavior of solute biomacromolecules in different solvents.


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