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Preparation of chitosan-g-polycaprolactone copolymers through ring-opening polymerization of epsilon-caprolactone onto phthaloyl-protected chitosan
Liu, L., Y. Wang, et al. (2005), Biopolymers 78(4): 163-70.
Abstract: The new biodegradable chitosan graft copolymer, chitosan-g-polycaprolactone, was synthesized by the ring-opening graft copolymerization of epsilon-caprolactone onto phthaloyl-protected chitosan (PHCS) at the hydroxyl group in the presence of tin(II) 2-ethylhexanoate catalyst via a protection-graft-deprotection procedure. Toluene acted as a swelling agent in this heterogeneous system. The grafting reactions were conducted with various PHCS/monomer/toluene feed ratios to obtain chitosan-g-polycaprolactone copolymers with various polycaprolactone contents. The chemical structure of the chitosan-g-polycaprolactone was characterized by Fourier transform infrared and one- and two-dimensional NMR spectroscopy. After deprotection, the phthaloyl group was removed and the amino group was regenerated. Thus the obtained chitosan-g-polycaprolactone was an amphoteric hybrid with a large amount of free amino groups and hydrophobic polycaprolactone side chains. Some properties of the final product were also investigated, such as crystallinity, thermal property, and solubility.

Preparation of dendrimer SAM on Au substrate and adsorption/desorption of poly-L-glutamate on the SAM
Yamazaki, T. and T. Imae (2005), J Nanosci Nanotechnol 5(7): 1066-71.
Abstract: A self-assembled monolayer (SAM) of a dendrimer has been fabricated by covalent bonding of amine-terminated dendrimers to 3-mercaptopropionic acid SAM on an Au substrate, where an amide bond was formed between the amine and the carboxylic acid using amide-coupling reagents. Each reaction step was inspected by transmission surface-enhanced infrared absorption spectroscopy. Reaction was affected by solvents of the coupling reagents and concentrations of the coupling reagents and dendrimers. The pH-dependent adsorption/desorption behavior of sodium poly-L-glutamate (PGA) has been examined on the dendrimer SAM prepared. The adsorbed amount was abundant at acid pH below the pK(a) of carboxylate, while desorption from PGA-adsorbed dendrimer SAM prepared at acid pH proceeded as the pH was raised. The reaction was reversible and reproducible within 30 min under controlled pH, although the carboxylic acid species adsorbed at pH 4.2 was deprotonated to a carboxylate species after more than 30 min of desorption at pH 9.4.

Preparation of elastic silk sericin hydrogel
Teramoto, H., K. Nakajima, et al. (2005), Biosci Biotechnol Biochem 69(4): 845-7.
Abstract: This paper reports a preparation method for silk sericin hydrogel using the Sericin-hope silkworm, whose cocoons consist almost exclusively of sericin. Sericin solution, prepared from Sericin-hope cocoons, contains intact sericin and forms elastic hydrogels with the addition of ethanol. The sericin hydrogel can be prepared without crosslinking by chemicals or irradiation and might be usable as a naturally occurring biomaterial.

Preparation of gamma-PGA/chitosan composite tissue engineering matrices
Hsieh, C. Y., S. P. Tsai, et al. (2005), Biomaterials 26(28): 5617-23.
Abstract: Gamma-poly(glutamic acid) (gamma-PGA), a hydrophilic and biodegradable polymer, was chosen to modify chitosan matrices to produce a gamma-PGA/chitosan composite biomaterial. Three types of both dense and porous composite matrices containing different amounts of gamma-PGA were fabricated. Chitosan and gamma-PGA matrices were also prepared as controls. Fluorescence staining indicated that chitosan and gamma-PGA were evenly distributed in the composite matrices. SEM micrographs showed that an interconnected porous structure with a pore size of 30-100 microm was present in all porous matrices except the gamma-PGA ones. By increasing the percentage of gamma-PGA from 0% to 20%, the swelling ratio of the matrices was enhanced from 1.6 to 3.2. Similarly, the contact angle of the matrices decreased from 113 degrees to 94 degrees. These data suggested that the surface hydrophilicity, water absorption rate, and swelling ratio were improved by adding gamma-PGA to the matrices. Additionally, the mechanical strength of the porous gamma-PGA/chitosan matrices was about 25-50%, higher than that of the unmodified chitosan matrices. The composite matrices were also examined and found to be an appropriate environment for cell attachment and proliferation. The cell density on the 20% gamma-PGA-modified matrices was almost triple that on the unmodified chitosan matrices on day 5. In summary, the gamma-PGA/chitosan composite matrices, due to their better hydrophilic, cytocompatible, and mechanical properties, are very promising biomaterials for tissue engineering applications.

Preparation of interpenetrating networks of gelatin and dextran as degradable biomaterials
Kosmala, J. D., D. B. Henthorn, et al. (2000), Biomaterials 21(20): 2019-23.
Abstract: Gelatin and dextran were blended and crosslinked to form enzymatically degradable interpenetrating polymeric networks (IPNs) as materials for degradable implants. Several crosslinking methods were investigated including treatment with glyceraldehyde, thermal hardening, and chelation of dextran by divalent metal cations. IPNs were characterized by an equilibrium swelling method. Gelatin/dextran IPNs were stable at 25 degrees C and reached peak volume equilibrium swelling ratios up to 17 and peak weight swelling ratios up to 15. When swollen at 37 degrees C, the gels dissolved denoting that a network had been formed by physical and not chemical crosslinks.

Preparation of mucoadhesive chitosan-poly(acrylic acid) microspheres by interpolymer complexation and solvent evaporation method II
Cho, S. M. and H. K. Choi (2005), Arch Pharm Res 28(5): 612-8.
Abstract: A mucoadhesive microsphere was prepared by an interpolymer complexation and solvent evaporation method, using chitosan and poly(acrylic acid) (PAA), to prolong the gastric residence time of the delivery system. The Fourier transform infrared results showed that microspheres were formed by an electrostatic interaction between the carboxyl groups of the PAA and the amine groups of the chitosan. X-ray diffraction and differential scanning calorimetry analysis showed that the enrofloxacin in the chitosan-PAA microsphere was molecularly dispersed in an amorphous state. Scanning electron microscopy of the surface and the quantity of mucin attached to the microspheres indicated that chitosan-PAA microspheres had a higher affinity for mucin than those of chitosan alone. The swelling and dissolution of the chitosan-PAA microspheres were found to be dependent on the pH of the medium. The rate of enrofloxacin released from the chitosan-PAA microspheres was slower at higher pH; therefore, based on their mucoadhesive properties and morphology, the chitosan-PAA microspheres can be used as a mucoadhesive oral drug delivery system.

Preparation of nanoparticles composed of chitosan/poly-gamma-glutamic acid and evaluation of their permeability through Caco-2 cells
Lin, Y. H., C. K. Chung, et al. (2005), Biomacromolecules 6(2): 1104-12.
Abstract: In this study, a novel nanoparticle system for paracellular transport was prepared using a simple and mild ionic-gelation method upon addition of a poly-gamma-glutamic acid (gamma-PGA) solution into a low-molecular-weight chitosan (low-MW CS) solution. The particle size and the zeta potential value of the prepared nanoparticles can be controlled by their constituted compositions. The results obtained by the TEM and AFM examinations showed that the morphology of the prepared nanoparticles was spherical in shape. Evaluation of the prepared nanoparticles in enhancing intestinal paracellular transport was investigated in vitro in Caco-2 cell monolayers. It was found that the nanoparticles with CS dominated on the surfaces could effectively reduce the transepithelial electrical resistance (TEER) of Caco-2 cell monolayers. After removal of the incubated nanoparticles, a gradual increase in TEER was noticed. The confocal laser scanning microscopy observations confirmed that the nanoparticles with CS dominated on the surface were able to open the tight junctions between Caco-2 cells and allowed transport of the nanoparticles via the paracellular pathways.

Preparation of nanoparticles composed of poly(gamma-glutamic acid)-poly(lactide) block copolymers and evaluation of their uptake by HepG2 cells
Liang, H. F., T. F. Yang, et al. (2005), J Control Release 105(3): 213-25.
Abstract: In the study, poly(gamma-glutamic acid) (gamma-PGA) and poly(lactide) (PLA) were used to synthesize block copolymers via a simple coupling reaction between gamma-PGA and PLA to prepare self-assembled nanoparticles. For the potential of targeting liver cancer cells, galactosamine was further conjugated on the prepared nanoparticles as a targeting moiety. gamma-PGA, a water-soluble, biodegradable, and non-toxic compound, was produced by microbial fermentation (Bacillus licheniformis, ATCC 9945a) and then was hydrolyzed. The hydrolyzed gamma-PGA with a molecular weight of 4 kDa and a polydispersity of 1.3 was used, together with PLA (10 kDa, polydispersity 1.1), to synthesize block copolymers. The prepared nanoparticles had a mean particle size of about 140 nm with a zeta potential of about -20 mV. The results obtained by the TEM and AFM examinations showed that the morphology of the prepared nanoparticles was spherical in shape with a smooth surface. In the stability study, no aggregation or precipitation of nanoparticles was observed during storage for up to 1 month, as a result of the electrostatic repulsion between the negatively charged nanoparticles. With increasing the galactosamine content conjugated on the rhodamine-123-containing nanoparticles, the intensity of fluorescence observed in HepG2 cells increased significantly. Additionally, the intensity of fluorescence observed in HepG2 cells incubated with the nanoparticles with or without galactosamine conjugated increased approximately linearly with increasing the duration of incubation. In contrast, there was no fluorescence observed in Hs68 cells (without ASGP receptors) incubated with the nanoparticles with galactosamine conjugated. The aforementioned results indicated that the galactosylated nanoparticles prepared in the study had a specific interaction with HepG2 cells via ligand-receptor recognition.

Preparation of poly(acrylic acid) modified polyurethane membrane for biomaterial by UV radiation without degassing
Yang, J. M., M. J. Huang, et al. (1999), J Biomed Mater Res 45(2): 133-9.
Abstract: Poly(acrylic acid) modified polyurethane (AA/PU) membranes were prepared by UV radiation without degassing. The chemical composition of the AA/PU membrane was studied by IR spectroscopy. In addition to those absorption peaks associated with pure PU, the absorption peak at 2400 cm-1 of poly(AA) was also found. The morphology of AA/PU membrane was studied by optical polarizing microscopy. We also measured the glass transition temperature and the decomposition temperature of the AA/PU membrane by differential scanning calorimetry and thermogravimetric analysis. A significant domain was found in the AA/PU membrane, which resulted in different glass transition temperature and decomposition temperature between AA/PU and pure PU membrane. The effect of AA content on the contact angle and water absorption of the AA/PU membrane was determined. It was found that the water content of AA/PU membrane increased with increasing AA content, whereas the contact angle decreased. By using Kaeble's equation and the contact angle data, the surface free energy of AA/PU membrane was determined. The increase of surface free energy resulted from the increase of the dispersion (gammad) term and polar (gammap) term. In order to evaluate the biocompatibility of these membranes, a cytotoxicity test and a cell adhesion and proliferation assay were conducted in cell culture. Immortal cells and primary lymphocytes were both used in this study. The results showed that these AA/PU membranes exhibited very low cytotoxicity and could support cell adhesion and growth. An animal primary test was also done in this study. It was found that the AA/PU membrane could possibly be employed in the treatment of bowel defect.

Preparation of porcine small intestinal submucosa sponge and their application as a wound dressing in full-thickness skin defect of rat
Kim, M. S., K. D. Hong, et al. (2005), Int J Biol Macromol 36(1-2): 54-60.
Abstract: Small intestinal submucosa (SIS) sponge was prepared by crosslinking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). The prepared SIS sponges exhibited elastic and soft property on touch and were ease to handle. The SIS sponges have the pore diameter of 100-200 microm and an interconnective porous structure. The SIS sponges exhibited high water absorption ability over 8000%. The water uptake of SIS sponges decreased as SIS concentration used to manufacture SIS sponge increased. In wound healing test, SIS sponge attained uniform adherence to the wound surface. The SIS sponges absorbed higher extent of exudation for wound than that covered with Tegaderm as control. Wound area contracted above 80% at the 21st postoperative day. The SIS sponge treated wound was almost completely covered with a thin layer of epidermis at 4 weeks. In addition, the dermal collagen in the wound regenerated at only SIS sponges treated wounds. The progress of granulous tissue formation was faster in SIS sponges as wound dressing than in Tegaderm. In conclusion, we found that the SIS sponges might be a potential material as a wound dressing.

Preparation of ready-to-use, stockable and reconstituted collagen
Habermehl, J., J. Skopinska, et al. (2005), Macromol Biosci 5(9): 821-8.
Abstract: Collagen is a widely used material in biomedical applications. Although processes that prepare collagen and collagen-based materials that show suitable properties after extraction exist, a ready-to-use, easily stockable, with tailored collagen concentration has not yet been developed. Using rat tail tendons, acid soluble collagen solutions were prepared by two different methods. To improve cell viability of pure collagen films, solutions with physiological pH were also prepared by mixing with NaOH solution. Specimens in the form of thin sheets were then fabricated by solvent evaporation. Next, IR spectroscopy, tensile testing techniques as well as human fibroblast cell morphology and cytotoxicity were used to validate the significant variations in the processes. The results demonstrated that, during the synthesis of collagen stock solution, lyophilization and mechanical blending had little effect on the final properties and therefore offers a method for obtaining solutions with a more homogeneous and modifiable collagen concentration and longer storage time. Neutralizing the stock solution with aqueous NaOH prior to solvent evaporation provided films that had lower mechanical properties but significantly improved biological performance.

Preparation of silicone coated biomaterials using plasma polymerizations and their preliminary evaluations
Chawla, A. S. (1979), Trans Am Soc Artif Intern Organs 25: 287-93.

Preparation of thermosensitive microgels via suspension polymerization using different temperature protocols
Zhang, Y., W. Zhu, et al. (2005), J Biomed Mater Res A 75(2): 342-9.
Abstract: A thermosensitive and biodegradable microgel for protein drug release was synthesized from a thermosensitive macromer via inverse suspension polymerization. Preparation was made under a constant temperature or under variable temperatures. In the latter protocol, dispersion was performed at a low temperature below lower critical solution temperature of the macromer aqueous solution and polymerization was performed at a high temperature above lower critical solution temperature. According to the experiments, the constant-temperature method was not suitable for preparation of microgels when the macromer concentration was high, because early physical gelation at the preparation temperature seriously influenced formation of dispersed droplets. If the macromer concentration was low, both temperature protocols resulted in spherical hydrogel microparticles, but the properties of the resulting microgels were different to a certain degree. In both cases, the model protein bovine serum albumin was loaded into microgels by a postfabrication encapsulation technique, which takes advantage of the microgels' negative thermosensitivity. The results demonstrate that, in microgel preparation, the variable-temperature protocol is useful in suspension polymerization of negatively thermosensitive macromers at a wide rage of monomer concentrations.

Preparation of TiO2-SiO2 mixed gel spheres for strontium adsorption
Gurboga, G. and H. Tel (2005), J Hazard Mater 120(1-3): 135-42.
Abstract: A simple external gelation process, taking full advantage of the gelation features of titanium and silica, was developed to prepare TiO2-SiO2 mixed gel spheres suitable for strontium adsorption. The source solutions used for the process were prepared from different mixtures of 1M TiCl4 and 1M Na2SiO3 solutions and converted into droplets in a gelation column. The suitable spheres for strontium adsorption were obtained using a hexone (methyl isobutyl ketone) solution as the drop formation medium and ammonia as the gelling agent. The mixed oxide gels were identified and characterized by DTA/TGA, FTIR and XRD analysis. The parameters affecting the strontium adsorption, such as weight ratio of TiO2, pH, temperature, shaking time and selectivity towards competing ions were investigated. Sorption data have been interpreted in terms of Freundlich, Langmuir and Dubinin-Radushkevich equations. Thermodynamic parameters for the sorption system have been determined at four different temperatures. The value of DeltaH degrees =39.553 kJ/mol and DeltaG degrees =-16.687 kJ/mol at 296 K prove that the sorption of strontium on mixed oxide gel is an endothermic and a spontaneous process.

Preparation of titania nanotubes and their environmental applications as electrode
Quan, X., S. Yang, et al. (2005), Environ Sci Technol 39(10): 3770-5.
Abstract: Titanium oxide nanotubes were successfully grown from a titanium plate by direct anodic oxidation with 0.2 wt % hydrofluoric acid being the supporting electrolyte. These nanotubes are of uniform size and are well-aligned into high-density arrays. They look like honeywell with the structure similar to that of porous alumina obtained by the same technique. TiO2 anatase phase was identified by X-ray diffraction. Significant blue-shift in the spectrum of UV- vis absorption was observed. The mechanism of the novel, simple, and direct growth of the nanotubes was postulated. To investigate their potentials in environmental applications, degradation of pentachlorophenol (PCP) in aqueous solution was carried out using photoelectrocatalytic (PEC) processes, comparing with electrochemical process (EP) and photocatalytic (PC). A significant photoelectrochemical synergetic effect was observed. The kinetic constant of PEC degradation of PCP using TiO2 nanotubes electrode was 86.5% higher than that using TiO2 film electrode. In degrading PCP, 70% of TOC was removed using the TiO2 nanotubes electrode against 50% removed using TiO2 film electrode formed by sol-gel method in 4 h under similar conditions.

Preparation, cellular transport, and activity of polyamidoamine-based dendritic nanodevices with a high drug payload
Kolhe, P., J. Khandare, et al. (2006), Biomaterials 27(4): 660-9.
Abstract: Dendrimers are emerging as a relatively new class of polymeric biomaterials with applications in drug delivery, and imaging. Achieving a high drug payload in dendrimers, and understanding the therapeutic effect of the dendrimer-drug conjugates are receiving increasing attention. A high drug payload nanodevice was obtained by covalent conjugation of ibuprofen to a polyamidoamine (PAMAM-G4-OH) dendrimer. Using DCC as a coupling agent, 58 molecules of ibuprofen were covalently conjugated to one molecule of generation 4 PAMAM-OH dendrimer. Cellular entry of the fluoroisothiocynate (FITC)-labeled dendrimer-drug conjugate was evaluated in vitro by using human lung epithelial carcinoma A549 cells by flow cytometry, confocal microscopy and UV/Visible spectroscopy. The pharmacological activity of the dendrimer-ibuprofen conjugate was compared to pure ibuprofen at various time points by measuring the suppression of prostaglandin E2. Significant amounts of the conjugate entered the cells rapidly within 15 min. Suppression of prostaglandin was noted within 30 min for the dendrimer-drug conjugates versus 1 h for the free ibuprofen. The results suggest that dendrimers with high drug payload improve the drug's efficacy by enhanced cellular delivery, and may produce a rapid pharmacological response. These dendrimer-drug conjugates can potentially be further modified by attaching antibodies and ligands for targeted drug delivery.

Preparations for the reinforcement of surgical adhesive dressings: comparative study
McNeil, S. K., P. Robinson, et al. (2005), Dermatol Surg 31(2): 254-5.

Present and emerging applications of polymeric biomaterials
Hoffman, A. S. (1992), Clin Mater 11(1-4): 13-8.
Abstract: An important trend in biomaterials research and development is the synthesis of polymers, which combine capabilities of biologic recognition ('biomimetic') with special physicochemical properties of the synthetic polymer system. For example, an antibody may be conjugated to the backbone of a polymer which precipitates upon small changes in pH, temperature, or ionic strength. Crosslinked gels may also be synthesized from such polymers, and a biomolecule such as an enzyme may be chemically or physically entrapped in these gels. Such gels will shrink and swell in response to small changes in environmental stimuli. Another approach is to 'engineer', perhaps via computer-aided molecular design, new artificial biomimetic systems by exact placement of functional groups on rigid polymer backbones, crosslinked structures, or macromolecular assemblies. In this way, biocatalytic functioning or biorecognition similar to enzymes and antibodies can be achieved without the inherent instability often encountered with the native biomolecules or assemblies. In addition to these synthetic approaches, new and exciting analytical tools, such as the scanning tunnelling microscope and the atomic force microscope, are permitting visualization of individual and small clusters of proteins and other biomolecules on surfaces. Cell attachments and spreading may also be visualized at various depths within the cell using the confocal laser microscope. Such analytical techniques can lead to important new knowledge about biologic interactions with biomaterials, and, therefore, to development of even more biocompatible implants and devices. This paper overviews the field of polymeric biomaterials and highlights the important emerging trends in synthesis and analysis of these materials.

Present and future applications of biomaterials in controlled drug delivery systems
Langer, R. S. and N. A. Peppas (1981), Biomaterials 2(4): 201-14.

Presentation and recognition of biotin on nanofibers formed by branched peptide amphiphiles
Guler, M. O., S. Soukasene, et al. (2005), Nano Lett 5(2): 249-52.
Abstract: A branched peptide amphiphile system was designed for enhanced recognition of biotin on nanofibers formed by self-assembly of these molecules. Branching at a lysine residue was used to design peptide amphiphiles that are capable of presenting more than one epitope per molecule. We found that biotinylated branched structures form nanofibers that enhance recognition by the avidin protein receptor relative to similar nanostructures formed by linear peptide analogues. Biotin-avidin binding to the supramolecular nanofibers was characterized by measurement of fluorescence from nanofibers incubated with chromophore-conjugated avidin.


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