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Functional integration of tissue-engineered bone constructs
Guldberg, R. E., M. Oest, et al. (2004), J Musculoskelet Neuronal Interact 4(4): 399-400.

Functional polyacetylenes
Lam, J. W. and B. Z. Tang (2005), Acc Chem Res 38(9): 745-54.
Abstract: Polyacetylene (PA) is a Nobel Prize-winning macromolecule. In this work, PA is molecularly functionalized, which endows it with an array of new functional properties. The molecular functionalization is realized by attachment of functional pendants to the polyene backbone. Our efforts in the catalyst exploration and reaction optimization have led to the syntheses of a large number of PA derivatives carrying functional groups. Polymer reactions are exploited as an alternative route to the functional PAs that are difficult or impossible to access by direct polymerizations of their monomers. The new PAs with appropriate backbone-pendant combinations show various functional properties such as liquid crystallinity, photoconductivity, light emission, ionic susceptibility, photoresistance, chromism, helical chirality, optical nonlinearity, self-assembly, cytocompatibility, and bioactivity. The properties of the PAs are tuned internally and manipulated externally: the former is achieved by changing their molecular structures, especially their functional pendants, while the latter is accomplished by applying thermal, mechanical, electrical, photonic, and chemical stimuli.

Functionalization of dental implant surfaces using adhesion molecules
Schliephake, H., D. Scharnweber, et al. (2005), J Biomed Mater Res B Appl Biomater 73(1): 88-96.
Abstract: The aim of the present study was to test the hypothesis that organic coating of titanium screw implants that provides binding sites for integrin receptors can enhance periimplant bone formation. Ten adult female foxhounds received experimental titanium screw implants in the mandible 3 months after removal of all premolar teeth. Four types of implants were evaluated in each animal: (1) implants with machined titanium surface, (2) implants coated with collagen I, (3) implants with collagen I and cyclic RGD peptide coating (Arg-Gly-Asp) with low RGD concentrations (100 micromol/mL), and (4) implants with collagen I and RGD coating with high RGD concentrations (1000 micromol/mL). Periimplant bone regeneration was assessed histomorphometrically after 1 and 3 months in five dogs each by measuring bone implant contact (BIC) and the volume density of the newly formed periimplant bone (BVD). After 1 month, BIC was significantly enhanced only in the group of implants coated with the higher concentration of RGD peptides (p = 0.026). Volume density of the newly formed periimplant bone was significantly higher in all implants with organic coating. No significant difference was found between collagen coating and RGD coatings. After 3 months, BIC was significantly higher in all implants with organic coating than in implants with machined surfaces. Periimplant BVD was significantly increased in all coated implants in comparison to machined surfaces also. It was concluded that organic coating of machined screw implant surfaces providing binding sites for integrin receptors can enhance bone implant contact and periimplant bone formation.

Functionalization of synthetic polymers for potential use as biomaterials: selective growth of hydroxyapatite on sulphonated polysulphone
Spanos, N., V. Deimede, et al. (2002), Biomaterials 23(3): 947-53.
Abstract: A novel composite made of biocompatible synthetic polymer (Sulphonated Polysulphone, SPSPH) which may be easily fabricated in various shapes and synthetic hydroxyapatite (HAP) was prepared. The preparation was done by the spontaneous precipitation of HAP in aqueous suspensions of the polymer particles. The time the precipitation process was allowed to proceed was used to regulate the inorganic content of the composite. The preparation thus obtained, in addition to its effectiveness in inducing HAP formation, could be easily fabricated in various shapes, including films. The SPSPH-HAP composite films, surface area totaling ca. 30 cm2 induced the exclusive formation of HAP with rates proportional to the solution supersaturation. No induction times preceded the formation of HAP. Kinetics analysis with respect to HAP yielded an apparent order of precipitation of 6.0+/-0.4, suggesting polynuclear growth with the formation of nuclei above nuclei. The surface energy calculated from the rates of crystal growth on the polymeric substrate gave for HAP the value of 185 mJ m(-2) of order of magnitude typical for crystalline solids.

Functionalized derivatives of hyaluronic acid oligosaccharides: drug carriers and novel biomaterials
Pouyani, T. and G. D. Prestwich (1994), Bioconjug Chem 5(4): 339-47.
Abstract: Oligosaccharides derived from hyaluronic acid (HA), a naturally occurring linear polysaccharide composed of repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronic acid, can be chemically modified to introduce a pendant amine-like functionality (patent application pending). Covalent attachment of steroidal and nonsteroidal antiinflammatory drugs to functionalized HA oligosaccharides was accomplished with the incorporation of hydrolytically labile bonds. Further derivatization of the pendant group with homobifunctional crosslinkers allowed the introduction of covalent crosslinks. Chemically-modified HA oligosaccharides were unambiguously characterized in solution by high-resolution 1H NMR spectroscopy.

Functionalized silk-based biomaterials for bone formation
Sofia, S., M. B. McCarthy, et al. (2001), J Biomed Mater Res 54(1): 139-48.
Abstract: Silks are being reassessed as biomaterial scaffolds due to their unique mechanical properties, opportunities for genetic tailoring of structure and thus function, and recent studies clarifying biocompatibility. We report on the covalent decoration of silk films with integrin recognition sequences (RGD) as well as parathyroid hormone (PTH, 1-34 amino acids) and a modified PTH 1-34 (mPTH) involved in the induction of bone formation. Osteoblast-like cell (Saos-2) responses to the decorated silk films indicate that the proteins serve as suitable bone-inducing matrices. Osteoblast-like cell adhesion was significantly increased on RGD and PTH compared to plastic, mPTH, and the control peptide RAD. At 2 weeks of culture, message levels of alkaline phosphatase were similar on all substrates, but by 4 weeks, alkaline phosphatase mRNA was greatest on RGD. At 2 weeks of culture, alpha 1(I) procollagen mRNA was elevated on silk, RGD, RAD, and PTH, and hardly detectable on mPTH and plastic. However, by 4 weeks RGD demonstrated the highest level compared to the other substrates. Osteocalcin message levels detected by RT-PCR were greatest on RGD at both time points. Calcification was also significantly elevated on RGD compared to the other substrates with an increase in number and size of the mineralized nodules in culture. Thus, RGD covalently decorated silk appears to stimulate osteoblast-based mineralization in vitro.

Functionalized TiO2 nanoparticles for use for in situ anion immobilization
Mattigod, S. V., G. E. Fryxell, et al. (2005), Environ Sci Technol 39(18): 7306-10.
Abstract: Anatase particles (40-60 nm) were coated with an organosilane monolayer terminated with an ethylenediamine (EDA) ligand. These functionalized nanoparticles (FNPs) were then treated with an aqueous solution of Cu(II) to create a cationic Cu-EDA complex bound to the nanoparticle surface. Cu(II) and EDA ligand incorporation were confirmed by X-ray photoelectron spectroscopy (XPS) analysis. The Cu(EDA)2 FNP was then studied for its binding affinity for pertechnetate anion from a Hanford groundwater matrix. The Cu(EDA)2 FNP was also evaluated for its injectability into a porous medium for possible application as a subsurface semipermeable reactive barrier. Injection was readily accomplished, and resulted in a highly uniform distribution of the FNP sorbent in the test column.

Functionalizing electrospun fibers with biologically relevant macromolecules
Casper, C. L., N. Yamaguchi, et al. (2005), Biomacromolecules 6(4): 1998-2007.
Abstract: The development of functionalized polymers that can elicit specific biological responses is of great interest in the biomedical community, as well as the development of methods to fabricate these biologically functionalized polymers. For example, the generation of fibrous matrices with biological properties and fiber diameters commensurate with those of the natural extracellular matrix (ECM) may permit the development of novel materials for use in wound healing or tissue engineering. The goal of this work is, therefore, to create a biologically active functionalized electrospun matrix to permit immobilization and long-term delivery of growth factors. In this work, poly(ethylene glycol) functionalized with low molecular weight heparin (PEG-LMWH) was fabricated into fibers for possible use in drug delivery, tissue engineering, or wound repair applications. Electrospinning was chosen to process the LMWH into fiber form due to the small fiber diameters and high degree of porosity that can be obtained relatively quickly and using small amounts of starting material. Both free LMWH and PEG-LMWH were investigated for their ability to be incorporated into electrospun fibers. Each of the samples were mixed with a carrier polymer consisting of either a 10 wt % poly(ethylene oxide) (PEO) or 45 wt % poly(lactide-co-glycolide) (PLGA). Field emission scanning electron microscopy (FESEM), energy-dispersive X-ray analysis (EDX), UV-vis spectroscopy, and multiphoton microscopy were used to characterize the electrospun matrices. The incorporation of heparin into the electrospun PEO and PLGA fibers did not affect the surface morphology or fiber diameters. The fibers produced had diameters ranging from approximately 100 to 400 nm. Toluidine blue assays of heparin suggest that it can be incorporated into an electrospun matrix at concentrations ranging from 3.5 to 85 mug per milligram of electrospun fibers. Multiphoton microscopy confirmed that incorporation of PEG-LMWH into the matrix permits retention of the heparin for at least 14 days. Improvements in the binding of basic fibroblast growth factor to the electrospun fibers were also observed for fibers functionalized with PEG-LMWH over those functionalized with LMWH alone. The combination of these results suggests the utility for producing electrospun fibers that are appropriately functionalized for use in biomaterials applications.

Fungicidal activity of new N-alkyl and N-aryl Chitosan derivatives
Rabea, E. I., M. E. Badawy, et al. (2004), Commun Agric Appl Biol Sci 69(4): 789-92.

Furanones as potential anti-bacterial coatings on biomaterials
Baveja, J. K., M. D. Willcox, et al. (2004), Biomaterials 25(20): 5003-12.
Abstract: A major barrier to the long-term use of medical devices is development of infection. Staphylococcus epidermidis is one of the most common bacterial isolates from these infections with biofilm formation being their main virulence factor. Currently, antibiotics are used as the main form of therapy. However with the emergence of staphylococcal resistance, this form of therapy is fast becoming ineffective. In this study, the ability of a novel furanone antimicrobial compound to inhibit S. epidermidis adhesion and slime production on biomaterials was assessed. Furanones were physically adsorbed to various biomaterials and bacterial load determined using radioactivity. Slime production was assessed using a colorimetric method. Additionally, the effect of the furanone coating on material surface characteristics such as hydrophobicity and surface roughness was also investigated. The results of this study indicated that there was no significant change in the material characteristics after furanone coating. Bacterial load on all furanone-coated materials was significantly reduced (p<0.001) as was slime production (p<0.001). There is a potential for furanone-coated biomaterials to be used to reduce medical device-associated infections.

Further biocompatibility testing of silica-chitosan complex membrane in the production of tissue plasminogen activator by epithelial and fibroblast cells
Suzuki, T., Y. Mizushima, et al. (1999), J Biosci Bioeng 88(2): 194-9.
Abstract: The effects of the physicochemical characteristics of a silica-chitosan complex membrane (SiCM) on the expression of tissue plasminogen activator (tPA) by contacting cells were investigated with the aim of improving the biocompatibility of the novel implant biomaterial. Expression of tPA is considered to be effective in wound healing by preventing thrombus formation, which causes inflammatory responses and rejection of implant materials. Inducing the epithelial cells surrounding implant materials to secrete tPA, which serves as an early signaling system to proliferate cells underlying connective tissues, would be further effective in accelerating wound healing. An epithelial 293 cell line derived from human embryonic kidney and a fibroblast IMR-90 cell line from human lung possessing the ability to secrete tPA were cultured on SiCMs, whose composition was stepwise controlled by adjusting the mixing ratio between silica and chitosan to give silica contents of 20, 33, 43, and 50wt%. Both strains showed strong adhesion on chitosan (0%-SiCM) and 50%-SiCM. The cell proliferation rates were also accelerated in a manner that was dependent on the increase in the adhesion strength of the cells cultured on the SiCMs. Furthermore, the tPA activity in the culture medium increased in accordance with the cell density, while the cellular specific activity of IMR-90 cells to secrete tPA was synergistically enhanced by strong adhesion and a high cell density on the surface of chitosan and 50%-SiCM. Analysis of the physico-chemical effects of the SiCMs revealed that the cells were dominantly affected by the surface hydrophobicity rather than by the zeta potential, as well as by the mixing ratio between chitosan and silica. The wet contact angles of 50%-SiCM and chitosan, which were 68 degrees and 65 degrees, respectively, were found to be suitable for adhesion and growth of both the epithelial 293 cells and fibroblast IMR-90 cells. A hydrophobic surface at 65 degrees -68 degrees was also effective for the production of tPA by IMR-90 cells, whereas the tPA activity of 293 cells reached its highest level on the SiCM with a wet contact angle of 63 degrees. These results suggest that a suitable adhesion strength is a significant factor in the expression of tPA by cells contacting an implant biomaterial.

Future developments and applications of biomaterials: an overview
Hench, L. L. (1979), Biomater Med Devices Artif Organs 7(2): 339-50.
Abstract: It is recommended that the emphasis of biomaterials research and development for the future should be to achieve improved reliability. Use of increasing numbers of implants per year coupled with decreasing long term (greater than 5 years) success rates are resulting in progressively larger numbers of reparative implant operations. This trend can be altered by emphasizing three areas of R&D: 1) Studies of composite biomaterial systems offering unique combinations of biological surface behavior and substrate mechanical performance; 2) Investigate mechanisms of interfacial reactions so that long term responses of the host-implant can be predicted; 3) Develop long term predictive relationships for biomaterials reliability based upon interfacial reactions, biomechanics, fracture mechanics, fatigue testing, and retrieval analysis. Brief examples of efforts to develop undrestanding in these three areas are described using bioglass coated metal and bioglass coated alumina implants.

Future directions in biomaterial implants and tissue engineering
Friedman, C. D. (2001), Arch Facial Plast Surg 3(2): 136-7.
Abstract: Over the last 50 years, we have gained much knowledge about biomaterial implants by incorporating the fields of basic biologic science and engineering science. Future implant developments will have a significant impact on facial cosmetic and reconstructive surgical therapy.

Future directions in biomaterials
Langer, R., L. G. Cima, et al. (1990), Biomaterials 11(9): 738-45.
Abstract: Biomaterials have made a great impact on medicine. However, numerous challenges remain. This paper discusses three representative areas involving important medical problems. First, drug delivery systems; major considerations include drug-polymer interactions, drug transformation, diffusion properties of drugs and, if degradation occurs, of polymer degradation products through polymer matrices developing a more complete understanding of matrix degradation in the case of erodible polymers and developing new engineered polymers designed for specific purposes such as vaccination or pulsatile release. Second, cell-polymer interactions, including the fate of inert polymers, the use of polymers as templates for tissue regeneration and the study of polymers which aid cell transplantation. Third, orthopaedic biomaterials, including basic research in the behaviour of chondrocytes, osteocytes and connective tissue-free interfaces and applied research involving computer-aided design of biomaterials and the creation of orthopaedic biomaterials.

Future potentials for using osteogenic stem cells and biomaterials in orthopedics
Oreffo, R. O. and J. T. Triffitt (1999), Bone 25(2 Suppl): 5S-9S.
Abstract: Ideal skeletal reconstruction depends on regeneration of normal tissues that result from initiation of progenitor cell activity. However, knowledge of the origins and phenotypic characteristics of these progenitors and the controlling factors that govern bone formation and remodeling to give a functional skeleton adequate for physiological needs is limited. Practical methods are currently being investigated to amplify in in vitro culture the appropriate autologous cells to aid skeletal healing and reconstruction. Recent advances in the fields of biomaterials, biomimetics, and tissue engineering have focused attention on the potentials for clinical application. Current cell therapy procedures include the use of tissue-cultured skin cells for treatment of burns and ulcers, and in orthopedics, the use of cultured cartilage cells for articular defects. As mimicry of natural tissues is the goal, a fuller understanding of the development, structures, and functions of normal tissues is necessary. Practically all tissues are capable of being repaired by tissue engineering principles. Basic requirements include a scaffold conducive to cell attachment and maintenance of cell function, together with a rich source of progenitor cells. In the latter respect, bone is a special case and there is a vast potential for regeneration from cells with stem cell characteristics. The development of osteoblasts, chondroblasts, adipoblasts, myoblasts, and fibroblasts results from colonies derived from such single cells. They may thus, theoretically, be useful for regeneration of all tissues that this variety of cells comprise: bone, cartilage, fat, muscle, tendons, and ligaments. Also relevant to tissue reconstruction is the field of genetic engineering, which as a principal step in gene therapy would be the introduction of a functional specific human DNA into cells of a patient with a genetic disease that affects mainly a particular tissue or organ. Such a situation is pertinent to osteogenesis imperfecta, for example, where in more severely affected individuals any improvements in long bone quality would be beneficial to the patient. In conclusion, the potentials for using osteogenic stem cells and biomaterials in orthopedics for skeletal healing is immense, and work in this area is likely to expand significantly in the future.

Future prospects for biomaterials
Williams, D. F. (1975), Biomed Eng 10(6): 207-12,218.
Abstract: Biomaterials have many uses in medicine and surgery but success in their use is often difficult to achieve. In this paper some of the deatures that contribute to the success or failure of biomaterials are discussed in relation to a hypothetical implant situation. The phenomena of biomaterial-tissue interfacial reactions, wear, prosthesis instability, infection, hypersensitivity and carcinogenesis are considered. Emphasis is given both to the causes and clinical significance of these phenomena and interpreted in terms of the furture prospects for the biomaterials.

Future role of biomaterials in dentistry and dental education
Phillips, R. W. (1976), J Dent Educ 40(11): 752-6.
Abstract: It is possible to make predictions on materials research and on its impact if one understands the background of materials science and appraises the constraints on research and practice. In the past ten years some significant advances have been implemented in dental practice. On the basis of these advances, some very optimistic predictions can be made for the next ten years. However, in some areas, little progress was made, and there are some reasons to believe that this limited success will continue. Planning in research and dental education must be based on realistic appraisals of research productivity.

Gas foamed open porous biodegradable polymeric microspheres
Kim, T. K., J. J. Yoon, et al. (2006), Biomaterials 27(2): 152-9.
Abstract: Highly open porous biodegradable polymeric microspheres were fabricated for use as injectable scaffold microcarriers for cell delivery. A modified water-in-oil-in-water (W1/O/W2) double emulsion solvent evaporation method was employed for producing the microspheres. The incorporation of an effervescent salt, ammonium bicarbonate, in the primary W1 droplets spontaneously produced carbon dioxide and ammonia gas bubbles during the solvent evaporation process, which not only stabilized the primary emulsion, but also created well inter-connected pores in the resultant microspheres. The porous microspheres fabricated under various gas foaming conditions were characterized. The surface pores became as large as 20 microm in diameter with increasing the concentration of ammonium bicarbonate, being sufficient enough for cell infiltration and seeding. These porous scaffold microspheres could be potentially utilized for cultivating cells in a suspension manner and for delivering the seeded cells to the tissue defect site in an injectable manner.

Gas phase trichloroethylene (TCE) photooxidation and byproduct formation: photolysis vs. titania/silica based photocatalysis
Mohseni, M. (2005), Chemosphere 59(3): 335-42.
Abstract: Photooxidation of trichloroethylene (TCE) was examined in comparative study using photolysis and photocatalysis. Degussa P25 titania coated on reactor wall and deposited on silica based microporous support were used as photocatalyst. The destruction of TCE and formation of potential byproducts were investigated under steady state conditions using annular photoreactors. Experimental work involved passing polluted air containing TCE through the UV photoreactor at varying concentrations and residence times. Ultraviolet illumination was provided by low pressure mercury lamps with outputs at either 254 nm, 365 nm, or 185/254 nm. Silica supported photocatalyst yielded maximum removal capacity of up to about 6 kg TCE per m3 per hour, nearly twice that provided by the coated titania. Direct photolysis with ozone generating UV also provided very high TCE conversion of up to 6kg TCE per m3 per hour. However, major quantities of phosgene and dichloroacetyle chloride (DCAC) were produced as byproducts. TCE removal using silica based photocatalyst did not result in any detectable DCAC. Only phosgene along with trace amounts of chloroform and carbon tetrachloride were identified as oxidation byproducts with silica based photocatalyst.

Gas-initiation under UV and liquid-grafting polymerization on the surface of polysulfone hollow fiber ultrafiltration membrane by dynamic method
Shen, Y. J., G. X. Wu, et al. (2005), J Environ Sci (China) 17(3): 465-8.
Abstract: Using the inner-surface of polysulfone hollow fiber ultrafiltration membranes as grafted layer, the method of gas-initiation and liquid-polymerization has been studied, which aimed to adjust the diameter of the pores in the membranes. The degree of polymerization varied with the changes of the parameters, such as irradiation time, monomer concentration, temperature and time of polymerization and soon. The results indicated that using benzophenone (BP) which is in a gaseous condition as photo-initiator, acrylamide as graft monomer, the polyacrylamide chain was grafted on the surface of membranes. After the surface membrane being modified, the water flux and retention altered, and thus it can be seen that the diameter of the pores in the membrane was altered. These experiments contribute to finding a new way to produce the hollow fiber membrane with the small pore size and are extraordinarily worth developing and studying.

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Last Modified: 8 February 2006