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Delivery of neurotrophin-3 to the cochlea using alginate beads
Noushi, F., R. T. Richardson, et al. (2005), Otol Neurotol 26(3): 528-33.
Abstract: OBJECTIVE: The aim of this study was to design a novel cochlear neurotrophin (NT) delivery system for the rescue of auditory neurons after ototoxicity-induced deafening. BACKGROUND: NT-3 is a trophic growth factor that promotes the survival of the auditory nerve and may have a potential therapeutic role in slowing neuron loss in progressive deafness, especially as an adjunct to the current cochlear implant. Beads made from alginate are biodegradable, slow release substances that can be placed at the round window or inside the cochlea. This study investigated the loading properties, release kinetics, and implantation potential of alginate beads loaded with NT-3. METHODS: Alginate beads were prepared using an ionic gelation technique and postloaded with NT-3. Release of NT-3 was measured using enzyme-linked immunosorbent assay over 5 days. Alginate beads were implanted into deafened guinea pigs for 28 days, after which survival of auditory neurons was assessed. RESULTS: Enzyme-linked immunosorbent assay studies demonstrated a 98% to 99% loading of NT-3 with a slow, partial release over 5 days in Ringer's solution. Furthermore, the addition of heparin to the delivery system modulated NT-3 release to a steadier pattern. Implantation of alginate-heparin beads in guinea pig cochleae produced minimal local tissue reaction. NT-3 loaded beads implanted at both the round window and within the scala tympani of the basal turn provided auditory neurons significant protection from degradation and apoptosis compared with unloaded beads or untreated cochleae. CONCLUSIONS: This study demonstrates alginate beads to be a safe, biodegradable and effective delivery system for NT-3 to the cochlea.

Delivery systems for small molecule drugs, proteins, and DNA: the neuroscience/biomaterial interface
Whittlesey, K. J. and L. D. Shea (2004), Exp Neurol 190(1): 1-16.
Abstract: Manipulation of cellular processes in vivo by the delivery of drugs, proteins or DNA is of paramount importance to neuroscience research. Methods for the presentation of these molecules vary widely, including direct injection (either systemic or stereotactic), osmotic pump-mediated chronic delivery, or even implantation of cells engineered to indefinitely secrete a factor of interest. Biomaterial-based delivery systems represent an alternative to more traditional approaches, with the possibility of increased efficacy. Drug-releasing biomaterials, either as injectable microspheres or as three-dimensional implants, can deliver a molecule of interest (including small molecule drugs, biologically active proteins, or DNA) over a more prolonged period of time than by standard bolus injection, avoiding the need for repeated administration. Furthermore, sustained-release systems can maintain therapeutic concentrations at a target site, thus reducing the chance for toxicity. This review summarizes applications of polymer-based delivery of small molecule drugs, proteins, and DNA specifically relevant to neuroscience research. We detail the fabrication procedures for the polymeric systems and their utility in various experimental models. The biomaterial field offers unique experimental tools with downstream clinical application for the study and treatment of neurologic disease.

Dendritic macromers as in situ polymerizing biomaterials for securing cataract incisions
Wathier, M., P. J. Jung, et al. (2004), J Am Chem Soc 126(40): 12744-5.

Density functional study of structural, electronic and vibrational properties of mg- and zn-doped tricalcium phosphate biomaterials
Yin, X., L. Calderin, et al. (2002), Biomaterials 23(20): 4155-63.
Abstract: Zn- and to a lesser extent Mg-releasing tricalcium phosphate (Zn- and Mg-TCP) have excellent bioactivities which do not exist in their parent TCP base. However, the mechanisms through which the dopants affect the properties are not known. In order to gain insight from geometrical and electronic structures and chemical bonding, ab initio density functional calculations have been performed for these materials using cluster models. The results show a distorted structure for Zn-TCP which may be related to its bioactivity, whereas no such distortion was found for TCP and Mg-TCP. The infrared spectra of these materials has been calculated, and the relationship to the structure investigated.

Dental biomaterials
Rekow, E. D. and V. P. Thompson (2000), J Biomed Mater Res 53(4): 287-8.

Dental biomaterials and the healing of dental tissue
Nakabayashi, N. (2003), Biomaterials 24(13): 2437-9.
Abstract: This paper addresses the application of new adhesive technologies to dentistry. The bonding of synthetic polymers to dentin is difficult and it has taken a long time to produce reliable methods. Success has been achieved suing a 4-methacryloyloxyethyltrimellitate anhydride/methyl methacrylate-tri-n-butyl borane system which allows the generation of a layer of hybridised dentin. This provides a pseudo-wound-healing layer that resists demineralisation and degradation, is impermeable and inhibits secondary caries and hypersensitivity.

Dental biomaterials in the 90s
Murray, G. A. (1996), J Tenn Dent Assoc 76(4): 40-4.

Dental biomaterials: status of the art, 1975-1978. Part I
Mohammed, H., J. W. Farrah, et al. (1979), Fla Dent J 50(1): 17-22.

Dental biomaterials: status of the art, 1975-1978. Part II
Mohammed, H., J. W. Farrah, et al. (1979), Fla Dent J 50(2): 19-25, 44.

Dental biomaterials: where are we and where are we going?
Bayne, S. C. (2005), J Dent Educ 69(5): 571-85.
Abstract: This article reviews the current state of the art for restorative biomaterials by examining the roles of 1) truly biological biomaterials, with respect to the "near-future" of five to ten years, 2) traditional synthetic biomaterials, and 3) performance outcomes for biomaterials. Biological biomaterials are discussed in terms of tissue engineering and stem cell research, self-assembling system opportunities, and nanotechniques or technologies. Future developments for major areas of synthetic biomaterials are considered for bonding systems, composites, VLC curing, ceramics, and cements. Performance outcomes are discussed for all biomaterials in terms of safety, efficacy, and longevity of materials.

Dental composite biomaterials
Jones, D. W. (1998), J Can Dent Assoc 64(10): 732-4.

Dental implant biomaterials
Lemons, J. E. (1990), J Am Dent Assoc 121(6): 716-9.
Abstract: Synthetic materials for surgical implant devices have evolved from the early metallic systems to a variety of material combinations and composites. Current biomaterial and biomechanical properties provide relatively optimal stable bone and soft tissue interfaces and simplified restorative treatments. Further improvements in existing systems require a continuation of the multidisciplinary approach to laboratory, experimental animal, and human clinical research.

Dental implant update on biomaterials and biomechanics
Lemons, J. E. (1983), Ala J Med Sci 20(1): 36-41.

Dental restorative biomaterials induce glutathione depletion in cultured human gingival fibroblast: protective effect of N-acetyl cysteine
Stanislawski, L., E. Soheili-Majd, et al. (2000), J Biomed Mater Res 51(3): 469-74.
Abstract: Eight biomaterials eluted from four different types of dental restorative biomaterials, that is, from glass-ionomer cement (GIC: Ketac-fil and Fuji II), resin-modified glass ionomer cement (RM-GIC: Fuji II LC and Photac-fil), composite (Z100 MP and Tetric-flow), and compomer (Compoglass F and F-2000), were studied for their cytotoxic properties in relation to glutathione (GSH) content in cultured human gingival fibroblasts. Z100 MP, Tetric-flow, and Compoglass F were less cytotoxic than the others, with a toxic concentration of 50% (TC 50) > 24% (of eluate), as determined by the MTT test. F-2000, Tetric-flow, and the other biomaterials were relatively more cytotoxic (TC 50 = 9-16%). With the exception of Z100 MP, all the biomaterials induced a depletion of cellular glutathione (GSH) that was variable depending upon the biomaterial eluates. The strongest GSH depletion was with F-2000, Fuji II, and Photac-fil. GSH depletion, with Compoglass and F-2000, was rapid-detectable after one h of cell treatment and complete within 3 h-whereas a longer period of incubation was required for the other biomaterials. Interestingly, the drug cytotoxic effects induced by all the biomaterials were prevented by cell treatment with the antioxidant N-acetylcysteine (NAC). This study provides evidence that the cytotoxic property of dental restorative biomaterials is associated with depletion of the glutathione level in gingival fibroblasts. While the molecular mechanisms of this phenomenon require further investigations, our data suggest that NAC may be useful in preventing the cellular damage induced by dental restorative biomaterials.

Deposition temperature effect on release rate of indomethacin microcrystals from microcapsules of layer-by-layer assembled chitosan and alginate multilayer films
Ye, S., C. Wang, et al. (2005), J Control Release 106(3): 319-28.
Abstract: Indomethacin (IDM) microcrystals sized 5 approximately 10 microm were directly encapsulated with nature polysaccharides chitosan (CHI) and sodium alginate (ALG) through layer-by-layer (LbL) self-assembly. Due to partial dissolution of IDM in the deposition solution, the retention of the IDM microcrystals gradually decreased with increasing deposition times and became 47.7% as 10 layers of polysaccharides formed. The release rate of the IDM from the microcapsules was monitored with UV absorbance. The half release time t(1/2) of IDM in the microcapsule increased with the layer number and the initial burst phenomenon was relieved after encapsulation. It was found that added NaCl did not affect the release rate even up to 0.5 M of its concentration, while increasing the release temperature remarkably speeded up the release process. The prolonged release of the encapsulated IDM was still observed when the aqueous release solution containing 20 vol.% ethanol. It was very significant that increasing deposition temperature from 20 to 60 degrees C reduced the release rate efficiently, owing to the increase in multilayer thickness and formation of a more perfect multilayer film. This finding provides a new and simple method to control the permeability of the LbL assembled multilayer films. Because of the biodegradability of CHI and ALG and various methods to tune the release rate, the LbL self-assembly on drug microcrystals promises high potential for encapsulation used in controlled release.

Depth profiling of peptide films with TOF-SIMS and a C60 probe
Cheng, J. and N. Winograd (2005), Anal Chem 77(11): 3651-9.
Abstract: A buckminsterfullerene ion source is employed to characterize peptide-doped trehalose thin films. The experiments are designed to utilize the unique sputtering properties of cluster ion beams for molecular depth profiling. The results show that trehalose films with high uniformity can be prepared on Si by a spin-coating technique. Bombardment of the film with C60+ results in high quality time-of-flight secondary ion mass spectrometry spectra, even during ion doses of up to 3 x 10(14) ions/cm2. This result is in contrast to atomic bombardment experiments in which the dose of incident ions must be kept below 10(12) ions/cm2 so as to retain mass spectral information. Moreover, since the films are of uniform thickness, it is possible to depth-profile through the film and into the Si substrate. This experimental protocol allows the yield of trehalose molecular equivalents and the degree of interface mixing to be evaluated in detail. When doped with a variety of small peptides up to a molecular weight of m/z 500, we find that the peptide molecular ion intensity remains stable under continuous C60+ bombardment, although some decrease in intensity is observed. The results are interpreted in terms of a model whereby the high trehalose yield and low damage depth of the C60 projectile combine to prevent damage accumulation. In general, the peptide-trehalose system provides a valuable model for evaluating the parameters that lead to effective 3-dimensional characterization of biomaterials.

Dermal fibroblasts cultured on small intestinal submucosa: Conditions for the formation of a neotissue
Cimini, M., D. R. Boughner, et al. (2005), J Biomed Mater Res A 75(4): 895-906.
Abstract: Small intestinal submucosa (SIS) is a naturally occurring, acellular biomaterial that has been used extensively as a soft tissue replacement, as a scaffold for tissue engineering, and as a substrate for the study of cells in 3D culture. The aim of this study is to define culture parameters that promote neotissue formation with the use of dermal fibroblasts and SIS. SIS sheets were seeded with dermal fibroblasts and cultured for 4 weeks. The resultant cell-scaffold composites (CSCs) were cultured with media alone, media supplemented with ascorbic acid, or fibronectin-pretreated SIS and ascorbic acid. CSCs were analyzed for cellular invasion into the scaffold, the rate of type I collagen production, MMP gelatinolytic activity, thickness, and ultrastructural morphology. CSCs treated with fibronectin and ascorbate showed an increase in Type I collagen production, no change in the MMP gelatinolytic activity, an increase in CSC thickness, and an organized neotissue on the surface of the SIS. Minimal cellular invasion was noted, suggesting that fibroblasts use the SIS as a template for neotissue growth rather than as a scaffold. These results indicate that fibronectin-treated SIS cultured with dermal fibroblasts in the presence of ascorbic acid will promote true neotissue formation for future cardiovascular tissue engineering efforts. (c) 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005.

Dermal fillers: complications and informed consent
Engelman, D. E., B. Bloom, et al. (2005), J Cosmet Laser Ther 7(1): 29-32.
Abstract: Dermal fillers are increasingly used for in-office cosmetic treatments. Although complications are rare, they can occur with any dermal filler. Such complications can lead to adverse medical, legal and economic difficulties. This article reviews the various complications most commonly seen with dermal fillers. In addition the appropriate consent prior to filler use and the legal implications of a lack of consent will be described.

Design and assessment of a tissue-engineered model of human phalanges and a small joint
Landis, W. J., R. Jacquet, et al. (2005), Orthod Craniofac Res 8(4): 303-12.
Abstract: OBJECTIVES: To develop models of human phalanges and small joints by suturing different cell-polymer constructs that are then implanted in athymic (nude) mice. DESIGN: Models consisted of bovine periosteum, cartilage, and/or tendon cells seeded onto biodegradable polymer scaffolds of either polyglycolic acid (PGA) or copolymers of PGA and poly-L-lactic acid (PLLA) or poly-epsilon-caprolactone (PCL) and PLLA. Constructs were fabricated to produce a distal phalanx, middle phalanx, or distal interphalangeal joint. SETTING AND SAMPLE POPULATION: Studies of more than 250 harvested implants were conducted at the Northeastern Ohio Universities College of Medicine. EXPERIMENTAL VARIABLE: Polymer scaffold, cell type, and implantation time were examined. OUTCOME MEASURE: Tissue-engineered specimens were characterized by histology, transmission electron microscopy, in situ hybridization, laser capture microdissection and qualitative and quantitative polymerase chain reaction analysis, magnetic resonance microscopy, and X-ray microtomography. RESULTS: Over periods to 60 weeks of implantation, constructs developed through vascularity from host mice; formed new cartilage, bone, and/or tendon; expressed characteristic genes of bovine origin, including type I, II and X collagen, osteopontin, aggrecan, biglycan, and bone sialoprotein; secreted corresponding proteins; responded to applied mechanical stimuli; and maintained shapes of human phalanges with small joints. CONCLUSION: Results give insight into construct processes of tissue regeneration and development and suggest more complete tissue-engineered cartilage, bone, and tendon models. These should have significant future scientific and clinical applications in medicine, including their use in plastic surgery, orthopaedics, craniofacial reconstruction, and teratology.

Design and function of novel osteoblast-adhesive peptides for chemical modification of biomaterials
Dee, K. C., T. T. Andersen, et al. (1998), J Biomed Mater Res 40(3): 371-7.
Abstract: Proactive, "next generation" dental/orthopedic biomaterials must be designed rationally to elicit specific, timely, and desirable responses from surrounding cells/tissues; for example, such biomaterials should support and enhance osteoblast adhesion (a crucial function for anchorage-dependent cells). In the past, integrin-binding peptides have been immobilized on substrates to partially control osteoblast adhesion; the present study focused on the design, synthesis, and bioactivity of the novel peptide sequence Lys-Arg-Ser-Arg that selectively enhances heparan sulfate-mediated osteoblast adhesion mechanisms. Osteoblast, but not endothelial cell or fibroblast, adhesion was enhanced significantly (p < 0.05) on substrates modified with Lys-Arg-Ser-Arg peptides, indicating that these peptides may be osteoblast- or bone cell specific. Blocking osteoblast cell-membrane receptors with various concentrations of soluble Arg-Gly-Asp-Ser peptides did not inhibit subsequent cell adhesion on substrates modified with Lys-Arg-Ser-Arg peptides, providing evidence that osteoblasts interact with Arg-Gly-Asp-Ser and with Lys-Arg-Ser-Arg peptides via distinct (i.e., integrin- and proteoglycan-mediated) mechanisms, each uniquely necessary for osteoblast adhesion. The present study constitutes an example of rational design/selection of bioactive peptides, confirms that osteoblast adhesion to substrates can be controlled selectively and significantly by immobilized peptides, and elucidates criteria and strategies for the design of proactive dental/orthopedic implant biomaterials.


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Last Modified: 8 February 2006
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