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      • Sol-gel-modified titanium with hydroxyapatite thin films and effect on osteoblast-like cell responses

        Kim, Hae-Won,Kim, Hyoun-Ee,Salih, Vehid,Knowles, Jonathan C. Wiley Subscription Services, Inc., A Wiley Company 2005 Journal of biomedical materials research. Part A Vol.a74 No.3

        <P>Titanium (Ti) surface was coated with hydroxyapatite (HA) films via the sol-gel method. The coating properties, such as crystallinity and surface roughness, were controlled and their effects on the osteoblast-like cell responses were investigated. The film crystallinity was controlled with different heat treatment temperatures (400, 500, and 600°C): Also the surface roughness was changed by using different heating rates (1 and 50°C/min). The obtained sol-gel films had a dense and homogeneous structure with a thickness about 1 μm. The film heat-treated at higher temperature had enhanced crystallinity (600 > 500 ≫ 400°C), while retaining similar surface roughness. When heat-treated rapidly (50°C/min), the film became quite rough, with roughness parameters being much higher (4–6 times) than that obtained at a low heating rate (1°C/min). The dissolution rate of the film decreased with increasing crystallinity (400 ≫ 500 > 600°C), and the rougher film had slightly higher dissolution rate. The attachment, proliferation, and differentiation behaviors of human osteosarcoma HOS TE85 cells were affected by the properties of the films. On the films with higher crystallinity (heat treated over 500°C), the cells attached and proliferated well and expressed alkaline phosphatase (ALP) and osteocalcin (OC) to a higher degree as compared to the poorly crystallized film (heat treated at 400°C). On the rough film, the cell attachment was enhanced, but the ALP and OC expression levels were similar as compared to the smooth films. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005</P>

      • Catalyst-free synthesis of high elongation degradable polyurethanes containing varying ratios of isosorbide and polycaprolactone: physical properties and biocompatibility.

        Park, Hyung-seok,Gong, Myoung-Seon,Knowles, Jonathan C Chapman and Hall ; Kluwer Academic Publishers 2013 Journal of materials science, Materials in medicin Vol.24 No.2

        <P>Biocompatible and biodegradable polyurethanes were prepared with fixed aliphatic diisocyanate level and varying ratios of isosorbide, and PCL diol via a simple one-shot polymerization without a catalyst. The successful synthesis of the polyurethanes was confirmed by gel permeation chromatography, H-1-nuclear magnetic resonance and Fourier transform-infrared spectroscopies and the thermal properties were determined by differential scanning calorimetry and showed glass transition temperatures of around 30-35 A degrees C. The degradation tests were performed at 37 A degrees C in phosphate buffer solution (approx. pH 7.3) and showed a mass loss of around 5 % after 12 weeks, except for the polymer with the highest isosorbide content which showed an initial rapid mass loss. The in vitro cytocompatibility test results following culture of osteoblasts on the polymer surface showed that relative cell number on all of the polyurethane films after 5 days of cultured on polymer films was lower compared to the proliferation rate on the optimized tissue culture plastic. These polymers offer significant promise due to the simplicity of the synthesis and the controlled degradation.</P>

      • Multifunctional Hybrid Nanocarrier: Magnetic CNTs Ensheathed with Mesoporous Silica for Drug Delivery and Imaging System

        Singh, Rajendra K.,Patel, Kapil D.,Kim, Jung-Ju,Kim, Tae-Hyun,Kim, Joong-Hyun,Shin, Ueon Sang,Lee, Eun-Jung,Knowles, Jonathan C.,Kim, Hae-Won American Chemical Society 2014 ACS APPLIED MATERIALS & INTERFACES Vol.6 No.4

        <P>Here we communicate the development of a novel multifunctional hybrid nanomaterial, magnetic carbon nanotubes (CNTs) ensheathed with mesoporous silica, for the simultaneous applications of drug delivery and imaging. Magnetic nanoparticles (MNPs) were first decorated onto the multiwalled CNTs, which was then layered with mesoporous silica (<I>m</I>SiO<SUB>2</SUB>) to facilitate the loading of bioactive molecules to a large quantity while exerting magnetic properties. The hybrid nanomaterial showed a high mesoporosity due to the surface-layered <I>m</I>SiO<SUB>2</SUB>, and excellent magnetic properties, including magnetic resonance imaging in vitro and in vivo. The mesoporous and magnetic hybrid nanocarriers showed high loading capacity for therapeutic molecules including drug gentamicin and protein cytochrome C. In particular, genetic molecule siRNA was effectively loaded and then released over a period of days to a week. Furthermore, the hybrid nanocarriers exhibited a high cell uptake rate through magnetism, while eliciting favorable biological efficacy within the cells. This novel hybrid multifunctional nanocarrier may be potentially applicable as drug delivery and imaging systems.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2014/aamick.2014.6.issue-4/am4056936/production/images/medium/am-2013-056936_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/am4056936'>ACS Electronic Supporting Info</A></P>

      • Phosphate Based Glasses for Hard and Soft Tissue Surgery

        Jonathan C Knowles 대한치과재료학회 2011 대한치과기재학회 학술대회 Vol.2011 No.5

        As with all glasses, phosphate based glasses offer a rich and diverse chemistry however the phosphate system offers the unique property of complete degradability. This coupled with the ability to alter the degradation rate over several orders of magnitude allow tailoring of the properties to suit a particular application. Considering the potential biomedical applications the structure of these glasses is poorly defined, but with the application of a range of advanced probes such as NMR, EXAFS and XANES, the structure is now more clearly understood. In particular doping of glasses has given an indirect way to determine the structure of the glasses. These dopants have also given rise to an understanding of the effect of trace elements on cell behaviour. More recently, developments in sol-gel synthesis have allowed compositions to be obtained, not normally attainable via traditional melt quenched routes and have also opened up the possibility of the use of phosphate based glasses for drug delivery applications.

      • SCIESCOPUS

        Novel Biodegradable and Biocompatible Poly(3‐hydroxyoctanoate)/Bacterial Cellulose Composites

        Basnett, Pooja,Knowles, Jonathan C.,Pishbin, Fatemah,Smith, Caroline,Keshavarz, Tajalli,Boccaccini, Aldo R.,Roy, Ipsita WILEY‐VCH Verlag 2012 Advanced Engineering Materials Vol.14 No.6

        <P><B>Abstract</B></P><P>Novel poly(3‐hydroxyoctanoate), P(3HO), and bacterial cellulose composites have been developed. P(3HO) is hydrophobic in nature whereas bacterial cellulose is extremely hydrophilic in nature. Therefore, homogenized bacterial cellulose has been chemically modified in order to achieve compatibility with the P(3HO) matrix. Modified bacterial cellulose microcrystals and P(3HO) have been physically blended and solvent casted into two‐dimensional composite films. Mechanical characterization shows that the Young's modulus of the P(3HO)/bacterial cellulose composites is significantly higher in comparison to the neat P(3HO) film. The melting temperature (<I>T</I><SUB>m</SUB>) of the composites is lower while the glass transition temperature (<I>T</I><SUB>g</SUB>) is higher than the neat P(3HO) film. Also, the composite film has a rougher surface topography as compared to the neat P(3HO) film. A month's in vitro degradation study has been carried out in Dulbeccos modified eagle medium and in phosphate buffer saline. The incorporation of modified bacterial cellulose microcrystal in the P(3HO) film has increased the degradability of the composite film. Finally, in vitro biocompatibility studies using human microvascular endothelial cells established the biocompatibility of the P(3HO)/bacterial cellulose microcrystal films. The cell proliferation was 50–110% higher on the P(3HO)/bacterial cellulose composites as compared to the neat P(3HO) film. Hence, in this study, for the first time, P(3HO)/bacterial cellulose composites have been developed. The addition of bacterial cellulose has resulted in properties that are highly desirable for medical applications including the development of biodegradable stents.</P>

      • Hydroxyapatite and gelatin composite foams processed via novel freeze-drying and crosslinking for use as temporary hard tissue scaffolds

        Kim, Hae-Won,Knowles, Jonathan C.,Kim, Hyoun-Ee Wiley Subscription Services, Inc., A Wiley Company 2005 Journal of biomedical materials research. Part A Vol.a72 No.2

        <P>Hydroxyapatite (HA) and gelatin composites were fabricated in a foam type via a novel freeze-drying and crosslinking technique. The morphological and mechanical properties of and in vitro cellular responses to the foams were investigated. The HA powder was added at up to 30 wt % into the gelatin solution, and the mixtures were freeze-dried and further crosslinked. The pure gelatin foam had a well-developed pore configuration with porosity and pore size of ∼90% and 400–500 μm, respectively. With HA addition, the porosity decreased and pore shape became more irregular. The HA particulates, in sizes of about 2–5 μm, were distributed within the gelatin network homogeneously and made the framework surface rougher. All the foams had high water absorption capacities, showing typical hydrogel characteristics, even though the HA addition decreased the degree of water absorption. The HA addition made the foam much stronger and stiffer (i.e., with increasing HA amount the foams sustained higher compressive stress and had higher elastic modulus in both dry and wet states). The osteoblast-like human osteosarcoma cells spread and grew actively on all the foams. The cell proliferation rate, quantified indirectly on the cells cultured on Ti discs coated with gelatin and gelatin-HA composites using MTT assay, exhibited an up-regulation with gelatin coating compared with bare Ti substrate, but a slight decrease on the composite coatings. However, the alkaline phosphatase activities expressed by the cells cultured on composites foams as well as their coatings on Ti discs were significantly enhanced compared with those on pure gelatin foam and coating. These findings suggest that the gelatin-HA composite foams have great potential for use as hard tissue regeneration scaffolds. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 72A: 136–145, 2005</P>

      • SCISCIE

        Porous scaffolds of gelatin–hydroxyapatite nanocomposites obtained by biomimetic approach: Characterization and antibiotic drug release

        Kim, Hae-Won,Knowles, Jonathan C.,Kim, Hyoun-Ee Wiley Subscription Services, Inc., A Wiley Company 2005 Journal of Biomedical Materials Research Part B Vol. No.

        <P>Gelatin–hydroxyapatite (HA) nanocomposite porous scaffolds were fabricated biomimetically, and their feasibility as a drug-delivery carrier for tissue-regeneration and wound-healing treatments was addressed. The composite sols were prepared by the precipitation of HA up to 30 wt % within a gelatin solution with the use of calcium and phosphate precursors, and the porous scaffold was obtained by casting the sols and further freeze drying. The obtained bodies were crosslinked with carbodiimide derivatives to retain chemical and thermal integrity. The apatite precipitates were observed to be a poorly crystallized carbonate-substituted HA. The nanocomposite scaffolds had porosities of ∼ 89–92% and exhibited a bimodal pore distribution, that is, the macropores (∼ 300–500 μm) of the framework structure, and micropores (∼ 0.5–1 μm) formed on the framework surface. Transmission electron microscopy (TEM) observation revealed the precipitation of highly elongated HA nanocrystals on the gelatin network. The well-developed porous structure and organized nanocomposite configurations were in marked contrast to the directly mixed gelatin–HA powder conventional composites. For drug-release tests, tetracycline, an antibiotic drug, was entrapped within the scaffold, and the drug-release profile was examined with processing parameters, such as HA amount in gelatin, crosslinking degree, and initial drug addition. The drug entrapment decreased with increasing HA amount, but increased with increasing crosslinking degree and initial drug addition. The crosslinking of the gelatin was the prerequisite to sustaining and controlling the drug releases. Compared to pure gelatin, the gelatin–HA nanocomposites had lower drug releases, because of their lower water uptake and degradation. All the nanocomposite scaffolds released drugs in proportion to the initial drug addition, suggesting their capacity to deliver drugs in a controlled manner. Based on the findings of the well-developed morphological feature and controlled drug-release profile, the gelatin–HA nanocomposite porous scaffolds are suggested to be potentially useful for hard-tissue regeneration. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005</P>

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