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Volume 8
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J. Funct. Biomater., Volume 8, Issue 3 (September 2017) – 21 articles

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8148 KiB  
Article
Biomineralization of Fucoidan-Peptide Blends and Their Potential Applications in Bone Tissue Regeneration
by Harrison T. Pajovich and Ipsita A. Banerjee
J. Funct. Biomater. 2017, 8(3), 41; https://doi.org/10.3390/jfb8030041 - 20 Sep 2017
Cited by 19 | Viewed by 8260
Abstract
Fucoidan (Fuc), a natural polysaccharide derived from brown seaweed algae, and gelatin (Gel) were conjugated to form a template for preparation of biomimetic scaffolds for potential applications in bone tissue regeneration. To the Fuc–Gel we then incorporated the peptide sequence MTNYDEAAMAIASLN (MTN) derived [...] Read more.
Fucoidan (Fuc), a natural polysaccharide derived from brown seaweed algae, and gelatin (Gel) were conjugated to form a template for preparation of biomimetic scaffolds for potential applications in bone tissue regeneration. To the Fuc–Gel we then incorporated the peptide sequence MTNYDEAAMAIASLN (MTN) derived from the E-F hand domain, known for its calcium binding properties. To mimic the components of the extracellular matrix of bone tissue, the Fuc–Gel–MTN assemblies were incubated in simulated body fluid (SBF) to induce biomineralization, resulting in the formation of β-tricalcium phosphate, and hydroxyapatite (HAp). The formed Fuc–Gel–MTN–beta–TCP/HAP scaffolds were found to display an average Young’s Modulus value of 0.32 GPa (n = 5) with an average surface roughness of 91 nm. Rheological studies show that the biomineralized scaffold exhibited higher storage and loss modulus compared to the composites formed before biomineralization. Thermal phase changes were studied through DSC and TGA analysis. XRD and EDS analyses indicated a biphasic mixture of β-tricalcium phosphate and hydroxyapatite and the composition of the scaffold. The scaffold promoted cell proliferation, differentiation and displayed actin stress fibers indicating the formation of cell-scaffold matrices in the presence of MT3C3-E1 mouse preosteoblasts. Osteogenesis and mineralization were found to increase with Fuc–Gel–MTN–beta–TCP/HAP scaffolds. Thus, we have developed a novel scaffold for possible applications in bone tissue engineering. Full article
(This article belongs to the Special Issue Biodegradable Scaffolds)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>SEM images of (<b>a</b>) fucoidan-gelatin (Fuc–Gel); (<b>b</b>) Fuc–Gel–MTNYDEAAMAIASLN (MTN); (<b>c</b>) Fuc–Gel–MTN biomineralized Beta–TCP/nano HaP after 2 weeks of growth; (<b>d</b>) Fuc–Gel–MTN-biomineralized nano HaP after 4 weeks of growth in simulated body fluid (SBF).</p> Full article ">Figure 2
<p>Comparison of FTIR spectra of each layer of the scaffold in the range of 500 and 3700 cm<sup>−1</sup> (F = fucoidan; G = Gelatin).</p> Full article ">Figure 3
<p>(<b>a</b>) XRD pattern of the dried Fuc–Gel–MTN-biomineralized Beta–TCP/nano HAp after 4 weeks of growth; (<b>b</b>) EDS spectrum of dried Fuc–Gel–MTN-biomineralized β–TCP/nano HAp after 4 weeks of growth.</p> Full article ">Figure 4
<p>Comparison of TGA curves obtained for composite scaffold (<b>a</b>) Fuc–Gel–MTN before biomineralization and (<b>b</b>) Fuc–Gel–MTN-biomineralized β–TCP/HAp; (<b>c</b>) DSC analysis of Fuc–Gel–MTN before biomineralization and (<b>d</b>) Fuc–Gel–MTN-biomineralized β–TCP/HAp.</p> Full article ">Figure 5
<p>(<b>a</b>) Force distance curves of Fuc–Gel–MTN-biomineralized β–TCP/nano HAp obtained at 5 different points on the scaffold using peak force microscopy; (<b>b</b>) AFM phase image of Fuc–Gel–MTN-biomineralized β–TCP/HAp.</p> Full article ">Figure 6
<p>Angular frequency (ω) dependence of storage (G′) and loss modulus (G″) (<b>a</b>) before and (<b>b</b>) after biomineralization of the biocomposite.</p> Full article ">Figure 7
<p>Percent Cell Viability of MC3T3-E1 cells in the presence of varying amount of scaffolds was carried out over a period of 96 h. Measurements were made after 24, 48 and 96 h using MTT assay. Each bar in the figure represents the mean of three independent studies with standard deviation (SD). Significant difference was analyzed by comparing the viability control with those of cells in the presence of scaffolds. * indicates <span class="html-italic">p</span> &lt; 0.05; ** represents <span class="html-italic">p</span> &lt; 0.01. The <span class="html-italic">p</span> values were determined by student’s <span class="html-italic">t</span>-test.</p> Full article ">Figure 8
<p>Interactions of MC3T3-E1 cells with Fuc–Gel–MTN-biomineralized β–TCP/HAp matrix showing formation of cell-scaffold matrices (<b>a</b>) in the presence of 20 μg/mL Fuc–Gel-MTN-biomineralized HAp; (<b>b</b>) in the presence of 40 μg/mL Fuc–Gel–MTN-biomineralized β–TCP/HAp. Scale bar for (<b>a</b>) = 30 μm; (<b>b</b>) = 30 μm. Arrows indicate cellular attachments.</p> Full article ">Figure 9
<p>Organization of actin stress fibers of MC3T3-E1 cells upon interacting with the scaffolds indicating that the scaffold strongly adhered to preosteoblasts in the presence of 20 μg/mL of scaffold (<b>left</b>) and in the presence of 40 μg/mL scaffold (<b>right</b>) Scale bar = 50 μm (<b>left</b>); 30 μm (<b>right</b>).</p> Full article ">Figure 10
<p>Alkaline phosphatase (ALP) activity was measured in MC3T3-E1 cells before and after incubation with the scaffolds over a period of 21 days. Values are standardized by the total amount of protein in the sample. Results are indicated as standard deviation of three experiments performed in. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, significantly different from control cells.</p> Full article ">Figure 11
<p>Alizarin S quantification using the assay carried out for MC3T3-E1 cells showing induction of osteogenesis in the presence and absence of different quantities of Fuc–Gel–MTN–beta–TCP/HAP scaffolds. Data are expressed as the mean (<span class="html-italic">n</span> = 3) with error bars indicating standard deviations. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01, significantly different from control cells.</p> Full article ">Figure 12
<p>Alizarin S staining (<b>a</b>,<b>c</b>) indicating staining and formation of calcium deposits after 7 and 21 days in the presence of 20 μg/mL of scaffold and preosteoblasts; (<b>b</b>,<b>d</b>) indicate staining and formation of calcium deposits after 7 and 21 days in the presence of 20 μg/mL of scaffold and preosteoblasts. Scale bar = 100 μm.</p> Full article ">
1444 KiB  
Article
Dental Composite Formulation Design with Bioactivity on Protein Adsorption Combined with Crack-Healing Capability
by Chen Chen, Junling Wu, Michael D. Weir, Lin Wang, Xuedong Zhou, Hockin H. K. Xu and Mary Anne S. Melo
J. Funct. Biomater. 2017, 8(3), 40; https://doi.org/10.3390/jfb8030040 - 7 Sep 2017
Cited by 14 | Viewed by 6927
Abstract
Fracture and secondary caries are the primary reasons for the failure of dental restorations. To face this omnipresent problem, we report the formulation design and synthesis of a protein-resistant dental composite composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) that also can self-repair damage and recover [...] Read more.
Fracture and secondary caries are the primary reasons for the failure of dental restorations. To face this omnipresent problem, we report the formulation design and synthesis of a protein-resistant dental composite composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) that also can self-repair damage and recover the load-bearing capability via microencapsulated triethylene glycol dimethacrylate (TEGDMA) and N,N-dihydroxy ethyl-p-toluidine (DHEPT). The bioactivity of the resulting MPC-microencapsulated TEGDMA-DHEPT was evaluated on protein adsorption through early bacterial attachment. Its mechanical properties were also investigated, including self-healing assessment. Microcapsules of poly (urea-formaldehyde) (PUF) were synthesized by incorporating a TEGDMA-DHEPT healing liquid. A set of composites that contained 7.5% of MPC, 10% of microcapsules, and without MPC/microcapsules were also prepared as controls. The two distinct characteristics of strong protein repellency and load-bearing recovery were achieved by the combined strategies. The novel dual composite with a combination of protein-repellent MPC and PUF microcapsules for restoring microcracks is a promising strategy for dental restorations to address the two main challenges of fracture and secondary caries. The new dual composite formulation design has the potential to improve the longevity of dental restorations significantly. Full article
(This article belongs to the Special Issue Journal of Functional Biomaterials: Feature Papers 2016)
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<p>Transmitting optical image of resulting poly (urea-formaldehyde) (PUF) microcapsules loaded with polymerizable TEGDMA and <span class="html-italic">N</span>,<span class="html-italic">N</span>-dihydroxy ethyl-<span class="html-italic">p</span>-toluidine (DHEPT) (an average diameter of 73 ± 31 μm).</p> Full article ">Figure 2
<p>Protein adsorption onto composite surfaces. The composite with 7.5% 2-methacryloyloxyethyl phosphorylcholine (MPC) had the lowest amount of protein adsorption, which was approximately 1/16 those of the composite control and the composite with 10% microcapsules (MCS) (<span class="html-italic">p</span> &lt; 0.05). Different letters indicate values that are significantly different from each other (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 3
<p>Representative live/dead staining images on the early attachment of oral biofilms of the disks (<b>A</b>–<b>D</b>). Live bacteria showed green, while dead bacteria showed red, and (<b>E</b>) shows the area fraction of the green staining of live bacteria coverage on composite surfaces (mean ± SD; <span class="html-italic">n</span> = 6). The composite control had much more bacterial attachment. All groups were covered with live bacteria and few dead bacteria; the images (<b>C</b>,<b>D</b>) show that the composite with incorporated MPC had noticeably fewer bacteria on the cover zone than the images of composites without MPC (<b>A</b>,<b>B</b>). Different letters in (<b>E</b>) indicate values that are significantly different from each other (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 4
<p>Mechanical properties of resin-containing microcapsules of various concentrations: (<b>A</b>) flexural strength, and (<b>B</b>) elastic modulus (mean ± SD; <span class="html-italic">n</span> = 6). The addition of up to 10% of microcapsules and/or 7.5% MPC resulted in no significant decrease in strength or the elastic modulus of the composite. Horizontal line indicates statistically similar values (<span class="html-italic">p</span> &gt; 0.5).</p> Full article ">Figure 5
<p>Fracture toughness and self-healing of a composite containing microcapsules and MPC. (<b>A</b>) Initial and post-healing fracture toughness (K<sub>IC</sub>), and (<b>B</b>) the damage recovery for K<sub>IC</sub> according to the formulation designed for each tested composite. In each plot, values with dissimilar letters are significantly different from each other (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">
3238 KiB  
Article
Evaluation of Polyethylene Glycol Diacrylate-Polycaprolactone Scaffolds for Tissue Engineering Applications
by Hari Kotturi, Alaeddin Abuabed, Haris Zafar, Elaine Sawyer, Bipin Pallipparambil, Harsha Jamadagni and Morshed Khandaker
J. Funct. Biomater. 2017, 8(3), 39; https://doi.org/10.3390/jfb8030039 - 5 Sep 2017
Cited by 20 | Viewed by 7620
Abstract
Polyethylene Glycol Diacrylate (PEGDA) tissue scaffolds having a thickness higher than 1 mm and without the presence of nutrient conduit networks were shown to have limited applications in tissue engineering due to the inability of cells to adhere and migrate within the scaffold. [...] Read more.
Polyethylene Glycol Diacrylate (PEGDA) tissue scaffolds having a thickness higher than 1 mm and without the presence of nutrient conduit networks were shown to have limited applications in tissue engineering due to the inability of cells to adhere and migrate within the scaffold. The PEGDA scaffold has been coated with polycaprolactone (PCL) electrospun nanofiber (ENF) membrane on both sides to overcome these limitations, thereby creating a functional PEGDA-PCL scaffold. This study examined the physical, mechanical, and biological properties of the PEGDA and PEGDA-PCL scaffolds to determine the effect of PCL coating on PEGDA. The physical characterization of PEGDA-PCL samples demonstrated the effectiveness of combining PCL with a PEGDA scaffold to expand its applications in tissue engineering. This study also found a significant improvement of elasticity of PEGDA due to the addition of PCL layers. This study shows that PEGDA-PCL scaffolds absorb nutrients with time and can provide an ideal environment for the survival of cells. Furthermore, cell viability tests indicate that the cell adhered, proliferated, and migrated in the PEGDA-PCL scaffold. Therefore, PCL ENF coating has a positive influence on PEGDA scaffold. Full article
(This article belongs to the Special Issue Biodegradable Scaffolds)
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<p>Schematic representation of a Polyethylene Glycol Diacrylate-Polycaprolactone (PEGDA-PCL scaffold [<a href="#B15-jfb-08-00039" class="html-bibr">15</a>]. (<b>A</b>) First syringe pump, (<b>B</b>) Glass syringe, (C) tube, (D) metallic needle, (E) two parallel wires, (F) high voltage source, (G) fixtures for holding fiber collector, (H) electrical signal controller, (I) connector to transfer electricity to wire, (J) robotic arm to transfer a mold from/to fiber collector to curing station, (K) mold for collection of fibers, (L) Second syringe pump, (M) sprayer, and (N) UV mask or mold to cure PEGDA.</p> Full article ">Figure 2
<p>(<b>a</b>) an integrated electrospun-UV photo polymerization-machine; (<b>b</b>) twelve layers of aligned PCL electrospun nanofiber deposited on the acrylic mold; fabricated samples; (<b>c</b>) PEGDA and (<b>d</b>) PEGDA-PCL. The thickness of each scaffolds is 1.5 mm.</p> Full article ">Figure 3
<p>SEM images of the top surface of (<b>a</b>) PEGDA and (<b>b</b>) PEGDA-PCL scaffolds. PEGDA-PCL samples show a higher amount of artifacts compared to PEGDA. SEM images of paraffin embedded and sectioned scaffolds: (<b>c</b>) PEGDA and (<b>d</b>) PEGDA-PCL. Red arrows in (<b>d</b>) show the presence of PCL ENF in PEGDA. The lengths of the scales bar in (<b>c</b>, <b>d</b>) are 200 micrometers.</p> Full article ">Figure 4
<p>The difference of load vs. displacement behavior between a PEGDA and PEGDA-PCL scaffold during the static compression tests.</p> Full article ">Figure 5
<p>Rheological tests were performed on the hydrogel using the Malvern CVO-100 rheometer at 5% strain rate at frequency 1 Hz. (<b>a</b>) shear stress vs. strain and (<b>b</b>) complex modulus with respect to time were found from the experiment.</p> Full article ">Figure 6
<p>Dulbecco’s Modified Eagle’s medium (DMEM) absorption rate with respect time for PEGDA and PEGDA-PCL scaffolds. Note: * <span class="html-italic">p</span> &lt; 0.05 (compared to PEGDA).</p> Full article ">Figure 7
<p>A confocal microscopy image from the top to the bottom surface of PEGDA and PEGDA-PCL scaffold with and without cells after 14 days of cell culture. The blue dots represent cells embedded in PEGDA and PEGDA-PCL scaffolds with DAPI (4’,6-diamidino-2-phenylindole) stained nucleus. The length of the scale bar in each image is 100 microns.</p> Full article ">Figure 7 Cont.
<p>A confocal microscopy image from the top to the bottom surface of PEGDA and PEGDA-PCL scaffold with and without cells after 14 days of cell culture. The blue dots represent cells embedded in PEGDA and PEGDA-PCL scaffolds with DAPI (4’,6-diamidino-2-phenylindole) stained nucleus. The length of the scale bar in each image is 100 microns.</p> Full article ">Figure 8
<p>Cell attachment with fiber in PEGDA-PCL scaffold (<b>B</b>) after 14 days of cell culture. White arrows point to cells attached to fiber. Panel (<b>A</b>) represents PEGDA-PCL without cells. The length of the scale bar in the image is 25 microns.</p> Full article ">Figure 9
<p>Liver-derived hepatoma cells attached to 12 layers of PCL nanofiber (<b>BF</b> and <b>CF</b>) sandwiching the PEGDA scaffold; (<b>BS</b> and <b>CS)</b> represent cells growing embedded in PEGDA; (<b>AF</b> and <b>AS</b>) are control scaffolds without cells. White arrows point to cells. All scaffolds were incubated for 7 and 14 days. Images were taken using a Leica light microscope at 100× total magnification. The length of the scale bar in each image is 100 microns.</p> Full article ">Figure 10
<p>Haemotoxylin and Eosin (H&amp;E) staining of PEGDA-PCL scaffolds with GS5 cells (<b>B</b>) after 7 days. Black arrows in (<b>B</b>) point to cells; (<b>A)</b> is control scaffold without any cells. Leica light microscope at 400× magnification. The length of the scale bar in each image is 100 microns.</p> Full article ">Figure 11
<p>Increase in cell number on PEGDA-PCL scaffold with time. GS5 cell Viability after 7, 14 and 21 days on PEGDA and PEGDA-PCL scaffolds using alamarBlue<sup>®</sup> assay. Our results indicate that cells remain viable in our scaffolds. Values are mean ± SOE of triplicates. In the figure, * <span class="html-italic">p</span> &lt; 0.05 (compared to Day 0) and + <span class="html-italic">p</span> &lt; 0.05 (compared to PEGDA for the same day).</p> Full article ">Figure 12
<p>Schematic to produce 3D scaffold using electrospun nanofiber (ENF) membranes.</p> Full article ">
2239 KiB  
Article
Bio-Corrosion of Magnesium Alloys for Orthopaedic Applications
by Emily K. Brooks and Mark T. Ehrensberger
J. Funct. Biomater. 2017, 8(3), 38; https://doi.org/10.3390/jfb8030038 - 1 Sep 2017
Cited by 34 | Viewed by 7581
Abstract
Three Mg alloys, Mg–1.34% Ca–3% Zn (MCZ), Mg–1.34% Ca–3% Zn–0.2% Sr (MCZS), and Mg–2% Sr (MS), were examined to understand their bio-corrosion behavior. Electrochemical impedance spectroscopy and polarization scans were performed after 6 days of immersion in cell culture medium, and ion release [...] Read more.
Three Mg alloys, Mg–1.34% Ca–3% Zn (MCZ), Mg–1.34% Ca–3% Zn–0.2% Sr (MCZS), and Mg–2% Sr (MS), were examined to understand their bio-corrosion behavior. Electrochemical impedance spectroscopy and polarization scans were performed after 6 days of immersion in cell culture medium, and ion release and changes in media pH were tracked over a 28 day time period. Scanning electron microscopy (SEM) of alloy microstructure was performed to help interpret the results of the electrochemical testing. Results indicate that corrosion resistance of the alloys is as follows: MCZ > MCZS > MS. Full article
(This article belongs to the Special Issue Metallic Biomaterials)
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<p>Backscattered SEM images of the MCZ (<b>a</b>), MCZS (<b>b</b>), and MS (<b>c</b>) alloys after polishing. Elemental mapping of the imaged area was completed (see <a href="#jfb-08-00038-f002" class="html-fig">Figure 2</a>). Regions marked A, B, C, D, and E represent the areas where composition was analyzed using EDS (energy dispersive X-ray spectroscopy). Results of the EDS analysis are presented in <a href="#jfb-08-00038-t001" class="html-table">Table 1</a>.</p> Full article ">Figure 2
<p>Distribution of alloying elements in MCZ, MCZS, and MS as determined by elemental mapping. Original backscatter SEM images of the areas that were mapped for each alloy are displayed in <a href="#jfb-08-00038-f001" class="html-fig">Figure 1</a>.</p> Full article ">Figure 3
<p>Trends in pH of the test electrolyte measured at each media exchange every 48 h over the 28 day immersion period. Results are plotted as mean ±1 standard deviation. The dotted line represents the pH of the fresh CCM (cell culture medium) substituted into the chambers during the media exchanges.</p> Full article ">Figure 4
<p>Cumulative ion release over the 28 day immersion period as measured by ICP-MS. Plotted data represent the sum of released elements each media exchange.</p> Full article ">Figure 5
<p>Cumulative ion release over the 28 day immersion period as measured by ICP-MS. The data display the release of individual elements for MCZ (<b>a</b>), MCZS (<b>b</b>), and MS (<b>c</b>).</p> Full article ">Figure 6
<p>Representative polarization scans of MCZ (<b>a</b>), MCZS (<b>b</b>), and MS (<b>c</b>) after 6 days of immersion in the cell culture medium.</p> Full article ">Figure 7
<p>Representative Nyquist plots of MCZ (<b>a</b>), MCZS (<b>b</b>), and MS (<b>c</b>) after 6 days of immersion in the cell culture medium.</p> Full article ">Figure 8
<p>The equivalent circuit model used to fit EIS data from the three alloys generated after 6 days of immersion. Abbreviations are as follows: R<sub>S</sub>, solution resistance; CPE<sub>1</sub>, double layer capacitance; R<sub>1</sub>, resistance related to initial metallic corrosion; CPE<sub>2</sub>, pseudo-capacitance; R<sub>2</sub>, resistance to discharge an intermediate; L, an inductor; R<sub>3</sub>, resistance related to the inductor.</p> Full article ">Figure 9
<p>The surface of MCZ (<b>a</b>), MCZS (<b>b</b>), and MS (<b>c</b>) after 28 days of immersion in cell culture medium. The field width of view for the images is 6 mm.</p> Full article ">
562 KiB  
Brief Report
Sujiaonori-Derived Algal Biomaterials Inhibit Allergic Reaction in Allergen-Sensitized RBL-2H3 Cell Line and Improve Skin Health in Humans
by Nlandu Roger Ngatu, Mamoru Tanaka, Mitsunori Ikeda, Masataka Inoue, Sakiko Kanbara and Sayumi Nojima
J. Funct. Biomater. 2017, 8(3), 37; https://doi.org/10.3390/jfb8030037 - 29 Aug 2017
Cited by 4 | Viewed by 6427
Abstract
Sujiaonori, a river alga growing in the Kochi prefecture, Japan, contains several bioactive compounds such as sulfated polysaccharides (ulvans), ω-3 fatty acids, and vitamins. Dietary intake of this alga-based supplement has been reported to increase circulatory adiponectin, a salutary hormone that is reported [...] Read more.
Sujiaonori, a river alga growing in the Kochi prefecture, Japan, contains several bioactive compounds such as sulfated polysaccharides (ulvans), ω-3 fatty acids, and vitamins. Dietary intake of this alga-based supplement has been reported to increase circulatory adiponectin, a salutary hormone that is reported to be associated with healthy longevity and prevents a number of cardiovascular and metabolic disorders. This report highlights the anti-allergic and skin health enhancing effects of Sujiaonori-derived ulvan (Tosalvan) and supplement, respectively. RBL-2H3 cell line was used to investigate the anti-allergic effect of algal SP through the evaluation of β-hexosaminidase activity. Algal sulfated polysaccharides or SP (Tosalvan, Yoshino SP) were extracted from powders of dried alga samples provided by local food manufacturers. Report on the effect of daily dietary intake of Sujiaonori-based supplement on skin health is part of a four-week clinical investigation that, in comparison with a supplement made of 70% corn starch powder and 30% spinach powder mixture (twice 3 g daily), explore the beneficial effects of Sujiaonori algal biomaterial (SBM; 3 g taken twice daily) on cardiovascular, gastrointestinal and skin health in a sample of Japanese women. Transepidermal water loss (TEWL) was the skin health marker used in this study and was measured with the use of a corneometer. Significant reduction of β-hexosaminidase activity was observed in Tosalvan and Yoshino SP-treated cells (vs. control; p < 0.05), whereas dietary intake of SBM markedly reduced TEWL level after four weeks of supplementation, as compared to baseline TEWL (p < 0.001). Additionally, SBM improved TEWL better than the control product (p < 0.001). Findings contained in this report suggest that Sujiaonori-derived Tosalvan and Yoshino SP have anti-allergic potential and that the dietary intake of SBM has a beneficial effect on skin health. Full article
(This article belongs to the Special Issue Functional Materials for Healthcare)
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<p>Inhibition of allergen-challenged RBL-2H3 cell activation and release of β-hexosaminidase by Tosalvan from Sujiaonori and Yoshino SP.</p> Full article ">Figure 2
<p>Transepidermal water loss (TEWL; g/m<sup>2</sup>-h) according to the supplementation group (N = 29).</p> Full article ">
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Article
Mn2+-ZnSe/ZnS@SiO2 Nanoparticles for Turn-on Luminescence Thiol Detection
by Mohammad S. Yazdanparast, William R. Jeffries, Eric R. Gray and Emily J. McLaurin
J. Funct. Biomater. 2017, 8(3), 36; https://doi.org/10.3390/jfb8030036 - 23 Aug 2017
Cited by 4 | Viewed by 7137
Abstract
Biological thiols are antioxidants essential for the prevention of disease. For example, low levels of the tripeptide glutathione are associated with heart disease, cancer, and dementia. Mn2+-doped wide bandgap semiconductor nanocrystals exhibit luminescence and magnetic properties that make them attractive for [...] Read more.
Biological thiols are antioxidants essential for the prevention of disease. For example, low levels of the tripeptide glutathione are associated with heart disease, cancer, and dementia. Mn2+-doped wide bandgap semiconductor nanocrystals exhibit luminescence and magnetic properties that make them attractive for bimodal imaging. We found that these nanocrystals and silica-encapsulated nanoparticle derivatives exhibit enhanced luminescence in the presence of thiols in both organic solvent and aqueous solution. The key to using these nanocrystals as sensors is control over their surfaces. The addition of a ZnS barrier layer or shell produces more stable nanocrystals that are isolated from their surroundings, and luminescence enhancement is only observed with thinner, intermediate shells. Tunability is demonstrated with dodecanethiol and sensitivities decrease with thin, medium, and thick shells. Turn-on nanoprobe luminescence is also generated by several biological thiols, including glutathione, N-acetylcysteine, cysteine, and dithiothreitol. Nanoparticles prepared with different ZnS shell thicknesses demonstrated varying sensitivity to glutathione, which allows for the tuning of particle sensitivity without optimization. The small photoluminescence response to control amino acids and salts indicates selectivity for thiols. Preliminary magnetic measurements highlight the challenge of optimizing sensors for different imaging modalities. In this work, we assess the prospects of using these nanoparticles as luminescent turn-on thiol sensors and for MRI. Full article
(This article belongs to the Special Issue Magnetic Nanoparticle Design for Medical Diagnosis and Therapy)
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<p>(<b>A</b>) Energy level diagram describing the Mn<sup>2+</sup> luminescence process. Following excitation from the ground state to the excitonic states, energy is rapidly transferred to the Mn<sup>2+</sup> ion. The resulting luminescence is due to the <sup>4</sup>T<sub>1</sub> → <sup>6</sup>A<sub>1</sub> spin-forbidden transition, and is therefore long-lived. (<b>B</b>) UV-vis absorption and photoluminescence (PL) spectra of Mn<sup>2+</sup>:ZnSe nanocrystals (NCs) illustrating the large Stokes shift present in these materials. (<b>C</b>) Photograph of a solution of orange-emitting Mn<sup>2+</sup>:ZnSe/ZnS NCs under UV light.</p> Full article ">Figure 2
<p>PL spectra of Mn<sup>2+</sup>:ZnSe/ZnS NCs suspended in chloroform with: (<b>A</b>) thin, (<b>B</b>) medium, and (<b>C</b>) thick ZnS shells in the presence of increasing amounts of dodecanethiol (DDT). Insets: corresponding plots of normalized PL (PL change) with increasing thiol. The increase in PL in the presence of DDT is large for samples with medium shells and thin shells, whereas the change in PL in the thick shell sample is negligible.</p> Full article ">Figure 3
<p>PL spectra of Mn<sup>2+</sup>:ZnSe/ZnS@SiO<sub>2</sub> NPs with medium ZnS shells encapsulated in silica suspended in phosphate-buffered saline (PBS) with successive addition of 1 mM (<b>A</b>) dithiothreitol (DTT), (<b>B</b>) L-cysteine (CYS), and (<b>C</b>) N-acetylcysteine (NAC). Insets: corresponding plots of normalized PL (PL change) with increasing thiol.</p> Full article ">Figure 4
<p>(<b>A</b>) PL spectra of Mn<sup>2+</sup>:ZnSe/ZnS@SiO<sub>2</sub> NPs with medium ZnS shells suspended in PBS with successive addition of 10 mM L-glutathione (GSH). As the concentration of GSH increases from 0–25 µM, the Mn<sup>2+</sup> PL also increases. (<b>B</b>) PL spectra of Mn<sup>2+</sup>:ZnSe/ZnS@SiO<sub>2</sub> NPs with thick ZnS shells suspended in PBS with successive addition of 10 mM GSH. The Mn<sup>2+</sup> PL increases as [GSH] approaches ~10 µM, and quickly levels off. Insets: corresponding plots of normalized PL (PL change) with increasing thiol. The medium shell sample shows linear PL restoration prior to plateauing at 37 µM. The thick shell sample shows nearly immediate stagnant PL response, with no significant change over a range of 9–420 µM.</p> Full article ">Figure 5
<p>(<b>A</b>) Scatter plot of normalized Mn<sup>2+</sup>:ZnSe/ZnS@SiO<sub>2</sub> PL vs analyte concentration for glutathione (GSH), glycine (GLY), MnCl<sub>2</sub>, and lysine (LYS). (<b>B</b>) PL response of NP solutions in the presence of various analytes. Relative intensities were obtained by averaging the PL response as a function of concentration. Multiple regression analysis results indicate that all control analyte PL intensities were significantly less than GSH, NAC, and DTT.</p> Full article ">
2101 KiB  
Article
Correlation and Comparison of Cortical and Hippocampal Neural Progenitor Morphology and Differentiation through the Use of Micro- and Nano-Topographies
by Sharvari Sathe, Xiang Quan Chan, Jing Jin, Erik Bernitt, Hans-Günther Döbereiner and Evelyn K.F. Yim
J. Funct. Biomater. 2017, 8(3), 35; https://doi.org/10.3390/jfb8030035 - 12 Aug 2017
Cited by 7 | Viewed by 7559
Abstract
Neuronal morphology and differentiation have been extensively studied on topography. The differentiation potential of neural progenitors has been shown to be influenced by brain region, developmental stage, and time in culture. However, the neurogenecity and morphology of different neural progenitors in response to [...] Read more.
Neuronal morphology and differentiation have been extensively studied on topography. The differentiation potential of neural progenitors has been shown to be influenced by brain region, developmental stage, and time in culture. However, the neurogenecity and morphology of different neural progenitors in response to topography have not been quantitatively compared. In this study, the correlation between the morphology and differentiation of hippocampal and cortical neural progenitor cells was explored. The morphology of differentiated neural progenitors was quantified on an array of topographies. In spite of topographical contact guidance, cell morphology was observed to be under the influence of regional priming, even after differentiation. This influence of regional priming was further reflected in the correlations between the morphological properties and the differentiation efficiency of the cells. For example, neuronal differentiation efficiency of cortical neural progenitors showed a negative correlation with the number of neurites per neuron, but hippocampal neural progenitors showed a positive correlation. Correlations of morphological parameters and differentiation were further enhanced on gratings, which are known to promote neuronal differentiation. Thus, the neurogenecity and morphology of neural progenitors is highly responsive to certain topographies and is committed early on in development. Full article
(This article belongs to the Special Issue Journal of Functional Biomaterials: Feature Papers 2016)
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<p>Neurons and astrocytes show a range of morphologies on different topographies and also show inherent differences based on progenitor source: (<b>a</b>) immunofluorescence images of cortical mNPC-derived neurons and astrocytes on the 14 topographies. Scale bar = 50 µm; (<b>b</b>) immunofluorescence images (from [<a href="#B10-jfb-08-00035" class="html-bibr">10</a>] with permission from John Wiley and Sons) of hippocampal mNPC-derived neurons and astrocytes on the 14 topographies. Scale bar = 50 µm. Green: neurons, red: astrocytes, blue: nuclei. Topographies are listed in <a href="#jfb-08-00035-t001" class="html-table">Table 1</a>. Boxes show schematic representation of underlying topography and its alignment (not to scale). Representative phase contrast images of differentiated cells on topography are presented in <a href="#app1-jfb-08-00035" class="html-app">Figure S1i–l</a>.</p> Full article ">Figure 2
<p>Morphological parameters of interest: the number of extensions (neurites for neurons or projections for astrocytes) from the cell center, the soma area (the area of the main cell body), the extension length, and the number of branches per extension.</p> Full article ">Figure 3
<p>Hippocampal cells show longer extension lengths. Graphs depict average length of the longest neurite per neuron derived (<b>a</b>) cortical NPCs; (<b>b</b>) hippocampal NPCs; and the average length of the longest projection per astrocyte derived from (<b>c</b>) cortical NPCs and (<b>d</b>) hippocampal NPCs; one-way ANOVA: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01; (<b>e</b>) comparison of extension lengths of differentiated cortical and hippocampal mNPCs on the same topographies. Two-way ANOVA: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001, ns: no significant difference. All data are represented as data ± SEM, <span class="html-italic">N</span> = 3 biological replicates.</p> Full article ">Figure 4
<p>Cortical mNPC-derived astrocytes show a high number of extensions from the cell center: graphs depict average number of neurites per neuron derived from (<b>a</b>) cortical NPCs; (<b>b</b>) hippocampal NPCs; and average number of projections per astrocyte derived from (<b>c</b>) cortical NPCs and (<b>d</b>) hippocampal NPCs. One-way ANOVA: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001; (<b>e</b>) Comparison of differentiated cortical and hippocampal mNPCs on the same topographies with respect to the number of neurites per neuron and projections per astrocyte. Two-way ANOVA: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001, ns- no significant difference. All data are represented as data ± SEM, <span class="html-italic">N</span> = 3 biological replicates.</p> Full article ">Figure 5
<p>Hippocampal mNPC-derived cells show fewer branches per extension than cortical mNPC-derived cells. Graphs depict average branches per neurite per neuron derived from (<b>a</b>) cortical NPCs with topography 12 showing no branches on neuritis; (<b>b</b>) hippocampal NPCs; and average branches per projection per astrocyte derived from (<b>c</b>) cortical NPCs and (<b>d</b>) hippocampal NPC. One-way ANOVA: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001; (<b>e</b>) comparison of the number of branches per neurite per neuron and the number of branches per projection per astrocyte on the same topographies derived from cortical and hippocampal mNPCs. Two-way ANOVA: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001, ns- no significant difference. All data are represented as data ± SEM, <span class="html-italic">N</span> = 3 biological replicates.</p> Full article ">Figure 6
<p>Hippocampal mNPC-derived astrocytes have very large soma areas. Graphs depict average soma areas for neurons derived from (<b>a</b>) cortical NPCs; (<b>b</b>) hippocampal NPCs; and for astrocytes derived from (<b>c</b>) cortical NPCs and (<b>d</b>) hippocampal NPCs. One-way ANOVA: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001. (<b>e</b>) Comparison of the soma areas of neurons and astrocytes on the same topographies derived from cortical and hippocampal mNPCs. Two-way ANOVA: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001, ns: no significant difference. All data are represented as data ± SEM, <span class="html-italic">N</span> = 3 biological replicates.</p> Full article ">Figure 7
<p>Cortical and hippocampal mNPC neuron differentiation efficiencies and their correlations with morphological parameters. Graphs depict neuronal differentiation efficiency for (<b>a</b>) cortical mNPCs, (<b>b</b>) hippocampal mNPCs, and astrocyte differentiation efficiency for (<b>c</b>) cortical mNPCs, and (<b>d</b>) hippocampal mNPCs. One-way ANOVA: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001. All data is represented as data ± SEM. (<b>e</b>) Heat map showing the correlation coefficients of neuronal and astrocyte differentiation on the 14 patterns with each measured morphological parameter on the corresponding patterns. Correlation coefficients were also calculated separately for cells differentiated on gratings patterns. Colour indicates the intensity of correlation as shown in the legend in the top left corner. Left: cortical cells. Right: hippocampal cells. <span class="html-italic">N</span> = 3 biological replicates.</p> Full article ">Figure 8
<p>Typical cell morphologies and correlations to differentiation. Typical morphological characteristics of differentiated cortical and hippocampal cells are illustrated alongside immunofluorescence images of typical cells (green: neurons, red: astrocytes, blue: nuclei. Scale bar = 20 μm). Labels indicate relative morphological peculiarities. Relations between morphological parameters and efficiency of differentiation into specific cell types are indicated in boxes below the illustrations.</p> Full article ">
1870 KiB  
Article
Collective Migration of Lens Epithelial Cell Induced by Differential Microscale Groove Patterns
by Chunga Kwon, Youngjun Kim and Hojeong Jeon
J. Funct. Biomater. 2017, 8(3), 34; https://doi.org/10.3390/jfb8030034 - 9 Aug 2017
Cited by 8 | Viewed by 6440
Abstract
Herein, a micro-patterned cell adhesive surface is prepared for the future design of medical devices. One-dimensional polydimethylsiloxane (PDMS) micro patterns were prepared by a photolithography process. We investigated the effect of microscale topographical patterned surfaces on decreasing the collective cell migration rate. PDMS [...] Read more.
Herein, a micro-patterned cell adhesive surface is prepared for the future design of medical devices. One-dimensional polydimethylsiloxane (PDMS) micro patterns were prepared by a photolithography process. We investigated the effect of microscale topographical patterned surfaces on decreasing the collective cell migration rate. PDMS substrates were prepared through soft lithography using Si molds fabricated by photolithography. Afterwards, we observed the collective cell migration of human lens epithelial cells (B-3) on various groove/ridge patterns and evaluated the migration rate to determine the pattern most effective in slowing down the cell sheet spreading speed. Microgroove patterns were variable, with widths of 3, 5, and 10 µm. After the seeding, time-lapse images were taken under controlled cell culturing conditions. Cell sheet borders were drawn in order to assess collective migration rate. Our experiments revealed that the topographical patterned surfaces could be applied to intraocular lenses to prevent or slow the development of posterior capsular opacification (PCO) by delaying the growth and spread of human lens epithelial cells. Full article
(This article belongs to the Special Issue Journal of Functional Biomaterials: Feature Papers 2016)
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<p>Schematic illustration of the fabrication process of patterned polydimethylsiloxane (PDMS). The master pattern of PDMS mold process using SU-8 photoresist and subsequent generation of the PDMS replication stamp.</p> Full article ">Figure 2
<p>(<b>a</b>) Cell seeding procedure. PDMS block is covered on the patterned surface to prevent from the cell seeding point. (<b>b</b>) After PDMS block is removed, the cells are placed on the pattern for 15 min for cell adhesion. (<b>c</b>) The cell migration rates were measured from starting point every 24 h.</p> Full article ">Figure 3
<p>(<b>a</b>) Scanning electronic microscopy and (<b>b</b>) Immunofluorescence images of B-3 on various surfaces. Cells on r3g5, r5g5, r5g3. r5g10, r10g5, and non-patterned surface acted as control. Blue, Green, and Red fluorescence represents nucleus, F-actin, and vinculin, respectively. Scale bars indicate (<b>a</b>) 50 µm and (<b>b</b>) 20 µm.</p> Full article ">Figure 4
<p>Elongation index. Elongation parameter is evaluated by dividing cell length into width. The different values indicate circular or linear cell shape (n = 10). Data expressed as mean ±SD. <span class="html-italic">p</span> &lt; 0.001 versus control.</p> Full article ">Figure 5
<p>Migration rates of B-3 for 4 days. (<b>a</b>) The cell migrations at different days are traced. Control group of the cell migration rate (left) and r3g5 group (right) from day 0 to day 4 and the cell migrations on day 2 (bottom), respectively. (<b>b</b>) The cell migration rates of B-3 on different types of pattern. Scale bars indicate 100 µm. Data represent the mean ±SD of three independent experiments. <span class="html-italic">p</span> &lt; 0.001 versus control.</p> Full article ">Figure 6
<p>Cell proliferation rates of different surfaces on day 1 (white), day 3 (light gray), and day 5 (black) after the seeding. The absorbance was read at 450 nm by a spectrophotometer microplate reader. Data represent the mean ±SD of three independent experiments. <span class="html-italic">p</span> &lt; 0.001 versus control.</p> Full article ">
250 KiB  
Review
Immunological Responses to Total Hip Arthroplasty
by Kenny Man, Lin-Hua Jiang, Richard Foster and Xuebin B Yang
J. Funct. Biomater. 2017, 8(3), 33; https://doi.org/10.3390/jfb8030033 - 1 Aug 2017
Cited by 35 | Viewed by 8059
Abstract
The use of total hip arthroplasties (THA) has been continuously rising to meet the demands of the increasingly ageing population. To date, this procedure has been highly successful in relieving pain and restoring the functionality of patients’ joints, and has significantly improved their [...] Read more.
The use of total hip arthroplasties (THA) has been continuously rising to meet the demands of the increasingly ageing population. To date, this procedure has been highly successful in relieving pain and restoring the functionality of patients’ joints, and has significantly improved their quality of life. However, these implants are expected to eventually fail after 15–25 years in situ due to slow progressive inflammatory responses at the bone-implant interface. Such inflammatory responses are primarily mediated by immune cells such as macrophages, triggered by implant wear particles. As a result, aseptic loosening is the main cause for revision surgery over the mid and long-term and is responsible for more than 70% of hip revisions. In some patients with a metal-on-metal (MoM) implant, metallic implant wear particles can give rise to metal sensitivity. Therefore, engineering biomaterials, which are immunologically inert or support the healing process, require an in-depth understanding of the host inflammatory and wound-healing response to implanted materials. This review discusses the immunological response initiated by biomaterials extensively used in THA, ultra-high-molecular-weight polyethylene (UHMWPE), cobalt chromium (CoCr), and alumina ceramics. The biological responses of these biomaterials in bulk and particulate forms are also discussed. In conclusion, the immunological responses to bulk and particulate biomaterials vary greatly depending on the implant material types, the size of particulate and its volume, and where the response to bulk forms of differing biomaterials are relatively acute and similar, while wear particles can initiate a variety of responses such as osteolysis, metal sensitivity, and so on. Full article
(This article belongs to the Special Issue Orthopaedic Biomaterials, Implants and Devices)
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1347 KiB  
Review
Potential New Non-Invasive Therapy Using Artificial Oxygen Carriers for Pre-Eclampsia
by Hidenobu Ohta, Maiko Kaga, Heng Li, Hiromi Sakai, Kunihiro Okamura and Nobuo Yaegashi
J. Funct. Biomater. 2017, 8(3), 32; https://doi.org/10.3390/jfb8030032 - 30 Jul 2017
Cited by 10 | Viewed by 6914
Abstract
The molecular mechanisms of pre-eclampsia are being increasingly clarified in animals and humans. With the uncovering of these mechanisms, preventive therapy strategies using chronic infusion of adrenomedullin, vascular endothelial growth factor-121 (VEGF-121), losartan, and sildenafil have been proposed to block narrow spiral artery [...] Read more.
The molecular mechanisms of pre-eclampsia are being increasingly clarified in animals and humans. With the uncovering of these mechanisms, preventive therapy strategies using chronic infusion of adrenomedullin, vascular endothelial growth factor-121 (VEGF-121), losartan, and sildenafil have been proposed to block narrow spiral artery formation in the placenta by suppressing related possible factors for pre-eclampsia. However, although such preventive treatments have been partly successful, they have failed in ameliorating fetal growth restriction and carry the risk of possible side-effects of drugs on pregnant mothers. In this study, we attempted to develop a new symptomatic treatment for pre-eclampsia by directly rescuing placental ischemia with artificial oxygen carriers (hemoglobin vesicles: HbV) since previous data indicate that placental ischemia/hypoxia may alone be sufficient to lead to pre-eclampsia through up-regulation of sFlt-1, one of the main candidate molecules for the cause of pre-eclampsia. Using a rat model, the present study demonstrated that a simple treatment using hemoglobin vesicles for placental ischemia rescues placental and fetal hypoxia, leading to appropriate fetal growth. The present study is the first to demonstrate hemoglobin vesicles successfully decreasing maternal plasma levels of sFlt-1 and ameliorating fetal growth restriction in the pre-eclampsia rat model (p < 0.05, one-way ANOVA). In future, chronic infusion of hemoglobin vesicles could be a potential effective and noninvasive therapy for delaying or even alleviating the need for Caesarean sections in pre-eclampsia. Full article
(This article belongs to the Special Issue Blood Substitutes: Evolution and Future Applications)
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<p>The safety and placental transfer of hemoglobin vesicles (HbV) to fetus in pregnancy. (<b>a</b>) Time course of the gains in body weights of pregnant mother rats before and after daily repeated infusions (DRI) of HbV or saline for 7 days at a dose rate of 2 mL/kg/day (<span class="html-italic">n</span> = 5 for each group; value: average ± s.d.). The weights of fetuses (<b>b</b>) and the placentas (<b>c</b>) after 7 days’ DRI of HbV or saline (<span class="html-italic">n</span> = 5 for each group; value: average ± s.d.). (<b>d</b>) Tissue distributions of 125I-HbV at 12 h after administration to pregnant rats. Rats received a single injection of 125I-HbV from the tail vein at a dose of 1400 mg/kg. Twelve hours after injection, each organ was collected. (<span class="html-italic">n</span> = 5 for each group; value: average ± s.d.).</p> Full article ">Figure 2
<p>Effects of hemoglobin vesicle (HbV) infusion on maternal blood pressure and sFlt-1/sEng production in pregnant rats. (<b>a</b>) Chronological changes in systolic blood pressure during pregnancy in saline (control), NG-nitro-<span class="html-small-caps">l</span>-arginine methyl ester (<span class="html-small-caps">l</span>-NAME)-only treated and <span class="html-small-caps">l</span>-NAME + HbV treated pregnant rats. Closed circles, saline control pregnant rats; open circles, <span class="html-small-caps">l</span>-NAME-only treated pregnant rats; closed triangles, <span class="html-small-caps">l</span>-NAME + HbV treated pregnant rats. The data for each group are expressed as mean values ± s.e. (<span class="html-italic">n</span> = 5). Significant difference between control and <span class="html-small-caps">l</span>-NAME-only treated rats or <span class="html-small-caps">l</span>-NAME + HbV treated rats was observed (* <span class="html-italic">p</span> &lt; 0.05, two-way ANOVA, Dunette); (<b>b</b>)The plasma sFlt-1 levels in <span class="html-small-caps">l</span>-NAME-only treated rats were significantly higher compared with those in saline control pregnant rats or <span class="html-small-caps">l</span>-NAME + HbV treated rats; (<b>c</b>)There was no statistical significance in the plasma sEng among the three groups. Data are expressed as mean ± s.e. (* <span class="html-italic">p</span> &lt; 0.05, one-way ANOVA, Dunette).</p> Full article ">Figure 3
<p>Effects of hemoglobin vesicle (HbV) infusion on placental hypoxia in pregnant rats. Hypoxic-inducible factor 1α (HIF-1α) (brown signal) shows stronger signal activity in the labyrinth and spongiotrophoblast of the <span class="html-small-caps">l</span>-NAME-only treated group (<b>b,e</b>) compared with that of the saline control group (<b>a</b>,<b>d</b>) or the <span class="html-small-caps">l</span>-NAME + HbV treated group (<b>c</b>,<b>f</b>). Arrows in (<b>b</b>) indicate representative HIF-1α positive cells (dark brown cells). Scale bar: 300 µm. Quantification of the HIF-1α-positive cells in the labyrinth (<b>g</b>) and spongiotrophoblast (<b>h</b>). Western blot analysis of HIF-1α in the placental tissues from saline, <span class="html-small-caps">l</span>-NAME, and <span class="html-small-caps">l</span>-NAME + HbV treated pregnant rats (<b>i</b>).</p> Full article ">Figure 4
<p>Effects of hemoglobin vesicle (HbV) infusion on fetal hypoxia. Photon flux (p/s/cm<sup>2</sup>/sr) from the heterozygous Rosa 26::luc fetuses is displayed according to the scale bar at the right side. Compared to the basal state of saline injection (<b>a</b>), 60 s exposures show that light emission increased after an acute HbV injection (<b>b</b>). Quantification of the HIF-1α-positive cells in the cortex (<b>c</b>) and hippocampus (<b>d</b>). Data are expressed as mean ± s.e. (* <span class="html-italic">p</span> &lt; 0.05, one-way ANOVA, Dunette). Maternal <span class="html-small-caps">l</span>-NAME injection induced fetal brain hypoxia, as indicated by more extensive HIF-1α positive staining at the cortex and hippocampus in fetal brain compared to the same areas of fetal brains from saline or <span class="html-small-caps">l</span>-NAME + HbV treated mothers. Note that HbV attenuated <span class="html-small-caps">l</span>-NAME-induced fetal brain hypoxia.</p> Full article ">Figure 5
<p>Effects of hemoglobin vesicle (HbV) infusion on fetal brain and body growth under hypoxic conditions. The hippocampus of G21 fetuses from the pregnant rats treated with saline (<b>a</b>, <span class="html-italic">n</span> = 5), <span class="html-small-caps">l</span>-NAME (<b>b</b>, <span class="html-italic">n</span> = 5), or <span class="html-small-caps">l</span>-NAME + HbV (<b>c</b>, <span class="html-italic">n</span> = 5) are shown. The glial fibrillary acidic protein (GFAP) positive staining in the hippocampus of fetuses (<b>b</b>) from <span class="html-small-caps">l</span>-NAME treated mothers was stronger compared with those from the saline treated mothers (<b>a</b>) or <span class="html-small-caps">l</span>-NAME + HbV treated mothers (<b>c</b>). This indicated that maternal <span class="html-small-caps">l</span>-NAME injection induced fetal brain astrogliosis and HbV reduced the <span class="html-small-caps">l</span>-NAME-induced fetal brain damage. Quantification of the GFAP-positive area in the hippocampus (<b>g</b>). Data are expressed as mean ± s.e. (* <span class="html-italic">p</span> &lt; 0.05, one-way ANOVA, Dunette). The number of NeuN-positive cells in the hippocampus of fetuses (<b>e</b>) from <span class="html-small-caps">l</span>-NAME treated mothers was smaller compared with that in the saline treated mothers (<b>d</b>) or <span class="html-small-caps">l</span>-NAME + HbV treated mothers (<b>f</b>). This indicated that maternal <span class="html-small-caps">l</span>-NAME injection induced neural damage in the fetal brain while HbV reduced the <span class="html-small-caps">l</span>-NAME-induced fetal brain damage. Quantification of the NeuN-positive cells in the hippocampus (<b>h</b>). Data are expressed as mean ± s.e. (* <span class="html-italic">p</span> &lt; 0.05, one-way ANOVA, Dunette). The weight gains of rat fetuses (<b>i</b>) and the placentas (<b>j</b>) after chronic HbV or saline infusion at a dose rate of 2 mL/kg/day (<span class="html-italic">n</span> = 5 for each group; value: average ± s.e.) for 7 days. Note that HbV rescued the fetal and placental weights in <span class="html-small-caps">l</span>-NAME + HbV treated groups compared those in <span class="html-small-caps">l</span>-NAME-only treated groups. Scale bar: 100 µm.</p> Full article ">
12584 KiB  
Article
Effect of a Particulate and a Putty-Like Tricalcium Phosphate-Based Bone-grafting Material on Bone Formation, Volume Stability and Osteogenic Marker Expression after Bilateral Sinus Floor Augmentation in Humans
by Christine Knabe, Doaa Adel Khattab, Esther Kluk, Rainer Struck and Michael Stiller
J. Funct. Biomater. 2017, 8(3), 31; https://doi.org/10.3390/jfb8030031 - 29 Jul 2017
Cited by 8 | Viewed by 8030
Abstract
This study examines the effect of a hyaluronic acid (HyAc) containing tricalcium phosphate putty scaffold material (TCP-P) and of a particulate tricalcium phosphate (TCP-G) graft on bone formation, volume stability and osteogenic marker expression in biopsies sampled 6 months after bilateral sinus floor [...] Read more.
This study examines the effect of a hyaluronic acid (HyAc) containing tricalcium phosphate putty scaffold material (TCP-P) and of a particulate tricalcium phosphate (TCP-G) graft on bone formation, volume stability and osteogenic marker expression in biopsies sampled 6 months after bilateral sinus floor augmentation (SFA) in 7 patients applying a split-mouth design. 10% autogenous bone chips were added to the grafting material during surgery. The grain size of the TCP granules was 700 to 1400 µm for TCP-G and 125 to 250 µm and 500 to 700 µm (ratio 1:1) for TCP-P. Biopsies were processed for immunohistochemical analysis of resin-embedded sections. Sections were stained for collagen type I (Col I), alkaline phosphatase (ALP), osteocalcin (OC) and bone sialoprotein (BSP). Furthermore, the bone area and biomaterial area fraction were determined histomorphometrically. Cone-beam CT data recorded after SFA and 6 months later were used for calculating the graft volume at these two time points. TCP-P displayed more advantageous surgical handling properties and a significantly greater bone area fraction and smaller biomaterial area fraction. This was accompanied by significantly greater expression of Col I and BSP and in osteoblasts and osteoid and a less pronounced reduction in grafting volume with TCP-P. SFA using both types of materials resulted in formation of sufficient bone volume for facilitating stable dental implant placement with all dental implants having been in function without any complications for 6 years. Since TCP-P displayed superior surgical handling properties and greater bone formation than TCP-G, without the HyAc hydrogel matrix having any adverse effect on bone formation or graft volume stability, TCP-P can be regarded as excellent grafting material for SFA in a clinical setting. The greater bone formation observed with TCP-P may be related to the difference in grain size of the TCP granules and/or the addition of the HyAc. Full article
(This article belongs to the Special Issue Biodegradable Scaffolds)
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<p>Two-dimensional radiographic image generated from the secondary cone beam CT acquired directly after SFA showing of a cross section through the augmented sinus floor (red) as well as the osseous anatomical structures of the native sinus floor (blue). This image was generated by merging the data sets of the primary and secondary cone-beam CTs. Sagittal view of the, left-sided maxillary sinus, patient 5.</p> Full article ">Figure 2
<p>Two-dimensional radiographic image generated from the tertiary cone-beam CT acquired at implant placement 6 months after SFA showing of a cross section through grafted area after the 6 months healing period (green) as well as the osseous anatomical structures of the native sinus floor (blue). This image was generated by merging the data sets of the primary and tertiary cone-beam CTs in combination with superimposing the image of the secondary cone beam CT (light grey). Sagittal view of the left-sided maxillary sinus, patient 5.</p> Full article ">Figure 3
<p>Decrease (%) in grafting volume observed 6 months after sinus floor augmentation with TCP-putty and TCP granules in 7 individual patients.</p> Full article ">Figure 4
<p>Graph depicting the mean values and 95% confidence interval (CI) for the decrease in grafting volume 6 months after SFA using CEROS<sup>®</sup>-TCP-putty (TCP-P) and CEROS<sup>®</sup>-TCP-granules (TCP-G).</p> Full article ">Figure 5
<p>Histomicrograph of resin embedded biopsy stained immunohistochemically for osteocalcin after deacrylation. The biopsy was sampled 6 months after augmentation of the sinus floor with TCP-G (B = bone, FM = fibrous matrix of the osteogenic mesenchym, TCP-G—residual TCP particles displaying a scalloped morphology). Undecalcified sawed section counterstained with hematoxylin. Bar = 2000 µm.</p> Full article ">Figure 6
<p>Histomicrograph of resin embedded biopsy stained immunohistochemically for osteocalcin after deacrylation. The biopsy was sampled 6 months after SFA with TCP-P (B = bone, FM = fibrous matrix, TCP-P = residual TCP particles of the putty scaffold material. The smaller grain size of these particles compared to the TCP-G material is evident. Undecalcified sawed section counterstained with hematoxylin. Bar = 2000 µm.</p> Full article ">Figure 7
<p>Histomicrographs of resin embedded biopsies sampled 6 months after SFA with TCP-P or TCP-G stained immunohistochemically for the osteogenic markers bone sialoprotein (<b>a</b>,<b>b</b>), osteocalcin (<b>c</b>,<b>d</b>), type I collagen (<b>e</b>,<b>f</b>), alkaline phosphatase (<b>g</b>,<b>h</b>) after deacrylation: (<b>a</b>) Immunodetection of bone sialoprotein in sawed section of biopsy sampled 6 months after SFA floor with TCP-P. Intense staining of osteoblasts, which have migrated into the degrading TCP-P particles is visible (white arrows), which exhibit excellent bone (B)-particle contact, i.e., bone-bonding behavior. Furthermore, bone formation within the degrading particles is visible (black arrow) as well as strong staining of the mineralizing but not yet fully mineralized bone matrix (black arrowhead) in contact with the TCP-P particles; (<b>b</b>) Immunodetection of bone sialoprotein in sawed section of biopsy sampled 6 months after SFA with TCP-G. Intense staining of osteoblasts, which have migrated into the degrading TCP-G particles is visible (white arrows), which exhibit excellent bone particle contact, i.e., bone-bonding behavior (yellow arrowheads). Furthermore, mild staining of the osteoid (black arrows) and mineralizing but not yet fully mineralized bone matrix, i.e., osteogenic mesenchym, (black arrowheads) in contact with the TCP-G particles is present; (<b>c</b>) Immunodetection of osteocalcin in hard tissue section of biopsy sampled 6 months after SFA floor with TCP-P. TCP-P-particles are visible, which exhibit excellent bone particle contact, (yellow arrowheads). Furthermore, strong staining of the osteoid (black arrows) and mineralizing but not yet fully mineralized bone matrix (black arrowheads) in contact with the TCP-P particles is present; (<b>d</b>) Immunodetection of osteocalcin in section of biopsy sampled 6 months after SFA floor with TCP-G. TCP-G-particles are present, which exhibit partial bone particle contact (yellow arrowheads). Osteoid (black arrows) and mineralizing but not yet fully mineralized bone matrix (black arrowheads) without any positive staining for osteocalcin are visible. In addition, osteoid with mild osteocalcin expression (white arrowheads) lining marrow spaces is visible. Undecalcified sawed section counterstained with hematoxylin. Bar = 200 µm; (<b>e</b>) Immunodetection of type I collagen in section of biopsy sampled 6 months after SFA floor with TCP-P. Intense staining of osteoblasts, which have migrated into the degrading TCP-P particles is visible (white arrows), which exhibit excellent bone-particle contact (yellow arrowheads). Furthermore, strong staining of the mineralizing but not yet fully mineralized bone matrix (black arrowheads) as well as of the fully mineralized bone matrix (green arrow) in contact with the TCP-P particles is present. Bar = 100 µm; (<b>f</b>) Immunodetection of type I collagen in section of biopsy sampled form TCP-G site. TCP-G particles are present, which exhibit partial bone particle contact (yellow arrowheads). Furthermore, moderate staining of the osteoid (black arrows) and mineralizing but not yet fully mineralized bone matrix (black arrowhead) in contact with the TCP-G particles is visible. This is in addition to mild staining of the mineralized matrix (green arrows); (<b>g</b>) Immunodetection of alkaline phosphatase in section of biopsy sampled from TCP-P site. TCP-P particles are visible, which exhibit excellent bone particle contact (yellow arrowheads). Furthermore, strong staining of the osteoblasts (white arrows) and of the mineralizing but not yet fully mineralized bone matrix (black arrowheads) in contact with the TCP-P particles is present; (<b>h</b>) Immunodetection of alkaline phosphatase in sawed section of biopsy sampled 6 months after SFA floor with TCP-G. TCP-G particles are present, which exhibit excellent bone particle contact (yellow arrowheads). Strong staining of the mineralizing but not yet fully mineralized bone matrix (black arrowheads) in contact with the TCP-G particles is visible. Bar = 200 µm; (<b>i</b>) histomicrograph of positive control section of experimental fracture site stained for TRAP activity enzymhistochemically. A TRAP-positive multinucleated osteoclast (black arrow) is visible. Bar = 20µm.</p> Full article ">Figure 7 Cont.
<p>Histomicrographs of resin embedded biopsies sampled 6 months after SFA with TCP-P or TCP-G stained immunohistochemically for the osteogenic markers bone sialoprotein (<b>a</b>,<b>b</b>), osteocalcin (<b>c</b>,<b>d</b>), type I collagen (<b>e</b>,<b>f</b>), alkaline phosphatase (<b>g</b>,<b>h</b>) after deacrylation: (<b>a</b>) Immunodetection of bone sialoprotein in sawed section of biopsy sampled 6 months after SFA floor with TCP-P. Intense staining of osteoblasts, which have migrated into the degrading TCP-P particles is visible (white arrows), which exhibit excellent bone (B)-particle contact, i.e., bone-bonding behavior. Furthermore, bone formation within the degrading particles is visible (black arrow) as well as strong staining of the mineralizing but not yet fully mineralized bone matrix (black arrowhead) in contact with the TCP-P particles; (<b>b</b>) Immunodetection of bone sialoprotein in sawed section of biopsy sampled 6 months after SFA with TCP-G. Intense staining of osteoblasts, which have migrated into the degrading TCP-G particles is visible (white arrows), which exhibit excellent bone particle contact, i.e., bone-bonding behavior (yellow arrowheads). Furthermore, mild staining of the osteoid (black arrows) and mineralizing but not yet fully mineralized bone matrix, i.e., osteogenic mesenchym, (black arrowheads) in contact with the TCP-G particles is present; (<b>c</b>) Immunodetection of osteocalcin in hard tissue section of biopsy sampled 6 months after SFA floor with TCP-P. TCP-P-particles are visible, which exhibit excellent bone particle contact, (yellow arrowheads). Furthermore, strong staining of the osteoid (black arrows) and mineralizing but not yet fully mineralized bone matrix (black arrowheads) in contact with the TCP-P particles is present; (<b>d</b>) Immunodetection of osteocalcin in section of biopsy sampled 6 months after SFA floor with TCP-G. TCP-G-particles are present, which exhibit partial bone particle contact (yellow arrowheads). Osteoid (black arrows) and mineralizing but not yet fully mineralized bone matrix (black arrowheads) without any positive staining for osteocalcin are visible. In addition, osteoid with mild osteocalcin expression (white arrowheads) lining marrow spaces is visible. Undecalcified sawed section counterstained with hematoxylin. Bar = 200 µm; (<b>e</b>) Immunodetection of type I collagen in section of biopsy sampled 6 months after SFA floor with TCP-P. Intense staining of osteoblasts, which have migrated into the degrading TCP-P particles is visible (white arrows), which exhibit excellent bone-particle contact (yellow arrowheads). Furthermore, strong staining of the mineralizing but not yet fully mineralized bone matrix (black arrowheads) as well as of the fully mineralized bone matrix (green arrow) in contact with the TCP-P particles is present. Bar = 100 µm; (<b>f</b>) Immunodetection of type I collagen in section of biopsy sampled form TCP-G site. TCP-G particles are present, which exhibit partial bone particle contact (yellow arrowheads). Furthermore, moderate staining of the osteoid (black arrows) and mineralizing but not yet fully mineralized bone matrix (black arrowhead) in contact with the TCP-G particles is visible. This is in addition to mild staining of the mineralized matrix (green arrows); (<b>g</b>) Immunodetection of alkaline phosphatase in section of biopsy sampled from TCP-P site. TCP-P particles are visible, which exhibit excellent bone particle contact (yellow arrowheads). Furthermore, strong staining of the osteoblasts (white arrows) and of the mineralizing but not yet fully mineralized bone matrix (black arrowheads) in contact with the TCP-P particles is present; (<b>h</b>) Immunodetection of alkaline phosphatase in sawed section of biopsy sampled 6 months after SFA floor with TCP-G. TCP-G particles are present, which exhibit excellent bone particle contact (yellow arrowheads). Strong staining of the mineralizing but not yet fully mineralized bone matrix (black arrowheads) in contact with the TCP-G particles is visible. Bar = 200 µm; (<b>i</b>) histomicrograph of positive control section of experimental fracture site stained for TRAP activity enzymhistochemically. A TRAP-positive multinucleated osteoclast (black arrow) is visible. Bar = 20µm.</p> Full article ">Figure 8
<p>Histogram illustrating the results of the histomorphometric evaluation (mean values) of the area fraction of the newly formed bony trabeculae, of the biomaterial/particle area fraction and the area fraction of the bone marrow spaces in biopsies sampled bilaterally from seven patients 6 months after SFA with TCP-P and TCP-G.</p> Full article ">Figure 9
<p>Histogram depicting the results of the histomorphometric analysis (mean values ± SEM) of the area fraction of the newly formed bony trabeculae and of the particle (residual biomaterial) area fraction in biopsies obtained bilaterally from seven patients 6 months after SFA with TCP-P and TCP-G. Asterisks indicate statistical significance.</p> Full article ">Figure 10
<p>Representative panoramic radiograph showing dental implants without any marginal periimplant bone loss (yellow arrows) 6 years after implant placement in the grafted sinus floors (TCP-P, left; TCP-G, right).</p> Full article ">
676 KiB  
Article
A Cell-Adhesive Plasma Polymerized Allylamine Coating Reduces the In Vivo Inflammatory Response Induced by Ti6Al4V Modified with Plasma Immersion Ion Implantation of Copper
by Uwe Walschus, Andreas Hoene, Maciej Patrzyk, Silke Lucke, Birgit Finke, Martin Polak, Gerold Lukowski, Rainer Bader, Carmen Zietz, Andreas Podbielski, J. Barbara Nebe and Michael Schlosser
J. Funct. Biomater. 2017, 8(3), 30; https://doi.org/10.3390/jfb8030030 - 20 Jul 2017
Cited by 14 | Viewed by 6846
Abstract
Copper (Cu) could be suitable to create anti-infective implants based on Titanium (Ti), for example by incorporating Cu into the implant surface using plasma immersion ion implantation (Cu-PIII). The cytotoxicity of Cu might be circumvented by an additional cell-adhesive plasma polymerized allylamine film [...] Read more.
Copper (Cu) could be suitable to create anti-infective implants based on Titanium (Ti), for example by incorporating Cu into the implant surface using plasma immersion ion implantation (Cu-PIII). The cytotoxicity of Cu might be circumvented by an additional cell-adhesive plasma polymerized allylamine film (PPAAm). Thus, this study aimed to examine in vivo local inflammatory reactions for Ti6Al4V implants treated with Cu-PIII (Ti-Cu), alone or with an additional PPAAm film (Ti-Cu-PPAAm), compared to untreated implants (Ti). Successful Cu-PIII and PPAAm treatment was confirmed with X-ray Photoelectron Spectroscopy. Storage of Ti-Cu and Ti-Cu-PPAAm samples in double-distilled water for five days revealed a reduction of Cu release by PPAAm. Subsequently, Ti, Ti-Cu and Ti-Cu-PPAAm samples were simultaneously implanted into the neck musculature of 24 rats. After 7, 14 and 56 days, peri-implant tissue was retrieved from 8 rats/day for morphometric immunohistochemistry of different inflammatory cells. On day 56, Ti-Cu induced significantly stronger reactions compared to Ti (tissue macrophages, antigen-presenting cells, T lymphocytes) and to Ti-Cu-PPAAm (tissue macrophages, T lymphocytes, mast cells). The response for Ti-Cu-PPAAm was comparable with Ti. In conclusion, PPAAm reduced the inflammatory reactions caused by Cu-PIII. Combining both plasma processes could be useful to create antibacterial and tissue compatible Ti-based implants. Full article
(This article belongs to the Special Issue Metallic Biomaterials)
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<p>X-ray photoelectron depth profile analysis of a polished Ti6Al4V plate surface treated with plasma immersion ion implantation of copper (Ti-Cu).</p> Full article ">Figure 2
<p>Cu concentrations released from Ti6Al4V plates treated with plasma immersion ion implantation of copper (Ti-Cu, dark bars) or Ti6Al4V plates treated with plasma immersion ion implantation of copper and an additional plasma polymerized allylamine film (Ti-Cu-PPAAm, gray bars) in 2 mL double distilled water over time. Bars represent the mean and whiskers the standard deviation of <span class="html-italic">n</span> = 3 different samples for each series.</p> Full article ">Figure 3
<p>Number of (<b>a</b>) CD68<sup>+</sup> total monocytes and pro-inflammatory macrophages; (<b>b</b>) CD163<sup>+</sup> anti-inflammatory tissue macrophages; (<b>c</b>) MHC-II<sup>+</sup> antigen-presenting cells; (<b>d</b>) total T lymphocytes; (<b>e</b>) mast cells; and (<b>f</b>) activated natural killer cells in the peri-implant tissue of Lewis rats after i.m. implantation of unmodified Ti6Al4V plates (Ti, white boxes), Ti6Al4V plates treated with plasma immersion ion implantation of copper (Ti-Cu, light gray boxes) or Ti6Al4V plates treated with plasma immersion ion implantation of copper and an additional plasma polymerized allylamine film (Ti-Cu-PPAAm, dark gray boxes) after 7, 14 and 56 days. Boxes represent median and interquartile range and whiskers minimum and maximum values; <span class="html-italic">p</span>-values indicate differences in pairwise comparison by non-parametric Wilcoxon signed rank test.</p> Full article ">
2181 KiB  
Article
Pilot Study Using a Chitosan-Hydroxyapatite Implant for Guided Alveolar Bone Growth in Patients with Chronic Periodontitis
by Fabiola Vaca-Cornejo, Héctor Macías Reyes, Sergio H. Dueñas Jiménez, Ricardo A. Llamas Velázquez and Judith M. Dueñas Jiménez
J. Funct. Biomater. 2017, 8(3), 29; https://doi.org/10.3390/jfb8030029 - 19 Jul 2017
Cited by 11 | Viewed by 6699
Abstract
Periodontitis is an infectious and inflammatory disease associated with significant loss of alveolar crest and soft tissue attached to the teeth. Chitosan and hydroxyapatite are biomaterials used for bone tissue repair because of their biodegradability and biocompatibility in nature. The present study evaluated [...] Read more.
Periodontitis is an infectious and inflammatory disease associated with significant loss of alveolar crest and soft tissue attached to the teeth. Chitosan and hydroxyapatite are biomaterials used for bone tissue repair because of their biodegradability and biocompatibility in nature. The present study evaluated the effects of chitosan (CH) in combination with hydroxyapatite (HAP) to promote alveolar bone growth. A chitosan implant mixed with hydroxyapatite was implanted into the affected area of 9 patients suffering chronic periodontitis. Patients were evaluated through X-ray images and a millimetric slide over a one year period. The application of CH/HAP produced an average alveolar bone growth of 5.77 mm (±1.87 mm). At the onset of the study, the dental pocket exhibited a depth level (DPDL) of 8.66 mm and decreased to 3.55 mm one year after the implant. Tooth mobility grade was 2.44 mm at the onset and 0.8 mm at the end of the study with a significant difference of p < 0.001. Moreover, the bone density in the affected areas was similar to the density of the bone adjacent to it. This result was confirmed with the software implant viewer from Anne Solutions Company. In conclusion, the CH/HAP implant promoted alveolar bone growth in periodontitis patients. Full article
(This article belongs to the Special Issue Biodegradable Scaffolds)
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<p>Pocket depth (mm) in patients with chronic periodontitis. Data are expressed as mean ± standard deviation (X ± SD). Left bar shows the pocket depth (mm) in periodontitis patients measured at the onset of the study, and the right bar exhibits the pocket at the end of the study. Data were analyzed by Student’s <span class="html-italic">t</span>-test. This change has a statistically significant difference of <span class="html-italic">p</span> &lt; 0.001 (<a href="#jfb-08-00029-f001" class="html-fig">Figure 1</a>).</p> Full article ">Figure 2
<p>Tooth mobility grade (mm) in periodontitis patients. Data is shown as mean ± SD and the results were compared at the onset and at the end of the study. Mobility grade in pp at the onset of study was of 2.44 mm ± 0.1757 and at the end of the end of the evaluation it decreased to 0.8889 ± 0.2003 mm (gray bar) with a statistically significant difference of <span class="html-italic">p</span> &lt; 0.001 evaluated by Student’s <span class="html-italic">t</span>-test. SD: Standard Deviation.</p> Full article ">Figure 3
<p>Maximum alveolar bone growth (mm) in periodontitis patients treated with the CH/HAP implant. Periodontitis patients treated with the CH/HAP implant were evaluated after the first month of treatment and subsequently every three months post-implant (pi), for a period of twelve months. Note that in patient 5, the highest level of alveolar bone growth (10 mm) occurred at twelve months pi (green bar) and some patients (1, 2, 3, 4 and 7) presented different alveolar bone growth after a period of six months pi. CH: Chitosan; HAP: Hydroxyapatite.</p> Full article ">Figure 4
<p>Alveolar bone size (mm) in local chronic periodontitis patients. The left bar represents the alveolar bone lost at the onset of the clinical study and the right bar represents the alveolar bone growth recovery at the end of the study. Data are expressed as the mean ± SD. The bone size defect at the onset of the study was larger than at the end of study with a statistically significant difference of * <span class="html-italic">p</span> &lt; 0.001 (Student’s <span class="html-italic">t</span>-test).</p> Full article ">Figure 5
<p>X-rays of one patient with local chronic periodontitis, at the onset of the CH/HAP implant and at the end of the treatment (12 months). The arrows show the alveolar bone growth (<b>c</b>) compared to the oral defect before the implant of the biomaterial (<b>d</b>). In (<b>a</b>) a considerable loss of mucous tissue is observed in the oral defect. In (<b>b</b>) a repair of mucous tissue on the implanted oral defect is observed. CH: Chitosan; HAP: Hydroxyapatite.</p> Full article ">Figure 6
<p>Histologic analysis of the biomaterial of CH/HAP taken three months after the implant in periodontitis patients. The biomaterial was stained with hematoxylin-eosin. In (<b>a</b>), the biomaterial is indicated by the arrow; the microphotography was taken with a 10× objective; in (<b>b</b>), the microphotography was taken at 40× amplification, where the collagen can be observed surrounding the biomaterial (pink color). The fibroblasts are stained in purple and are fusiform in shape, osteoblasts are purple rounded cells and they are infiltrated into biomaterial, these histological characteristics are indicated by the arrows; in (<b>c</b>), the biomaterial is stained in dark purple and the osteoblasts can be appreciated by the arrow. CH: Chitosan; HAP: Hydroxyapatite.</p> Full article ">Figure 7
<p>Image in 3D of one patient after the treatment was complimented. Bone density in tooth 37 in a treated patient is illustrated in the top left panel, five cuts were made every 2 mm, following the shape of the dental arch in order to evaluate the amount of bone by the vestibular side. Three measures were taken, one at the crest level, another in the middle zone and the third one at the apical level. The density is given in Hounsfield units. In the upper right panel a mandibular axial cut is illustrated. The 5 lines are shown as a reference to indicate the zone where the cuts were made. In the lower left panel, a 3D reconstruction of the oral cavity is shown. The lower right panel illustrates a panoramic lateral mandibular reconstruction of 20 mm wide.</p> Full article ">
3004 KiB  
Article
The Feasibility and Functional Performance of Ternary Borate-Filled Hydrophilic Bone Cements: Targeting Therapeutic Release Thresholds for Strontium
by Kathleen MacDonald, Richard B. Price and Daniel Boyd
J. Funct. Biomater. 2017, 8(3), 28; https://doi.org/10.3390/jfb8030028 - 14 Jul 2017
Cited by 3 | Viewed by 6218
Abstract
We examine the feasibility and functionality of hydrophilic modifications to a borate glass reinforced resin composite; with the objective of meeting and maintaining therapeutic thresholds for Sr release over time, as a potential method of incorporating antiosteoporotic therapy into a vertebroplasty material. Fifteen [...] Read more.
We examine the feasibility and functionality of hydrophilic modifications to a borate glass reinforced resin composite; with the objective of meeting and maintaining therapeutic thresholds for Sr release over time, as a potential method of incorporating antiosteoporotic therapy into a vertebroplasty material. Fifteen composites were formulated with the hydrophilic agent hydroxyl ethyl methacrylate (HEMA, 15, 22.5, 30, 37.5 or 45 wt% of resin phase) and filled with a borate glass (55, 60 or 65 wt% of total cement) with known Sr release characteristics. Cements were examined with respect to degree of cure, water sorption, Sr release, and biaxial flexural strength over 60 days of incubation in phosphate buffered saline. While water sorption and glass degradation increased with increasing HEMA content, Sr release peaked with the 30% HEMA compositions, scanning electron microscope (SEM) imaging confirmed the surface precipitation of a Sr phosphate compound. Biaxial flexural strengths ranged between 16 and 44 MPa, decreasing with increased HEMA content. Degree of cure increased with HEMA content (42 to 81%), while no significant effect was seen on setting times (209 to 263 s). High HEMA content may provide a method of increasing monomer conversion without effect on setting reaction, providing sustained mechanical strength over 60 days. Full article
(This article belongs to the Special Issue Recent Advances in Bioactive Glasses)
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<p>(<b>a</b>)Cement working time, and (<b>b</b>) cement setting time, significant differences are marked with “*” (<span class="html-italic">p</span> &lt; 0.05) or “**” (<span class="html-italic">p</span> &lt; 0.01).</p> Full article ">Figure 2
<p>Representative Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectra collected on unset cement pastes (red and pink traces for paste one and two respectively), and set cement samples (blue trace) of cement composition A1 (15% hydroxyl ethyl methacrylate (HEMA), 55% glass).</p> Full article ">Figure 3
<p>Degree of conversion measured through ATR-FTIR analysis with standard deviation, showing increased degree of conversion as the HEMA content increased, (<span class="html-italic">p</span> &lt; 0.01, unless otherwise noted).</p> Full article ">Figure 4
<p>Cement biaxial flexural strength (MPa) at 1, 7, 30 and 60 days incubation, with standard deviations.</p> Full article ">Figure 5
<p>Cement weight gains over 60 days of incubation in phosphate buffered saline (PBS) (with standard deviations), and weight loss from max (calculated as difference between maximum weight gain, and final weight gain at 60 days) as a measure of glass filler loss.</p> Full article ">Figure 6
<p>Sr release from cements into PBS in mg/L, relative to (A) in vitro osteoblast activation threshold [<a href="#B6-jfb-08-00028" class="html-bibr">6</a>]; (B) serum Sr concentration reported in the Treatment of Peripheral Osteoporosis (TROPOS) study (10.8 mg/L) [<a href="#B4-jfb-08-00028" class="html-bibr">4</a>] and (C) in vitro osteoclast inhibition threshold [<a href="#B15-jfb-08-00028" class="html-bibr">15</a>].</p> Full article ">Figure 7
<p>Ion release efficiency as % of initial elemental loading for B and Sr demonstrating preferential release of B from the cements.</p> Full article ">Figure 8
<p>Representative scanning electron microscope images of resin surfaces for (<b>a</b>) control unreacted surface of group E, 60% glass cement (<b>b</b>) Group E 60% glass cement, 1 day of incubation in PBS; (<b>c</b>) group E 60% glass, 60 days of incubation in PBS; (<b>d</b>) group A 60% glass, 1 day of incubation in PBS; and (<b>e</b>) group A, 60% glass 60 days of incubation in PBS, demonstrating the development of a strontium rich surface precipitate during incubation.</p> Full article ">Figure 9
<p>Schematic of two paste resin fabrication, all compositions represented in weight percentage.</p> Full article ">
567 KiB  
Article
Orthodontic Metallic Lingual Brackets: The Dark Side of the Moon of Bond Failures?
by Maria Francesca Sfondrini, Paola Gandini, Andrea Gioiella, Feng Xiao Zhou and Andrea Scribante
J. Funct. Biomater. 2017, 8(3), 27; https://doi.org/10.3390/jfb8030027 - 7 Jul 2017
Cited by 7 | Viewed by 6435
Abstract
Lingual orthodontics, among both young and adult patients, increased in popularity during last years. The purposes of the present investigation were to evaluate the shear bond strength (SBS) values and Adhesive Remnant Index (ARI) scores of different lingual brackets compared with a vestibular [...] Read more.
Lingual orthodontics, among both young and adult patients, increased in popularity during last years. The purposes of the present investigation were to evaluate the shear bond strength (SBS) values and Adhesive Remnant Index (ARI) scores of different lingual brackets compared with a vestibular control bracket. One hundred bovine teeth were extracted and embedded in resin blocks. Four different lingual brackets (Idea, Leone; STB, Ormco; TTR, RMO; 2D, Forestadent) and a vestibular control bracket (Victory, 3M) were bonded to the bovine enamel surfaces and subsequently shear tested to failure utilizing a Universal Testing Machine. SBS values were measured. A microscopic evaluation was performed to obtain ARI scores. Statistical analysis was performed at a statistically significant level of p < 0.05 to determine significant differences in SBS values and ARI Scores. No statistically significant variations in SBS were reported among the different groups. Conversely, significant differences were shown in ARI scores among the various groups. Clinical relevance of the present study is that orthodontists can expect similar resistance to debonding forces from lingual appliances as with vestibular brackets. Full article
(This article belongs to the Special Issue Metallic Biomaterials)
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<p>Different bracket bases. Lingual bracket bases: (<b>A)</b> Idea (Leone; Sesto Fiorentino, Italy); (<b>B)</b> STB (Ormco; Glendora, CA, USA); (<b>C)</b> TTR (RMO; Denver, CO, USA ); (<b>D)</b> 2D (Forestadent; Pforzheim, Germany); Vestibular bracket base: (<b>E</b>) Victory (3M Unitek; Monrovia, CA, USA).</p> Full article ">Figure 2
<p>Box plot of shear bond strength (MPa) of the different groups. The band inside the box represents the second quartile. The bottom and top of the box are the first and third quartiles. The ends of the whiskers represent the minimum and maximum. No significant differences were reported among the various groups.</p> Full article ">
1279 KiB  
Article
Color Stability of New Esthetic Restorative Materials: A Spectrophotometric Analysis
by Claudio Poggio, Lodovico Vialba, Anna Berardengo, Ricaldone Federico, Marco Colombo, Riccardo Beltrami and Andrea Scribante
J. Funct. Biomater. 2017, 8(3), 26; https://doi.org/10.3390/jfb8030026 - 6 Jul 2017
Cited by 26 | Viewed by 7833
Abstract
The aim of this in vitro study was to evaluate and compare the color stability of different esthetic restorative materials (one microfilled composite, one nanofilled composite, one nanoceramic composite, one microfilled hybrid composite, one microfilled hybrid composite, one nanohybrid Ormocer based composite and [...] Read more.
The aim of this in vitro study was to evaluate and compare the color stability of different esthetic restorative materials (one microfilled composite, one nanofilled composite, one nanoceramic composite, one microfilled hybrid composite, one microfilled hybrid composite, one nanohybrid Ormocer based composite and one supra-nano spherical hybrid composite) after exposure to different staining solutions (physiological saline, red wine, coffee). All materials were prepared and polymerized into silicon rings (2 mm × 6 mm × 8 mm) to obtain specimens identical in size. Thirty cylindrical specimens of each material were prepared. Specimens were immersed in staining solutions (physiological saline, coffee and red wine) over a 28-day test period. A colorimetric evaluation according to the CIE L*a*b* system was performed by a blind trained operator at 7, 14, 21, 28 days of the staining process. The Shapiro–Wilk test and ANOVA were applied to assess significant differences among restorative materials. A paired t-test was applied to test which CIE L*a*b* parameters significantly changed after immersion in staining solutions. All restorative materials showed significant color differences after immersion in coffee. Coffee caused a significant color change in all types of tested composite resins. Only Filtek Supreme XTE demonstrated a staining susceptibility to red wine; no other significant differences among the materials were demonstrated. Long-term exposure to some food dyes (coffee in particular) can significantly affect the color stability of modern esthetic restorative materials regardless of materials’ different compositions. Full article
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<p>Evolution of the color variation for each material over the course of the study when immersed in control solution. 1 day (D0), 1 week (D1), 2 weeks (D2), 3 weeks (D3), 4 weeks (D4).</p> Full article ">Figure 2
<p>Evolution of the color variation for each material over the course of the study when immersed in wine. 1 day (D0), 1 week (D1), 2 weeks (D2), 3 weeks (D3), 4 weeks (D4).</p> Full article ">Figure 3
<p>Evolution of the color variation for each material over the course of the study when immersed in coffee. 1 day (D0), 1 week (D1), 2 weeks (D2), 3 weeks (D3), 4 weeks (D4).</p> Full article ">
5138 KiB  
Article
An Injectable Glass Polyalkenoate Cement Engineered for Fracture Fixation and Stabilization
by Basel A. Khader, Sean A. F. Peel and Mark R. Towler
J. Funct. Biomater. 2017, 8(3), 25; https://doi.org/10.3390/jfb8030025 - 5 Jul 2017
Cited by 13 | Viewed by 6298
Abstract
Glass polyalkenoate cements (GPCs) have potential as bio-adhesives due to their ease of application, appropriate mechanical properties, radiopacity and chemical adhesion to bone. Aluminium (Al)-free GPCs have been discussed in the literature, but have proven difficult to balance injectability with mechanical integrity. For [...] Read more.
Glass polyalkenoate cements (GPCs) have potential as bio-adhesives due to their ease of application, appropriate mechanical properties, radiopacity and chemical adhesion to bone. Aluminium (Al)-free GPCs have been discussed in the literature, but have proven difficult to balance injectability with mechanical integrity. For example, zinc-based, Al-free GPCs reported compressive strengths of 63 MPa, but set in under 2 min. Here, the authors design injectable GPCs (IGPCs) based on zinc-containing, Al-free silicate compositions containing GeO2, substituted for ZnO at 3% increments through the series. The setting reactions, injectability and mechanical properties of these GPCs were evaluated using both a hand-mix (h) technique, using a spatula for sample preparation and application and an injection (i) technique, using a 16-gauge needle, post mixing, for application. GPCs ability to act as a carrier for bovine serum albumin (BSA) was also evaluated. Germanium (Ge) and BSA containing IGPCs were produced and reported to have working times between 26 and 44 min and setting times between 37 and 55 min; the extended handling properties being as a result of less Ge. The incorporation of BSA into the cement had no effect on the handling and mechanical properties, but the latter were found to have increased compression strength with the addition of Ge from between 27 and 37 MPa after 30 days maturation. Full article
(This article belongs to the Special Issue Journal of Functional Biomaterials: Feature Papers 2016)
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Full article ">Figure 1
<p>Disposable syringe with the capacity of 3 mL with an opening nozzle size of 2 mm in diameter attached with 16-gauge needle filled with KT cement.</p> Full article ">Figure 2
<p>The preparation of the compressive strength samples. (<b>a</b>) hand technique (h); (<b>b</b>) injection technique (i).</p> Full article ">Figure 3
<p>The preparation of the Biaxial Flexural Strength samples. (<b>a</b>) hand technique (h); (<b>b</b>) injection technique (i).</p> Full article ">Figure 4
<p>X-ray diffraction (XRD) patterns of the formulated glasses (KT) series confirming all glasses were fully amorphous. (<b>a</b>) KT1; (<b>b</b>) KT2 and (<b>c</b>) KT3.</p> Full article ">Figure 5
<p>Particle size analysis (PSA) and scanning electron microscopy (SEM) micrographs. (<b>a</b>) KT1; (<b>b</b>) KT2; (<b>c</b>) KT3. S.D: standard deviation.</p> Full article ">Figure 6
<p>(<b>a</b>) Working times (T<sub>W</sub>) of the cement series and working times of the injectable cement (T<sub>Wi</sub>) with PAA40; (<b>b</b>) T<sub>W</sub> and T<sub>Wi</sub> with PAA200. Red arrows show statistical significance (<span class="html-italic">p</span> &lt; 0.05) between the cement groups.</p> Full article ">Figure 7
<p>(<b>a</b>) Setting times (Ts) of the cement series and setting times of the injectable cement (Tsi) with PAA40; (<b>b</b>) Ts and Tsi with PAA200. Red arrows show statistical significance (<span class="html-italic">p</span> &lt; 0.05) between the cements groups.</p> Full article ">Figure 8
<p>Injectability of cements depending on the time after mixing (<b>a</b>) PAA40 and (<b>b</b>) PAA200.</p> Full article ">Figure 9
<p>Compressive strength for the cement series over 1, 7 and 30 days maturation with PAA40, (h) the hand version and (i) the injection version, error bars represent SD, X and red arrows (between (h) and (i) version groups) show statistically significant difference (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 9 Cont.
<p>Compressive strength for the cement series over 1, 7 and 30 days maturation with PAA40, (h) the hand version and (i) the injection version, error bars represent SD, X and red arrows (between (h) and (i) version groups) show statistically significant difference (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 10
<p>Compressive strength for the cement series over 1, 7 and 30 days maturation with PAA200, (h) the hand version and (i) the injection version, error bars represent SD, X and red arrows (between (h) and (i) version groups) show statistically significant difference (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 11
<p>Biaxial flexural strength for the cement series over 1, 7 and 30 days maturation with PAA40, (h) the hand version and (i) the injection version, error bars represent SD, X and red arrows (between (h) and (i) version groups) show statistically significant difference (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 12
<p>Biaxial flexural strength for the cement series over 1, 7 and 30 days maturation with PAA200, (h) the hand version and (i) the injection version, error bars represent SD, X and red arrows (between (h) and (i) version groups) show statistically significant difference (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 13
<p>SEM images of the fracture surface of KT1 (<b>a</b>,<b>b</b>); KT2 (<b>c</b>,<b>d</b>) and KT3 (<b>e</b>,<b>f</b>) cements after 30 days with PAA200 for (h) and (i) technique.</p> Full article ">Figure 14
<p>Calculated results for ion release of the (i) technique over 1, 7 and 30 days. (<b>a</b>) The average for each glass with PAA40; (<b>b</b>) The average for each glass with PAA200. Error bars represent the SD.</p> Full article ">Figure 15
<p>BSA release profiles for KT3 (i) technique containing BSA of 3 loads (3%, 6% and 9%) in mg/mL. Error bars represent SD.</p> Full article ">
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Review
Biocompatibility of HbV: Liposome-Encapsulated Hemoglobin Molecules-Liposome Effects on Immune Function
by Hiroshi Azuma, Mitsuhiro Fujihara and Hiromi Sakai
J. Funct. Biomater. 2017, 8(3), 24; https://doi.org/10.3390/jfb8030024 - 28 Jun 2017
Cited by 12 | Viewed by 6514
Abstract
Hemoglobin vesicles (HbVs) are oxygen carriers consisting of Hb molecules and liposome in which human hemoglobin (Hb) molecules are encapsulated. Investigations of HbV biocompatibility have shown that HbVs have no significant effect on either the quality or quantity of blood components such as [...] Read more.
Hemoglobin vesicles (HbVs) are oxygen carriers consisting of Hb molecules and liposome in which human hemoglobin (Hb) molecules are encapsulated. Investigations of HbV biocompatibility have shown that HbVs have no significant effect on either the quality or quantity of blood components such as RBC, WBC, platelets, complements, or coagulation factors, reflecting its excellent biocompatibility. However, their effects on the immune system remain to be evaluated. HbVs might affect the function of macrophages because they accumulate in the reticuloendothelial system. Results show that splenic T cell proliferation is suppressed after injection of not only HbV but also empty liposome into rat, and show that macrophages that internalized liposomal particles are responsible for the suppression. However, the effect is transient. Antibody production is entirely unaffected. Further investigation revealed that those macrophages were similar to myeloid-derived suppressor cells (MDSCs) in terms of morphology, cell surface markers, and the immune-suppression mechanism. Considering that MDSCs appear in various pathological conditions, the appearance of MDSC-like cells might reflect the physiological immune system response against the substantial burden of liposomal microparticles. Therefore, despite the possible induction of immunosuppressive cells, HbVs are an acceptable and promising candidate for use as a blood substitute in a clinical setting. Full article
(This article belongs to the Special Issue Blood Substitutes: Evolution and Future Applications)
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Figure 1
<p>Effect of HbVs on proliferation of Con A-stimulated rat splenic T cells. 20% (<span class="html-italic">v</span>/<span class="html-italic">v</span>) of HbV solution was injected intravenously into rats. The spleen was excised 6 h to 3 days after injection. Then, the proliferative response of splenic T cells to Con A was evaluated. Compared to controls, T cell proliferation was inhibited from 6 h to 3 days after injection of HbVs (** <span class="html-italic">p</span> &lt; 0.01). No suppression was observed after 7 days. (Figure modified from [<a href="#B10-jfb-08-00024" class="html-bibr">10</a>]).</p> Full article ">Figure 2
<p>Effects of HbVs and Empty vesicles on proliferation of Con A-stimulated rat splenic T cells. Spleen was excised from rat 24 h after injection of HbVs, empty vesicle (liposome), or saline. Then splenocytes were stimulated with Con A. The proliferative response of splenic T cells derived from both HbV-loaded and empty vesicle-loaded rats were significantly lower than those of controls (** <span class="html-italic">p</span> &lt; 0.01).</p> Full article ">Figure 3
<p>Inhibition of lymphocyte blastoid formation in liposome-loaded splenocytes. Even the lower dose of liposome (1% (<span class="html-italic">v</span>/<span class="html-italic">v</span>) × 2) can inhibit blastoid formation (cell proliferation).</p> Full article ">Figure 4
<p>Correlation between inhibition of cell division and the production of NO. Splenocytes derived from liposome-loaded rat were cultured in the presence of Con A (mg/mL). Inhibition of T cell proliferation was visible for a wide range of Con A concentrations associated with enhanced production of NO. Inhibition of cell division was completely eliminated in the presence of iNOS inhibitor (L-NMMA, 2 mM).</p> Full article ">Figure 5
<p>Induction of iNOS in the spleen after injection of liposome. iNOS became detectable in splenocyte lysate after liposome injection. As a positive control, splenocyte lysate after LPS injection was used.</p> Full article ">Figure 6
<p>Dose-dependent inhibition effects of liposome-loaded splenocyte on T cell proliferation. Saline-loaded splenocyte suspension (S) was mixed with liposome-loaded splenocyte suspension (L) at the indicated volumes and was stimulated with Con A. The inhibition of T cell proliferation was enhanced as the volume of L increased (* <span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 7
<p>Antibody production against KLH was not influenced by HbV injection. Immunization with KLH was conducted under HbV injection into rat. Neither the primary response nor the secondary response was suppressed by the injection of HbVs into rats.</p> Full article ">
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Article
Synergy of Iron Chelators and Therapeutic Peptide Sequences Delivered via a Magnetic Nanocarrier
by Gayani S. Abayaweera, Hongwang Wang, Tej B. Shrestha, Jing Yu, Kyle Angle, Prem Thapa, Aruni P. Malalasekera, Leila Maurmann, Deryl L. Troyer and Stefan H. Bossmann
J. Funct. Biomater. 2017, 8(3), 23; https://doi.org/10.3390/jfb8030023 - 26 Jun 2017
Cited by 5 | Viewed by 6398
Abstract
Here, we report the synthesis, characterization, and efficacy study of Fe/Fe3O4-nanoparticles that were co-labeled with a tumor-homing and membrane-disrupting oligopeptide and the iron-chelator Dp44mT, which belongs to the group of the thiosemicarbazones. Dp44mT and the peptide sequence PLFAERL(D [...] Read more.
Here, we report the synthesis, characterization, and efficacy study of Fe/Fe3O4-nanoparticles that were co-labeled with a tumor-homing and membrane-disrupting oligopeptide and the iron-chelator Dp44mT, which belongs to the group of the thiosemicarbazones. Dp44mT and the peptide sequence PLFAERL(D[KLAKLAKKLAKLAK])CGKRK were tethered to the surface of Fe/Fe3O4 core/shell nanoparticles by utilizing dopamine-anchors. The 26-mer contains two important sequences, which are the tumor targeting peptide CGKRK, and D[KLAKLAK]2, known to disrupt the mitochondrial cell walls and to initiate programmed cell death (apoptosis). It is noteworthy that Fe/Fe3O4 nanoparticles can also be used for MRI imaging purposes in live mammals. In a first step of this endeavor, the efficacy of this nanoplatform has been tested on the highly metastatic 4T1 breast cancer cell line. At the optimal ratio of PLFAERD[KLAKLAK]2CGKRK to Dp44mT of 1 to 3.2 at the surface of the dopamine-coated Fe/Fe3O4-nanocarrier, the IC50 value after 24 h of incubation was found to be 2.2 times lower for murine breast cancer cells (4T1) than for a murine fibroblast cell line used as control. Based on these encouraging results, the reported approach has the potential of leading to a new generation of nanoplatforms for cancer treatment with considerably enhanced selectivity towards tumor cells. Full article
(This article belongs to the Special Issue Magnetic Nanoparticle Design for Medical Diagnosis and Therapy)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Intended molar ratio of PLFAER<sub>D</sub>[KLAKLAK]<sub>2</sub>CGKRK to Dp44mT-derivative at the surface of the Fe/Fe<sub>3</sub>O<sub>4</sub>-nanocarriers vs. the experimentally determined ratio. The maximal error is shown for each measurement. The curve represents the best data fit.</p> Full article ">Figure 2
<p>TEM of dopamine-stabilized Fe/Fe<sub>3</sub>O<sub>4</sub>-nanoparticles. (<b>A</b>): Dop-Fe/Fe<sub>3</sub>O<sub>4</sub> Peptide/Dp44mT (10:1); (<b>B</b>) and (<b>C</b>): Dop-Fe/Fe<sub>3</sub>O<sub>4</sub> Peptide/Dp44mT (1:5) (see <a href="#jfb-08-00023-t001" class="html-table">Table 1</a>).</p> Full article ">Figure 3
<p>Size-distribution of Dop-Fe/Fe<sub>3</sub>O<sub>4</sub> Peptide/Dp44mT (1:5) (see <a href="#jfb-08-00023-t001" class="html-table">Table 1</a>) according to TEM imaging results.</p> Full article ">Figure 4
<p>Growth inhibition of 4T1 cells (red) and murine fibroblasts (blue) after 24 h of incubation as a function of nanocarrier concentration. (<b>A</b>): dopamine-coated Fe/Fe<sub>3</sub>O<sub>4</sub>; (<b>B</b>): dopamine-coated Fe/Fe<sub>3</sub>O<sub>4</sub>-Peptide; All other graphs: dopamine-coated Fe/Fe<sub>3</sub>O<sub>4</sub>-Peptide/Dp44mT; (<b>C</b>): Peptide/Dp44mT: 1/1.1; (<b>D</b>): 1/3.2; (<b>E</b>): 1/27; (<b>F</b>): 1/74; (<b>G</b>): 1/103. The experimental errors in all curves are negligible (&lt;±3 percent).</p> Full article ">Figure 5
<p>Light microscopy (15×) of Fe/Fe<sub>3</sub>O<sub>4</sub>-uptake by 4T1 cells after 24 h of incubation, followed by a washing procedure, as described in the Methods section. The concentration of all Fe/Fe<sub>3</sub>O<sub>4</sub>-containing nanoparticles in B, C, and D was 5 μg·mL<sup>−1</sup>. (<b>A</b>): 4T1 cells, reagent control; (<b>B</b>): dopamine-coated Fe/Fe<sub>3</sub>O<sub>4</sub> nanoparticles; (<b>C</b>): Fe/Fe<sub>3</sub>O<sub>4</sub>-Peptide nanocarriers; (<b>D</b>): dopamine-coated Fe/Fe<sub>3</sub>O<sub>4</sub>-Peptide/Dp44mT nanocarriers.</p> Full article ">Figure 6
<p>Light microscopy (40×) of Fe/Fe<sub>3</sub>O<sub>4</sub>-uptake by 4T1 cells after 24 h of incubation, followed by a washing procedure, as described in the Methods section. The concentration of all Fe/Fe<sub>3</sub>O<sub>4</sub>-containing nanoparticles in A, B, and C was 5 μg·mL<sup>−1</sup>. (<b>A</b>): dopamine-coated Fe/Fe<sub>3</sub>O<sub>4</sub> nanoparticles; (<b>B</b>): Fe/Fe<sub>3</sub>O<sub>4</sub>-Peptide nanocarriers; (<b>C</b>): dopamine-coated Fe/Fe<sub>3</sub>O<sub>4</sub>-Peptide/Dp44mT nanocarriers.</p> Full article ">Figure 7
<p>Measurement of T1 relaxation times as a function of dopamine-coated Fe/Fe<sub>3</sub>O<sub>4</sub>-nanocarrier: Bruker Ascend, 14.1 T MRI employing an optimized T1_map_RARE sequence, T<sub>R</sub> = 2500 ms, and T<sub>E</sub> = 5.5 ms, slice thickness = 1.5 mm. The plot of the relaxation rate R1 = 1/T1 vs. the iron concentration in mM leads to the relaxivity r1 = 0.285 mM<sup>−1</sup>·s<sup>−1</sup>.</p> Full article ">Figure 8
<p>Measurement of T2 relaxation times as a function of dopamine-coated Fe/Fe<sub>3</sub>O<sub>4</sub>-nanocarrier: Bruker Ascend, 14.1 T MRI employing an optimized T2_map_MSME sequence. The plot of the relaxation rate R2 = 1/T2 vs. the iron concentration in mM leads to the relaxivity r2 = 30.0 mM<sup>−1</sup>·s<sup>−1</sup>.</p> Full article ">Scheme 1
<p>Dopamine-coated Fe/Fe<sub>3</sub>O<sub>4</sub>-nanocarriers carrying both a therapeutic peptide sequence and a Dp44mT-derivative (thiosemicarbazone).</p> Full article ">Scheme 2
<p>Synthesis of the thiosemicarbazone iron chelator, N′-(Di-pyridin-2-yl-methylene)-hydrazinecarbodithioic acid methylester (Dp44mT).</p> Full article ">Scheme 3
<p>Attachment of a dopamine-unit to PLFAERL<sub>D</sub>[KLAKLAKKLAKLAK]CGKRK. DMF: dimethylformamide; HBTU: <span class="html-italic">N,N,N′,N′</span>-Tetramethyl-<span class="html-italic">O</span>-(1<span class="html-italic">H</span>-benzotriazol-1-yl)uronium hexafluorophosphate; DIEA: <span class="html-italic">N</span>,<span class="html-italic">N</span>-Diisopropylethylamine; TFA: trifluoroacetic acid (+TIPS: triisopropylsilane).</p> Full article ">Scheme 4
<p>Ligand exchange of the dopamine-glutaric acid-modified peptide sequence PLFAERL<sub>D</sub>[KLAKLAKKLAKLAK]CGKRK against oleylamine and octadecene at the surface of Fe<sub>3</sub>O<sub>4</sub>, followed by additional exchange against dopamine. The latter was then reacted with methyl-2-(di(pyridine-2-yl)methylene)hydrazinecarbodithioate <b>3</b> to obtain a Fe/Fe<sub>3</sub>O<sub>4</sub>-nanoparticle- tethered Dp44mT derivative. The structure of Dp44mT is provided in the SI section for comparison.</p> Full article ">
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Article
Metal Ion-Loaded Nanofibre Matrices for Calcification Inhibition in Polyurethane Implants
by Charanpreet Singh and Xungai Wang
J. Funct. Biomater. 2017, 8(3), 22; https://doi.org/10.3390/jfb8030022 - 23 Jun 2017
Cited by 4 | Viewed by 7196
Abstract
Pathologic calcification leads to structural deterioration of implant materials via stiffening, stress cracking, and other structural disintegration mechanisms, and the effect can be critical for implants intended for long-term or permanent implantation. This study demonstrates the potential of using specific metal ions (MI)s [...] Read more.
Pathologic calcification leads to structural deterioration of implant materials via stiffening, stress cracking, and other structural disintegration mechanisms, and the effect can be critical for implants intended for long-term or permanent implantation. This study demonstrates the potential of using specific metal ions (MI)s for inhibiting pathological calcification in polyurethane (PU) implants. The hypothesis of using MIs as anti-calcification agents was based on the natural calcium-antagonist role of Mg2+ ions in human body, and the anti-calcification effect of Fe3+ ions in bio-prosthetic heart valves has previously been confirmed. In vitro calcification results indicated that a protective covering mesh of MI-doped PU can prevent calcification by preventing hydroxyapatite crystal growth. However, microstructure and mechanical characterisation revealed oxidative degradation effects from Fe3+ ions on the mechanical properties of the PU matrix. Therefore, from both a mechanical and anti-calcification effects point of view, Mg2+ ions are more promising candidates than Fe3+ ions. The in vitro MI release experiments demonstrated that PU microphase separation and the structural design of PU-MI matrices were important determinants of release kinetics. Increased phase separation in doped PU assisted in consistent long-term release of dissolved MIs from both hard and soft segments of the PU. The use of a composite-sandwich mesh design prevented an initial burst release which improved the late (>20 days) release rate of MIs from the matrix. Full article
(This article belongs to the Special Issue Journal of Functional Biomaterials: Feature Papers 2016)
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Figure 1
<p>Scanning electron microscopy (SEM) micrographs of electrospun (<b>a</b>) Polyurethane (PU); (<b>b</b>) MgSO<sub>4</sub>-loaded sample (PU-MS); (<b>c</b>) MgCl<sub>2</sub>-loaded sample (PU-MC); and (<b>d</b>) FeCl<sub>3</sub>-loaded sample (PU-FC) films.</p> Full article ">Figure 2
<p>Fourier transform infra red (FTIR) spectrum of electrospun polyurethane film.</p> Full article ">Figure 3
<p>FTIR spectrum of electrospun control PU and metal ion (MI) loaded PU films in the 2500–4000 cm<sup>−1</sup> frequency range.</p> Full article ">Figure 4
<p>FTIR spectrum of electrospun control and MI-loaded PU films in the 1500–2300 cm<sup>−1</sup> frequency range.</p> Full article ">Figure 5
<p>FTIR spectrum of electrospun control and MI-loaded PU films in the 900–1500 cm<sup>−1</sup> frequency range.</p> Full article ">Figure 6
<p>Stress-strain relation of control and MI loaded PU films.</p> Full article ">Figure 7
<p>Release profile of MIs from PU-MI matrices in (<b>A</b>) solid-sandwich; and (<b>B</b>) composite-sandwich configurations.</p> Full article ">Figure 8
<p>SEM micrographs of (<b>a</b>) PU; (<b>b</b>) PU-MS; (<b>c</b>) PU-MC; and (<b>d</b>) PU-FC films after calcium solution incubation for 60 days. Calcium deposits are visible as randomly segregated crystals adhering to fibres.</p> Full article ">Figure 9
<p>SEM micrographs of large calcium deposits on the surface of Control PU film after calcium solution incubation for 60 days.</p> Full article ">Figure 10
<p>Light microscopy of (<b>a</b>) PU; (<b>b</b>) PU-MS; (<b>c</b>) PU-MC; and (<b>d</b>) PU-FC films after Von Kossa staining and calcium solution incubation for 60 days. Dark black-brown spots indicate aggregated calcium deposits.</p> Full article ">Figure 10 Cont.
<p>Light microscopy of (<b>a</b>) PU; (<b>b</b>) PU-MS; (<b>c</b>) PU-MC; and (<b>d</b>) PU-FC films after Von Kossa staining and calcium solution incubation for 60 days. Dark black-brown spots indicate aggregated calcium deposits.</p> Full article ">Figure 11
<p>Light microscopy of (<b>a</b>) PU; (<b>b</b>) PU-MS; (<b>c</b>) PU-MC; and (<b>d</b>) PU-FC films after Alizarin Red staining and calcium solution incubation for 60 days. Dark red-orange spots on the surface indicate aggregated calcium deposits.</p> Full article ">Figure 12
<p>FTIR spectrum of control PU and MI loaded PU films after 90 days of incubation in calcification solution.</p> Full article ">Figure 13
<p>Schematic of electrospinning setup for developing metal salt-loaded PU films.</p> Full article ">Figure 14
<p>Representation showing cross-section of (<b>A</b>) solid-sandwich; and (<b>B</b>) composite-sandwich electrospun films.</p> Full article ">
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Article
Experimental Investigation of Magnetic Nanoparticle-Enhanced Microwave Hyperthermia
by Brogan T. McWilliams, Hongwang Wang, Valerie J. Binns, Sergio Curto, Stefan H. Bossmann and Punit Prakash
J. Funct. Biomater. 2017, 8(3), 21; https://doi.org/10.3390/jfb8030021 - 22 Jun 2017
Cited by 16 | Viewed by 7464
Abstract
The objective of this study was to evaluate microwave heating enhancements offered by iron/iron oxide nanoparticles dispersed within tissue-mimicking media for improving efficacy of microwave thermal therapy. The following dopamine-coated magnetic nanoparticles (MNPs) were considered: 10 and 20 nm diameter spherical core/shell Fe/Fe [...] Read more.
The objective of this study was to evaluate microwave heating enhancements offered by iron/iron oxide nanoparticles dispersed within tissue-mimicking media for improving efficacy of microwave thermal therapy. The following dopamine-coated magnetic nanoparticles (MNPs) were considered: 10 and 20 nm diameter spherical core/shell Fe/Fe3O4, 20 nm edge-length cubic Fe3O4, and 45 nm edge-length/10 nm height hexagonal Fe3O4. Microwave heating enhancements were experimentally measured with MNPs dissolved in an agar phantom, placed within a rectangular waveguide. Effects of MNP concentration (2.5–20 mg/mL) and microwave frequency (2.0, 2.45 and 2.6 GHz) were evaluated. Further tests with 10 and 20 nm diameter spherical MNPs dispersed within a two-compartment tissue-mimicking phantom were performed with an interstitial dipole antenna radiating 15 W power at 2.45 GHz. Microwave heating of 5 mg/mL MNP-agar phantom mixtures with 10 and 20 nm spherical, and hexagonal MNPs in a waveguide yielded heating rates of 0.78 ± 0.02 °C/s, 0.72 ± 0.01 °C/s and 0.51 ± 0.03 °C/s, respectively, compared to 0.5 ± 0.1 °C/s for control. Greater heating enhancements were observed at 2.0 GHz compared to 2.45 and 2.6 GHz. Heating experiments in two-compartment phantoms with an interstitial dipole antenna demonstrated potential for extending the radial extent of therapeutic heating with 10 and 20 nm diameter spherical MNPs, compared to homogeneous phantoms (i.e., without MNPs). Of the MNPs considered in this study, spherical Fe/Fe3O4 nanoparticles offer the greatest heating enhancement when exposed to microwave radiation. These nanoparticles show strong potential for enhancing the rate of heating and radial extent of heating during microwave hyperthermia and ablation procedures. Full article
(This article belongs to the Special Issue Magnetic Nanoparticle Design for Medical Diagnosis and Therapy)
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Figure 1
<p>Transmission electron microscopy (TEM) images of the respective magnetic nanoparticles (MNPs) used in this study: (<b>a</b>) 10 and (<b>b</b>) 20 nm diameter spherical Fe/Fe<sub>3</sub>O<sub>4</sub>, respectively, (<b>c</b>) 45 nm edge-length and 10 nm height hexagonal Fe<sub>3</sub>O<sub>4</sub>, and (<b>d</b>) 20 nm edge-length cubic Fe<sub>3</sub>O<sub>4</sub>.</p> Full article ">Figure 2
<p>Experimental set up used to characterize microwave heating of MNPs in a rectangular waveguide. DC: Direct Current</p> Full article ">Figure 3
<p>Experimental setup to induce a standing wave within the waveguide, yielding locations with E- and H-field maxima.</p> Full article ">Figure 4
<p>Two-compartment model to characterize microwave heating enhancements with an interstitial dipole antenna. The outer compartment consists of a tissue-mimicking (TM) phantom and the inner compartment is a 30 mm diameter sphere of TM with a 10mg/mL concentration of 10 or 20 nm diameter spherical MNPs.</p> Full article ">Figure 5
<p>Measured transient temperature profiles of MNPs dispersed within agar at varying concentrations. MNPs considered were: (<b>a</b>) 10 nm and (<b>b</b>) 20 nm diameter spherical Fe/Fe<sub>3</sub>O<sub>4,</sub> (<b>c</b>) 45 nm edge-length/10 nm height hexagonal Fe<sub>3</sub>O<sub>4</sub>, and (<b>d</b>) 20 nm edge-length cubic MNPs. Each curve represents the average of five experiments.</p> Full article ">Figure 6
<p>Transient temperature profiles measured in MNP-agar mixtures within the rectangular waveguide at (<b>a</b>) 2.0 GHz, (<b>b</b>) 2.45 GHz and (<b>c</b>) 2.6 GHz. Each curve represents the average of five experiments.</p> Full article ">Figure 7
<p>Temperature measured at locations with (<b>a</b>) E-field maximum and (<b>b</b>) H-field maximum.</p> Full article ">Figure 8
<p>Measured transient temperature profiles within the two-compartment phantom radiated with a 2.45 GHz interstitial dipole antenna. Temperature measurements are shown at (<b>a</b>) 5 mm, (<b>b</b>) 10 mm, (<b>c</b>) 15 mm and (<b>d</b>) 20 mm from the antenna. Each curve represents the average of five experiments.</p> Full article ">Figure 9
<p>Experimentally measured radial temperature plots at (<b>a</b>) 1 min and (<b>b</b>) 3 min within the two-compartment phantom.</p> Full article ">
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