Wankei Wan

The University of Western Ontario, London, Ontario, Canada

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Publications (16)39.66 Total impact

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    Article: Growth Kinetics of Lipid-Based Nanodiscs to Unilamellar Vesicles - A Time-Resolved Small Angle Neutron Scattering (SANS) Study.
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    ABSTRACT: Mixtures of dimyristoyl-phosphatidylcholine (DMPC), dimyristoyl-phosphatidylglycerol (DMPG) and dihexanoyl-phosphatidylcholine (DHPC) in aqueous solutions spontaneously form monodisperse, bilayered nanodiscs (also known as "bicelles") at or below the melting transition temperature of DMPC (T(M)~23°C). In dilute systems above the main transition temperature T(M) of DMPC, bicelles coalesce (increasing in diameter) and eventually self-fold into unilamellar vesicles (ULVs). Time-resolved small angle neutron scattering is used to study the growth kinetics of nanodiscs below and equal to T(M) over a period of hours as a function of temperature at two lipid concentrations in presence or absence of NaCl salt. Bicelles seem to undergo a sudden initial growth phase with increased temperature which is then followed by a slower reaction-limited growth phase that depends on ionic strength, lipid concentration and temperature. The bicelle interaction energy was derived from the Derjaguin and Landau, and Verwey and Overbeek (DLVO) colloidal theory. While the calculated total energy between discs is attractive and proportional to the growth rate, a more detailed mechanism is proposed to describe the mechanism of disc coalescence. After annealing at low temperature (low-T), samples were heated to 50°C in order to promote the formation of ULVs. Although the low-T annealing of samples has only a marginal effect on the mean size of the end-state ULVs, it does affect the ULV polydispersity, which increases with increased T, presumably driven by the entropy of the system.
    Biochimica et Biophysica Acta 11/2012; · 4.66 Impact Factor
  • Article: Exploring cell compatibility of a fibronectin-functionalized physically crosslinked poly(vinyl alcohol) hydrogel.
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    ABSTRACT: Physically crosslinked poly(vinyl alcohol) (PVA) hydrogels prepared using a low-temperature thermally cycled process have tunable mechanical properties that fall within the range of soft tissues, including cardiovascular tissue. An approach to render it hemocompatible is by endothelization, but its hydrophilic nature is not conducive to cell adhesion and spreading. We investigated the functionalization reaction of this class of PVA hydrogel with fibronectin (FN) for adhesion and spreading of primary porcine radial artery cells and vascular endothelial cells. These are cells relevant to small-diameter vascular graft development. FN functionalization was achieved using a multistep reaction, but the activation step involving carbonyl diimidazole normally required for chemically crosslinked PVA was found to be unnecessary. The reaction resulted in an increase in the elastic modulus of the PVA hydrogel but is still well within the range of cardiovascular tissue. Confocal microscopy confirmed the adhesion and spreading of both cell types on the PVA-FN surfaces, whereas cells failed to adhere to the PVA control. This is a first step toward an alternative for the realization of a synthetic replacement small-diameter vascular graft.
    Journal of Biomedical Materials Research Part B Applied Biomaterials 01/2012; 100(1):1-10. · 2.15 Impact Factor
  • Article: Effect of static magnetic fields on the growth, photosynthesis and ultrastructure of Chlorella kessleri microalgae.
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    ABSTRACT: Microalgal biotechnology could generate substantial amounts of biofuels with minimal environmental impact if the economics can be improved by increasing the rate of biomass production. Chlorella kessleri was grown in a small-scale raceway pond and in flask cultures with the entire volume, 1% (v/v) at any instant, periodically exposed to static magnetic fields to demonstrate increased biomass production and investigate physiological changes, respectively. The growth rate in flasks was maximal at a field strength of 10 mT, increasing from 0.39 ± 0.06 per day for the control to 0.88 ± 0.06 per day. In the raceway pond the 10 mT field increased the growth rate from 0.24 ± 0.03 to 0.45 ± 0.05 per day, final biomass from 0.88 ± 0.11 to 1.56 ± 0.18 g/L per day, and maximum biomass production from 0.11 ± 0.02 to 0.38 ± 0.04 g/L per day. Increased pigment, protein, Ca, and Zn content made the biomass produced with magnetic stimulation nutritionally superior. An increase in oxidative stress was measured indirectly as a decrease in antioxidant capacity from 26 ± 2 to 17 ± 1 µmol antioxidant/g biomass. Net photosynthetic capacity (NPC) and respiratory rate were increased by factors of 2.1 and 3.1, respectively. Loss of NPC enhancement after the removal of magnetic field fit a first-order model well (R(2)  = 0.99) with a half-life of 3.3 days. Transmission electron microscopy showed enlarged chloroplasts and decreased thylakoid order with 10 mT treatment. By increasing daily biomass production about fourfold, 10 mT magnetic field exposure could make algal oil cost competitive with other biodiesel feedstocks. Bioelectromagnetics. © 2011 Wiley Periodicals, Inc.
    Bioelectromagnetics 09/2011; · 1.84 Impact Factor
  • Article: Local delivery of therapeutics for percutaneous coronary intervention.
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    ABSTRACT: Percutaneous coronary intervention (PCI) has become a highly effective alternative for the treatment of coronary artery disease. The use of stents has reduced the rates of restenosis by preventing elastic recoil and negative remodeling, however neointima formation still remains an issue. Local drug delivery is an attractive option to maintain effective drug concentrations at the site of arterial injury without risking systemic toxicity. Drug-eluting stents (DESs) are implanted to provide local drug delivery to combat neointima formation by slowing cell proliferation and migration. However, problems still remain with DES use including the non-specificity of therapeutics, incomplete endothelialization leading to late thrombosis, necessity for longer term anti-platelet drug use, and local hypersensitivity to polymer delivery matrices. This review describes recent advances in local drug delivery for the prevention of restenosis. Many different drug therapeutics have been considered, as well as the material properties of the drug delivery systems. Systems for delivery include DESs, balloon catheters, polymeric cuffs and nanoparticles. Our own experience designing a controlled release device for a new therapeutic agent, Serp-1, an anti-inflammatory protein, is briefly presented. The release of Serp-1 can be extended using diffusion controlled release from physically crosslinked poly(vinyl alcohol) hydrogels, where its release properties can be tuned by the processing parameters of the hydrogel.
    Current Drug Delivery 06/2011; 8(5):534-56.
  • Article: Synthesis and in vitro biocompatibility assessment of a poly(amic acid) derived from ethylenediaminetetraacetic dianhydride.
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    ABSTRACT: Poly(amic acid) (PAA) derived from ethylenediaminetetracetic dianhydride shows great potential as a biomaterial suitable for biomedical applications. To evaluate this polymer class further, in vitro cell toxicity (WST-1/ECS, ELISA based) and cell compatibility (cell adhesion and cell proliferation) tests were conducted to establish structure-toxicity relationships. PAAs with a number-average molecular weight ranging between 100 to 200 kg/mol were synthesized at 37°C after 24 h. Porcine radial artery cells (RACs) and descending aorta endothelial cells (ECs) were seeded independently in a 96-well cell culture plate at a cell density of 5000 cells/cm(2) to observe toxic effects. Similarly, RACs and ECs were seeded independently onto PAA coated and uncoated cover slips at a cell density of 7000 cells/cm(2) to observe growth patterns. Our results showed no toxicity after 96 h of incubation and in addition, both RACs and ECs adhered and proliferated on the PAA films, preserving their phenotype during this time. The tested synthetic material seems promising as a future biomaterial and should elicit a desired cellular response upon implantation.
    Journal of Biomaterials Science Polymer Edition 01/2011; 22(4-6):683-700. · 1.69 Impact Factor
  • Article: Synthesis, characterization and in vitro cell compatibility study of a poly(amic acid) graft/cross-linked poly(vinyl alcohol) hydrogel.
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    ABSTRACT: Although physically cross-linked poly(vinyl alcohol) (PVA) hydrogels have tunable mechanical properties to match that of soft tissues, such as vascular tissue, their hydrophilic nature is not conducive to cell adhesion and spreading. For applications such as small diameter vascular grafts for coronary bypass both mechanical matching and hemocompatibility are important. Poly(amic acid) (PAA), derived from ethylene diamine tetraacetic dianhydride, is a cell-compatible polymer. It was grafted/cross-linked onto physically cross-linked PVA to provide cell compatibility. Functionalization was achieved via a one-step esterification reaction using 1,3-dicyclohexylcarbodiimide as the coupling agent and 4-dimethylaminopyridine as the catalyst. The success of the grafting reaction was verified using Fourier transform infrared spectroscopy, solid-state nuclear magnetic resonance spectroscopy and X-ray photoelectron spectroscopy. The mechanical properties of the starting PVA hydrogel were largely preserved after the grafting reaction within the physiological strain range of vascular tissue. In vitro cell culture studies using primary porcine endothelial cells confirmed cell compatibility of the PAA graft PVA hydrogel, making it an attractive candidate for small diameter vascular graft development.
    Acta biomaterialia 01/2011; 7(1):258-67. · 3.98 Impact Factor
  • Article: Genipin-Cross-linked Electrospun Collagen Fibers.
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    ABSTRACT: The fabrication of a fibrous collagen scaffold using electrospinning is desirable for tissue-engineering applications. Previously, electrospun collagen fibers were shown to be unstable in aqueous environments and, therefore, cross-linking is essential to stabilize these fibers. In this study genipin, a significantly less cytotoxic cross-linking agent compared to glutaraldehyde, was used to cross-link electrospun collagen fibers. The significance of this research lies in the use of four alcohol/water solvent systems to carry out the cross-linking reaction to maintain fibrous morphology during cross-linking. The four cross-linking conditions established were: (1) ethanol, 5% water and 3 days, (2) ethanol, 3% water and 5 days, (3) ethanol, 5% water and 5 days, and (4) isopropanol, 5% water and 5 days at a genipin concentration of 0.03 M. Results illustrated that genipin-cross-linking was effective in maintaining collagen fiber integrity in aqueous and cell culture media environments for up to 7 days. In addition, it was shown that fiber swelling could be controlled by using different cross-linking conditions. Swelling of cross-linked fibers immersed in Dulbecco's modified eagle medium for 7 days ranged from 0 to 59±4%. The cross-linked fibers were analyzed using scanning electron microscopy, Fourier transform infrared spectroscopy and ninhydrin assay. Finally, studies using primary human fibroblasts indicated good cell adhesion to these scaffolds. Overall, our data suggest that these stabilized fibrous collagen scaffolds provide a promising environment for tissue-regeneration applications.
    Journal of Biomaterials Science Polymer Edition 11/2010; · 1.69 Impact Factor
  • Article: Effects of charge density and thermal history on the morphologies of spontaneously formed unilamellar vesicles.
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    ABSTRACT: A phospholipid mixture consisting of dimyristoyl phosphatidylcholine (DMPC), dihexanoyl phosphatidylcholine (DHPC), and the negatively charged dimyristoyl phosphatidylglycerol (DMPG) lipid is found to spontaneously form uniform-size unilamellar vesicles (ULVs). Small angle neutron scattering (SANS) is used to examine ULV size as a function of net charge, dilution, and thermal history. It shows that ULVs only exist within a narrow window of charge densities, where larger size ULVs can be obtained at a lower charge density through slow temperature annealing. There is also a 6-fold change in the size of low polydispersity ULVs, confirming a previously proposed model for spontaneously forming ULVs [Nieh, M.-P. et al. Langmuir 2005, 21, 6656]. Finally, the stability of these ULVs was confirmed through a series of high temperature dilution experiments, further making the case that these nanoparticles can be used as carriers for drugs and contrast imaging agents.
    The Journal of Physical Chemistry B 04/2010; 114(17):5729-35. · 3.70 Impact Factor
  • Article: Advanced modeling strategy for the analysis of heart valve leaflet tissue mechanics using high-order finite element method.
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    ABSTRACT: Modeling soft tissue using the finite element method is one of the most challenging areas in the field of biomechanical engineering. To date, many models have been developed to describe heart valve leaflet tissue mechanics, which are accurate to some extent. Nevertheless, there is no comprehensive method to modeling soft tissue mechanics, This is because (1) the degree of anisotropy in the heart valve leaflet changes layer by layer due to a variety of collagen fiber densities and orientations that cannot be taken into account in the model and also (2) a constitutive material model fully describing the mechanical properties of the leaflet structure is not available in the literature. In this framework, we develop a new high-order element using p-type finite element formulation to create anisotropic material properties similar to those of the heart valve leaflet tissue in only one single element. This element also takes the nonlinearity of the leaflet tissue into consideration using a bilinear material model. This new element is composed a two-dimensional finite element in the principal directions of leaflet tissue and a p-type finite element in the direction of thickness. The proposed element is easy to implement, much more efficient than standard elements available in commercial finite element packages. This study is one step towards the modeling of soft tissue mechanics using a meshless finite element approach to be applied in real-time haptic feedback of soft-tissue models in virtual reality simulation.
    Medical Engineering & Physics 09/2009; 31(9):1110-7. · 1.62 Impact Factor
  • Article: Compression properties of polyvinyl alcohol--bacterial cellulose nanocomposite.
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    ABSTRACT: Despite the established use of total joint replacement for the treatment of advanced degeneration of articular cartilage, component loosening due to wear and osteolysis limits the lifespan of these joint prostheses. In the present study, nanocomposites consisting of poly(vinyl alcohol) (PVA) and bacterial cellulose (BC) nanofibers were investigated as possible improved cartilage replacement materials. Nanocomposites were synthesized by adding small amounts (<1%) of BC to PVA, and subjecting the mixture to thermal cycling. The mechanical properties of the resulting material were evaluated using unconfined compression testing. By the addition of BC nanofibers to the PVA matrix, a nanocomposite with a wide range of compressive mechanical properties control was obtained, with elastic modulus values similar to those reported for native articular cartilage. The nanocomposite also showed improved strain-rate dependence and adequate viscoelastic properties. The PVA-BC nanocomposite is therefore a promising biomaterial to be considered as a possible replacement material for localized articular cartilage injuries and other orthopedic applications such as intervertebral discs.
    Journal of Biomedical Materials Research Part B Applied Biomaterials 05/2009; 90(2):922-9. · 2.15 Impact Factor
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    Article: Characterization of anisotropic poly(vinyl alcohol) hydrogel by small- and ultra-small-angle neutron scattering.
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    ABSTRACT: Poly(vinyl alcohol) (PVA) hydrogels are formed from PVA solution when physical cross-links form during freeze/thaw cycling. By applying a stress during the freeze/thaw process, PVA hydrogels with anisotropic mechanical properties are produced. We have used small- and ultra-small-angle neutron scattering to study the structure at length scales of 2 nm to 10 mum. By supplementing the neutron data with data from atomic force microscopy, we have probed a large range of length scales within which structural changes responsible for bulk anisotropy occur. We model the gel as interconnected PVA blobs of size 20-50 nm arranged in fractal aggregates extending to micrometers or tens of micrometers. Bulk mechanical anisotropy appears to be due to the alignment of blobs and connections between blobs. This information is essential for tailoring mechanical properties for applications where anisotropy is desirable such as to match the properties of natural tissue in coronary grafts and to control diffusive properties in active wound dressings.
    The Journal of chemical physics 02/2009; 130(3):034903. · 3.09 Impact Factor
  • Article: Anisotropic polyvinyl alcohol-Bacterial cellulose nanocomposite for biomedical applications.
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    ABSTRACT: Compliance mismatch between the synthetic graft and the surrounding native tissue has been reported as a major factor in ultimate failure of the currently used cardiovascular graft replacements. Thus, developing biomaterials that display close mechanical properties as the tissue it is replacing is an important objective in biomedical devices design. Polyvinyl alcohol (PVA) is a biocompatible hydrogel with characteristics desired for biomedical applications. It can be crosslinked by a low temperature thermal cycling process. By using a novel thermal processing method under an applied strain and with the addition of a small amount of bacterial cellulose (BC) nanofibers, an anisotropic PVA-BC nanocomposite was created. The stress-strain tensile properties of porcine aorta were closely matched in both the circumferential and the axial directions by one type of anisotropic PVA-BC nanocomposite (10% PVA with 0.3% BC at 75% initial strain and cycle 2) within physiological range, with improved resistance to further stretch beyond physiological strains. The PVA-BC nanocomposite gives a broad range of mechanical properties, including anisotropy, by controlling material and processing parameters. PVA-BC nanocomposites with controlled degree of anisotropy that closely match the mechanical properties of the soft tissue it might replace, ranging from cardiovascular to other connective tissues, can be created.
    Journal of Biomedical Materials Research Part B Applied Biomaterials 09/2008; 86(2):444-52. · 2.15 Impact Factor
  • Article: Fluoride release from dental cements and composites: a mechanistic study.
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    ABSTRACT: The purpose of this study was (1) to compare the fluoride release profile of an experimental composite to commercial GICs, resin-modified GICs, and composite resins; (2) to assess the fluoride release process. Commercial materials (n = 3) were prepared according to manufacturers' directions. The experimental composite (n = 3) consisted of 78 wt% filler and 22 wt% resin. The resin consisted of 19 wt% BisGMA, 38 wt% UDMA, 19 wt% TEGDMA, and 24 wt% HEMA. Disc specimens were placed into 25 ml of deionized water in sealed polyethylene vials and shaked at 1.4 Hz at 37 degrees C. Fluoride release was measured using a fluoride-ion specific electrode at different time intervals up to 284 days. The fluoride release rate of the experimental composite demonstrated the highest rate of release within the first day (p = 0.05), but decreased significantly by day 7. Release rates of the commercial glass-ionomer cements and resin-modified glass-ionomer cements thereafter were significantly higher than the experimental and commercial composites at p = 0.05. Among the materials studied, cumulative fluoride release is adequately described by a two-term equation consisting of an initial fluoride release via a rapid dissolution process followed by a long-term diffusive release. An increase in the hydrophilicity of the polymer matrix through the introduction of HEMA improved the fluoride release over the short term during which dissolution occurs. Such a release behavior could be beneficial if it results in a fluoride reservoir that could be maintained by a prolonged slower release thereafter.
    Dental Materials 05/2006; 22(4):366-73. · 3.13 Impact Factor
  • Article: Measurement of the elastic modulus of single bacterial cellulose fibers using atomic force microscopy.
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    ABSTRACT: The ability of the atomic force microscope to measure forces with subnanonewton sensitivity at nanometer-scale lateral resolutions has led to its use in the mechanical characterization of nanomaterials. Recent studies have shown that the atomic force microscope can be used to measure the elastic moduli of suspended fibers by performing a nanoscale three-point bending test, in which the center of the fiber is deflected by a known force. We extend this technique by modeling the deflection measured at several points along a suspended fiber, allowing us to obtain more accurate data, as well as to justify the mechanical model used. As a demonstration, we have measured a value of 78 +/- 17 GPa for Young's modulus of bacterial cellulose fibers with diameters ranging from 35 to 90 nm. This value is considerably higher than previous estimates, obtained by less direct means, of the mechanical strength of individual cellulose fibers.
    Langmuir 08/2005; 21(14):6642-6. · 4.19 Impact Factor
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    Article: Simultaneous measurement of Young's and shear moduli of multiwalled carbon nanotubes using atomic force microscopy
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    ABSTRACT: Carbon nanotubes CNTs are widely hailed as the strongest material known to mankind. However, experimental measurements—and even theoretical estimates—of their mechanical properties span a wide range. We present an atomic force microscopy study of multiwalled CNTs, which, unlike previous such studies, measures the tube compliance as a function of position along suspended tubes. This permits a simultaneous determination of the effective Young's and shear moduli of CNTs: 350± 110 and 1.4± 0.3 GPa, respectively. © 2007 American Institute of Physics.
  • Article: Statistical optimization of culture conditions for bacterial cellulose production by Acetobacter xylinum BPR 2001 from maple syrup
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    ABSTRACT: Bacterial cellulose production by Acetobacter xylinum BPR 2001 was optimized using maple syrup as a carbon source. Twelve culture parameters were screened by the Plackett–Burman design and significant parameters were optimized by the response surface methodology using a three-level, four-factor Box–Behnken design. For fermentation in a rotary shaker, the optimal conditions for bacterial cellulose production were: maple syrup 30 g carbohydrate/l, (NH4)2SO4 3.3 g/l, KH2PO4 1 g/l, yeast extract 20 g/l, citric acid 1.6 g/l, trisodium citrate dehydrate 2.4 g/l, ethanol 0.5% (v/v), acetic acid 0.5 g/l, MgSO4·7H2O 0.8 g/l, inoculum age 3 days, inoculum volume 6% (v/v), shaking speed 135 rpm, and incubation temperature 25 °C. Comparison of bacterial cellulose production with maple syrup or pure sugars showed maple syrup was a suitable carbon source. This was the first demonstration of conversion of maple syrup, a plentiful renewable resource, into bacterial cellulose, a nanobiomaterial ideal for many applications.
    Carbohydrate Polymers 85(3):506-513. · 3.63 Impact Factor