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1.  An In Vitro Assessment of Fibroblast and Osteoblast Response to Alendronate-Modified Titanium and the Potential for Decreasing Fibrous Encapsulation 
Tissue Engineering. Part A  2013;19(17-18):1919-1930.
Fibrous encapsulation can impair implant osseointegration and cause implant failure but currently there are limited strategies to address this problem. Since bisphosphonates (BPs), a class of drugs widely used to treat bone diseases, was recently found to induce fibroblast apoptosis, we hypothesize that by loading BPs on titanium (Ti) implant surface, fibrous encapsulation may be inhibited with simultaneous enhancement of implant osseointegration. This strategy of local administration can also be expected to minimize the adverse side effects of BPs, which are associated with intravenous injections. To verify this hypothesis, alendronate was loaded on Ti surface via a hydroxyapatite (CaP) coating, and the effects of the loaded alendronate on fibroblast proliferation and apoptosis, and osteoblast proliferation, alkaline phosphatase (ALP) activity, and apoptosis were investigated in vitro. With a surface density of loaded alendronate 0.046 mg/cm2 or higher, fibroblast proliferation was suppressed due to increased apoptosis, while osteoblast proliferation and ALP activity increased with minimal apoptosis. In a coculture of fibroblasts and osteoblasts in a 1:1 ratio, ∼60% of the cells on these alendronate-loaded substrates were osteoblasts 1 day after cell seeding. The percentage of osteoblasts increased to about 75% 4 days after cell seeding. These results suggest that fibroblasts and osteoblasts respond differently toward the alendronate-modified substrates, and this phenomenon can potentially be capitalized to reduce fibrous encapsulation.
doi:10.1089/ten.tea.2012.0218
PMCID: PMC3725798  PMID: 23540949
2.  Efficient Derivation of Lateral Plate and Paraxial Mesoderm Subtypes from Human Embryonic Stem Cells Through GSKi-Mediated Differentiation 
Stem Cells and Development  2013;22(13):1893-1906.
The vertebrae mesoderm is a source of cells that forms a variety of tissues, including the heart, vasculature, and blood. Consequently, the derivation of various mesoderm-specific cell types from human embryonic stem cells (hESCs) has attracted the interest of many investigators owing to their therapeutic potential in clinical applications. However, the need for efficient and reliable methods of differentiation into mesoderm lineage cell types remains a significant challenge. Here, we demonstrated that inhibition of glycogen synthase kinase-3 (GSK-3) is an essential first step toward efficient generation of the mesoderm. Under chemically defined conditions without additional growth factors/cytokines, short-term GSK inhibitor (GSKi) treatment effectively drives differentiation of hESCs into the primitive streak (PS), which can potentially commit toward the mesoderm when further supplemented with bone morphogenetic protein 4. Further analysis confirmed that the PS-like cells derived from GSKi treatment are bipotential, being able to specify toward the endoderm as well. Our findings suggest that the bipotential, PS/mesendoderm-like cell population exists only at the initial stages of GSK-3 inhibition, whereas long-term inhibition results in an endodermal fate. Lastly, we demonstrated that our differentiation approach could efficiently generate lateral plate (CD34+KDR+) and paraxial (CD34−PDGFRα+) mesoderm subsets that can be further differentiated along the endothelial and smooth muscle lineages, respectively. In conclusion, our study presents a unique approach for generating early mesoderm progenitors in a chemically directed fashion through the use of small-molecule GSK-3 inhibitor, which may be useful for future applications in regenerative medicine.
doi:10.1089/scd.2012.0590
PMCID: PMC3685395  PMID: 23413973
3.  Acid-Sensitive Magnetic Nanoparticles as Potential Drug Depots 
Superparamagnetic magnetic nanoparticles were successfully functionalized with poly(methacrylic acid) via atom transfer radical polymerization, followed by conjugation to doxorubicin (Dox). Because of pH-sensitive hydrazone linkages, the rate and extent of Dox release from the particles was higher at a lower pH and/or a higher temperature than at physiological conditions. Appropriate changes to the pH and temperature can increase the drug release from the particles. Because of the released drug, the particles were found to be cytotoxic to human breast cancer cells in vitro. Such magnetic nanoparticles, with the potential to retain drug under physiological conditions and release the drug in conditions where the pH is lower or temperature is higher, may be useful in magnetic drug targeting by reducing the side effects of the drug caused to healthy tissues. In addition, they may serve as hyperthermia agents where the high temperatures used in hyperthermia can trigger further drug release.
doi:10.1002/aic.12373
PMCID: PMC3134249  PMID: 21760639
magnetic nanoparticles; cancer cells; conjugation; doxorubicin; poly(methacrylic acid); hydrazone linkages; magnetic drug targeting
4.  HER-2-mediated endocytosis of magnetic nanospheres and the implications in cell targeting and particle magnetization 
Biomaterials  2008;29(14):2270-2279.
Polypyrrole-Fe3O4 nanospheres were synthesized via an emulsion polymerization method with hyaluronic acid as the surfactant. Hyaluronic acid offers the advantages of biocompatibility, cell adhesive property and the availability of functional groups for attachment of other molecules. The nanospheres were further functionalized with herceptin, and the efficacy of uptake of the functionalized nanospheres by human breast cancer cells was evaluated. It is envisioned that the combination of hyaluronic acid with its cell adhesive property and herceptin would result in high efficacy of internalization of the nanospheres by the cancer cells via a HER-2-mediated endocytosis. Our results showed that this is indeed the case and that the high concentration of herceptin-functionalized magnetic nanospheres in the cancer cells offers great potential in cancer cell-targeting and treatment. In addition, the magnetic property of these nanospheres was also critically investigated and magnetization was found to be affected by the particles’ environment. The combination of these cell-targeting magnetic carriers with chemotherapeutic agents will be highly advantageous for the preferential killing of cancer cells in hyperthermia treatment.
doi:10.1016/j.biomaterials.2008.01.028
PMCID: PMC2312094  PMID: 18289668
Polypyrrole-Fe3O4 nanospheres; herceptin; HER-2; mediated endocytosis; cell-targeting; magnetization
5.  In vitro effect of a corrosive hostile ocular surface on candidate biomaterials for keratoprosthesis skirt 
The British Journal of Ophthalmology  2012;96(9):1252-1258.
Aim
Keratoprosthesis (KPro) devices are prone to long-term corrosion and microbiological assault. The authors aimed to compare the inflammatory response and material dissolution properties of two candidate KPro skirt materials, hydroxyapatite (HA) and titania (TiO2) in a simulated in vitro cornea inflammation environment.
Methods
Lipopolysaccharide-stimulated cytokine secretions were evaluated with human corneal fibroblasts on both HA and TiO2. Material specimens were subjected to electrochemical and long-term incubation test with artificial tear fluid (ATF) of various acidities. Topography and surface roughness of material discs were analysed by scanning electron microscopy and atomic force microscopy.
Results
There were less cytokines secreted from human corneal fibroblasts seeded on TiO2 substrates as compared with HA. TiO2 was more resistant to the corrosion effect caused by acidic ATF in contrast to HA. Moreover, the elemental composition of TiO2 was more stable than HA after long-term incubation with ATF.
Conclusions
TiO2 is more resistant to inflammatory degradation and has a higher corrosion resistance as compared with HA, and in this regard may be a suitable material to replace HA as an osteo-odonto-keratoprosthesis skirt. This would reduce resorption rates for KPro surgery.
doi:10.1136/bjophthalmol-2012-301633
PMCID: PMC3432489  PMID: 22802307
OOKP; microbial infection; material dissolution; artificial tear fluid; cornea; biochemistry; prosthesis; microbiology; contact lens; stem cells; lens and zonules; treatment surgery; epidemiology; experimental and animal models; ocular surface; genetics; imaging; treatment lasers

Results 1-5 (5)