Strontium functionalized scaffold for bone tissue engineering.

Drug functionalized scaffolds are currently being employed to improve local delivery of osteoprotective drugs with the aim of reducing their loading dose as well as unwanted systemic complications. In this study we tested a poly-(ε) caprolactone (PCL)-laponite-strontium ranelate (SRA) composite scaffold (PLS3) for its abilities to support growth and osteogenic differentiation of human marrow derived stromal stem cells (hMSC). The in vitro experiments showed the PLS3 scaffold supported cell growth and osteogenic differentiation. The in vivo implantation of hMSC seeded PLS3 scaffold in immunocompromised mice revealed vascularized ectopic bone formation. PLS3 scaffolds can be useful in bone regenerative applications in the fields of orthopaedics and dentistry.

False Positive Uptake in Bilateral Gynecomastia on 68Ga-PSMA PET/CT Scan.

A 66-year-old man on hormonal therapy with prostate cancer was referred for Ga-PSMA PET/CT scan for biochemical recurrence. Ga-PSMA PET/CT scan detected moderate heterogeneous tracer concentration in bilateral breast parenchyma, in addition to the abnormal tracer concentration in enlarged prostate gland, right external iliac lymph node, and sclerotic lesion in L4 vertebra. On clinical examination, he was found to have bilateral gynecomastia. Abnormal concentration of Ga-PSMA in breast cancer is now well known, and in this context, it is important to know that tracer localization can occur in gynecomastia as well, as evidenced in this case.

Polycaprolactone-laponite composite scaffold releasing strontium ranelate for bone tissue engineering applications.

We report polycaprolactone-laponite composite scaffold for the controlled release of strontium ranelate (SRA), a drug for osteoporosis. Laponite-SRA complex with electrostatic interaction between the drug and laponite was obtained through an aqueous phase reaction. Structural evaluation verified complexation of the bulky SRA molecules with the negatively charged laponite tactoid surfaces, leading to extended ordering of the tactoids, leaving behind the interlayer spacing of the laponite unchanged. The laponite-SRA complex was solution blended with polycaprolactone to obtain composite scaffolds. The strategy was found improving the dispersibility of laponite in PCL due to partial organomodification imparted through interaction with the SRA. The composite scaffolds with varying laponite-SRA complex content of 3-12wt% were evaluated in vitro using human osteosarcoma cells. It was confirmed that an optimum composition of the scaffold with 3wt% laponite-SRA complex loading would be ideal for obtaining enhanced ALP activity, by maintaining cell viability.

Fabrication of Epoxy Vesicles using Self-Assembling Polystyrene-Montmorillonite Nanocomposite Reusable Template.

We report the fabrication of thermoset vesicles using a thermoplastic-clay nanocomposite vesicle reusable template. Epoxy polymer vesicles (EPV) of micrometer diameters were synthesized from bisphenol-A diglycidyl ether resin encapsulated within a self-assembled, polystyrene-montmorillonite hybrid nanocomposite (PCN) template and in situ cross-linked with polyamine curing agent. The size and wall thickness of the EPV vesicles were shown to be controlled by the epoxy resin concentration up to a critical epoxy concentration of 20 wt %, beyond which the wall thickness alone was found to be increasing. The EPVs dispersed in a polystyrene matrix at a loading of 2 wt % were found to reduce the dielectric constant of polystyrene from 3.1 to 2.0, and a linear decrease with decreasing wall thickness of the EPV, attributed to the increase in free volume involving the intrinsic porosity from the rigid epoxy vesicles and the composite, exhibited improved thermal stability also. The result suggests that vesicles produced by micromolding using self-assembled PCN can be utilized for the synthesis of polymer microcomposites having good interfacial bonding as well as low dielectric constant and good thermal stability for use in electronic packaging applications.

Hybrid scaffold bearing polymer-siloxane Schiff base linkage for bone tissue engineering.

Scaffolds that can provide the requisite biological cues for the fast regeneration of bone are highly relevant to the advances in tissue engineering and regenerative medicine. In the present article, we report the fabrication of a chitosan-gelatin-siloxane scaffold bearing interpolymer-siloxane Schiff base linkage, through a single-step dialdehyde cross-linking and freeze-drying method using 3-aminopropyltriethoxysilane as the siloxane precursor. Swelling of the scaffolds in phosphate buffered saline indicates enhancement with increase in siloxane concentration, whereas compressive moduli of the wet scaffolds reveal inverse dependence, owing to the presence of siloxane, rich in silanol groups. It is suggested that through the strategy of dialdehyde cross-linking, a limiting siloxane loading of 20 wt.% into a chitosan -gelatin matrix should be considered ideal for bone tissue engineering, because the scaffold made with 30 wt.% siloxane loading degrades by 48 wt.%, in 21 days. The hybrid scaffolds bearing Schiff base linkage between the polymer and siloxane, unlike the stable linkages in earlier reports, are expected to give a faster release of siloxanes and enhancement in osteogenesis. This is verified by the in vitro evaluation of the hybrid scaffolds using rabbit adipose mesenchymal stem cells, which revealed osteogenic cell-clusters on a polymer-siloxane scaffold, enhanced alkaline phosphatase activity and the expression of bone-specific genes, whereas the control scaffold without siloxane supported more of cell-proliferation than differentiation. A siloxane concentration dependent enhancement in osteogenic differentiation is also observed.

Fabrication of a microvesicles-incorporated fibrous membrane for controlled delivery applications in tissue engineering.

A scaffold, which can provide mechanical support for tissue regeneration and simultaneously release functionally active biomolecules are highly desirable for tissue engineering applications. Herein, we report the fabrication of a fibrous mesh of polycaprolactone (PCL) incorporating PCL-pluronic (F127) microvesicles through electrospinning, by exploiting the slow dissolution of PCL in glacial acetic acid (g-AA). Micro-vesicles 1-10 µm in diameter were fabricated through a non-solubility driven spontaneous self-assembly and stabilization of F127 with low molecular weight PCL in tetrahydrofuran-water mixture. Time-dependent stability of the vesicles in g-AA was confirmed prior to the electrospinning. The electrospun membrane was found to be comprised of microvesicles entangled in a fibrous mesh of PCL with a fiber diameter ranging from 50-300 nm. Significant reduction in the release rate of rhodamine-B, an indicator dye from the electrospun membrane, when compared to that from the vesicle alone, evidences the surface coating of the vesicles with high molecular weight PCL during electrospinning. The vesicle incorporated membrane exhibited increased hydrophilicity when compared to the control PCL membrane, possibly due to surface unevenness and the hydrophilic F127. This enhanced surface hydrophilicity led to an increased cell viability of L929 cells on the membrane.

Polyhedral oligomeric silsesquioxane-F68 hybrid vesicles for folate receptor targeted anti-cancer drug delivery.

Polyhedral Oligomeric Silsesquioxane (POSS)-F68 hybrid vesicles with an average diameter of 700 nm are produced using a stable solution of heterofunctional POSS having 3-aminopropyl and vinyl groups and pluronic F68 in ethanol-water mixture. Thermogram and zeta potential values evidence the spontaneous self-assembly of POSS into bilayers through H-bonding interaction between the aminopropyl groups, and the effective stabilization of the POSS-bilayers by amphiphilic F68 during solvent-evaporation to form the vesicles. The vesicles are noncytotoxic and dispersible in aqueous solvents through steric stabilization provided by the hydrophilic F68. A highly facile coinclusion method has been used for making doxorubicin and folic acid loaded vesicles. Doxorubicin loaded in the vesicles exhibits a controlled release profile in phosphate buffered saline. Confocal microscopic and flow cytometric studies on the endocytosis of the vesicles by HeLa and HOS cells prove that a noncovalent entrapment of excess folic acid in the vesicles through H-bonding is sufficient to enhance the uptake significantly. POSS-F68 vesicles in combination with folic acid and a chemotherapeutic can have potential for targeted intracellular anti-cancer drug delivery.

Improved dielectric and mechanical properties of polystyrene-hybrid silica sphere composite induced through bifunctionalization at the interface.

Hybrid silica spheres (HS) of size 270-350 nm with vinyl and aminopropyl surface groups were incorporated in polystyrene (PS), and its effect on dielectric properties, coefficient of thermal expansion (CTE), and strength of PS-HS composite was studied. Incorporation of HS in PS followed a decrease in the dielectric constant from 3.2 for PS to 2.6 for composite with 7.5 vol % HS. The decrease in the dielectric constant was attributed to (i) increased interfacial porosity, (ii) formation of anhydrous HS having low dielectric constant, during hot processing of the composites, and (iii) dispersion and preservation of the anhydrous HS in the hydrophobic matrix. The dielectric constant of the composites with HS content up to 7.5 vol % does not vary much with temperature in the range from -20 to 65 °C. These composites also exhibited reduced CTE and improved flexural strength/stiffness due to good interfacial bonding through HS vinyl groups and dispersion of the filler in the matrix. The dielectric loss increased with HS content, and the loss measured for 7.5 vol % PS-HS composite was 6 × 10(-3), as compared to 10(-4) for PS. At HS loading above 7.5 vol %, the tendency of HS to agglomerate and form percolated structure lead to an increase in the dielectric constant and decrease in the mechanical properties of the composites.

Poly(lactide-co-glycolide)-laponite-F68 nanocomposite vesicles through a single-step double-emulsion method for the controlled release of doxorubicin.

Poly(lactide-co-glycolide) (PLGA)-laponite-F68 nanocomposite (PNC) vesicles were prepared through a technically facile, single-step water/oil/water double-emulsion method using ethyl acetate/water mixture. Vesicles of diameter 100 nm to 1.2 µm and average membrane thickness 30 nm were produced. Encapsulation with chemotherapeutic drug doxorubicin revealed unilamellar nature of the vesicle wall. PNC exhibited exfoliated morphology, enhanced thermal stability over neat PLGA, and a glass transition temperature of 54.29 °C. The zeta potential of -14.1 ± 0.231 for the vesicles revealed that the negatively charged PLGA surface is covered with neutral F68 in the vesicle wall. F68-Assisted formation of water/oil/water double emulsion of PNC in ethyl acetate/water mixture is proposed for the formation of the vesicles. Release characteristics of doxorubicin in phosphate-buffered saline (pH 7.4), cytotoxicity of bare and drug-loaded PNC vesicles with L929 cells, and uptake of doxorubicin with C6 fibroblast glioma cell line were also investigated.

Micropatterned surfaces through moisture-induced phase-separation of polystyrene-clay nanocomposite particles.

We report micropatterned polystyrene-clay nanocomposite (PCN) surfaces with concavities by moisture-induced phase separation of PCN particles. Micropatterned film with concavity size of 800 nm to 1.3 microm and a high number density of 2 x 10(8) features/cm(2) was obtained by drop-casting PCN solution (20 mg/mL PCN/THF) under ambient relative humidity of 70-80%. It is proposed that water droplets were channeled through the hydrophilic interfaces between the PCN particles, and the two-dimensional array of concavities was formed by spontaneous phase separation due to the presence of rigid clay platelets. The concavity size and number density can be tuned by varying the solvent for PCN. Micropatterned film with concavity size in the range of 650 nm to 1.1 microm with a number density of 5 x 10(7) features/cm(2) was obtained using chloroform as solvent, whereas a concavity size of 150-740 nm and number density of 10(8) features/cm(2) were obtained using carbon disulfide.

Microvesicles through self-assembly of polystyrene-clay nanocomposite.

Polystyrene-clay nanocomposite (PCN) particles, which exhibited concentration dependent self-assembling property in THF were synthesized by in situ intercalative polymerization of styrene with vinyl POSS amine-modified organoclay. While the particles from dilute solution of 0.001 mg mL(-1) showed a lateral dimension of 190-800 nm and thickness of 120 nm, microvesicles of diameter of 2.5-3.5 microm and average membrane thickness of 85 nm were produced from solution concentration of 2.5 mg mL(-1) by consuming the particles. The particle possessed a sandwich structure consisting of polystyrene(PS)-POSS-intercalated clay tactoid of thickness of 12.6 nm at the core and PS chains growing from the tactoid surfaces on either side, exposing the hydroxylated edges of the silicate layers. Vesicle was formed by edge-edge association of the silicate layers so that the layers lie flat along the vesicle membrane. Guest-encapsulated vesicles were obtained when prepared from solutions containing guest molecules.