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Effect of Bioglass Particle Size and Titania Morphology on the Bioactivity and Kinetics of Tissue Growth in Three-Dimensional Poly(ɛ-Caprolactone) Scaffolds with Controlled Pore Structure Produced by 3D-Printing Process

Tamjid Shabestary, Elnaz | 2011

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 42061 (48)
  4. University: Sharif University of Technology
  5. Department: Institute for Nanoscience and Nanotechnology
  6. Advisor(s): Bagheri, Reza; Vossoughi, Manouchehr; Simchi, Abdolreza
  7. Abstract:
  8. Polycaprolactone (PCL) scaffolds and its composites containing bioactive glass particles (45S5) and TiO2 nanostructures with pre-defined and controlled external and internal architecture were prepared via an indirect three-dimensional (3D) printing process. The scaffolds had an interconnected structure with macro- (400-500 μm) and micro- (~25 μm) pores. Bioactivity, mechanical behavior and kinetics of tissue growth in 3D scaffolds were studied. The size effect of biogactive glass particles (6 μm, 250 nm, <100 nm) and morphology of titania nanostructures (spherical, tube, leaf-like, and flower-like particles) were elaborated. The biogactive glass particles with different sizes were prepared by high energy ball-milling of commercial 45S5 Bioglass® particles while the titania nanostructures were synthesized via hydrothermal methods. Polymeric and composite films as well as 3D scaffolds were prepared by solvent casting and freeze-drying processes. Materials characterizations were performed via various analytical techniques including field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), energy dispersive spectrometry (EDS), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), atomic force microscopy, contact-angle measurement, quasi-static compression, and nanoindentation. In vitro bioactivity of the films was examined via immersion in simulated body fluid (SBF) and kinetics of tissue growth in 3D scaffolds was evaluated by culturing of MC3T3-E1 cells in α-MEM medium for up to 28 days. Histological staining and alkaline phosphate enzyme activity analysis were also performed. A non-equilibrium thermodynamic model was proposed to justify different mechanisms involving in the tissue growth rate depending on the shape and size of the pore structure. It was found that partial crystallization of amorphous bioactive glass particles to form calcium silicates occurred during ball milling. The degree of crystallization and agglomeration of the particles increased with prolonging the milling time and/or intensifying the milling energy. The PCL-based composite containing ultrafine bioactive glass particles with an average size of 250 nm exhibited improved bioactivity compared to micro-size and nano-scale particles. It was also shown that the size, morphology, and phase constitution (anatase or rutile) of TiO2 nanostructures remarkably influence the bioactivity of the PCL-based nanocomposite. The highest bioactivity was achieved for the nanocomposite containing spherical nanoparticles (21nm) with a high specific surface area (~33 m2/g) and having 70% anatase phase. It was shown a change in the hydrophilicity and surface roughness of polymer by the bioactive glass particles and TiO2 nanostructures contribute in the bioactivity of PCL. Evaluation of the kinetics of tissue growth in 3D scaffolds revealed a four-stage mechanism including (1) cell adhesion and spreading, (2) shape accommodation, (3) steady-state growth, and (4) diffusion/geometry-controlled growth. It was shown that the steady state growth rate was independent to the substrate material (scaffold); however, cell adhesion and spreading was influenced by the surface roughness, stiffness, and nanotopography. In overall, the results of mechanical and biological examinations indicated that the prepared scaffolds can be used for non-load-bearing applications in bone regenerative medicine.
  9. Keywords:
  10. Bioactivity ; Mechanical Properties ; Titania ; Bioactive Glass ; Polycaprolactone Composite ; Three Dimensional Scaffolds ; Tissue Growth Kinetics

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