Kemik dokusu mühendisliğinde solvent olmayan indüklenmiş faz ayırma tekniği kullanarak pcl-nha kompozit iskeleme fabrikasyonu ve karakterizasyonu

Bone fracture, one of the widespread injuries all around the world, is associated with individual disability and loss of social productivity resulting in very high treatment costs exceeding billion dollars. Well-designed scaffold implants are good alternatives in bone tissue engineering known to result in effective healing. An ideal bone scaffold should be biocompatible, porous, interconnected and strong, i.e. multi-functional. Therefore, composite materials with multi-scale porosities stand out as key desired scaffold features. Solid free-form fabrication (SFF) techniques exist with mechanical and biological functions tailorable to specific bone defects. However, only a few attempts have been made to create scaffolds with macro-micro porosity, despite their potential to more closely mimic the hierarchical architecture of native bones. Non-solvent induced phase separation technique (NIPS), mostly used in literature for the fabrication of membranes, is an effective technique capable to produce scaffolds with desired tunable porosities at different scales and offers the potential to be integrated to 3D printing. Towards that goal, this thesis focuses on an in-depth study of the pore morphology and its dependence on the composition of porous poly(ε-caprolactone) (PCL)/hydroxyapatite (HA) composites substrates at various thicknesses using the NIPS process. More specifically, the aim of this study is to fabricate and characterize PCL-nHA composite porous scaffolds having various nHA content (0, 10, 20% w/w) and thicknesses (800-900 and 1600-1800 microns) based on NIPS and understand its potential to produce 3D scaffolds when integrated to 3D printing. Effect of PCL concentration, nHA content and scaffold thickness were investigated on scaffold porosity and morphology such as pore size and its distribution, pore orientation and overall porosity. Internal micro-structure of the substrates are analyzed by micro-CT and SEM analysis was used for surface porosity analysis and validation of micro-CT results. Pore size distrubution, overall porosity and anistropy of pore network were evaluated based on micro-CT images and CTAnalyzer software. Rheological anlysis and UTM tests were also performed to analyze the solution's viscosity and resulting composite's strength. Atomic composition evaluation of scaffolds was conducted with EDS. Bone mineral density -for the detection of amount of Hydroxyapatite- measurement was computed by micro-CT. In addition to analysis of film scaffolds, the NIPS process is used to produce 2D layers of interconnected scaffolds using a commercial bioprinter as an initial step towards its use for the production of 3D scaffolds with controlled macro-porosity. Our results demonstrated that scaffold thickness and addition of nHA both enhance pore diameter in size. Micro-CT and SEM analyses showed that PCL-nHA scaffolds with various nHA content have multiscale porosities in micro (<50 microns) and macro (>50 microns) scale. While increase of thickness enhances pore size, increase of PCL concentration decreases pore size and overall porosity. Addition of nHA is linked to higher strength and lower viscosity upto a threshold value whereas leading to overall porosity, larger pore size, higher pore network orientation (anisotropy). SEM images confirm the pore size distribution result obtained by micro CT at the cross section and inhomogeneous porosity at the surface as well as a more homogeneous porosity distribution in the cross sections of both film scaffolds and the printed 2D grid scaffold. For surface functionalization, the scaffolds were coated with p(HEMA-co-EGDMA) via iCVD to increase surface hydrophilicity which is known to improve cell adhesion. Result of FTIR, and ellipsometer demonstrated that scaffold surface was coated successfully, and contact angle measurement showed that a hydrophilic surface was obtained. This thesis has demonstrated that NIPS can be integrated to 3D printing and successfully produce scaffolds with well controlled macro-pores and tunable micro-pores.