Simvastatin loaded porous hydroxyapatite based microcarriers for bone tissue engineering /

Güldiken, Merve
Bone tissue engineering provides a new medical therapy as an alternative to conventional bone replacement grafts. Carriers designed for bone tissue engineering applications should be biocompatible, bioactive, and porous and should also meet certain minimal requirements to obtain functional engineered tissues. Polymers, ceramic materials and their composites are widely used for developing such carriers. The objective of this study was to develop and characterize a simvastatin (SIM) loaded porous hydroxyapatite microcarrier system by water in oil emulsion method for bone tissue engineering applications. In order to obtain spherical and structurally stable microcarriers, powder size should be submicron with a narrow size range. For this purpose, firstly, HAp powders (~10-17 µm) were synthesized using co-precipitation and sol-gel methods. It was found that powder characteristics synthesized by both methods were not suitable to form porous microcarriers. Therefore, the microcarriers were then prepared using Nano-HAp powders (<200nm). Spherical shaped and structurally stable microcarriers were obtained with Nano-HAp powders. The average size of microcarriers prepared by Nano-HAp was determined to be 426 µm. The fabricated microcarriers were loaded with SIM and also coated with human decellularized adipose tissue (DAT). DAT coated and SIM loaded microcarriers were used for enhancing attachment, proliferation and osteoblastic differentiation of cells as well as for controlling SIM release. Drug loadings results were 59%, 61% and 32%, for different concentrations of SIM (1, 0.5 and 0.1 mg/ml), respectively. Release kinetics of drug loaded microcarriers could not be determined because of poor water solubility of SIM (13 µg/ml in dH2O). In vitro cell viability of SIM loaded and DAT coated microcarriers were conducted by using PrestoBlue assay with two different cell types, Saos-2 and human adipose derived stem cells (hASCs) for 10 days. The results showed that although the loaded SIM amounts were higher than the toxic dose, microcarriers were not cytotoxic on both cell types. A higher cell attachment on DAT coated microcarriers was observed compared to un-coated microcarriers. A time dependent increase in cell number was observed on both coated and DAT un-coated microcarriers. Therefore, it can be concluded that both DAT coated and uncoated SIM loaded HA microcarriers have a potential in treating bone defects with tissue engineering applications.


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Citation Formats
M. Güldiken, “Simvastatin loaded porous hydroxyapatite based microcarriers for bone tissue engineering /,” M.S. - Master of Science, Middle East Technical University, 2014.