Abstract
The use of injectable scaffolds as a minimally invasive method is a good choice in tissue engineering applications. A critical parameter for the tissue engineering scaffolds is a suitable morphology with interconnected pores. We present the development of a simvastatin loaded scaffold that forms in situ and provides the porous structure with interconnected pores. The formulation of these scaffolds includes a polymeric solution of poly lactic-co-glycolic acid (25 wt%) in N-methyl-2-pyrrolidone containing 6 wt% deionized water and porogen (mannitol, four times the weight of the polymer). We have grafted simvastatin to poly lactic-co-glycolic acid by the esterification reactions. Simvastatin or simvastatin-grafted poly lactic-co-glycolic acid in different levels was added to polymer solution and finally the solution was injected into phosphate buffered saline. The simvastatin-grafted poly lactic-co-glycolic acid was characterized by attenuated total reflection Fourier-transform infra-red and 1H-nuclear magnetic resonance spectroscopy. The morphology, porosity, and biocompatibility of the scaffolds were evaluated. The in vitro simvastatin release from the various formulations was studied. Osteogenic differentiation of the adipose-derived stem cells was investigated using alkaline phosphatase activity assay and cell mineralization was evaluated using Alizarin red staining. The morphology results showed the resultant scaffold was porous with the interconnected pores. The scaffolds presented 91% porosity. Non-toxic doses of simvastatin in the scaffolds were determined by methyl-thiazolyl diphenyl-tetrazolium bromide assay. The released simvastatin from the scaffolds continues over 80 days. Alkaline phosphatase activity and Alizarin red results indicated that cell osteogenic differentiation is promoted. The results demonstrated that release of simvastatin from the injectable scaffolds can have positive effects on osteogenic differentiation of the adipose-derived stem cells.
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