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Local Delivery Of Mesenchymal Stem Cells Expressing Osteogenesis-Inducing Microrna For Bone Tissue Engineering Applications, Marco Antonio Arriaga

Theses and Dissertations

Bone is capable of regenerating autonomously when the injury is small (< 2.5 cm), however, large (> 2.5 cm) or insufficiently vascularized defects require intervention to repair. The overall goal of this project is to contribute towards the development of novel strategies to aid bone tissue regeneration by delivering mesenchymal stem cells expressing microRNAs that induce expression of the runt-related transcription factor 2 (RUNX2). It was determined that porous polycaprolactone (PCL) scaffolds fabricated to have a higher surface area to volume ratio (SVR) (> 80) compared to lower SVR (< 80) were hydrolyzed at a higher rate. Scaffolds fabricated with 80 vol. %/300–500 µm porogen were optimal for cell colonization as higher absorbance of metabolized MTT was detected compared to other scaffold types. From the subset of 5 miRNAs tested, miRNA-26a, miRNA-196 and miRNA-218 demonstrated higher upregulation of RUNX2 gene expression and calcium mineralization and thus, are promising candidates for bone tissue regeneration.