Master of Engineering Science
The successful repair of bone defects and injuries is enhanced by the delivery of osteoinductive factors, such as drugs, growth factors, and genetic material that can promote the osteogenic differentiation of stem/stromal cells into osteoblasts. Nanoparticle delivery systems are being studied to enable the sustained release of these factors but suffer from limitations such as cytotoxicity issues, poor loading capacity, and poor cellular uptake. In this project, we developed cell-derived nanoparticles (CDNs), a biomimetic nanoparticle delivery system with high drug loading efficiency, to deliver a glucocorticoid drug, dexamethasone (Dex), to promote the osteogenic differentiation of stem/stromal cells. The synthesized Dex-loaded CDNs had a consistent size range of 30-920 nm, spherical shape, high drug loading efficiency, good cytocompatibility, and were internalized by human adipose-derived stem/stromal cells (hADSCs). Drug-loaded CDNs were able to induce the osteogenic differentiation of hADSCs in vitro, indicating their potential as an efficient drug delivery vehicle for bone regeneration and other applications.
Summary for Lay Audience
The use of bone tissue or grafts obtained from the same or different individuals is the most widely used method for the repair of bone defects and injuries in clinics today. Successful bone repair requires three components: a scaffold that supports the growth of new bone, molecules that promote the differentiation of stem/stromal cells in the area surrounding the injury into bone or osteoblast cells, and the cells which can give rise to new bone. The molecules that promote osteoblast formation are called osteoinductive molecules and they can be growth factors, drugs, or genetic material. The focus of current research is to efficiently deliver these molecules to the site of injury for the enhanced repair and regeneration of bone tissue. Nanoparticle delivery systems are being studied to enable the sustained and prolonged release of these factors, which is essential for the successful repair of the injury. However, they suffer from limitations such as toxicity to cells in high doses, inability to encapsulate large quantities of osteoinductive molecules, and inability to be taken up by cells which are essential to effectively deliver osteoinductive molecules to the target cells. In this project, we developed cell-derived nanoparticles (CDNs), which are synthesized from cell membranes of cells. During the preparation process, the cell membranes are broken into small fragments. These fragments can self-assemble to form nanoparticles. These nanoparticles mimic the properties of cell surfaces due to the presence of proteins, phospholipids, and carbohydrates carried over from the source cells. CDNs can encapsulate osteoinductive molecules within them during the self-assembly process. Here, CDNs were used to deliver dexamethasone (Dex), a well-known osteoinductive molecule, to promote the osteogenic differentiation of stem/stromal cells. They were able to induce the differentiation of these stem/stromal cells to bone cells, indicating they could be used as efficient drug delivery vehicles.
Polla Ravi, Shruthi, "Investigation of Cell Derived Nanoparticles for Drug Delivery and Osteogenic Differentiation of Human Stem/Stromal Cells" (2022). Electronic Thesis and Dissertation Repository. 8480.
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Available for download on Monday, October 31, 2022