Magnetic Nanoparticle Drug Delivery System for Promotion of Vascularization in Tissue Regeneration

The delivery of growth factors is a key aspect of tissue regeneration. Current technologies to deliver growth factors within an implanted device rely on systems which cannot be controlled once they are implanted. There is a need for a broadly applicable delivery method which can be triggered after implantation using external stimulus. The purpose of this project was to develop a delivery system which can delivery commonly used growth factors, release the factors on demand, and does not interact with existing imaging modalities. The delivery system used for these purposes utilizes magnetic iron oxide nanoparticles (MNPs) which are stimulated by an alternating magnetic field (AMF) to release their drug payload. When stimulated, the MNPs generate heat, which cleaves the linking molecule, 2,2'-azobis-(2,4-dimethylvaleronitrile) (ADVN), releasing the drug into surrounding tissue. The first aim of the project was to develop the MNP delivery system and asses its ability to deliver a target growth factor, VEGF using quantitative assays. The second aim was to assess the effectiveness of the delivery system in vitro. The final aim was to incorporate the MNP system into an in vivo subcutaneous implant model and assess its impact on tissue vascularization. The MNP system developed was successful in loading VEGF and releasing it upon AMF stimulation. The released VEGF promoted vascularization in the surrounding tissue. The delivery platform is adaptable to deliver a wide range of factors and could be useful for increasing the effectiveness of existing and future regenerative devices.