Bioprinting of MSC Exosomes for Bone Regeneration

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Abstract Mesenchymal stem cell (MSC) derived exosomes are versatile agents that possess immunomodulatory and regenerative properties and can be engineered for enhanced tissue-specific activity. To extend the advantages of such engineered exosomes, challenges to targeting, delivery and biomaterial loading need to be addressed both spatially and temporally. Addressing this knowledge gap will be a primary aspect of my independent research and this proposal is designed to provide me with the training and experience to transition into an independent investigator. I propose that 3D encapsulation and bioprinting of engineered exosomes in hydrogel carriers can address some of these challenges. On the foundations of my doctoral and postdoctoral work, I propose to engineer a tunable hydrogel system that can serve as a versatile exosome carrier and delivery platform. Two specific aims have been designed to test this hypothesis. In aim 1, I will encapsulate engineered osteoinductive exosomes in a novel hydrogel system that contains exosome binding motifs that have been identified in preliminary studies. The binding, release kinetics and functionality of the encapsulated exosomes will be quantitatively analyzed and based on application-specific (bone regeneration here) selection criteria, one candidate will be selected for aim 2. In aim 2, conditions for 3D bioprinting will be standardized for generation of photo crosslinked bioprinted 3D scaffolds with encapsulated engineered exosomes. The potency of these scaffolds to regenerate bone will be evaluated in vivo in a rat calvarial defect model. The successful completion of this project will provide a foundational knowledge for the controlled release of engineered exosomes and for their customized use in regenerative medicine using 3D bioprinting technology. This is a newly emerging field that provides an opportunity for me establish a recognized expertise and foster an academic career that focuses on regeneration using bioprinting of engineered exosomes.