Multi Scale In Vitro D Tissue Model of Vascularized Bone Cartilage Interactions

Abstract Current in vitro models of vascularized bone tissues do not mimic the in vivo microenvironment comprising of diverse cell types in communication with each other through stromal barriers In addition they are hampered by lack of real time visualization and quantitation of vasculature bone as well as bone cartilage interactions In contrast animal models while providing useful information are time consuming expensive and in recent years have increasingly raised ethical concerns Furthermore animal studies provide limited understanding of mechanistic behavior compared to well controlled in vitro studies Thus there is an unmet need for an in vitro platform for improved monitoring and analysis of vascularized bone cartilage interactions We propose to develop and demonstrate a multi scale model of vascularized bone cartilage tissue for the understanding of cellular signaling with a Phase I focus on the interactions between endothelial cells bone cells specifically osteoblasts bone building cells and osteoclasts bone degrading cells and chondrocytes cartilage cells The multi scale nature of the proposed approach is based on the use of a a microscale based vascular bone cartilage model using microfluidics and tissue engineering to study cell signaling which informs b a meso scale vascular bone cartilage model interrogating both engineered constructs and native tissues for structural and functional studies Phase I will clearly and unequivocally demonstrate the use of this multiscale model of vascularized osteochondral tissue interactions for cell signaling The developed platform will mimic the morphology physiological flow and D multi cellular compositions observed in vivo and enable an easy and robust system for evaluation of cellular responses In Phase II the platform will be expanded to include other stromal cells e g fibroblasts and immune cells e g macrophages followed by detailed characterization of the signaling molecules and therapeutic screening A multi disciplinary industry academic partnership with expertise in microfluidics cell based assays and musculoskeletal biology and tissue regeneration has been assembled for successful completion of this project By providing an accurate quantitative and predictive model of physiological interactions the developed multi scale platform promises to establish a new paradigm for in vitro assessment of the physiological response to therapeutics Narrative The overall objective of this study is to develop an in vitro D tissue model for understanding of vascularized bone cartilage interactions in both normal and diseased tissues The developed model will have critical applications both in basic research where it can be used to understand vascularized bone tissue interactions and in drug development where it can be used to screen for and develop next generation therapeutics