Abstract

Organ-specific Models of Barrier Function

Roger Kamm, Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, Massachusetts Institute of Technology (MIT)

Barrier function, the ability to selectively allow passage of molecules or nanoparticles based on their physicochemical properties, is critical in numerous physiological and pathological settings. Here we discuss two examples.  The first is transport across the blood-brain barrier of therapeutic molecules or nanoparticles.  Focusing on the exchange of proteins of varying size and functionalized nanoparticles for targeting cytotoxic agents to glioblastoma multiform the mechanisms and control of delivery will be discussed.  The second model involves subcutaneous delivery of monoclonal antibodies and their bioavailability.  Brain and skin models are all human-derived and utilize either primary cells or iPSC-derived cells. Studies are based on a common microfluidic platform in which vascular networks (both blood and lymphatic) are grown by self-assembly within a 3D matrix.  Flows and pressures are controlled via simple onboard pumping systems capable of continuous circulation of a small volume of medium at physiological flow rates, with or without circulating immune cells.  These systems are compatible with moderate throughput studies in a standard 96-well format.