A Bottom-Up Assembly Of Vascularized Bioartificial Constructs Using Ecm Based Microscale Modules

A BOTTOM-UP ASSEMBLY OF VASCULARIZEDBIOARTIFICIAL CONSTRUCTS USING ECM BASEDMICROSCALE MODULESby:RAMKUMAR TIRUVANNAMALAI ANNAMALAIAugust 2014Advisor: Dr. Howard MatthewMajor: Biomedical EngineeringDegree: Doctor of Philosophy Tissue engineering aims to create functional biological tissues to treat diseases anddamaged organs. A primary goal is to fabricate a 3D construct that can promote cell-cellinteraction, extra cellular matrix (ECM) deposition and tissue level organization. Accomplishingthese prerequisites with the currently available conventional scaffolds and fabrication techniquesstill remains a challenge. To reproduce the full functionality there is a need to engineer tissueconstructs that mimic the innate architecture and complexity of natural tissues. The limited abilityto vascularize and perfuse thick, cell-laden tissue constructs has hindered efforts to engineercomplex tissues and organs, including liver, heart and kidney. The emerging field of modular tissueengineering aims to address this limitation by fabricating constructs from the bottom up, with theobjective of recreating native tissue architecture and promoting extensive vascularization. Here, we report the elements of a simple yet efficient method for fabricating vascularizedtissue constructs by fusing biodegradable microcapsules with tunable interior environments.Parenchymal cells of various types, (i.e. trophoblasts, vascular smooth muscle cells, hepatocytes)were suspended in glycosaminoglycan (GAG) solutions (4%/1.5% chondroitin