Date on Master's Thesis/Doctoral Dissertation

12-2019

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Mechanical Engineering

Degree Program

Mechanical Engineering, PhD

Committee Chair

Keynton, Robert

Committee Co-Chair (if applicable)

Williams, Stuart

Committee Member

Soucy, Patricia

Committee Member

Kate, Kunal

Committee Member

Sumanasekera, Gamini

Author's Keywords

direct-write; biopolymer; mircrovascular; endothelial; collagen gel

Abstract

Engineering of bulk tissues has been limited by the lack of nutrient and waste exchange in these tissues without an adjacent capillary network. To produce microvasculature, a scaffold must be produced that provides temporary mechanical support and stimulate endothelial cell adhesion, growth, and morphogenesis into a vessel. However, current well-established techniques for producing microvasculature, such as electrospinning, are limited since they lack both the precision to control fiber placement in three-dimensional space and the ability to create fiber networks with predefined diameters to replicate the physiological microvascular progression from arteriole to capillary to venule. Our group has developed a “Direct-write” technique using a 3-Axis robotic dispensing system to process polymers into precisely positioned, three-dimensional, suspended fibers with controlled diameters. Within this dissertation, a conceptual scaffold-covering strategy is presented for the formation of the precisely positioned, three-dimensional microvascular structure with a controlled diameter in vitro. This study considers ways to extend the 3-Axis robotic dispensing system by incorporating new biodegradable materials into micro-fibers. First, a number of different biopolymers (natural, synthetic, composites, and copolymers) were used for demonstrating the capability of direct-writing micro-fibers and branched structures with microvascular-scale diameter through the 3-Axial robotic dispensing system. Then, the fabrication process was characterized by a design of experiments and a generalized mathematical model was developed through dimensional analysis. The empirical model determined the correlation between polymer fiber diameter and intrinsic properties of the polymer solution together with the processing parameters of the robotic dispensing system and allows future users the ability to employ the 3-Axis robotic dispensing system to direct-write micro-fibers without trial-and-error work. This study also considers ways to broaden the pre-vascularization methods by covering Human Dermal Microvascular Endothelial Cells (HDMECs) on the fabricated scaffold to generate the microvascular structure. HDMECs cultured on the produced micro-fiber scaffolds were observed to form a confluent monolayer spread along the axis and around the circumference of the fibers within two days of seeding. Once confluency was reached, the cell-covered scaffold was embedded into a collagen gel and a hybrid structure was formed. Through these experiments, we demonstrate the ability to obtain a cell-viable, flexible, and free-standing “modular tissue”, which could be potentially assembled to a three-dimensional microvascular network through angiogenesis mechanism.

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