Design and development of an in vitro vascular model using 3D printing-enabled hydrogel casting technique

Liang Yang

Date of Award

7-31-2016

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical and Chemical Engineering

Advisor(s)

Pranav Soman

Subject Categories

Engineering

Abstract

The inability to adequately vascularize tissues in vivo or in vitro currently limits the development of tissue engineering. Especially, to fabricate formation of functional vascular bed within the tissue construct is becoming the key challenge in tissue engineering. Answering the question on how to build up micro-channels in 3D environment to mimic the vascular structure and function inevitably becomes the essence of this challenge. As a first step towards address this problem, we aim to develop a functional blood vessel by using a Microfluidic device with relevant cell types using an easy-to-use 3D printing approach. In this work, we developed a strategy to mimic the vascular structure by using multicellular vascular channels are formed using a 3D printed template, which is then coated by using gelatin methacrylate hydrogel construct encapsulated with murine 10T1/2, and lined with human endothelial cells (HUVECs) within the channels. This approach has multiple advantages. 3D printing techniques offer an approach to fabricate complex geometries capable of controlling the geometry-induced flow changes precisely. Gelatin methacrylate (GelMA) was coated inside of the PDMS channel to form an inner layer. Then, GelMA layer laden with murine 10T1/2s cells is lined with a monolayer of human endothelial cells (HUVECs) to form the vascular inner environment. Lastly, high/low molecular weight dextran molecules conjugated with fluoresces were flowed through the channel to test the integration and diffusion features of the L-shape hydrogel microfluidic. Corresponding shear flow effects were demonstrated using COMSOL simulations. Overall, our work demonstrates a robust, inexpensive, and biocompatible method of developing a vascular model in user-defined geometry, with a potential for drug delivery research, tumor cells invasion research and disease modeling applications. Results prove that, first, 3D printing technique can be used to fabricate microfluidic devices. 3D printing is a low-cost, easy-to-use, fabrication method as compared to the expensive expertise-driven clean-room based lithography process used conventionally to fabricate microfluidic chips/devices. Secondly, gelatin methacrylate is an optimal biomaterial to facilitate nutrient diffusion and is sufficient to support cell viability of encapsulated 10T1/2 cells and HUVECs binding. Last, the L-shaped hydrogel microfluidic model performs a functional barrier both large/small molecular weight dextran molecules. This functional micro-vessel platform serves as a unique experimental tool for investigating fundamental mechanisms of vascular remodeling. In the future use, the fabrication strategy used in this work can be used for the tumor cell invasive research and vascular drug delivery tests.

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