Date of Award

12-31-2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemical Engineering - (Ph.D.)

Department

Chemical and Materials Engineering

First Advisor

Murat Guvendiren

Second Advisor

Edward L. Dreyzin

Third Advisor

Treena Livingston Arinzeh

Fourth Advisor

Roman S. Voronov

Fifth Advisor

Xiaoyang Xu

Abstract

Tissue engineering is a multidisciplinary field that investigates and develops new methods to repair, regenerate and replace damaged tissues and organs, or to develop biomaterial platforms as in vitro models. Tissue engineering approaches require the fabrication of scaffolds using biomaterials or fabrication of living tissues using cells. As the demands of customized, implantable tissue/organs are increasing and becoming more urgent, conventional scaffold fabrication approaches are difficult to meet the requirements, especially for complex large-scale tissue fabrication. In this regard, three-dimensional (3D) printing attracted more interest over the past decades due to its unrivaled ability to fabricate highly customized tissues or scaffolds from patients’ medical images using computer aided design (CAD), as well as its flexibility, cost-effectiveness, and high efficiency. And more recently, 3D bioprinting can fabricate cellular constructs using a “bioink”, an aqueous composite formulation that contained live cells as a mandatory component, which is a big step towards functional organ fabrications.

However, to fully realize the potential of 3D (bio)printing in tissue engineering, there are still a lot of barriers before implantable artificial organs, including but not limited to vascularization of fabricated tissue/organs, multicellular biofabrication, limited functional biomaterial, and dynamic maintenance/remodeling. To address some of these problems, this dissertation aims to develop novel inks and approaches for printing tissue and organs. Firstly, a novel bioprinting approach is developed to create user-defined complex perfusable channels within cell-laden hydrogels, which uses commercially available bioprinters, hydrogels, and open-source software. The printing process is cell-friendly, and the channels could be further endothelialized to make the cell-laden hydrogel a vascularized tissue. Secondly, novel bioinks from UV-responsive norbornene-functionalized carboxymethyl cellulose macromers are developed. The cost-effectiveness, tunability, degradability, and cytocompatibility make this bioink platform a good addition to the current available bioink library. Thirdly, considering the demands of fabricating hard degradable scaffolds for bone tissue engineering, a polyester-based ink platform with tunable bioactivity is developed. Functionalized 3D printed scaffolds show a significant impact that enhanced the osteogenesis of human stem cells. Finally, the impact of the architectures of the 3D printed scaffolds on stem cell differentiation is investigated, which demonstrated enhanced osteogenesis of human stem cells on scaffolds with wavy architectures, compared with on scaffolds with orthogonal architectures.

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