Date of Award

12-2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Bioengineering

Committee Member

Michael J. Yost, Committee Chair

Committee Member

Martine Laberge

Committee Member

Hai Yao

Committee Member

Ying Mei

Abstract

The primary focus of tissue engineering is to develop biological substitutes capable of restoring, maintaining, or improving native tissue function. This field advances an exciting array of solutions for organ repair and wound healing. In the United States alone over 6.5 million people are affected by chronic wounds every year, which account for over $25 billion of healthcare expenses. Vascularization and fast anastomosis with the host are essential in engineering cellular constructs that survive once implanted. In the last decade, there has been extensive investigation into fabrication techniques to create tissue replacements that are rapidly perfused post-implantation to address this issue. Three-dimensional bioprinting is a methodology used for generating 3D constructs of various sizes and shapes from a digital model using a layer-by-layer approach. These digital models can be derived from patient images, such as CT and MRI scans, to produce patient-specific tissue replacements. The fabrication of biomimetic constructs plays an essential role in the advancement of tissue engineering, and provides the ability to form 3D constructs that are able to recapitulate the in vivo structure and function of complex tissues. The Palmetto Printer, developed at the Medical University of South Carolina, is a custom-built multi-dispenser system that uses programmable robotic manufacturing methods to generate 3D heterogeneous tissue constructs. The assessment of the Palmetto bioprinter showed high cell viability (>95%) and significant cell proliferation within the printed constructs over 8 days. Therefore, this technique proves its ability to generate scaffolds that allow cell growth, communication, and the formation of networks; each a requirement of vascularization. Scaffold-free tissue engineering aims to produce physiologically-relevant 3D multicellular constructs through the process of cellular self-assembly. We have developed a scaffold-free prevascular implant model with dense endothelial networks surrounded by extracellular matrix, similar to capillary vasculature. Upon implantation, we found that the host rapidly endothelialized these constructs (<6hr), and were perfused by 72 hours post-implantation. We have demonstrated that this technology can be modified by growth factors and can be scaled up into larger, more complex geometries. Furthermore, bioprinter fabrication could allow the creation of personalized implants. As an application for these fabrication techniques, we developed a novel wound dressing for the treatment of chronic wounds. The Smart Wound Dressing is a multi-component device made up of three separate layers that individually address different facets of the chronic wound environment. This combinatorial approach will provide an exciting new option for the treatment of these non-healing wounds.

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