Graduate Studies
First Advisor
Dr. Ali Tamayol
Second Advisor
Dr. Michael Sealy
Third Advisor
Dr. Ruiguo Yang
Date of this Version
Spring 4-2020
Citation
Jacob Quint, Development of a handheld bioprinter for in situ delivery of vascular endothelial growth factor for the treatment of volumetric muscle loss. Master's Thesis. The University of Nebraska-Lincoln. 2020.
Abstract
The skeletal muscular system is composed of over 600 different muscles and accounts for 45 percent of the total weight of the human body. The skeletal muscular system is required for the support and protection of the skeleton and internal organs, dynamic movement, and metabolic regulation. When large muscle mass is lost as the result of a trauma, disease, or surgical ablation, the regenerative capabilities of muscle become overwhelmed. If over 20% of a specific muscle is lost, the result is overactive fibrosis that results in disabling scar tissue classified as volumetric muscle loss (VML). Skeletal muscle injuries have an economic impact on the order of hundreds of billions of dollars annually. The current clinical standards, including muscle flap transfer and prosthetics, are inadequate to treat VML injuries. Regenerative medicine and tissue engineering have vast potential to develop new treatment options. Unfortunately, injected cells, delivered growth factors, and fabricated scaffolds have failed to overcome their respective hurdles to become commercially and clinically viable options. Therefore, our research goal was to develop a rapid and portable treatment for the local, controlled delivery of therapeutic growth factors for improved functional recovery from VML injuries. Our work consisted of the development of a partially automated handheld printer for the in situ delivery of growth factor eluting hydrogel-based bioinks. Laponite® nanosilicates were employed as the delivery vehicle of vascular endothelial growth factor (VEGF) for the functional recovery from a VML injury. The protein release kinetics from the Laponite® were studied. The material and mechanical properties of the composite hydrogel, called Muscle Ink, were assessed. In vitro material biocompatibility and angiogenic activation of endothelial cells was performed. Ex vivo printing tests validated the ability to fill and adhere to a muscle wound. Finally, an in vivo VML model was treated with the VEGF releasing composite hydrogel bioinks and resulted in functional improvement.
Advisor: Ali Tamayol
Comments
A THESIS Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Master of Science, Major: Mechanical Engineering and Applied Mechanics, Under the Supervision of Professor Ali Tamayol. Lincoln, Nebraska: May, 2020
Copyright 2020 Jacob P. Quint