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Title:Methodologies to promote muscle development for engineering functional skeletal muscle tissue
Author(s):Ko, Eunkyung
Director of Research:Kong, Hyunjoon
Doctoral Committee Chair(s):Kong, Hyunjoon
Doctoral Committee Member(s):Bashir, Rashid; Gillette, Martha L.; Saif, M. Taher
Department / Program:Bioengineering
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Skeletal muscle, Muscle tissue engineering, Neuromuscular Junctions, Connexin, Gap junction proteins
Abstract:Skeletal muscle related diseases cause loss and weakness in the muscle and affect the quality of life of the patients. Although skeletal muscle tissue can regenerate when the damage is small, a patient must receive a surgery when the volumetric loss is too large. Skeletal muscle tissue engineering aims to recapitulate the physiology and function of the natural muscle. The engineered tissue holds potential as a transplantable material that can help regeneration in vivo. In this thesis, we used different methodologies to recapitulate the natural skeletal muscle and enhance muscle development. The first part of the thesis uses physical approach to engineer functional skeletal muscle. A grooved substrate with controlled width was used to promote myogenic differentiation and enhance muscle maturity. After the mature muscle was generated, we cultured neural stem cells and let them innervate into the skeletal muscle to form a neuron-muscle interface to finally engineer a functional skeletal muscle (Chapter 3). The next study focuses on chemically stimulating the skeletal myoblasts to express more gap junction proteins and prolong the expression time. After confirming the genetic changes occurring in the muscle cells, we assembled a pump-bot device with the pre-stimulated skeletal muscle tissue engineered in a 3D ring. We compared how the fluid movement in the pump-bot was changed when the myoblasts had been chemically stimulated (Chapter 4). Lastly, we biologically modified the skeletal myoblasts to express gap junction proteins in myotubes (Chapter 5). We delivered connexin genes to the skeletal myoblasts. We examined how the presence of connexin in the cells contributes to myogenic differentiation and muscle development. Overall, the studies herein will be useful to engineer skeletal muscle for biomedical uses such as developing platforms for in vitro drug screening, engineering tissue for transplantation, and assembling a biologically actuated machinery.
Issue Date:2019-04-16
Rights Information:In regards to chapter 3; This chapter is adapted from Ko, E.; Yu, S. J.; Pagan-Diaz, G. J.; Mahmassani, Z.; Boppart, M. D.; Im, S. G.; Bashir, R.; Kong, H. Matrix Topography Regulates Synaptic Transmission at the Neuromuscular Junction. Advanced Science 2018, advs.201801521. Copyright Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission. Wiley-VCH hereby licenses back to the Contributor the following rights with respect to the final published version of the Contribution:
Date Available in IDEALS:2019-08-23
Date Deposited:2019-05

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