Elongated fascicle-inspired 3D tissues consisting of high-density, aligned, optogenetically excitable muscle tissue using sacrificial outer molding

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2014.

Bibliographic Details
Main Author: Neal, Devin Michael
Other Authors: Harry Asada.
Format: Thesis
Language:eng
Published: Massachusetts Institute of Technology 2014
Subjects:
Online Access:http://hdl.handle.net/1721.1/92166
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author Neal, Devin Michael
author2 Harry Asada.
author_facet Harry Asada.
Neal, Devin Michael
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description Thesis: Ph. D., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2014.
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spelling mit-1721.1/921662019-04-11T11:34:24Z Elongated fascicle-inspired 3D tissues consisting of high-density, aligned, optogenetically excitable muscle tissue using sacrificial outer molding Neal, Devin Michael Harry Asada. Massachusetts Institute of Technology. Department of Mechanical Engineering. Massachusetts Institute of Technology. Department of Mechanical Engineering. Mechanical Engineering. Thesis: Ph. D., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2014. Cataloged from PDF version of thesis. Includes bibliographical references (pages 80-89). The majority of muscles, nerves, and tendons are composed of fiber-like fascicle morphology. Each fascicle has a) elongated cells highly aligned with the length of the construct, b) a high volumetric cell density, and c) a high length-to-width ratio with a diameter small enough to facilitate perfusion. Fiber-like fascicles are important building blocks for forming those tissues of various sizes and cross-sectional shapes, yet no effective technology is currently available for producing long and thin fascicle-like constructs with aligned, high-density cells. Here we present a method for molding cell-laden hydrogels that generate cylindrical tissue structures that are ~100 [mu]m in diameter with an extremely high length to diameter ratio (>100:1). Using this method we have successfully created skeletal muscle tissue with a high volumetric density (~50%) and perfect cell alignment along the axis. A new molding technique, Sacrificial Outer Molding, allows us to i) create long and thin cavities of desired shape in a mold that is solid at a low temperature, ii) release gelling agents from the sacrificial mold material after cellladen hydrogel is injected into fiber cavities, iii) generate a uniform axial tension between anchor points at both ends that promotes cell alignment and maturation, and iv) perfuse the tissue effectively by exposing it to media after melting the sacrificial outer mold at 37°C. Effects of key parameters and conditions, including initial cavity diameter, axial tension, and concentrations of hydrogel and gelling agent, upon tissue compaction, volumetric cell density, and cell alignment are presented. Furthermore, the tissue is characterized in a custom designed mechanical characterization system. Characterization has shown that an optimal diameter exists at which muscle constructs exhibit the greatest contraction performance, and that optical and electrical stimulation of optogenetic muscle cells result in similar performance if the tissue is developed sufficiently. by Devin Michael Neal. Ph. D. 2014-12-08T18:53:48Z 2014-12-08T18:53:48Z 2014 2014 Thesis http://hdl.handle.net/1721.1/92166 897133010 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 142 pages application/pdf Massachusetts Institute of Technology
spellingShingle Mechanical Engineering.
Neal, Devin Michael
Elongated fascicle-inspired 3D tissues consisting of high-density, aligned, optogenetically excitable muscle tissue using sacrificial outer molding
title Elongated fascicle-inspired 3D tissues consisting of high-density, aligned, optogenetically excitable muscle tissue using sacrificial outer molding
title_full Elongated fascicle-inspired 3D tissues consisting of high-density, aligned, optogenetically excitable muscle tissue using sacrificial outer molding
title_fullStr Elongated fascicle-inspired 3D tissues consisting of high-density, aligned, optogenetically excitable muscle tissue using sacrificial outer molding
title_full_unstemmed Elongated fascicle-inspired 3D tissues consisting of high-density, aligned, optogenetically excitable muscle tissue using sacrificial outer molding
title_short Elongated fascicle-inspired 3D tissues consisting of high-density, aligned, optogenetically excitable muscle tissue using sacrificial outer molding
title_sort elongated fascicle inspired 3d tissues consisting of high density aligned optogenetically excitable muscle tissue using sacrificial outer molding
topic Mechanical Engineering.
url http://hdl.handle.net/1721.1/92166
work_keys_str_mv AT nealdevinmichael elongatedfascicleinspired3dtissuesconsistingofhighdensityalignedoptogeneticallyexcitablemuscletissueusingsacrificialoutermolding