Organization and differentiation of stem cells on delivery scaffold for retinal tissue engineering

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2011.

Bibliographic Details
Main Author: Ko, Chi Wan
Other Authors: Sarah Tao and Carol Livermore.
Format: Thesis
Language:eng
Published: Massachusetts Institute of Technology 2011
Subjects:
Online Access:http://hdl.handle.net/1721.1/67633
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author Ko, Chi Wan
author2 Sarah Tao and Carol Livermore.
author_facet Sarah Tao and Carol Livermore.
Ko, Chi Wan
author_sort Ko, Chi Wan
collection MIT
description Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2011.
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spelling mit-1721.1/676332019-04-10T16:48:02Z Organization and differentiation of stem cells on delivery scaffold for retinal tissue engineering Ko, Chi Wan Sarah Tao and Carol Livermore. Massachusetts Institute of Technology. Dept. of Mechanical Engineering. Massachusetts Institute of Technology. Dept. of Mechanical Engineering. Mechanical Engineering. Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2011. Cataloged from PDF version of thesis. Includes bibliographical references (p. 82-84). Retinal degenerative diseases, including retinitis pigmentosa and age-related macular degeneration, affect more than ten million people in the US. Currently, there is no proven visually beneficial treatment for these types of disease; however, stem cell-based therapy is a recent strategy which has the potential to preserve and restore vision in these conditions. In addition to replacing lost or diseased cells, transplanted cells may be able to rescue dying photoreceptors of the host retina. While studies have shown that retinal progenitor cells (RPCs) delivered by bolus injection can differentiate into retinal specific neurons after subretinal transplantation, they have not been able to maintain morphologic development, lamination, or extensive integration with the host retina. Therefore, a mechanism is needed to confer organization and instructional cues to these grafted cells. In this research, micro and nano-electro-mechanical systems (MEMS/NEMS) processing techniques were used to create biodegradable thin-film scaffolds to guide the differentiation and organization of stem cells for retinal tissue engineering. Through standard MEMS processes, including photolithography and reactive ion etching, a high throughput array of sub-micron features (500 nm to 1 pm) was fabricated into silicon wafers. A novel templating process was developed to then imprint these structures into biodegradable polycaprolactone (PCL) thin films (5 -10 pm) with minimal deformation to the imprinted features. PCL was chosen due to its low melt temperature, adaptability to microfabrication processing, as well as its mechanical and bioresorptive properties. Furthermore, PCL thin films have been shown to be well tolerated long term when transplanted in the subretinal space of mice. RPCs were cultured on PCL thin films, and cell responses to sub-micron topography of varying dimension and geometry were characterized using scanning electron microscopy and immunocytochemistry. Sub-micron features were found to definitively affect cell behavior. For example, while RPCs cultured on post structures demonstrated an early upregulation of differentiation markers, including rhodopsin and recoverin, RPCs cultured on a ridge-groove topography developed substantial elongation and parallel alignment in addition to upregulation. This unique structured PCL thin-film platform therefore provides a means to organize and differentiate RPCs in a controlled manner and offers potential as a clinical treatment for retinal degenerative diseases. by Chi Wan Ko. S.M. 2011-12-12T14:24:15Z 2011-12-12T14:24:15Z 2011 2011 Thesis http://hdl.handle.net/1721.1/67633 765948832 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 84 p. application/pdf Massachusetts Institute of Technology
spellingShingle Mechanical Engineering.
Ko, Chi Wan
Organization and differentiation of stem cells on delivery scaffold for retinal tissue engineering
title Organization and differentiation of stem cells on delivery scaffold for retinal tissue engineering
title_full Organization and differentiation of stem cells on delivery scaffold for retinal tissue engineering
title_fullStr Organization and differentiation of stem cells on delivery scaffold for retinal tissue engineering
title_full_unstemmed Organization and differentiation of stem cells on delivery scaffold for retinal tissue engineering
title_short Organization and differentiation of stem cells on delivery scaffold for retinal tissue engineering
title_sort organization and differentiation of stem cells on delivery scaffold for retinal tissue engineering
topic Mechanical Engineering.
url http://hdl.handle.net/1721.1/67633
work_keys_str_mv AT kochiwan organizationanddifferentiationofstemcellsondeliveryscaffoldforretinaltissueengineering