Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

First Advisor's Name

Wei-Chiang Lin

First Advisor's Committee Title

Committee chair

Second Advisor's Name

Anthony J. McGoron

Second Advisor's Committee Title

Committee Member

Third Advisor's Name

Lidia Kos

Third Advisor's Committee Title

Committee Member

Fourth Advisor's Name

Nikolaos Tsoukias

Fourth Advisor's Committee Title

Committee Member

Keywords

Embryonic Stem Cells, Motor Neuron differentiation, Metabolites, Poly (glycerol-dodecanedioate), Poly (glycerol- dodecanedioate co-fumarate), Electrospinning, Fiber scaffolds, Neural Tissue Engineering

Date of Defense

3-27-2015

Abstract

Peripheral nerves have demonstrated the ability to bridge gaps of up to 6 mm. Peripheral Nerve System injury sites beyond this range need autograft or allograft surgery. Central Nerve System cells do not allow spontaneous regeneration due to the intrinsic environmental inhibition. Although stem cell therapy seems to be a promising approach towards nerve repair, it is essential to use the distinct three-dimensional architecture of a cell scaffold with proper biomolecule embedding in order to ensure that the local environment can be controlled well enough for growth and survival. Many approaches have been developed for the fabrication of 3D scaffolds, and more recently, fiber-based scaffolds produced via the electrospinning have been garnering increasing interest, as it offers the opportunity for control over fiber composition, as well as fiber mesh porosity using a relatively simple experimental setup. All these attributes make electrospun fibers a new class of promising scaffolds for neural tissue engineering. Therefore, the purpose of this doctoral study is to investigate the use of the novel material PGD and its derivative PGDF for obtaining fiber scaffolds using the electrospinning. The performance of these scaffolds, combined with neural lineage cells derived from ESCs, was evaluated by the dissolvability test, Raman spectroscopy, cell viability assay, real time PCR, Immunocytochemistry, extracellular electrophysiology, etc. The newly designed collector makes it possible to easily obtain fibers with adequate length and integrity. The utilization of a solvent like ethanol and water for electrospinning of fibrous scaffolds provides a potentially less toxic and more biocompatible fabrication method. Cell viability testing demonstrated that the addition of gelatin leads to significant improvement of cell proliferation on the scaffolds. Both real time PCR and Immunocytochemistry analysis indicated that motor neuron differentiation was achieved through the high motor neuron gene expression using the metabolites approach. The addition of Fumaric acid into fiber scaffolds further promoted the differentiation. Based on the results, this newly fabricated electrospun fiber scaffold, combined with neural lineage cells, provides a potential alternate strategy for nerve injury repair.

Identifier

FI15032147

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