Rauck, Britta
(2014)
Minimally Invasive Biomaterials for Central Nervous System Therapies.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
The inability of the adult central nervous system (CNS) to regenerate combined with the progressive nature of many CNS pathologies poses a significant challenge in developing effective treatments. Biomaterials-based systems designed to deliver drugs and/or cells hold immense potential for moderating disease progression and promoting repair. Ideally, such systems should (1) allow minimally invasive administration, (2) provide localized and controlled delivery, and (3) protect the activity of their cargo for maximal therapeutic effect. Additionally, the ability to incorporate multiple treatment modalities is desirable as many CNS disorders are multi-faceted and complex in nature. Designing delivery systems that incorporate these features while simultaneously improving therapeutic outcomes, however, poses a significant challenge. This dissertation covers the formulation and application of polymer-based delivery systems for CNS repair, with specific focus given to the spinal cord and visual systems.
We first demonstrated the biocompatibility and feasibility of a reverse thermal gel, poly(ethylene glycol)–poly(serinol hexamethylene urethane) (ESHU) for intraocular drug delivery. This injectable formulation is capable of sustaining the bevacizumab release in vivo, and ultimately may be used to reduce the injection frequency in patients with ocular diseases such as age-related macular degeneration. To emphasize the versatility of ESHU, it was combined with bone marrow stromal cells (BMSCs) for treatment of traumatic spinal cord injury in rats. ESHU improved BMSC survival 3.5-fold one week post-injury compared to BMSCs injected in PBS, which was accompanied by increased nervous tissue sparing and functional recovery. Finally, we demonstrated the feasibility of a coacervate-based growth factor delivery system for treatment of traumatic spinal cord injury. Ultimately, we hope the coacervate may be used in combination to augment cell therapy and drive the development of innovative solutions to treat injuries for where there are no cures.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
16 June 2014 |
| Date Type: |
Publication |
| Defense Date: |
26 March 2014 |
| Approval Date: |
16 June 2014 |
| Submission Date: |
17 March 2014 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
155 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Regenerative Medicine; Drug Delivery; Central Nervous System; Biomaterials; Cell Transplantation |
| Date Deposited: |
16 Jun 2014 18:42 |
| Last Modified: |
15 Nov 2016 14:18 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/20760 |
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