Hobson, Christopher
(2015)
Tracheal Tissue Engineering.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Large airway defects pose a substantial problem to surgeons in both pediatric and adult
populations. For example, primary tracheal cancers can result in neoplastic lesions, which
are often not diagnosed until the tumor has become inoperable. These patients are palliated,
but have a poor prognosis, with only 5% survival after 5 years. Tissue engineered transplants
over a life saving new therapeutic option. Recent reports have demonstrated good midterm
results with decellularized human homograft tissue. However, these experiments have been
limited to compassionate use. To achieve effcacy necessary for more widespread use further
study is necessary to investigate alternate approaches and optimize the decellularization
technique. Additionally, clinical application of this technology will require translation to a
decellularized xenograft to obviate human tissue supply limitations. To this end, we compare
the use of 3 alternate detergents (SDS, Triton X-100, and CHAPS) to sodium deoxycholate
in the commonly accepted detergent enzymatic method (DEM). Fresh donor rat tracheas
were decellularized using a modified 9-day DEM protocol. The pre-implant scaffolds were
thoroughly characterized for each experimental group and implanted for 12 weeks using an
orthotopic rat tracheal reconstruction model. It was found that detergent choice strongly
affects the host remodeling response including host cell infiltration and epithelial differentiation.
The clinically relevant sodium deoxycholate and Triton X-100 groups were retested
with a final peracetic acid (PAA) rinse. It was determined that the use of PAA greatly
improved the in vivo response of the previously poor performing sodium deoxycholate and
made little improvement to the Triton X-100 scaffold. The optimum configuration, Triton
X-100 with a PAA rinse, was selected for translation to a clinically relevant porcine model. Porcine tracheal decellularization was achieved using a modified 14 day DEM protocol with a novel cyclical pressure approach. The suitability of these porcine tracheas for pre-clinical
large animal testing was verified through mechanical analysis (pressure-diameter and suture
retention) and in vitro seeding experiments with human bronchial epithelial cells.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
9 April 2015 |
| Date Type: |
Publication |
| Defense Date: |
19 March 2014 |
| Approval Date: |
9 April 2015 |
| Submission Date: |
27 February 2014 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
148 |
| 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: |
Tissue Engineering, Trachea, Regenerative Medicine |
| Date Deposited: |
09 Apr 2016 05:00 |
| Last Modified: |
19 Dec 2016 14:41 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/20658 |
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