Nationally, coronary artery disease is a tremendous health care burden. Current therapies for coronary artery disease suffer from multiple risks to the patient including restenosis, thrombosis, infection, and other graft disease. A completely biological bioartificial artery graft would circumvent these issues and improve the outcome for sufferers of coronary artery disease. Fibrin-based tissue engineering has already shown significant progress but as yet has not produced a bioartificial artery with sufficient mechanical strength for implantation without risk. A new strategy is needed to exploit signaling pathways for cellular stimulation. The hypothesis for the proposed work is that: Prolonged ERK signaling during in vitro culture will improve the mechanical strength of fibrin-based bioartificial arteries, via stimulation of type I collagen transcription and increased collagen content. By manipulating extracellular signal-regulated kinase (ERK) signaling by the cells seeded in tubular fibrin- based constructs, this project will improve the collagen content of bioartificial arteries and ultimately their mechanical strength.
The specific aims of the proposed work are as follows: #1. Establish that ERK activity is necessary for the production of mechanically strong bioartificial arteries. #2. Promote prolonged ERK activation in bioartificial arteries by inhibiting negative feedback pathways. #3. Promote prolonged ERK activation in bioartificial arteries by mechanical stimulation. The primary readouts for the response to ERK signal manipulation will be type I collagen transcription, using a luciferase reporter, collagen content, using a biochemical assay, and mechanical strength, using mechanical testing systems. Significant training in tissue engineering and biomechanics from experts at the University of Minnesota will be a key goal for this fellowship. It is expected that this project will produce bioartificial arteries that can withstand physiological blood pressure.

Public Health Relevance

The proposed research will accelerate the production of a completely biological implantable bioartificial artery, which is a current need for proper treatment of coronary artery disease. By manipulating cellular signaling during artery development, collagen content will be increased, leading to enhanced mechanical strength.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL104768-02
Application #
8207809
Study Section
Special Emphasis Panel (ZRG1-F15-D (20))
Program Officer
Meadows, Tawanna
Project Start
2010-12-10
Project End
2013-02-28
Budget Start
2011-12-10
Budget End
2013-02-28
Support Year
2
Fiscal Year
2012
Total Cost
$55,670
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455