Microfabrication Approaches for Understanding the Role of Vascular Mechanics in Progressive Diseases
2016-08
Loading...
View/Download File
Persistent link to this item
Statistics
View StatisticsJournal Title
Journal ISSN
Volume Title
Title
Microfabrication Approaches for Understanding the Role of Vascular Mechanics in Progressive Diseases
Authors
Published Date
2016-08
Publisher
Type
Thesis or Dissertation
Abstract
Vascular disease is a common cause of death that typically results from long-term alteration of vessel structure and function. The underlying mechanisms that lead to pathologic changes in the vasculature are largely unclear, especially in progressive diseases of the cerebral vessels. With the growing prevelance of blast traumatic brain injury in modern warfare, never before has investigation of cerebral vascular disease been more pertinent. Here, we focus on the development of microfabrication experimental approaches for probing the critical mechanical and biochemical pathways involved in progression of diseases, such as cerebral vasospasm, subarachnoid hemorrhage, and Alzheimer’s disease, that often result from TBI. First, we develop a microfluidic patterned deposition technique for studying functional mechanics in chronic vascular disease at the tissue scale. We modify substrate surfaces with genipin, a natural crosslinker, to extend culture times of in vitro vascular tissues that mimic native tissue structure and function. We successfully validate our technique, showing maintenance of patterned structural alignment and mechanical function over the course of two weeks. Lastly, we investigate the relationship between vascular disease and Alzheimer’s disease. Amyloid beta is a key precursor in the development of Alzheimer’s disease that accumulates in neuronal and cerebrovascular tissue and can result in neurodegeneration. During the development of cerebral amyloid angiopathy (CAA), which is present in over 80% of Alzheimer's disease cases, amyloid beta plaques form in the cerebral vessel walls and lead to severe attenuation of physiologic vasodilation. We measured the effect of amyloid beta treatment on vascular smooth muscle cell functional contractility using a single-cell traction force microscopy technique and developed a thin-walled arterial model for growth and remodeling response to mechanical perturbations. We found that amyloid beta induces a reduction in vascular smooth muscle cell mechanical output. We implemented this loss of function into a constrained mixture arterial model that suggests vessel growth and remodeling, in response to amyloid beta-mediated alteration of smooth muscle function, can lead to an inability of cerebral vessels to vasodilate. Our findings provide a possible explanation for the vascular injury and malfunction often associated with the development of neurodegeneration in Alzheimer’s disease.
Description
University of Minnesota Ph.D. dissertation. August 2016. Major: Biomedical Engineering. Advisor: Patrick Alford. 1 computer file (PDF); xi, 118 pages.
Related to
Replaces
License
Collections
Series/Report Number
Funding information
Isbn identifier
Doi identifier
Previously Published Citation
Suggested citation
Hald, Eric. (2016). Microfabrication Approaches for Understanding the Role of Vascular Mechanics in Progressive Diseases. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/191352.
Content distributed via the University Digital Conservancy may be subject to additional license and use restrictions applied by the depositor. By using these files, users agree to the Terms of Use. Materials in the UDC may contain content that is disturbing and/or harmful. For more information, please see our statement on harmful content in digital repositories.