Research

Ocular Biomechanics

The lamina cribrosa is a trabeculated soft tissue in the optic nerve head that is responsible for protecting the axons of the retinal ganglion cells as they pass from the inside of the eye to the brain. Axonal damage of retinal ganglion cells occurs in primary open angle glaucoma as this structure is grossly remodeled during the disease process. Our laboratory is assessing the biomechanical environment of this important ocular tissue in both normal and diseased human and animal tissue.


Primary open angle glaucoma (POAG) is a loss of vision caused by death of the retinal ganglion cells in the back of your eye. Intraocular pressure in the anterior and posterior chambers of your eye both play a role in the onset and development of this disease. It is clear that an optimum tissue stiffness and fluid permeability of tissues in both the anterior and posterior chambers is necessary to promote the health, viability, and function of retinal ganglion cells.  Our research laboratory is utilizing a porohyperelastic computational approach to better understand how the mechanical stiffness and fluid resistance properties of the eye govern its biomechanical environment. We are using simulations in which both the anterior and posterior chambers are considered to generate exploratory hypotheses regarding IOP regulation and biomechanical homeostasis in the eye (Ayyalasomayajula A et al., 2016).

Nerve Biomechanics

Unilateral vocal fold paralysis (UVP) occurs related to recurrent laryngeal nerve (RLN) impairment associated with impaired swallowing, voice production, and breathing functions. The majority of UVP cases occur subsequent to surgical intervention with approximately 12–42% having no known cause for the disease (i.e., idiopathic). Approximately two-thirds of those with UVP exhibit left-sided injury with the average onset at ≥50 yr of age in those diagnosed as idiopathic. Given the association between the RLN and the subclavian and aortic arch vessels, we hypothesized that changes in vascular tissues would result in increased aortic compliance in patients with idiopathic left-sided UVP compared with those without UVP. Gated MRI data enabled aortic arch diameter measures normalized to blood pressure across the cardiac cycles to derive aortic arch compliance. Compliance was compared between individuals with left-sided idiopathic UVP and age- and sex-matched normal controls. Three-way factorial ANOVA test showed that aortic arch compliance (P = 0.02) and aortic arch diameter change in one cardiac cycle (P = 0.04) are significantly higher in patients with idiopathic left-sided UVP compared with the controls. As previously demonstrated by other literature, our finding confirmed that compliance decreases with age (P < 0.0001) in both healthy individuals and patients with idiopathic UVP. Future studies will investigate parameters of aortic compliance change as a potential contributor to the onset of left-sided UVP.

Vascular Mechanobiology

Integration of Mechanobiology, Continuum Mechanics, and Nonlinear Optical Microscopy

This research project is focused on combining novel STBL bioreactors with an advanced intravital imaging modality in order to develop robust techniques for determining the growth laws of soft tissues.  The continuum theory of soft tissue growth and remodeling is nascent and requires the development of new approaches for hypothesizing, testing, and validating rate equations required in soft tissue growth and remodeling simulations. Our laboratory is well positioned to make significant advances in this area of research having developed multiphasic growth and remodeling theory (see Harper J et al. 2014 and Armstrong et al. 2016) while also developing new optomechanical intravital imaging techniques to visualize the mechanobiology of soft tissues in real time (see Keyes JT et al., 2013, Haskett DG et al. 2016 amongst others). Paramount in the experimental arm of this research aim is the ability to intravitally image collagen, elastin, and protease activity in real time using an advanced multiphoton microscope, all as a function of mechanical stimulation in bioreactor culture.

Development of a Compliance Matched Biopolymer Tissue Engineered Vascular Graft (TEVG)

Stenotic vascular disease represents a significant health concern in the United States and around the world.  Current bypass procedures in both the coronary and peripheral vasculature where small diameter vascular substitutes are required suffer from graft thrombosis and/or restenosis. The STBL and collaborators are developing a small diameter compliance matched tissue engineered vascular graft (TEVG) for use as a small diameter vascular substitute. Novel native biopolymers are being synthesized using state of the art techniques in biomanufacturing using a computationally optimized approach. Significant efforts are also being made to improve the antithrombogenicity and vasoactivity of our TEVG. Preclinical in-vivo assessment of our graft has been initiated as well as in-vitro assessment of our TEVGs remodeling dynamics using a physiological in-vito bioreactor in combination with an intravital microscope. This project is a multi-disciplinary effort spanning several basic science disciplines across multiple universities. Collaborators on this project include:

• William Wagner (University of Pittsburgh)
• Thomas Gleason (University of Pittsburgh)
• Kang Kim (University of Pittsburgh)
• Thomas Doetschman (University of Arizona)
• David Harris (University of Arizona)
• Oliver McIntyre (Vanderbilt University)
• Rob Kellar (N. Arizona University)
• Burt Ensley (Protein Genomics)

Structure Function Relationships of the Aorta

The STBL has devoted significant effort into understanding the remodeling of the aorta in the context of complex aortic disease. Our work has spanned from large human aortic mechanical and microstructural characterization (see Haskett DG et al., 2010) to the ECM remodeling in murine models of Marfan (see Haskett DG et al., 2012) and abdominal aortic aneurysm (see Haskett DG et al., 2012, 2013 and 2016).

Drug Eluting Stents   

Optimum drug delivery for the treatment of vascular disease is governed by several interacting factors including both biological and physical phenomena. The STBL is using a combined experimental and computational approach as a platform to improve endovascular drug delivery from eluting devices. For example, we have used this platform to demonstrate significant differences in the mass transport of drug surrogates in the porcine coronary vasculature (see Keyes JT et al. 2013). Our approach includes modeling the contribution of both convective and diffusive transport of species in a highly deforming fully saturated porous media (see Vande Geest JP et al. 2011, Keyes JT et al. 2013, Harper J 2014 et al., Armstrong MH et al., 2016). Transport of drug surrogate in our laboratory is made possible using an in house two photon microscope.