Project abstract for group alfordpw

High-Throughput Microscale Assays for Vascular Contractility and Remodeling

Tissue engineered models of muscular contraction and remodeling are necessary to relate in vivo function to in vitro experimental platforms. These researchers are developing an assay that will improve upon previous muscular thin film (MTF) methods developed to measure contractility of cardiovascular smooth and striated muscle in vitro. This assay will be employed to determine the effects of growth factor stimulation on remodeling of tissues subjected to pressure pulses simulating blast traumatic brain injuries. The researchers employ soft lithography techniques, such as microcontact printing, to provide guidance cues for tissue organization in order to engineer realistic in vitro tissue mimics. Previously, MTFs have been used to characterize the effect of blast-like vascular injury in the initiation of cerebral vasospasm. The researchers are combining the current MTF assay with a traction force microscopy approach that will allow significant increases in experimental efficiency. New methods for microcontact printing will be developed and employed to construct arrays with multiple MTF-like tissue constructs whose mechanical function can be tested simultaneously using fluorescent beads and confocal microscopy. Imaris or a memory-intensive MATLAB digital image correlation code will be used to track bead positions, yielding datasets that can be used to determine the mechanical properties of the tissues. The researchers will create arrays of structurally identical tissues for high-throughput screening of growth factor-stimulated perturbation of vascular function. They expect to find a link between platelet-released growth factors and the progression from hypercontractility to large-scale remodeling typical of cerebral vasospasm onset. This assay will provide a platform for development of therapeutics for cerebral vasospasms caused by blast traumatic brain injury.