Design of a Biodegradable Vascular Construct Andrew Jallouk Paul Guillod Patrick Boyer Dr. Hak-Joon Sung, PhD

Motivation Cardiovascular disease is the leading cause of death in the United States. Many of these deaths are due to atherosclerotic plaques which build up on the walls of the coronary arteries.     Surgery is often performed to remove the sections of artery affected by plaque. Our construct will serve as a temporary replacement for the vessel wall and aid in the regeneration of vascular tissue.  http://en.wikipedia.org/wiki/Atherosclerosis

Objective Design a vascular construct composed of biodegradable materials that is capable of:   Withstanding normal physiological conditions  Slowly degrading while being replaced by vascular tissue  Utilizing the body's natural inflammatory response to encourage angiogenesis and the regeneration of vascular tissue     

Biodegradable Materials Two polymers will be used to fabricate the structural component of the construct:   poly(e-caprolactone) poly(ethylene-glycol) http://en.wikipedia.org/wiki/Polycaprolactone Both are biocompatible and biodegradable.

Construct Fabrication Electrospinning utilizes a high-voltage syringe tip to create nanofibers of a desired polymer.   The vascular construct will be composed of electrospun PEG and PCL.   Collagen IV will also be incorporated and cross-linked within the construct to provide mechanical strength and encourage cellular proliferation onto the construct. 

Atherosclerotic Pathway Damage to endothelial cell layer initiates inflammatory response.    Inflammatory response causes an increase in local reactive oxygen species (ROS) concentration.   Low-density lipoprotein (LDL) is oxidized by free radicals.  Monocytes attach to damaged vessel wall and differentiate into macrophages. http://www.resverlogix.com/upload/body_image/46/06/website-atherosclerosis_rgb.jpg

Atherosclerotic Pathway Macrophages ingest oxidized LDL and combine to form foam cells.   Smooth muscle cells  proliferate and form a fibrous capsule over foam cells. The fibrous capsule bulges into the artery and interferes with flow. Rupture of the fibrous capsule may result in an embolism.

Atherosclerosis http://www.youtube.com/watch?v=fwlLddvcBsc&feature=related

Inflammation and Tissue Regeneration M1 macrophages ingest foreign materials and play a critical role in the inflammatory response.   M2 macrophages encourage angiogenesis and tissue regeneration.  Small interfering RNA (siRNA) may be used to change macrophage phenotype from M1 to M2.   We plan to incorporate quantum dots bearing siRNA into our construct. siRNA will alter the phenotype of macrophages and encourage tissue regeneration.

Future Work Set up electrospinning apparatus and generate polymer scaffolds. Incorporate collagen into the polymer scaffolds and crosslink them.    Measure mechanical properties of the scaffold.