Date of Award

8-2017

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Bioengineering

Committee Member

Jeoung Soo Lee, Committee Chair

Committee Member

Martine LaBerge

Committee Member

Robert O Brown

Abstract

There are multiple surgical procedures that require vascular or microvascular anastomosis; some of which include free tissue transfer for soft tissue reconstruction, vascular grafts and bypass surgeries. The two most common complications with a procedure involving vascular anastomosis are thrombosis and stenosis. The current method to prevent anastomotic thrombosis is the use of an anti-coagulant such as heparin. Heparin has also shown to reduce vascular smooth muscle cell proliferation which is an initiating factor for intimal hyperplasia and ultimately, stenosis. Another well-known treatment for stenosis prevention in vascular injuries is the anti-proliferative drug, paclitaxel. Previously in our 4D lab, we have fabricated and characterized heparin-immobilized electrospun sutures to prevent coagulation after vascular anastomosis. The objective of this project is to develop an electrospun paclitaxel-eluting suture incorporating a novel, amphiphilic block copolymer, polyethylenimine-g-poly (D, L-lactide-co-glycolide) (PgP), which we have synthesized in our 4D lab, in order to prevent the proliferation of vascular smooth muscle cells (VSMCs) after anastomosis procedures. We hypothesize that paclitaxel, a hydrophoboic molecule and anti-proliferative drug, will bind to the hydrophobic block of our copolymer. Adding this novel copolymer into the suture is expected to provide sustained and controlled release of paclitaxel in order to prevent stenosis. We have already successfully immobilized heparin onto the electrospun fibers and assessed the release kinetics and therapeutic activity in-vitro. In this study, we incorporated paclitaxel into the electrospun fiber composition and evaluated physicochemical properties of the paclitaxel loaded electrospun fiber yarns, paclitaxel loading efficiency, release kinetics and therapeutic activity in-vitro. In the future, we will combine both heparin and paclitaxel into the fiber and evaluate the therapeutic effect of the dual-drug loaded electrospun suture in a rat vein anastomosis model in vivo as well as optimize the mechanical performance of the fibers to be used as commercial sutures.

Share

COinS