Date of Award

Spring 5-16-2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Wei Tan

Second Advisor

Fernando Rosario-Ortiz

Third Advisor

Yifu Ding

Fourth Advisor

Lupita Montoya

Fifth Advisor

Yunping Xi

Abstract

The field of percutaneous coronary intervention has seen a plethora of advances over the past few decades, which have allowed for its development into safe and effective treatments for patients suffering from cardiovascular diseases. However, in-stent thrombosis and restenosis remain clinically significant problems.

This dissertation proposes a methodology to potentially overcome in-stent thrombosis and restenosis by designing and fabricating a polymeric coating with mechanical and surface properties inert to cell adhesion and platelet attachment. First, conventional electrospinning technique was used to fabricate polyethylene glycol dimethacrylate/ poly l-lactide acid (PEGDMA/PLLA) blend fiber substrate with different composition ratios. Next, coaxial electrospinning techniques were used to fabricate PLLA, the hydrophobic core and PEGDMA, the hydrophilic sheath with tunable elasticity and controlled surface chemistry for use as stent coatings.

Conventional electrospinning with three blend PEGDMA/PLLA ratios of 1-1, 2-1, and 4-1 were assessed for attachment of platelets and arterial smooth muscle cells (SMC) as well as the secretory effect of mesenchymal stem cells cultured on the coatings on the proliferation and migration of arterial endothelial cells and SMCs. It was demonstrated that electrospun PEGDMA/PLLA coating with 1-1 ratio on the nitinol stent material reduced platelet and SMC attachment and increased stem cell secretory factors that enhance endothelial proliferation.

Coaxial electrospinning with three UV photopolymerization times of 2, 15, and 60 min were selected to compare coatings in terms of mechanical properties and biological responses. Attenuated total reflection-Fourier transformed infrared spectroscopy demonstrated PEGDMA coated around PLLA. Transmission electron microscopy images illustrated the core-sheath structures in PLLA-PEGDMA nanofibers, and scanning electron microscopy images exhibited a similar uniform fibrous structure from all conditions. Tensile testing demonstrated that the elastic modulus of the hydrated matrices varied with polymerization time. Attachment and spreading of arterial SMCs and platelet adhesion onto the coatings were found to be affected by the material stiffness.

We show the impact of substrate's elasticity on SMC and platelet attachment reduction. We postulate that electrospun PEGDMA fibrous coatings would enhance hemocompatibility of nitinol stents and truncate the potential stent failure caused by restenosis and thrombosis.

Available for download on Sunday, December 05, 2021

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