Date of Award

12-2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Bioengineering

Committee Member

Martine LaBerge, Ph.D., Committee Chair

Committee Member

Igor Luzinov, Ph.D.

Committee Member

Agneta Simionescu, Ph.D.

Committee Member

Vladimir Reukov, Ph.D.

Committee Member

Eugene M. Langan III, M.D.

Abstract

Current endovascular stents and synthetic vascular grafts have poor clinical outcomes in small diameter applications due to high incidence of thrombogenicity and intimal hyperplasia. To address this, we have developed an albumin film for mitigation of the complications of platelet adhesion and smooth muscle cell hyperplasia and hypertrophy. A human serum albumin (HSA) film is fabricated on an anchoring layer of poly (glycidyl methacrylate) on surfaces of metallic and polymeric substrates. The PGMA and HSA layers are characterized by FT-IR spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy and contact angle analysis. We have confirmed the thromboresistance of albumin film by in vitro measurement of adsorption of human fibrinogen and platelets. We found that albumin film controlled the adsorption of fibrinogen evidenced by measurement of fluorescently labeled protein and adhesion force measurement. Human platelet adhesion was significantly lower on albumin coated compared to uncoated substrates. Smooth muscle cells play a key role in progression of intimal hyperplasia and hence we assessed the proliferation, hypertrophy and contractile state of cells in static and flow conditions. A vascular simulator was employed to provide forces of cyclic strain and flow shear to smooth muscle cells on albumin coated and uncoated ePTFE grafts. It was found that albumin film controlled proliferation and maintained the contractile state of smooth muscle cells on nitinol and ePTFE substrates. We developed a flow circulation loop model to assess the response of fibrinogen and platelets on albumin coated and uncoated e PTFE grafts. A significantly lower adsorption of fibrinogen and platelet adhesion was measured on albumin coated e PTFE grafts compared to uncoated grafts. Exhibiting strong adhesion strength to polymeric and metallic substrates, human albumin film fabricated using PGMA as an anchoring layer has been shown to shield the surface from adhesive protein fibrinogen and prevents adhesion of platelets thereby providing an anti-thrombogenic layer. Human albumin has been shown to maintain a controlled proliferation profile and spindle shaped morphology of vascular smooth muscle cells with increased expression of contractile protein smooth muscle alpha actin mitigating the complication of intimal hyperplasia post a percutaneous interventional procedure and bypass surgery.

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