טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentFeingold Dana
SubjectComposite Biomaterial Scaffolds Made from Electrospun
Nano-Fibers and Biosynthetic Hydrogels for Blood
Vessel Tissue Engineering
DepartmentDepartment of Biotechnology
Supervisor Professor Dror Seliktar
Full Thesis textFull thesis text - English Version


Abstract

Atherosclerosis is a disease that is characterized by thickening and hardening of the artery wall. For coronary arteries, atherosclerosis causes the narrowing of the vessel lumen and this narrowing leads to a weakening of the myocardium, i.e. the wall of the heart, and ultimately to myocardial infarction. The most common form of treatment is coronary artery bypass graft (CABG) surgery. There are many patients in need of such surgery for whom a CABG procedure is not possible because their native vessels are not available for use. It is this need for an alternative to native blood vessels that led to one of the Holy Grails of tissue engineering of the cardiovascular system, creating a small-diameter blood vessel substitute. Early attempts to develop a blood vessel substitute focused on the use of bypass grafts engineered from synthetic materials. When replacing larger vessels, these grafts have met with success, but when used in the coronary system, where diameters are 3-4 mm, thrombotic events rapidly close them off. Hence, tissue engineering moved toward engineering a blood vessel substitute that exhibited all the functional characteristics of a normal blood vessel.

The design of a composite biodegradable scaffold for tissue engineering a blood vessel substitute was the main focus of this investigation. The composite material was made from poly (epsilon-carpolactone) (PCL) nanofibers, fabricated by electrospinning and permeated by a hydrogel phase made from PEGylated fibrinogen. The architectural and mechanical properties of the PCL nanofiber mesh were examined using scanning electron microscopy (SEM) and uniaxial tensile testing. Aortic smooth muscle cells (SMCs) were encapsulated in the hydrogel phase and cultured in the composite scaffold for up to one week in vitro.


Time-lapse microscopy showed that the SMCs migrated towards the PCL nanofiber region of the scaffold where they populated the mesh at a high cell density. In the PCL mesh region, the SMCs expressed a more contractile phenotype as indicated by smooth muscle alpha-actin staining. In contracts, the hydrogel region contained few SMCs exhibiting positive staining for smooth muscle alpha-actin. The electrospun PCL nanofibers exhibited significantly higher elastic modulus in comparison to the PEGylated fibrinogen hydrogel, suggesting that mechanics may play a role in the preferential migration and phenotype expression of the SMCs. We concluded that the composite material exhibited suitable biocompatibility for SMC culture and adequate mechanical properties for use as a scaffold material in vascular tissue engineering.