Creating a hemocompatible small-diameter vascular graft

Ali SerpeSouth Carolina Governor’s School for Science and

Mathematics, SCGSSM

Mentor: Dr. Ning ZhangClemson-MUSC Joint Bioengineering Program

Charleston, SC

Small-diameter Vascular Graft

Vascular grafting is a common surgical procedure in the repair or replacement of occluded, dysfunctional, or diseased blood vessels that underlie strokes and many cardiovascular pathologies/traumas.

Mechanisms of Graft FailureThrombosis – formation/presence of a blood clot in the blood vesselNeointimal Thickening – thickening of the walls of the blood vessel which prevents blood from flowing properlyInfection

Current grafts are made of Dacron and TeflonRelatively successful for large diameter vesselsPoor patency (state of being open) for small-diameter grafts (<6mm)

Usually due to neointimal thickening

Project Aims:

The long-term goal is to create a small-diameter vascular graft with:

Microstructures and mechanical properties of the native vesselsHemocompatiblity

Prevention of clotting and adhesion of blood

Long-term patency in vivo

Progress 1Mimicking the mechanical properties of the native small- diameter blood vessels using nanofiber composites

•Electrospinning technique

•Nanofiber array composites to mimic native vessels

• Straight PU (elastin)

• Wavy PCL (collagen)

Vince Beachley (PhD Candidate)

•Pictures of the Natural Vessel

•Wavy and straight components

Mechanical testing indicates a match of the “J” shape Mechanical testing indicates a match of the “J” shape stress-strain behaviors of natural blood vesselsstress-strain behaviors of natural blood vessels

0.00 0.20 0.40 0.60 0.80Strain

Str

ess

Native AortaPU/Waved PCLControl PU/Straight PCL

Progress 1 Continued

Progress 2 (Current Project)

Immobilization of heparinStandard technique to impart hemocompatibility to surfaces

EDC as a crosslinkerActs as a spacerChemically binds heparin

to the surface

Enhancing the hemocompatibility of the vascular graft through heparin immobilization

EDC reaction scheme for carboxyl-to-amine

crosslinking

Experimental Design and Methods

Creating Films of nanofiber composites

Electrospinning

Spin Coating

Water Contact Angle

Heparinization

Toluidine Blue Assay

Plasma Recalcification Time

Activated Partial Thromboplastin Time

Water Contact Angle (Spin-coated flims)

Water Contact Angle (Electrospun fiber

composites)

Results- Toluidine Results- Toluidine BlueBlue

% PEG 0% 1% 1% 10%

30%

NH2No No Yes Yes Ye

s

Molecular Weight

n/a 300 800 800 800

Results- Plasma Recalcification Time

Results: Results: Activated Partial Activated Partial Thromboplastin TimeThromboplastin Time

ConclusionsConclusionsThe toluidine blue shows favorable The toluidine blue shows favorable results to heparin binding, but could results to heparin binding, but could not be quantifiednot be quantified

The water contact angle measurements The water contact angle measurements and the APTT showed favorable results and the APTT showed favorable results to heparin bindingto heparin binding

The PRT showed results unfavorable to The PRT showed results unfavorable to heparin bindingheparin binding

Further testing must be conductedFurther testing must be conducted

Future work

Move to the animal modelMove to the animal model

Use arteriotomy model in ratsUse arteriotomy model in rats

Implant graft and evaluateImplant graft and evaluateLong-term efficacyLong-term efficacy

Long-term patencyLong-term patency

Long-term stabilityLong-term stability

AcknowledgmentsAcknowledgmentsThe Governor’s School for Science and The Governor’s School for Science and MathematicsMathematics

The Medical University of South The Medical University of South CarolinaCarolina

Dr. Ning ZhangDr. Ning Zhang

Vince BeachleyVince Beachley

Clyde SmithClyde Smith