Transcript PEG Hydrogel Coating for Medical Devices

PEG Hydrogel Coating for Medical Devices
B. Mulawka, B. Roedl, P. Schenk, D. Patel
Advisor: Professor William Murphy, Client: Arthur J. Coury Ph.D, Vice President of Biomaterials Research, Genzyme Corporation
Motivation
Our ultimate goal is to coat a urinary catheter
with a uniform biocompatible hydrogel with
sufficient material adhesion which we believe
will improve upon the problems associated with
existing long-term catheters.
Client Specifications
•Stain specimen in 50ppm
Eosin Y solution from two
hours to one week
•Rinse with distilled water:
heavy, light, no rinse, bath
•Immerse specimen in
macromer (PEG) solution and
apply light from source for 40s
•Soak in saline to equilibrate
any gel formed on surface
•View specimen under
microscope to measure
thickness by comparison to 6
micron polystyrene beads
•Used subjective test to
measure adherence
Visible Light Initiating System
35
Na
COO
Br
Br
514 nm
O
O
*
[Eosin Y]
+
:N(CH2CH2OH)3
O
Na
Br
Br
Eosin Y
Urinary Catheters
•Made of latex, PVC, silicon, PTFE (Teflon)
•Chance of failure 100% within weeks to months
•Catheter obstruction due to crystallization of
proteins and bacteria collection
•Dependent upon patient and coating
•Silver nitrate, antibiotics, Norfloxacin
•Difficult to coat due to curvature of surface
25
Polystyrene
Glass
PVC
20
15
10
5
2 hrs
POLYMERIZATION
Macromer
:N(CH2CH2OH)2
+
H
1 day
1 week
Thickness of Hydrogel vs.
Rinsing Technique
60
50
Polystyrene
40
Glass
30
PVC
20
10
0
Bath
Time in Eosin Solution
Heavy
Light
None
Rinse Technique
CHCH2OH
+
COO
Br
Na
Br
O
O
OH
Na
Br
COO
Br
O
O
O
Na
Br
Na
Br
Br
Br
Interfacial Polymerization
•Testing of thickness and adherence of hydrogel
coatings
•bovine albumin solution, pH 7.35
70
30
0
•Create a detailed process for applying a
hydrogel to surfaces
•Testing of fouling resistance of hydrogels in
physiologically imitated environments
Thickness of Hydrogel vs.
Time in Eosin
Thickness (microns)
Form a microlayer of PEG based hydrogel onto
material surfaces in order to examine and
improve upon their characteristics and
biocompatibility.
Results
Procedure
Thickness (microns)
Problem Statement
Na
•All surfaces showed poor hydrogel adhesion
•Eosin did not adhere to surface
•All thicknesses were under 40 microns
•Client specifies 25-100 microns
•Non-uniform surface coatings
•Increased time in eosin Y solution did not affect
hydrogel adhesion
•Increased rinsing of material before
photopolymerization caused a decrease in
hydrogel thickness but did not affect hydrogel
adhesion
Future Work
Materials
•PEG: Nontoxic polymer. In water, helical structure,
viscous, neutral, repulsive of charged molecules.
Minimizes protein and cell interaction and
decreases host response.
•Uses: drug delivery matrix, biomaterial
synthesis, food additives, wound dressings, soft
tissue replacement
•PVC: Hydrophobic surface. Used as tubing for
blood transfusion, dialysis, and feeding.
Biologically inert, can be used as a negative
control
•Polystyrene: Hydrophobic surface. Polar groups
can be introduced to give the surface ionic or
dipole-dipole bonding properties. Used to make
Petri dishes and cell culture wells, good material
for testing cell adhesion.
•Glass: Hydrophilic and negatively charged
surface. Used for eyeglasses, chemical ware,
thermometers, tissue culture flasks, and optics in
endoscopy.
•Modify Staining Procedure
•Increase concentration of Eosin Y
•Change to Ethyl Eosin stain (more
hydrophobic)
•Allow material to dry after Ethyl Eosin is
applied
•Increase light application time during
photopolymerization
•Focus on coating of latex and PVC
•Continue to test adhesion of hydrogel to
substrate surface
•Test biocompatibility by exposing hydrogel
coated material to bovine albumin solution
References
•Kenneth Messier, Genzyme Corp.
•McNair, Andrew M. "Using Hydrogel Polymers for Drug Delivery." Medical
Device Technology (1996).
•Kizilel, Seda, Victor H. Perez-Luna, and Fouad Teymour.
"Photopolymerization of Poly(Ethylene Glycol) Diacrylate on EosinFunctionalized Surfaces." Langmuir (2004).
•Levillian, Pierre, Dominique Fompeyide. “Demonstration of Equilibrium
Constants by Derivative Spectrophotometry. Aplication to the pKas of Eosin”.
Anal. Chem. (1988).
•Cruise, Gregory. Scharp, David. Hubbell, Jeffrey. “Characterization of
permeability and network structure of interfacially photopolymerized
poly(ethylene glycol) diacrylate hydrogels.” Biomaterials. (1998)