Hydrogels for Coating Medical Devices University of Wisconsin BME 400

Our Team Brett Mulawka – Team Leader Brett Mulawka – Team Leader Patrick Schenk – Communicator Patrick Schenk – Communicator Benjamin Roedl – BWIG Benjamin Roedl – BWIG Darshan Patel - BSAC Darshan Patel - BSAC

Client & Advisor Client: Arthur J. Coury, Ph.D. Client: Arthur J. Coury, Ph.D. Vice President Biomaterials Research Genzyme CorporationVice President Biomaterials Research Genzyme Corporation Advisor: William Murphy, Professor of Biomedical Engineering Advisor: William Murphy, Professor of Biomedical Engineering

Genzyme Corporation One of world’s foremost biotechnology companies with the goal of applying the most advanced technologies to address unmet medical needs. One of world’s foremost biotechnology companies with the goal of applying the most advanced technologies to address unmet medical needs.

Problem Statement To form PEG macromer-based hydrogels on a latex Foley catheter surface in an interfacial photopolymerization process and to screen the coatings for interactions with cells and media that mimic physiologic fluids. It is hypothesized that these coatings will resist fouling and may be useful for reducing infections resulting from the use of urinary catheters. To form PEG macromer-based hydrogels on a latex Foley catheter surface in an interfacial photopolymerization process and to screen the coatings for interactions with cells and media that mimic physiologic fluids. It is hypothesized that these coatings will resist fouling and may be useful for reducing infections resulting from the use of urinary catheters.

Motivation Our ultimate goal is to coat a urinary catheter with a uniform hydrogel with sufficient material adhesion. We believe that the hydrogel will improve upon the problems associated with existing long-term catheters.

Catheters Made of various materials Made of various materials Latex, PVC, silicon, PTFE (Teflon)Latex, PVC, silicon, PTFE (Teflon) Why focus on catheters? Why focus on catheters? Chance of failure 100% within weeks to monthsChance of failure 100% within weeks to months Catheter obstruction and leakage Catheter obstruction and leakage Caused by bacteria and protein buildupCaused by bacteria and protein buildup Dependant upon patient and coating Dependant upon patient and coating

Latex Our primary material choice Our primary material choice Most common material for urinary cathetersMost common material for urinary catheters Sulfur bridges formed during vulcanization Sulfur bridges formed during vulcanization Cis

Polyethylene Glycol (PEG) Properties Properties Clear, viscous, odorless, miscible in water, non-toxicClear, viscous, odorless, miscible in water, non-toxic Uses Uses Wound dressing, soft tissue replacement, drug deliveryWound dressing, soft tissue replacement, drug delivery

Last Semester What we coated What we coated PVC, Polystyrene and GlassPVC, Polystyrene and Glass All showed very All showed very poor adhesion poor adhesion Why? Why? Hydrophilic and Hydrophobic interactionsHydrophilic and Hydrophobic interactions

This Semester Focused on latex substrates Focused on latex substrates Modified staining procedure Modified staining procedure 125ppm Ethyl Eosin in acetone solution125ppm Ethyl Eosin in acetone solution Hydrophobic stain Hydrophobic stain Poor adhesion persisted Poor adhesion persisted

Adhesion We reject our hypothesis that stain adhesion correlates to hydrogel adhesion We reject our hypothesis that stain adhesion correlates to hydrogel adhesion Why? Why? The Eosin molecule does not bind with PEG hydrogelThe Eosin molecule does not bind with PEG hydrogel Intermediate compounds continue the free- radical reaction and form the covalent bonds Intermediate compounds continue the free- radical reaction and form the covalent bonds

Continued Poor Adhesion

Alter Substrate Increase porosity of latex Increase porosity of latex Stretching when in contact with PEGStretching when in contact with PEG Increases surface area for PEG interaction with substrate Increases surface area for PEG interaction with substrate Opens pores on substrate surface Opens pores on substrate surface Allows PEG to interact with crevicesAllows PEG to interact with crevices

Experiment Stain latex with Ethyl Eosin solution Stain latex with Ethyl Eosin solution Rinse with acetone Rinse with acetone Stretch latex and place in PEG solution overnight Stretch latex and place in PEG solution overnight Photopolymerize Photopolymerize Test adhesion Test adhesion

Modified PEG Molecules PEG has many variations of end chains PEG has many variations of end chains HydrophobicHydrophobic HydrophilicHydrophilic Also could use “block” polymer Also could use “block” polymer PEG--PLA--PEGPEG--PLA--PEG

Experiment Stain latex with Ethyl Eosin Stain latex with Ethyl Eosin Rinse with acetone Rinse with acetone Place in modified PEG solution and polymerize the monomer Place in modified PEG solution and polymerize the monomer Test adhesion Test adhesion

Covalent Link Use chemical reaction to form covalent bond between PEG and latex Use chemical reaction to form covalent bond between PEG and latex PEG molecule with a sulfhydryl endPEG molecule with a sulfhydryl end Similar to vulcanization process used to form latex bonds Similar to vulcanization process used to form latex bonds Cons to covalent link Cons to covalent link Need to find safe chemical reactionNeed to find safe chemical reaction Reaction could be difficult to runReaction could be difficult to run

Experiment Stain latex with Ethyl Eosin Stain latex with Ethyl Eosin Rinse with acetone Rinse with acetone Place in PEG solution Place in PEG solution Run chemical reaction to covalently bond PEG to substrate Run chemical reaction to covalently bond PEG to substrate Polymerize PEG monomer Polymerize PEG monomer Test adhesion of macromer Test adhesion of macromer

Future Work Once strong gel adhesion to the substrate is established… Once strong gel adhesion to the substrate is established… Modify procedure to obtain homogenous thickness under 100 micronsModify procedure to obtain homogenous thickness under 100 microns Want it thin enough to restrict entry of bacteria Want it thin enough to restrict entry of bacteria Test PEG coated latex for protein interactionTest PEG coated latex for protein interaction Minimize protein adhesion Minimize protein adhesion Test with common plasma protein: albuminTest with common plasma protein: albumin

Thank you Questions?