Hydrogels for Coating Medical Devices University of Wisconsin BME 400

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

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

Problem Statement To form PEG based hydrogels on biomaterial surfaces 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 implantable devices. To form PEG based hydrogels on biomaterial surfaces 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 implantable devices.

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.

Motivation Development of blood compatible hydrogel could have many applications Development of blood compatible hydrogel could have many applications Orthopedic applications Orthopedic applications Urinary Catheter Urinary Catheter Tissue Repair Tissue Repair Create a hydrogel application procedure that results in accurate and reproducible results Create a hydrogel application procedure that results in accurate and reproducible results

Background-Hydrogels Polymeric structures that absorbs water Polymeric structures that absorbs water Crosslinks, Polymer, Liquid (Water) Crosslinks, Polymer, Liquid (Water)

Crosslinking Covalent Bonds Linking One Polymer Chain to Another Covalent Bonds Linking One Polymer Chain to Another Can be Caused by Heat, Pressure, Chemicals Can be Caused by Heat, Pressure, Chemicals Form free radicals Form free radicals We use a chemical that is light initiated We use a chemical that is light initiated By Crosslinking, Hydrogels are Capable of Remarkable Water Retention/Adsorption By Crosslinking, Hydrogels are Capable of Remarkable Water Retention/Adsorption

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

Eosin Y One Part of a Two Part Photoinitiator System One Part of a Two Part Photoinitiator System Maximum Adsorption at 514 nm (visible) Maximum Adsorption at 514 nm (visible) Passes Free Radical to Triethanolamine Passes Free Radical to Triethanolamine Taken from OLMC.Ogi.edu

Triethanolamine Accepts Free Radical from Eosin Y Accepts Free Radical from Eosin Y Combines with Macromer to polymerize reaction Combines with Macromer to polymerize reaction

Procedure Stain specimen with Eosin Solution Stain specimen with Eosin Solution Immerse stained specimen in macromer solution Immerse stained specimen in macromer solution Apply visible light Apply visible light An adherent, thin, hydrogel forms by polymerization of the macromer (PEG) An adherent, thin, hydrogel forms by polymerization of the macromer (PEG) Expose specimen to cells to test for fouling Expose specimen to cells to test for fouling

Testing Thickness Thickness Need to maintain consistent thickness for reliable test data / Toughness Need to maintain consistent thickness for reliable test data / Toughness Adherence Adherence Durability through many cycles Durability through many cycles Fouling Resistance Fouling Resistance Biocompatibility Biocompatibility Most important Most important

Thickness Place fully swollen coated substrate on edge under optical microscope Place fully swollen coated substrate on edge under optical microscope Microscope with camera would be ideal Microscope with camera would be ideal Hydrogel thickness goal: 25 – 100 microns Hydrogel thickness goal: 25 – 100 microns Alternate method: Alternate method: Peel/slice piece of gel off at interface, cut to straight edge and measure with optical microscope Peel/slice piece of gel off at interface, cut to straight edge and measure with optical microscope

Adherence Using a pointed spatula or needle, one person (control) will estimate adherence on a specific scale Using a pointed spatula or needle, one person (control) will estimate adherence on a specific scale 0 = Has fallen off 0 = Has fallen off 1 = Lifts off almost intact with mild force 1 = Lifts off almost intact with mild force - 2 = Lifts off in large chunks with some force - 3 = Lifts off in small pieces with some force - 4 = Does not delaminate even by destroying gel with pushing force

Fouling Resistance Expose to proteins found in blood in solution Expose to proteins found in blood in solution Stain with appropriate dye to view adhered proteins Stain with appropriate dye to view adhered proteins

Future Work: Protein Adsorption Determine the concentration of proteins we must measure Determine the concentration of proteins we must measure Establish the best protein assay method to use Establish the best protein assay method to use Acceptable resolution Acceptable resolution Ease of procedure Ease of procedure UV adsorption, BCA assay… etc UV adsorption, BCA assay… etc

References Arthur J. Coury, Ph.D. Arthur J. Coury, Ph.D. Kenneth Messier Kenneth Messier McNair, Andrew M. "Using Hydrogel Polymers for Drug Delivery." Medical Device Technology (1996). 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 Eosin-Functionalized Surfaces." Langmuir (2004). Kizilel, Seda, Victor H. Perez-Luna, and Fouad Teymour. "Photopolymerization of Poly(Ethylene Glycol) Diacrylate on Eosin-Functionalized Surfaces." Langmuir (2004).

Thank you Questions?

Hydrogel Preparation Radical chain reaction used to form cross links Radical chain reaction used to form cross links Initiated using electrons, gamma-rays, x-rays, UV light to excite polymer chain and form radicals Initiated using electrons, gamma-rays, x-rays, UV light to excite polymer chain and form radicals (We will use visible light 514nm for eosin) (We will use visible light 514nm for eosin) Crosslinkers Crosslinkers Acrylate, double bond forms radical Acrylate, double bond forms radical

Polyethylene Glycol (PEG) Non-toxic Non-toxic Laxatives, Skin Creams, Lubricants Laxatives, Skin Creams, Lubricants

Light Source Using a xenon light source Using a xenon light source Applied to sample for 40 Seconds at a Distance of One Inch Applied to sample for 40 Seconds at a Distance of One Inch Light Source Supplies Energy to Remove Electron from Eosin Y Light Source Supplies Energy to Remove Electron from Eosin Y Leads to a propagation of crosslinking between the macromer and triethanolamine Leads to a propagation of crosslinking between the macromer and triethanolamine