The Development of a Poly(N-isopropylacrylamide) Bioadhesive

Sealant for Ocular Wounds Sustained in Combat

Leah Ho-Israel and Janve SobersGrade 12

The Thacher School and Sage Hill School

Mark HumayunJohn Jack Whalen, Yi Zhang, Stacey Rauen

SHSARP Program 2013University of Southern California

Introduction

• Hypothesis: that a thermoresponsive bioadhesive of PNIPAAM would be useful in sealing ocular injuries sustained in combat, as it adheres to tissue at body temp.

• Increase in ocular injuries sustained in combat due to use of fragmentary explosives. Novel bioadhesive can help treat perforating + penetrating injuries caused by shrapnel– Head and Neck injuries high in modern warfare:

• 21% in WWII • 21.4% in Korean War• 16.0% in Vietnam War• 30% in Operations Iraqi Freedom and Enduring Freedom

– Incidents of war-related eye injuries:• 0.5% in American Civil War• 2% in World War I and World War II• 9% in Vietnam War• 13% in Arabian Gulf War

– Rehabilitation, family support, Veterans Affairs benefits, and workers’ compensation costs the U.S. $24 billion

Introduction

• The thermoresponsive properties of PNIPAAM are very well known, however adhesive strength as it relates to concentration, molecular weight, and form (liquid, gel) has not been quantified.

• PNIPAAM has been primarily studied for use in drug delivery and in growing cell cultures

• In developing a suture replacement for ocular wounds, our project is working to find the most efficacious form of PNIPAAM

Procedures

• Bose Uniaxial Tension Tester (left)

• Cadaveric porcine eye tissue

• Replicate conditions of real surgery (i.e. pressure, holding time)

• Heated water bath

Experiments Run Components

Exp. 1 Sclera/Sclera

Exp. 2 Conjunctiva/Conjunctiva

Exp. 3 Parylene/Cyanoacrylate/Conjunctiva

Exp. 4 Conjunctiva/Cyanoacrylate/Conjunctiva

Exp. 5 Conjunctiva/PNIPAM/Conjunctiva

Exp. 6 Conjunctiva/PNIPAM/Conjunctiva (+ heat)

Procedures

• Holding times tested: 2 min, 5 min• Application pressures: -5 (g?), -15• 50g load cell, 1 kg load cell • Conditions most favorable to ophthalmic surgeon

PNIPAM Concentration High/Low Molecular Weight0.8% High2.0% High5.26% High10% Low14.26% Low25% Low30% Low

Experimental Set Up

PNIPAM

Eye tissue

Load cell

Actuated arm

Waterline

Experimental Set Up for PNIPAM tests

Control Results

• (Show bar graph of scl-scl, conj-conj, pary-cyano, tiss-cyano)

• (Show line graph w/ time tables marked)

• Do both of above on Excel• Baseline: 50mN• Benchmark (different word): 250 mN

PNIPAM Results

• (Show results of initial inconclusive PNIPAM tests)

• Lowered molecular weight, increased concentration

• (Show bar graph w/ all the [PNIPAM] tested)

• (Show line graphs)

Conclusions

1. Clearly and logically state your conclusions.2. Relate your data to your conclusions. Explain how your data supports your conclusions.3. Explain how your data supports or does not support your originally stated hypothesis.4. Offer modifications to you original hypothesis if need be.

Future Goals

1. Research investigations never completely answer or address all the issues.

Indicate which areas still need investigation.

2. State the next steps you will undertake in lab to continue your investigation. What further data needs to be collected?

Acknowledgements

Thank you John Jack Whalen Yi Zhang, Stacey Rauen, Nikki Bayat, Joe Cocozza, Diana Sabogal

Thank you to Windsong Trust for its generous support!