“Excuse me, sir, but I think you have some aeroplane in your eye.” THANKS TO SIR HAROLD RIDLEY, M.D., WE CAN SAY THAT WITHOUT A HINT OF ABSURDITY. A STEP-BY-STEP GUIDE TO BIOCOMPATIBILITY Review the questions below to ask your students. In the process of answering these questions, they’ll need to cover the stages of free radical polymerization, as shown in the drawings: ADDITIONAL QUESTIONS TO ASK: • Mixing bone cement is an exothermic reaction. What considerations need to be taken as a result? • What processing/ storing/transporting considerations need to be taken with bone cement, due to its properties? • What other applications do we use bone cement for? • What else could we apply biocompatibility to? What other problems could we solve now that we know about the intraocular lens and bone cement? • Why is the bottle of liquid MMA brown? • How long will the reaction between PMMA and MMA take? • What happens physically to the properties of PMMA and MMA during polymerization? • What is a radio pacifier? • How does the initiation reaction work? • What’s the hydroquinone for? STEP ONE: Put a Plane in Your Eye. World War II was winding down, but Ridley’s commitment to his country was just beginning. In Britain, Ridley was examining Royal Air Force pilots returning from duty. As an ophthalmologist, he noted that pilots whose planes had been hit, often had shrapnel in their eyes. Oddly, some of them weren’t experiencing adverse reactions to the debris. Specifically, when it was shrapnel from the plastic canopies that had shattered and lodged in the eye. When the eye healed, it accepted the shrapnel into the organ. What Ridley noticed confused him. The medical knowledge at the time stated that any foreign object implanted into the body would cause some sort of adverse reaction. For instance, a splinter in the hand could cause an infection. However, these shards of plastic were causing no inflammation or irritation after the initial trauma—a definition of biocompatibility. The eye was especially thought of as an organ that would not tolerate foreign objects, but here Ridley had pilots cycling through his clinic, all with the same shrapnel in their eyes, causing no problems. Ridley called up the plane manufacturers and ordered sheets of methyl methacrylate, the material used to create the plane canopies. If this plastic could be accepted by the eye, then surgeons could remove cataracts and replace them with intraocular lenses made of methyl methacrylate. This hypothesis was not without controversy. Biocompatibility was a divisive topic, especially for the eye. No one had ever implanted a biomaterial before, and many prominent doctors thought that at some point the body would reject the foreign materials, leaving the patient in worse shape than before. Even though Ridley was able to fine-tune his methods in the 1960s, it wasn’t until the 1980s before his intraocular lens received FDA approval. Today, over 7 million people a year get a little bit of plane in their eyes, combating a cataract diagnosis that at one point resulted in sure blindness. STEP TWO: Mix Crushed Windows with a Carcinogen and Stick it on Your Bones. PMMA—Poly(methyl methacrylate) is widely known as Plexiglass—the stuff we use in windows and castings due to its durability. That’s why the planes the Royal Air Force was flying—Spitfires and Hurricanes—used the stuff in its windows. When Ridley discovered PMMA’s biocompatibility and proved that biocompatible substances even existed, though, the medical world was excited to find other uses for PMMA. One use for PMMA that was discovered early on was bone cement. Surgeons were struggling with finding a substance that the body wouldn’t reject that would allow them to affix implants or repair bones, but would also be strong enough to stand up to wear. In order to be able to shape the PMMA bone cement, it needed to be supplied as a powder and mixed with a liquid MMA monomer to catalyze the polymerization. The catch is this: by itself, MMA is an irritant and a carcinogen. However, though free radical polymerization, MMA combines with PMMA to avoid the problems that MMA would cause on its own. BIOCOMPATIBILITY TEACHING NOTES There are, of course other issues to consider with the use of PMMA. Students should consider the properties of the powder and liquid and the list of questions below and come to class ready to apply their knowledge of free radical polymerization to these ideas. POWDER • PMMA (Polymethyl Methacrylate) base • ZrO2 or BaSO4 radio pacifier • Benzoyl Peroxide (initiator) • Chlorophyll (dye) LIQUID • MMA (Methyl Methacrylate) Monomer • N-N-dimethyl-p- toluidine (DMPT)- Initiator • Benzoyl Peroxide: Reacts with DMPT to catalyze polymerization • Hydroquinone: Inhibitor 34 35