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Polymers In Medicine Jeremy C. Robinson Pierre M. Saint Louis Anoop Padmaraju Overview • Introduction • Brief History • Applications – – – – – – Cellophane PGA, PLA, PLGA Polydimethylsiloxane Polyethylene and PMMA Polytetrafluoroethylene Polyurethane • The Future Biomaterials What are they? • Substances other than food or drugs contained in therapeutic or diagnostic systems that are in contact with tissue or biological fluids Why use Biomaterials? • Improve patient’s quality of life by replacing a defective body part with a substitute. • Physicians were limited to use off-the shelf supplies. • Novel biodegradable polymers and modified natural substances. Table 1 Applications of Biomaterials2 Polymer Applications Polymer Applications PDMS Catheters, heart Polytetrafluoroe Heart valves Valves thylene Vascular grafts Nerve repair Polyurethane ventricular assist Polyethylene Devices Catheters, hip prostheses Polymethylmetha Fracture fixation PGA, PLA, Drug delivery, devices crylate (PMMA) And PLGA Cellophane Dialysis membranes History • Biomaterials not practical till 1860’s • 1900’s Biomaterials first used • WWII, PMMA used to replace damaged cornea Cellophane • “Saran Wrap”, Rayon (fiber) • “Regenerated” Cellulose • Invented 1908, Jacques E. Brandenberger • Kidney Dialysis • Invented 1959, William J. Kolff • Vegetable Parchment, Natural Casings early membranes Fig. 2 A schematic of an artificial kidney (hemodialysis) Fig. 3 The regeneration of Cellulose (cellophane). PGA, PLA, PLGA PGA, PLA, PLGA • First synthesized by Dupont from Glycolic acid • PGA, originally Dexon, absorbable suture • 1963 Schmitt & Polistina Invents Biodegradable suture • PLA & PLGA Drug delivery systems PGA, PLA, PLGA • All polymers have low polydisparity index (PLA 1.6-1.9) • Depending on structure, polymers can be fit for different applications • Amorphous forms used in drug delivery systems • Crystalline forms good for scaffolding, or sutures PGA, PLA, PLGA • Two essentials in scaffolding: high surface to volume ratio, highly porous – Allows cells to easily proliferate for setup of pathways – Setup of pathways for nutrients Polydimethylsiloxane •“Silicon” •Lubricants and Foaming agents •Pacemakers and Vaccine Delivery systems Polydimethylsiloxane • Discovered 1927, Dr. Frederick Stanley Kipping • Vulcanized rubber, can’t be melted or dissolved • Low glass transition • Produced by hydroxyl, groups through hydrolysis, replace the 2 Cl in the monomer • Ring opening polymerization, Higher MW Polydimethylsiloxane • Used in treatment of prostate carcinoma • Small biodegradable pellets (188 m) injected into area of body where needed. • Smaller doses, less toxic effects for patient Polyethylene and PMMA • Thermoplastics, exhibit moderate to high tensile strength with moderate elongation • Used for Hip replacement and Fracture Fixation • Annual procedures approaching 5 Million • Metal alternatives have corrosive problems PMMA Fig. 4a PMMA disc over femoral window during the molding process Fig. 4b PMMA template after polymerization, showing molded plug Polytetrafluoroethylene • High strength and Chemical resistance • High modulus and tensile properties with negligible elongation • Used for orthopedic and dental devices • Mechanical heart valve and implants Polytetrafluoroethylene • Excellent wear and fatigue resistance • Vascular grafts patch injured and diseased areas of arteries • Must be flexible to allow for the difficulties of implantation and to avoid adjacent tissue irritation Polyurethane • Shoe soles, tires and foams • Thermoset, non-condensation step growth • Low molecular weight polymer (47,000) • “Bridges” the gap between rubber and plastic Polyurethane • One of the best load-bearing capacities • Discovered 1937, Otto Baker • Major medical uses Ventricular assist device • Developed by Dr. Liotta, Baylor, 1950’s • Redefined by Pierce and Donachy in 1971 Ventricular Assist Device Polyurethane • VAD, used during open heart surgery, postoperatively and in case of extreme cardiac trauma • Pierce and Donachy used segmented polyurethane in their VAD • Safe contact barrier compressive properties made function similar to heart ventricle Polyurethane • Obtained through step-growth polymerization of diisocyanates and dihydroxl compounds • Injection molded • R.I.M. • Failures attributed to poor processing, not physical material properties The Future • Opportunities are limitless • We as scientists and engineers are faced with big challenges • Potential and promise are tremendous Questions! References 1. 2. 3. 4. 5. 6. 7. 8. Peppas, N., Langer, R. “New challenges in biomaterials”, Science, Vol. 263, March, 1994 Andreadis, S., “Applications of Biomaterials”, Tissue engineering handout, February 2001, University at Buffalo. “History and Development of Biomaterials”, www.bae.ncsu.edu/Courses/bae465 Fried, J. R., “Polymer Science and Technology.”, Prentice Hall, New Jersey 1995 “Cellophane Invention”, http://inventors.about.com/science/inventors/library /inventors/blcellophane.htm “First Dialysis Unit”, www.ucl.ac.uk/uroneph/history/dialysis.htm “Dialysis and the Artificial Kidney”, www.chemengineer.about.com/science/chemengineer/libr ary/weekly/aa120897.htm www.beyonddiscovery.com References 9. Ikada, Y, Yoshihiko, S, “Tissue Engineering for Therapeutic Use 4.” Elsevier, 2000, New York 10. Pulverer, G., Schierholz, J. M., “Development of New CSF-shunt With Sustained Release of Antimicrobial Broad-Spectrum Combination.”, Baktercologie, Vol. 286, 107-123 11. Loomes, L. M., Jian Xiong, J., Brook, M. A., Underdown, B. J., McDermott, M. R., “Novel Polymergrafted Starch Microparticles for Mucosal Delivery of Vaccines.”, Immunology, Vol. 56, 162-168, 1996 12. www.britannica.com, (keyword “polyethylene”) 13. “Uses of Polymehtylmethacrylate”, www.rcsed.ac.uk (Feb 2001) 14. www.britannica.com, (keyword “Polytetrafluoroethylene”) References 15. “Polyurethane – Features and Benefits”, www.elastchem-ca.com/poly.html 16. “Pierce-Donachy Ventricular Assist Device”, www.asme.org/history/Roster/H142.html 17. Liotta, D. “The Ventricular Assist Device”, www.fdliotta.org The End Thank You!