1. Biomaterials By Dr. Tejal Ashwin Desai, U. Illinois Chicago Modified, P. H. King, Vanderbilt U.

2. What is a biomaterial? What are the design constraints?

3. Biomaterial — A biomaterial is a nonviable material used in a medical device intended to interact with biological systems (Williams 1987) Biocompatibility — The ability of a material to perform with an appropriate host response in a specific application (Williams 1987) Host Response — The response of the host organism (local and systemic) to the implanted material or device.

4. Keywords ßMetallic/glass/Polymeric/Ceramic/Composite ßFracture/fatigue/creep/corrosion/degredation ßTissue response/healing/biocompatability/host response/carcinogenicity ßHard/soft tissue implants ßVascular/Breast/Urological/Art. Organ ßMucosal contacting …

5. Material Selection Parameters ßMechanical ßThermal/Electrical Conductivity ßDiffusion ßWater Absorption ßBiostability ßBiocompatibility

6. Test Conditions: Length of implant: Day: Month: Longer: Where used: skin/blood/brain/mucosal/etc.

8. Test Animals ßRabbits – ear, skin, pyrogen ßGuinea Pigs – skin, esp C@ ßMice – genotoxicity ßHorseshoe Crab – endotoxins ßPig – implant ßBacteria - genotoxicity ßTest actual & elutants & extracts… ßPeople – long term

9. Some Commonly Used Biomaterials Material Applications Silicone rubber Catheters, tubing Dacron Vascular grafts Cellulose Dialysis membranes Poly(methyl methacrylate) Intraocular lenses, bone cement Polyurethanes Catheters, pacemaker leads Hydogels Opthalmological devices, Drug Delivery Stainless steel Orthopedic devices, stents Titanium Orthopedic and dental devices Alumina Orthopedic and dental devices Hydroxyapatite Orthopedic and dental devices Collagen (reprocessed) Opthalmologic applications, wound dressings

10. An Interdisciplinary Field Bioengineers Material Scientists Immunologists Chemists Biologists Surgeons...

11. Journals ßBiomaterials ßJournal of Biomedical Materials Research ßCells and Materials ßJournal of Biomaterials Science ßArtificial Organs ßASAIO Transactions ßTissue Engineering ßAnnals of Biomedical Engineering

12. A Little History on Biomaterials ßRomans, Chinese, and Aztecs used gold in dentistry over 2000 years ago, Cu not good. ßIvory & wood teeth ßAseptic surgery 1860 (Lister) ßBone plates 1900, joints 1930 ßTurn of the century, synthetic plastics came into use ßWWII, shards of PMMA unintentionally got lodged into eyes of aviators ßParachute cloth used for vascular prosthesis ß1960- Polyethylene and stainless steel being used for hip implants

13. Uses of Biomaterials ßReplace diseased part – dialysis ßAssist in healing – sutures ßImprove function – contacts ßCorrect function – spinal rods ßCorrect cosmetic – nose, ear ßAid dx – probe ßAid tx – catheter ßReplace rotten – amalgam ßReplace dead - skin

14. Problems/test for w Biomaterials ßAcute toxicity (cytotoxicity) arsenic ßSub chronic/chronic Pb ßSensitization Ni, Cu ßGenotoxicity ßCarcinogenicity ßReproductive &/or developmental Pb ßNeurotoxicity ßImmunotoxicity ßPyrogen, endotoxins

15. FDA & ISO 10993 ßFDA mandates tests based on length of contact (24 Hr, 1-30 Days, >30 days) ßSee table for details ßISO 10993 – required for European Union Certification – see flowchart for exemptions ßSee Device Categories & examples ßHarmonization – in process…

16. First Generation Implants ß“ad hoc” implants ßspecified by physicians using common and borrowed materials ßmost successes were accidental rather than by design Examples — First Generation Implants gold fillings, wooden teeth, PMMA dental prosthesis steel, gold, ivory, etc., bone plates glass eyes and other body parts dacron and parachute cloth vascular implants

17. Intraocular Lens

18. Vascular Grafts

19. Second generation implants ßengineered implants using common and borrowed materials ßdeveloped through collaborations of physicians and engineers ßbuilt on first generation experiences ßused advances in materials science (from other fields) titanium alloy dental and orthopaedic implants cobalt-chromium-molybdinum orthopaedic implants UHMW polyethylene bearing surfaces for total joint replacements heart valves and pacemakers Examples — Second generation implants

20. Artificial Hip Joints

21. Third generation implants ßbioengineered implants using bioengineered materials ßfew examples on the market ßsome modified and new polymeric devices ßmany under development Example - Third generation implants tissue engineered implants designed to regrow rather than replace tissues Integra LifeSciences artificial skin Genzyme cartilage cell procedure some resorbable bone repair cements genetically engineered “biological” components (Genetics Institute and Creative Biomolecules BMPs)

22. Substitute Heart Valves

23. SEM displaying the cross section of a composite disk, which had been seeded with cultured bone marrow stromal cells.

24. Synthetic polymer scaffolds... in the shape of a nose (left) is "seeded" with cells called chondrocytes that replace the polymer with cartilage over time (right) to make a suitable implant.

25. Evolution of Biomaterials Structural Functional Tissue Engineering Constructs Soft Tissue Replacements

26. Advances in Biomaterials Technology ßCell matrices for 3-D growth and tissue reconstruction ßBiosensors, Biomimetic, and smart devices ßControlled Drug Delivery/ Targeted delivery ßBiohybrid organs and Cell immunoisolation ßNew biomaterials - bioactive, biodegradable, inorganic ßNew processing techniques

27. MetalsSemiconductor Materials CeramicsPolymers Synthetic BIOMATERIALS Orthopaedics screws/fixation Dental Implants Heart valves Bone replacements Biosensors Implantable Microelectrodes Skin/cartilage Drug Delivery Devices Ocular implants

28. Biomaterials for Tissue Replacements ßBioresorbable vascular graft ßBiodegradable nerve guidance channel ßSkin Grafts ßBone Replacements

29. Biomaterials - An Emerging Industry ßNext generation of medical implants and therapeutic modalities ßInterface of biotechnology and traditional engineering ßSignificant industrial growth in the next 15 years -- potential of a multi-billion dollar industry

30. Biomaterials Companies BioForma Research & Consulting, Inc., fibrinolytic systems, protein-material interactions Baxter International develops technologies related to the blood and circulatory system. Biocompatibles Ltd. develops commercial applications for technology in the field of biocompatibility. Carmeda makes a biologically active surface that interacts with and supports the bodys own control mechanisms Collagen Aesthetics Inc. bovine and human placental sourced collagens, recombinant collagens, and PEG-polymers Endura-Tec Systems Corp. bio-mechanical endurance testing ofstents, grafts, and cardiovascular materials Howmedica develops and manufactures products in orthopaedics. MATECH Biomedical Technologies, development of biomaterials by chemical polymerization methods. Medtronic, Inc. is a medical technology company specializing in implantable and invasive therapies. Molecular Geodesics Inc., biomimetic materials for biomedical, industrial, and military applications Polymer Technology Group is involved in the synthesis, characterization, and manufacture of new polymer products. SurModics, offers PhotoLink(R) surface modification technology that can be used to immobilize biomolecules W.L. Gore Medical Products Division, PTFE microstructures configured to exclude or accept tissue ingrowth. Zimmer, design, manufacture and distribution of orthopaedic implants and related equipment and supplies

31. What are some of the Challenges? ßTo more closely replicate complex tissue architecture and arrangement in vitro? ßTo better understand extracellular and intracellular modulators of cell function? ßTo develop novel materials and processing techniques that are compatible with biological interfaces ßTo find better strategies for immune acceptance