Massachusetts Institute of Technology Harvard Medical School Brigham and Women’s/Massachusetts General Hosp. VA Boston Healthcare System 2.79J/3.96J/BE.441/HST522J BIOMATERIALS FOR JOINT REPLACEMENT M. Spector, Ph.D. and I.V. Yannas, Ph.D. http://stellar.mit.edu/S/course/2/fa02/2.79j TISSUES COMPRISING JOINTS Permanent Regeneration Prosthesis Scaffold Bone Yes Yes Articular cartilage No Yes* Meniscus No Yes* Ligaments No Yes* Synovium No No * In the process of being developed JOINT REPLACEMENT PROSTHESES ? Fit – Anatomy ? Function – Kinematics; Range of Motion ? Fixation – Bone cement, bone interdigitation with an irregular surface, bone ingrowth into a porous coating ? Tribology – Friction, Wear, and Lubrication ? Other Effects – Stress Shielding Bone Cement Self-Curing Polymethylmethacrylate Images removed due to copyright considerations. Images removed due to copyright considerations.Porous Coatings for Bone Ingrowth Images removed due to copyright considerations.Porous Coated Tibial Component JOINT REPLACEMENT PROSTHESES ? Fit – Anatomy ? Function – Kinematics; Range of Motion ? Fixation ? Tribology – Friction, Wear, and Lubrication – Cell response to particulate wear debris ? Other Effects – Stress Shielding PROGRESSION OF OSTEOLYSIS: “HYLAMER” CUP Image removed due to copyright considerations. Why Artificial Joints Fail Image removed due to copyright considerations Spice, Byron. “Particle Disease Seen As Plague on Total Joint Replacement” Pittsburgh Post-Gazette. J. Charnley, 1979 Photo removed due to copyright considerations PROSTHESIS WEAR Particles Bone Resorption (Osteolysis) Macrophage (15-25μm) IL-1 PGE 2 Enzymes Chemoattractants MACROPHAGE RESPONSE TO PARTICLES BONE Osteoclast precursor cells Osteoclast Osteoblasts POLYETHYLENE WEAR PARTICLES H. McKellop, 1994 Hip Society The number of particles generated by a hip prosthesis 7 x 10 11 particles/yr. 700,000 particles/step NUMBER OF INHALED PARTICLES Avg. particle burden of urban atmosphere: 10 5 particles/liter Respired volume in man = 1 liter/min. Therefore, 10 5 particles are inhaled/min. 10% of the inhaled particles are deposited in the lungs. Therefore, 10 4 particles are deposited in the lungs per min. 5 x 10 9 particles/yr. Titanium Wear Debris Images removed due to copyright considerations Co-Cr Particles CELL RESPONSE TO METAL PARTICLES ? Macrophages in vitro ? Particles of Ti alloy not toxic; Co-Cr highly toxic ? Ti induced more release of PGE 2 than Co-Cr ? Exp. to Ti increased the release of PGE 2 , IL-1, TNF, and IL-6; exp. to Co-Cr decreased release of PGE 2 and IL-6 and had little effect on IL-1 and TNF ? “release of Ti....worse than....Co-Cr” D.R. Haynes, et al., JBJS 75-A: 825 (1993) CELL RESPONSE TO METAL PARTICLES ? Bovine articular chondrocytes ? Co was toxic to cells at all conc. ? At high conc. Cr, Ti, and Ti alloy were toxic ? At high conc. all metals decreased enzyme activity ? PGE 2 increased with conc., except for Ti alloy W.J. Maloney, et al., J. Appl. Biomat. 5: 109 (1994) BIOLOGICAL RESPONSE TO METAL PARTICLES AND IONS Summary ? Metal particles and ions are released from TJR prostheses; the amounts can be reduced by careful design and manufacturing. ? Cellular response to metal particles has some of the same elements as the response to particles of other materials. ? No indication yet that metal particles and ions are responsible for profound adverse responses. Drainage of Particles by the Lymphatics Image removed due to copyright considerations H. Willert, et al. SMALL PARTICLE DISEASE: LYMPHADENOPATHY ? Enlargement of the node ? Particles drained from tissue by the lymphatic system are phagocytosed by macrophages in the nodes – histiocytes derived from cells that line the sinuses of the node and macrophages derived from circulating monocytes ? Sinus histiocytosis ? No adverse clinical sequelae yet noted MIGRATION OF PARTICLES AND CELLULAR RESPONSES BLOOD VESSEL Macrophage Histiocyte Tissue- Resident, Tissue-Fixed Phagocyte Fusion Maturation M-CSF Monocyte Migration Fusion PROSTHESIS Particles >10μm Multinucleated Foreign Body Giant Cell (less active than macrophages) Bone Resorbing Agents PGE 2 , IL-1 Micromotion Particles <10μm LYMPHATIC VESSEL BONE RESORPTION Activation Particles Lymph Node Particles (PE) from the joint Lymphadenopathy Images removed due to copyright considerations METAL SENSITIVITY IN PATIENTS ? 10-15% of population have dermal sensitivity to metal (14% to Ni) ? Metal ions bind to proteins to form immunogenic complexes ? Metals known as sensitizers: – Ni > Co and Cr >>> Ti and V ? 60% of pts. with failed TJRs were metal sensitive vs. 25% with well-functioning implants – Did metal sensitivity cause failure or did the failed implant cause metal sensitivity? Hallab, Merritt, Jacobs, JBJS 83-A:428 (2001) METAL SENSITIVITY IN PATIENTS ? “May exist as an extreme complication in only a few highly susceptible patients (< 1%), or it may be a more common subtle contributor to implant failure.” ? “It is likely that cases involving implant-related metal sensitivity have been underreported because of the difficulty of diagnosis.” ? Patients who have displayed sensitivity to metal jewelry are at higher risk. Hallab, Merritt, Jacobs, JBJS 83-A:428 (2001) JOINT REPLACEMENT PROSTHESES ? Fit – Anatomy ? Function – Kinematics; Range of Motion ? Fixation ? Tribology – Friction, Wear, and Lubrication ? Other Effects – Stress Shielding Bone (Trabecular) Structure Osteoporotic: Postmenopausal Normal Images removed due to copyright considerations Bone Loss Under the Femoral Component of a Total Knee Replacement Prosthesis: Stress Shielding 1 year post-op Image removed due to copyright considerations Image removed due to copyright considerations Total Knee Replacement Prosthesis Knee Joint Bone Co-Cr Alloy Art. Cart. Bone Image removed due to copyright considerations Image removed due to copyright considerations Polyethylene Ligament Meniscus Bone Bone TISSUES COMPRISING JOINTS Permanent Regeneration Prosthesis Scaffold Bone Yes Yes Articular cartilage No Yes* Meniscus No Yes* Ligaments Failed Yes* Synovium No No * In the process of being developed LIGAMENT DEVICES Prosthesis ? Does not require an autograft for support ? Sufficient strength for immediate stabilization ? Do not rely on intra-articular healing to augment strength Augmentation Device ? Acts as mechanical support to reinforce autograft to increase initial strength ? Load sharing with graft tissue to prevent stress shielding LIGAMENT REPLACEMENT AND AUGMENTATION DEVICES Issues ? Strength ? Load-deformation ? Insertion site integrity ? Tensioning LIGAMENT PROSTHESES HISTORICAL PERSPECTIVE 1960 Emery & Rostrup Teflon tube; fraying in tunnel 1969 Gupta and Brinker Dacron cord/rubber coat; fragmentation 1973 James, et al. Proplast; breakage 1977 Polyethylene; breakage 1978 Jenkins Carbon fibers; fragmentation; migration to lymph nodes SYNTHETIC LIGAMENTS Device Material Indication Prostheses Gore-Tex PTFE (Teflon) Failed intra-art. reconstruction Stryker Dacron Failed intra-art. reconstruction Augmentation Device Kennedy Polypropylene Augmentation of autograft ACL Polyethylene Fiber Braid: Canine Model Images removed due to copyright considerations Image removed due to copyright considerations Olson, Eric J. et al. “The biochemical and histological effects of artificial ligament wear particles: In vitro and in vivo studies.” American Journal of Sports Medicine, vol. 16 no. 6 (1988). LIGAMENT PROSTHESES ? Wear/fraying occurs ? Wear particles of all synthetic ligaments elicit production of inflammatory agents JOINT REPLACEMENT PROSTHESES ? Fit – Anatomy ? Function – Kinematics; Range of Motion ? Fixation – Bone cement, bone interdigitation with an irregular surface, bone ingrowth into a porous coating ? Tribology – Friction, Wear, and Lubrication – Cell response to particulate wear debris ? Other Effects – Stress Shielding