麻省理工大学：《生物材料——组织交互作用》教学讲义（英文版）RESPONSE TO PARTICLES

Massachusetts Institute of Technology VE RII TAS Harvard Medical School Brigham and women's/Massachusetts General Hosp VA Boston Healthcare System 2.79J3.96J/BE.441/HST522J RESPONSE TO PARTICLES M. Spector, Ph. D

Massachusetts Institute of Technology Massachusetts Institute of Technology Harvard Medical School Harvard Medical School Brigham and Wo Brigham and Women’s/Massachusetts General Hosp. men’s/Massachusetts General Hosp. VA Boston Healthcare System VA Boston Healthcare System 2.79J/3.96J/BE.441/HST522J 2.79J/3.96J/BE.441/HST522J RESPONSE TO PARTICLES RESPONSE TO PARTICLES M. Spector, Ph.D. M. Spector, Ph.D

BIOMATERIALS-TISSUE INTERACTIONS BIOMATERIAL TISSUE Strength Size scale 1Onm 100nm lum 10 um 100 umImm Modulus of Elasticity Fracture mechanics I sec I day 10 days 100 days Time Scale Protein Adsorption Tissue Remodeling Particles BONE Cell-cell ear Cell interactions Metal corrosion R esponse Polymer degradation Ic on ECM proteins Release Cytokines Eicosanoids E nzymes

BIOMATERIALS BIOMATERIALS -TISSUE INTERACTIONS INTERACTIONS Particles Particles BIOMATERIAL BIOMATERIAL TISSUE 10nm100nm 1µm 10 µm 100 µm 1mm 1 sec 1 day 10 days 10 days 100 days 100 days Size Scale Size Scale Time Scale Time Scale Strength Strength Modulus of Elasticity Modulus of Elasticity Fracture mechanics Fracture mechanics Protein Protein Adsorption Adsorption Cell Response Response Ion Release Release Wear Metal corrosion Metal corrosion Polymer degradation er degradation BONE Tissue Remodeling Remodeling Cell -cell interactions interactions ECM proteins ECM proteins Cytokines Cytokines Eicosanoids Eicosanoids Enzymes Enzymes

BIOMATERIALS-TISSUE INTERACTIONS Tissue Response to Implant Breakdown IMPLANT TISSUE RESPONSE Fibroblast Degradation: Fibrous tissuc Fracture (Cell Contraction?) Bone Particles Wear Macrophage Metal corrosion Polymer Degradation Osteoclast Degradation Products/Ions

BIOMATERIALS BIOMATERIALS -TISSUE INTERACTIONS: TISSUE INTERACTIONS: Tissue Response to Implant Breakdown Tissue Response to Implant Breakdown Particles Particles IMPLANT IMPLANT TISSUE RESPONSE TISSUE RESPONSE Degradation Degradation Products/Ions Products/Ions Fracture Fracture Wear Metal Corrosion Metal Corrosion Polymer Polymer Degradation Degradation Degradation: Degradation: Fibrous Tissu Fibrous Tissu e Bone Fibroblast Fibroblast Macrophage Macrophage Osteoclast Osteoclast (Cell Contraction?) (Cell Contraction?)

LOCAL AND SYSTEMIC RESPONSES SMALL PARTICLE DISEASE ° Local component Osteolysis- particle induced focal destruction of bone around the prosthesis Systemic Component Lymphadenopathy

LOCAL AND SYSTEMIC RESPONSES LOCAL AND SYSTEMIC RESPONSES SMALL PARTICLE DISEASE SMALL PARTICLE DISEASE • Local Component Local Component Osteolysis Osteolysis - particle induced particle induced focal destruction of bone focal destruction of bone around the prosthesis around the prosthesis • Systemic Component Systemic Component Lymphadenopathy Lymphadenopathy

PROGRESSION OF OSTEOLYSIS CHYLAMER CUP Image removed due to copyright considerations

PROGRESSION OF OSTEOLYSIS: “HYLAMER” CUP Image removed due to copyright considerations Image removed due to copyright considerations

Why Artificial Joints Faill Image removed due to copyright considerations Spice, Byron "Particle Disease Seen As Plague on Total Joint Replacement" Pittsburgh Post-Gazette

Why Artificial Joints Fail Image removed due to copyright considerations Image removed due to copyright considerations Spice, Byron. “Particle Disease Seen As Plague on Total Joint Replacement” Pittsburgh Post-Gazette

POLYETHYLENE WEAR PARTICLES H McKellop, 1994 Hip Society The number of particles generated by a hip prosthesis 7x 10 particles/yr 700,000 particles/step

POLYETHYLENE WEAR POLYETHYLENE WEAR PARTICLES PARTICLES H. McKellop McKellop, 1994 Hip Society , 1994 Hip Society The number of particles generated by a hip The number of particles generated by a hip prosthesis prosthesis 7 x 1011 particles/yr. particles/yr. 700,000 particles/step 700,000 particles/step

NUMBER OF INHALED PARTICLES Avg particle burden of urban atmosphere 105 particles/liter Respired volume in man= l liter/min Therefore, 105 particles are inhaled/min, 10%of the inhaled particles are deposited in the ungs Therefore, 104 particles are deposited in the lungs per min 5x 10 particles/yr

NUMBER OF INHALED PARTICLES NUMBER OF INHALED PARTICLES Avg. particle burden of urban atmosphere: Avg. particle burden of urban atmosphere: 10 5 particles/liter particles/liter Respired volume in man = 1 liter/min. Respired volume in man = 1 liter/min. Therefore, 10 Therefore, 10 5 particles are inhaled/min. particles are inhaled/min. 10% of the inhaled particles are deposited in the 10% of the inhaled particles are deposited in the lungs. Therefore, 10 Therefore, 10 4 particles are deposited in the lungs particles are deposited in the lungs per min. per min. 5 x 10 9 particles/yr. particles/yr

Titanium Wear Debris Images removed due to copyright considerations Co-Cr Particles

Titanium Wear Debris Images removed due to ved due to copyright considerations copyright considerations Co-Cr Particles

MACROPHAGE RESPONSE TO MOTION AND PARTICLES UNSTABLE PROSTHESIS Osteoblasts Particles← Motion Bone resorption a (Osteolysis BONE Enzyme PGE IL-1 Macrophage Chemoattractants Osteoclast (15-25μm) Osteoclast precursor cells

UNSTABLE PROSTHESIS UNSTABLE PROSTHESIS Particles Particles Motion Bone Resorption Bone Resorption (Osteolysis) (Osteolysis) Macrophage Macrophage (15 -25 µm) IL - 1 PGE 2 Enzymes Enzymes Chemoattractants Chemoattractants MACROPHAGE RESPONSE MACROPHAGE RESPONSE TO MOTION AND PARTICLES TO MOTION AND PARTICLES BONE Osteoclast Osteoclast precursor cell precursor cell s Osteoclast Osteoclast Osteoblasts Osteoblasts