REVIEW : LECTURE 16 NANOMECHANICS OF CARTILAGE BIOCOMPATIBILITY OF MATERIALS IMPLANTED IN VIVO: DEFINITIONS TEMPORAL BIOLOGICAL RESPONSES TO IMPLANTED BIOMATERIALS BLOOD-BIOMATERIAL INTERACTIONSKINETICS OF PROTEIN ADSORPTIONUSE OF STERIC REPULSION TO INHIBIT PROTEIN ADSORPTIONTHERMAL MOTION OF POLYMER BRUSHES : MOVIES (left) : (J. Marko (Cornell U) : http://www.lassp.cornell.edu/marko/thinlayer.html) POLY(ETHYLENE OXIDE) AS A BIOINERT COATING3.052 Nanomechanics of Materials and Biomaterials Thursday 04/19/07 Prof. C. Ortiz, MIT-DMSE I LECTURE 17: NANOMECHANICS AND BIOCOMPATIBILITY : PROTEIN-BIOMATERIAL INTERACTIONS Outline : REVIEW LECTURE #16 : NANOMECHANICS OF CARTILAGE.............................................................. 2BIOCOMPATIBILITY OF MATERIALS IMPLANTED IN VIVO: DEFINITIONS.......................................... 3TEMPORAL BIOLOGICAL RESPONSES TO IMPLANTED BIOMATERIALS .......................................... 4 BLOOD-BIOMATERIAL INTERACTIONS ................................................................................................. 5 KINETICS OF PROTEIN ADSORPTION................................................................................................... 6 USE OF STERIC REPULSION TO INHIBIT PROTEIN ADSORPTION .................................................... 7 THERMAL MOTION OF POLYMER BRUSHES : MOVIE ......................................................................... 8 POLY(ETHYLENE GLYCOL) AS A BIOINERT COATING ........................................................................ 9 Objectives: To establish a fundamental qualitative and quantitative scientific foundation in understanding the biocompatibility of biomaterials implanted in vivo Readings: Course Reader Documents 29, 30 Multimedia : Polymer Brush Demos (posted on stellar) 13.052 Nanomechanics of Materials and Biomaterials Thursday 04/19/07 Prof. C. Ortiz, MIT-DMSE REVIEW : LECTURE 16 NANOMECHANICS OF CARTILAGE -Definitions; articular cartilage function and structure, proteoglycan, aggrecan, hyaluronan, link protein, collagen, chondrocyte, glycosaminoglycan (GAG), chondroitin sulfate - Loading Conditions : withstands ~3 MPa compressive stress and 50% compressive strain (static conditions), equilibrium compressive moduli ~0.1-1MPa - Composition : 80% HOH, collagen (50-60% solid content, mostly type II), aggrecan (30-35% solid content), hyaluronan, ~3-5% cartilage cells (chondrocytes) 0 400 800 12000246810Distance (nm)Force (nN)1M0.1M0.01M0.001MAggrecan Tip vs. Aggrecan Substrate0 400 800 12000246810Distance (nm)Force (nN)1M0.1M0.01M0.001MAggrecan Tip vs. Aggrecan Substrate00.511.50 0.2 0.4 0.6 0.8 1StrainStiffness (MPa)M(Seog+ J. Biomech 2005 in press, online &Dean, Han+ unpublished data 2005)● stiffens nonlinearly with increasing strain at the molecular level→mechanism to prevent large strains that could result in permanent deformation, fracture, or tearing.(Macro)compressive moduli : human ankle cartilage + (approximate) 50% prestrain(Nano) Ag-Ag colloid00.511.50 0.2 0.4 0.6 0.8 1StrainStiffness (MPa)M(Seog+ J. Biomech 2005 in press, online &Dean, Han+ unpublished data 2005)(Macro)compressive moduli : human ankle cartilage + (approximate) 50% prestrain(Nano) Ag-Ag colloid● stiffens nonlinearly with increasing strain at the molecular level→mechanism to prevent large strains that could result in permanent deformation, fracture, or tearing. - Force vs. Distance converted into Stress, , where As= surface interaction area vs. Strain 11(aggrecan)ε=−= −fooLDLh Fσ=sAwhere ho(aggrecan)= initial uncompressed height of aggrecan (zero force),0dd→⎛⎞=⎜⎟⎝⎠εσεStiffness 23.052 Nanomechanics of Materials and Biomaterials Thursday 04/19/07 Prof. C. Ortiz, MIT-DMSE Lecture 16 Nanomechanics of Cartilage: Definitions articular cartilage : connective avascular (contains no blood vessels) tissue covering the ends of the bones in synovial joints that allow smooth, low friction, painless motion proteoglycan: A molecule that contains both a protein core and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and many other connective tissues. aggrecan: the largest aggregating proteoglycan, found in cartilage tissue and the intervertebral disc, has a bottle-brush configuration composed of a protein core backbone and densely spaces glycosaminoglycans glycosaminoglycan (GAGs) : Polysaccharides containing repeating disaccharide units that contain either of two amino sugar compounds -- N-acetylgalactosamine or N-acetylglucosamine, and a uronic acid such as glucuronate (glucose where carbon six forms a carboxyl group). Also called mucopolysaccharides in the older literature. GAGs are found in the lubricating fluid of the joints and as components of cartilage, synovial fluid, vitreous humor, bone, and heart valves. chondroitin sulfate (CS) : One of several classes of sulfated glycosaminoglycans that is a major constituent in various connective tissues, especially in the ground substance of blood vessels, bone, and cartilage. Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of a chain of alternating sugars (N-acetylgalactosamine and glucuronic acid). It is usually found attached to proteins as part of a proteoglycan. CS→ ← HA hyaluronan (HA) : Hyaluronan (HA also called hyaluronic acid or hyaluronate) is an anionic polysaccharide composed of repeating disaccharides of beta-1-4-glucuronate-beta-1-3-N-acetylglucosamine distributed widely throughout connective, epithelial, and neural tissues. The polysaccharide appears to be unique amongst glycosaminoglycans as it is synthesized, and exists in vivo, without attachment to any protein. (As such, it is not synthesized via the usual intracellular organelles that involve protein synthesis; rather, it is extruded from the cell membrane, catalyzed by the enzyme hyaluronan synthetase.) It can be synthesized with a very large molecular weight (1,000 - 5,000 kDa). In cartilage, a globular domain at the N-terminus of aggrecan, termed G1 or the hyaluronic acid binding region (HABR). binds to HA in an interaction that is stabilized by link protein. link protein : A ~45 kDa globular protein that stabilizes the interaction between aggrecan and HA. chondrocyte : cartilage cells responsible for the synthesis and maintenance of the extracellular