can provide contractile force to support the mechanical integrity of vessels under blood pressure Artificial blood vessels(vascular grafts) have been studied for many years and are in extensive clinical use, however, the simple synthetic grafts typically used(e.g Dacron or poly(tetrafluoroethylene)(Teflon)polymer tubes)are not safe for small-diameter blood vessel replacement(vessel diameters 6 mm) and show loss of patency, due to rapid occlusion of the grafts by depositing platelets (Patentcy is the term used to describe an open, viable vessel ) Read the attached brief discussion of approaches to blood vessel engineering, and then answer the design questions below for an improved small-diameter artificial vessel based on the biomaterials design principles discussed in class so far and the prototype design sketched below: The prototype is to be sutured to the ends of natural blood vessels to replace diseased/blocked sections of vasculature Native blood vessel structure Endothelial cell lining prototype artificial vessel structure: mooth muscle cells Porous tubular Intima(supportive polymer structure ECM layer) Blood flow with 50 um-diam a. Describe the first events that will occur at the surface of a hydrophobic polymer like poly(tetrafluoroethylene)(structure shown below) when it is implanted as a vascular graft and how these events could lead to graft occlusion Upon exposure to blood, protein adsorption will occur within seconds, as proteins from serum make hydrophobic contacts with the surface. Depending on the quantity and physical arrangement of adsorbed protein, mononuclear cells in the blood or platelets may be triggered to adhere to the vessel surface b. Would you choose a degradable or non-degradable polymer for the artificial vessel scaffolding? Explain your choice. (5 pt. s extra credit: describe what polymer in particular you would choose and motivate why you'd make that choice. One might choose a degradable scaffold, in hopes of achieving entirely native tissue in place of the initially artificial implant. if the degradation rate of the scaffold is tuned to the rate at which new natural extracellular matrix can be produced by cells from the surrounding tissue, this approach could lead to a blood vessel with no artificial components after some time C. One strategy that could be applied to this artificial vessel would be to implant the polymer and seek to have native endothelial cells and smooth muscle cells from the adjacent native vessels migrate into the polymer scaffold to recreate the native inner and outer cellular lining of the graft. Describe a strategy to modify the prototype scaffold in order to promote this process, and outline a preliminary experiment you could use to test the utility of your approach BE4623.962JPS1 20f3can provide contractile force to support the mechanical integrity of vessels under blood pressure. Artificial blood vessels (vascular grafts) have been studied for many years and are in extensive clinical use, however, the simple synthetic grafts typically used (e.g. Dacron or poly(tetrafluoroethylene) (Teflon) polymer tubes) are not safe for small-diameter blood vessel replacement (vessel diameters < 6 mm) and show loss of patentcy, due to rapid occlusion of the grafts by depositing platelets. (Patentcy is the term used to describe an open, viable vessel.) Read the attached brief discussion of approaches to blood vessel engineering, and then answer the design questions below for an improved small-diameter artificial vessel based on the biomaterials design principles discussed in class so far and the prototype design sketched below: The 'prototype' is to be sutured to the ends of natural blood vessels to replace diseased/blocked sections of vasculature. a. Describe the first events that will occur at the surface of a hydrophobic polymer like poly(tetrafluoroethylene) (structure shown below) when it is implanted as a vascular graft, and how these events could lead to graft occlusion. Upon exposure to blood, protein adsorption will occur within seconds, as proteins from serum make hydrophobic contacts with the surface. Depending on the quantity and physical arrangement of adsorbed protein, mononuclear cells in the blood or platelets may be triggered to adhere to the vessel surface. b. Would you choose a degradable or non-degradable polymer for the artificial vessel scaffolding? Explain your choice. (5 pt.s extra credit: describe what polymer in particular you would choose and motivate why you’d make that choice.) One might choose a degradable scaffold, in hopes of achieving entirely native tissue in place of the initially artificial implant. If the degradation rate of the scaffold is tuned to the rate at which new natural extracellular matrix can be produced by cells from the surrounding tissue, this approach could lead to a blood vessel with no artificial components after some time. c. One strategy that could be applied to this artificial vessel would be to implant the polymer and seek to have native endothelial cells and smooth muscle cells from the adjacent native vessels migrate into the polymer scaffold to recreate the native inner and outer cellular lining of the graft. Describe a strategy to modify the ‘prototype’ scaffold in order to promote this process, and outline a preliminary experiment you could use to test the utility of your approach. BE.462J/3.962J PS 1 2 of 3