Tissue engineering the aortic heart valve is a challenging endeavor because of the particular hem... more Tissue engineering the aortic heart valve is a challenging endeavor because of the particular hemodynamic and biologic conditions present in the native aortic heart valve. The backbone of an ideal valve substitute should be a scaffold that is strong enough to withstand billions of repetitive bending, flexing and stretching cycles, while also being slowly degradable to allow for remodeling. In this review we highlight three overlooked aspects that might influence the long term durability of tissue engineered valves: replication of the native valve trilayered histoarchitecture, duplication of the three-dimensional shape of the valve and cell integration efforts focused on getting the right number and type of cells to the right place within the valve structure and driving them towards homeostatic maintenance of the valve matrix. We propose that the trilayered structure in the native aortic valve that includes a middle spongiosa layer cushioning the motions of the two external fibrous l...
ASAIO journal (American Society for Artificial Internal Organs : 1992), Jan 8, 2014
Respiration influences the subdiaphragmatic venous return in the total cavopulmonary connection (... more Respiration influences the subdiaphragmatic venous return in the total cavopulmonary connection (TCPC) of the Fontan circulation whereby both the inferior vena cava (IVC) and hepatic vein flows can experience retrograde motion. Controlling retrograde flows could improve patient outcomes. Using a patient-specific model within a Fontan mock circulatory system with respiration, we inserted a valve into the IVC to examine its effects on local hemodynamics while varying retrograde volumes by changing vascular impedances. A bovine valved conduit reduced IVC retrograde flow to within 3% of antegrade flow in all cases. The valve closed only under conditions supporting retrograde flow and its effects on local hemodynamics increased with larger retrograde volume. Liver and TCPC pressures improved only while the valve leaflets were closed while cycle-averaged pressures improved only slightly (<1 mm Hg). Increased pulmonary vascular resistance raised mean circulation pressures but the valve ...
Fibroblast growth factor receptor (FGFR) activation by basic fibroblast growth factor (FGF-2) ser... more Fibroblast growth factor receptor (FGFR) activation by basic fibroblast growth factor (FGF-2) serves to naturally repress the myofibroblast activation of valvular interstitial cells (VICs). Co-receptors for FGF-2, the heparan sulfate proteoglycans (HSPGs), are key participants in the formation of active FGF-2 signaling complexes. Bioactive environments regulating the myofibroblast phenotype were created by utilizing heparin glycosaminoglycan as a competitive inhibitor of HSPGs. First, soluble heparin was delivered to compete with cell-surface HSPG for the binding of FGF-2. Exogenous soluble heparin prevented serum-dependent activation of the classic mitogen-activated protein kinase (MAPK) and induced myofibroblast alpha smooth muscle actin (alphaSMA) expression and collagen production. Next, heparin-functionalized hydrogel cell substrates were polymerized from vinyl-modified precursors and rendered adhesive through incorporation of RGDS peptide. Culture of VICs on heparin-modified g...
Tissue engineering the aortic heart valve is a challenging endeavor because of the particular hem... more Tissue engineering the aortic heart valve is a challenging endeavor because of the particular hemodynamic and biologic conditions present in the native aortic heart valve. The backbone of an ideal valve substitute should be a scaffold that is strong enough to withstand billions of repetitive bending, flexing and stretching cycles, while also being slowly degradable to allow for remodeling. In this review we highlight three overlooked aspects that might influence the long term durability of tissue engineered valves: replication of the native valve trilayered histoarchitecture, duplication of the three-dimensional shape of the valve and cell integration efforts focused on getting the right number and type of cells to the right place within the valve structure and driving them towards homeostatic maintenance of the valve matrix. We propose that the trilayered structure in the native aortic valve that includes a middle spongiosa layer cushioning the motions of the two external fibrous l...
ASAIO journal (American Society for Artificial Internal Organs : 1992), Jan 8, 2014
Respiration influences the subdiaphragmatic venous return in the total cavopulmonary connection (... more Respiration influences the subdiaphragmatic venous return in the total cavopulmonary connection (TCPC) of the Fontan circulation whereby both the inferior vena cava (IVC) and hepatic vein flows can experience retrograde motion. Controlling retrograde flows could improve patient outcomes. Using a patient-specific model within a Fontan mock circulatory system with respiration, we inserted a valve into the IVC to examine its effects on local hemodynamics while varying retrograde volumes by changing vascular impedances. A bovine valved conduit reduced IVC retrograde flow to within 3% of antegrade flow in all cases. The valve closed only under conditions supporting retrograde flow and its effects on local hemodynamics increased with larger retrograde volume. Liver and TCPC pressures improved only while the valve leaflets were closed while cycle-averaged pressures improved only slightly (<1 mm Hg). Increased pulmonary vascular resistance raised mean circulation pressures but the valve ...
Fibroblast growth factor receptor (FGFR) activation by basic fibroblast growth factor (FGF-2) ser... more Fibroblast growth factor receptor (FGFR) activation by basic fibroblast growth factor (FGF-2) serves to naturally repress the myofibroblast activation of valvular interstitial cells (VICs). Co-receptors for FGF-2, the heparan sulfate proteoglycans (HSPGs), are key participants in the formation of active FGF-2 signaling complexes. Bioactive environments regulating the myofibroblast phenotype were created by utilizing heparin glycosaminoglycan as a competitive inhibitor of HSPGs. First, soluble heparin was delivered to compete with cell-surface HSPG for the binding of FGF-2. Exogenous soluble heparin prevented serum-dependent activation of the classic mitogen-activated protein kinase (MAPK) and induced myofibroblast alpha smooth muscle actin (alphaSMA) expression and collagen production. Next, heparin-functionalized hydrogel cell substrates were polymerized from vinyl-modified precursors and rendered adhesive through incorporation of RGDS peptide. Culture of VICs on heparin-modified g...
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Papers by Mike Jaeggli