For the foreseeable future, bioprosthetic heart valves (BHV) fabricated from xenograft biomaterials will remain the dominant replacement prosthetic valve design. However, BHV durability remains limited to 10-15 years. Failure is usually the result of leaflet tructural deterioration mediated by fatigue and/or tissue mineralization. Thus, independent of valve design specifics (e.g. standard stented valve, percutaneous delivery), the development of novel xenograft biomaterials with improved durability remains an important clinical goal. This represents a unique cardiovascular engineering challenge resulting from the extreme valvular mechanical demands that occur with blood contact. Yet, current BHV assessment relies exclusively on device-level evaluations, which are confounded by simultaneous and highly coupled biomaterial mechanical behaviors and fatigue, valve design, hemodynamics, and calcification. Thus, despite decades of clinical BHV usage and growing popularity, there exists no acceptable method for assessing and simulating BHV durability at the component biomaterial level. This situation has contributed to the current stagnation in BHV biomaterial development, limiting rationally developed improvements in BHV durability. We hypothesize that a biomechanically rigorous and physiologically realistic in-vivo approach can be developed for a mechanistic understanding of intrinsic BHV biomaterial performance. Once developed, such an approach can be used to rationally design novel biomaterials that significantly improve BHV durability. While calcification prevention has not been completely solved, ethanol post-treatment has been shown to strongly reduce its onset. Moreover, others and we have shown that tissue degeneration is a major independent mechanism underlying BHV limited durability both in-vitro and in-vivo. Thus, our focus will be on mechanisms of early tissue degeneration and means to reduce damage accumulation, leading to improving BHV durability.
By developing a biomechanically and biologically realistic in vivo approach unique to develop novel biomaterials for heart valve bioprostheses, coupled to comprehensive simulations, we will develop more durable biomaterials for high stress valvular replacement consistently engineered for improved BHV durability.
|Lee, Chung-Hao; Amini, Rouzbeh; Gorman, Robert C et al. (2014) An inverse modeling approach for stress estimation in mitral valve anterior leaflet valvuloplasty for in-vivo valvular biomaterial assessment. J Biomech 47:2055-63|
|Tripi, Daniel R; Vyavahare, Naren R (2014) Neomycin and pentagalloyl glucose enhanced cross-linking for elastin and glycosaminoglycans preservation in bioprosthetic heart valves. J Biomater Appl 28:757-66|
|Jassar, Arminder S; Vergnat, Mathieu; Jackson, Benjamin M et al. (2014) Regional annular geometry in patients with mitral regurgitation: implications for annuloplasty ring selection. Ann Thorac Surg 97:64-70|
|Fan, Rong; Sacks, Michael S (2014) Simulation of planar soft tissues using a structural constitutive model: Finite element implementation and validation. J Biomech 47:2043-54|
|Witschey, Walter R T; Pouch, Alison M; McGarvey, Jeremy R et al. (2014) Three-dimensional ultrasound-derived physical mitral valve modeling. Ann Thorac Surg 98:691-4|
|Pouch, Alison M; Vergnat, Mathieu; McGarvey, Jeremy R et al. (2014) Statistical assessment of normal mitral annular geometry using automated three-dimensional echocardiographic analysis. Ann Thorac Surg 97:71-7|
|Allukian 3rd, Myron; Xu, Junwang; Morris, Michael et al. (2013) Mammalian cardiac regeneration after fetal myocardial infarction requires cardiac progenitor cell recruitment. Ann Thorac Surg 96:163-70|
|Sugimoto, Hiroatsu; Sacks, Michael S (2013) Effects of Leaflet Stiffness on In Vitro Dynamic Bioprosthetic Heart Valve Leaflet Shape. Cardiovasc Eng Technol 4:2-15|
|Eckert, Chad E; Fan, Rong; Mikulis, Brandon et al. (2013) On the biomechanical role of glycosaminoglycans in the aortic heart valve leaflet. Acta Biomater 9:4653-60|
|Vergnat, Mathieu; Levack, Melissa M; Jackson, Benjamin M et al. (2013) The effect of surgical and transcatheter aortic valve replacement on mitral annular anatomy. Ann Thorac Surg 95:614-9|
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