Soft Tissue Biomechanics Laboratory

What we do:

Design of implantable cardiovascular devices
My lab has recently started collaborations with two cardiovascular surgery teams in Texas and Michigan. Together we are planning to address significant challenges in the treatment of mitral and tricuspid valve regurgitation. Aside from basic science projects in which we use large animal models and human tissue, we are also evaluating and designing implantable medical devices. To this end, we combine reverse engineering technology (3D scanning), rapid prototyping technology (3D printing), and CAD modeling to develop novel prototypes.

Sonomicrometry crystal-based kinematics of the tricuspid annulus and the right ventricle in large animals
The right ventricle and the tricuspid valve, for a long time, were considered unimportant in comparison to the left ventricle and the mitral valve. However, it has become quite clear that a healthy right ventricle and tricuspid valve are vital to our well-being. Because the right and left ventricles are actually quite different we cannot simply extrapolate what we know about the one onto the other. Thus, there is a significant gap in our knowledge which I and my collaborators aim to fill. Similarly, the tricuspid valve varies significant from the mitral valve. Here, too, much work is needed to improve current surgical outcomes and medical treatment. To address these gaps in our knowledge we combine sonomicrometry with large animal models to understand better the kinematics of the right ventricle and the annulus in health, in disease, and after repair.

• Rausch MK, Malinowski M, Wilton P, Khaghani A, Timek TA. Engineering Analysis of Tricuspid Annular Dynamics in the Beating Ovine Heart. Annals of Biomedical Engineering, 2017. (PDF)

Histomechanical characterization and constitutive modeling of biological soft tissues
We use planar biaxial testing, uniaxial testing, bulge testing, digital image correlation, optical coherence tomography, and 2-photon/fluorescent microscopy to characterize various biological soft tissues. Current projects look at changes in murine skin during the process of aging and the formation of pressure ulcers, healthy and diseased human heart valve tissue. Additionally, we are interested in human fetal membranes and microstructural/mechanical changes that may contribute to preterm premature rupture of these membranes.

Small animal models, histomechanical methods, and numerical analyses to characterize thrombus remodeling
I recently became interested in the histo-bio-mechanical evolution of thrombus, from first deposition to maturation. Thrombus initially forms as a gel-like fibrin mesh that may over time transform into a collagen dominated pseudo-tissue. Of course, its mechanical properties drastically change during this transformation. Understanding these changes is important as they determine largely the fate of the thrombus in many devastating cardiovascular conditions such as stroke, heart attack, deep vein thrombosis, aortic dissections and many others. Combining classic biorheologic methods with a mouse model of venous thrombosis allows us to study the evolution of important metrics of thrombus mechanics at time points other than late maturation as otherwise dictated by human samples. 

• Rausch MK, Humphrey JD. A microstructurally inspired damage model for early thrombus. Journal of the Mechanical Behavior of Biomedical Materials, 2015; 55:12-20. (PDF)

• Y-U Lee, AY Lee, Humphrey JD, Rausch MK. Histological and biomechanical changes in a mouse model of venous thrombus remodeling. Biorheology, 2015; 52:235-245. (PDF)

Modeling soft tissue damage and failure - analytical & particle methods
Modeling damage and failure in engineering materials has a long history in which mathematical frameworks and standardized tests have been established. However, very little effort has been focused on developing soft tissue specific models and experiments. Most damage models used for soft tissue analysis are borrowed from the elastomer literature, despite significant differences in damage and failure behavior between soft tissues and elastomers. In addition, few of these models have actually been calibrated, let alone validated. Especially in the cardiovascular system, damage and failure are matters of life and death, with death often being the first symptom of cardiovascular soft tissue failure. Examples include aortic dissections, rupture of aneurysms as well as thrombus embolization. I propose to combine soft tissue specific continuum damage models with discontinuous methods and to validate this framework in tissue specific experimental tests. 

• Rausch MK, Humphrey JD. Modeling soft tissue damage and failure using a hybrid particle/continuum approach. In preparation.
• Rausch MK, Humphrey JD. A microstructurally inspired damage model for early thrombus. Journal of the Mechanical Behavior of Biomedical Materials, 2015. Accepted.

What we have done in the past:

Importance of prestrain/residual strain in biological soft tissue
Residual strain is strain inherent to a material after all external forces have been removed, a phenomenon observed in essentially all biological tissues. In arteries for example, the existence of residual strain has first been proven by Fung et al. and has since then been shown to play an important role in arterial mechanics. While residual strain in arterial tissue has received considerable attention over the past decades, very little is understood about residual strain in ventricular myocardium and mitral valve tissue. I authored and coauthored a number of papers exploring the effect of residual strain/prestrain on the in-vivo stiffness of the anterior mitral valve tissue and its importance to cardiac mechanics.

• Rausch MK, Kuhl E. On the effect of prestrain and residual stress on the mechanics of thin biological membranes. Journal of the Mechanics and Physics of Solids, 2013; 61:1955-69. (PDF)
• Rausch MK, Famaey N, O'Brien Shultz T, Bothe W, Miller DC, Kuhl E. Mechanics of the mitral valve: A critical review, an in vivo parameter identification, and the effect of prestrain. Biomechanics and Modeling in Mechanobiology, 2013; 12:1053-71. (PDF)
• Genet M, Rausch MK, Lee LC, Choyh S, Zhaoh X, Kassab GS, Kozerke S, Guccione JM, Kuhl E. Heterogeneous growth-induced prestrain in the heart. Journal of Biomechanics, 2015. Accepted. (PDF)

Medical device design and evaluation
Over the past decades cardiovascular devices have been a major driver behind improvements to the cardiovascular death rate which, in contrast to the prevalence of cardiovascular disease, has decreased significantly. Paradigm shifting inventions such as trans-catheter aortic valve replacements have made “inoperable” patients operable, improving their quality of life and life expectancy considerably.  To contribute to the development of more effective medical devices I developed a novel method of using continuous mechanical metrics such as displacement fields, strain, and curvature to systematically evaluated and compare the performance of mitral valve annuloplasty devices in-vivo. Furthermore, as the Director of R&D at Micro Interventional Devices, I directed the development an apical access and closure device for use with trans-catheter repair and replacement technologies.

• Rausch MK, Zöllner AM, Genet M, Baillargeon B, Bothe W, Kuhl E. A virtual sizing tool for mitral valve annuloplasty, 2015. Submitted.
• Rausch MK, Bothe W, Kvitting JP, Swanson JC, Miller DC, Kuhl E. Mitral valve annuloplasty - A quantitative clinical and mechanical comparison of different annuloplasty devices. Annals of Biomedical Engineering, 2012;40: 750-61. (PDF)
• Baillargeon B, Leach J, Costa I, Lee LC, Genet M, Wenk JF, Rausch MK, Rebelo N, Acevedo-Bolton G, Kuhl E, Navia JL, Guccione JM. Human cardiac function simulator for the optimal design of a novel sub-valvular device for correcting mitral regurgitation. Cardiovascular Engineering & Technology, 2015; 6:105-16. (PDF)
• Bothe W, Rausch MK, Kvitting JP, Echtner DK, Walther M, Ingels NB, Kuhl E, Miller DC. How do annuloplasty rings affect mitral annular strains in the normal beating ovine heart? Circulation, 2012; 126:S231-S38. (PDF)
• Bothe W, Kuhl E, Kvitting JP, Rausch MK, Goktepe S, Swanson JC, Ingels NB, Miller DC. Rigid, complete annuloplasty rings increase anterior mitral leaflet strains in the normal beating ovine heart. Circulation, 2011; 124:S81-S96. (PDF)

Growth and remodeling in cardiovascular tissue
One of the most fundamental differences between classic engineering materials and biological tissues is the ability of the latter to adapt to physiologic challenges and pathologic conditions. It is vital to our understanding of biological tissues and our ability to predict changes in tissue morphology and mechanics to develop reliable and robust methods that accurately capture growth and remodeling. During my PhD and since then I've used finite growth theory to model the adaptation of cardiac tissue to a spectrum of pathologic conditions such as systemic and pulmonary hypertension as well as ischemic disease.

• Rausch MK, Kuhl E. On the mechanics of growing thin biological membranes. Journal of the Mechanics and Physics of Solids, 2014; 63:128-40. (PDF)
• Rausch MK, Tibayan FA, Miller DC, Kuhl E. Evidence of adaptive mitral leaflet growth. Journal of the Mechanical Behavior of Biomedical Materials, 2012; 15:208-17. (PDF)
• Rausch MK, Dam A, Goktepe S, Abilez OJ, Kuhl E. Computational modeling of growth: Systemic and pulmonary hypertension in the heart. Biomechanics and Modeling in Mechanobiology, 2011; 10:799-811. (PDF)
• Rausch MK. Continuum mechanical modelling of biological growth. Biomedical Computation Review, 2011;7: 25. (PDF)

Mitral valve mechanics
The mitral valve is one of four heart valve that direct blood flow through the heart. Situated between the left ventricle and the left atria, its role is to allow for efficient filling during diastole and to prevent retrograde blood flow during systole. The mitral valve opens and closes approximately 60 times per minute and an estimated total of 1 trillion times during our lifetime. I wrote my PhD thesis on the mechanics of the healthy, diseased, and repaired mitral valve (PDF). Combining computational methods with experimental data from large animal models, I elucidated the physiological mechanics of the mitral annulus and the mitral leaflets, studied how the mechanics of annulus and leaflets change in a model of ischemic mitral regurgitation, and quantified the effect of implanting various mitral annuloplasty rings.

• Rausch MK, Tibayan FA, Ingels NB, Miller DC, Kuhl E. Mechanics of the mitral valve annulus in chronic ischemic cardiomyopathy. Annals of Biomedical Engineering, 2013; 41:2171-80. (PDF)
• Rausch MK, Famaey N, O'Brien Shultz T, Bothe W, Miller DC, Kuhl E. Mechanics of the mitral valve: A critical review, an in vivo parameter identification, and the effect of prestrain. Biomechanics and Modeling in Mechanobiology, 2013; 12:1053-71. (PDF)
• Rausch MK, Tibayan FA, Miller DC, Kuhl E. Evidence of adaptive mitral leaflet growth. Journal of the Mechanical Behavior of Biomedical Materials, 2012; 15:208-17. (PDF)
• Rausch MK, Bothe W, Kvitting JP, Swanson JC, Miller DC, Kuhl E. Mitral valve annuloplasty - A quantitative clinical and mechanical comparison of different annuloplasty devices. Annals of Biomedical Engineering, 2012;40: 750-61. (PDF)
• Rausch MK, Bothe W, Kvitting JP, Goktepe S, Miller DC, Kuhl E. In vivo dynamic strains of the ovineanterior mitral valve leaflet. Journal of Biomechanics, 2011; 44:1149-57. (PDF)
• Rausch MK, Bothe W, Kvitting JP, Swanson JC, Ingels NB, Miller DC, Kuhl E. Characterization of mitral valve annular dynamics in the beating heart. Annals of Biomedical Engineering, 2011; 39:1690-1702. (PDF)