living matter lab
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<div class="publicationheader">mission statement</div>
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<div class="publicationheader">check out our latest COVID-19 outbreak predictions... </div>
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college campuses are COVID-19 superspreaders [https://www.forbes.com/sites/mishagajewski/2021/01/13/college-campuses-are-covid-19-superspreaders-study-says/?sh=2578217052fd forbes], [https://www.usnews.com/news/health-news/articles/2021-01-13/college-campuses-are-covid-superspreaders-study-finds US news & world report]<br>
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are colleges superspreaders [https://www.insidehighered.com/news/2021/01/13/college-openings-led-increase-community-cases-research-says inside higher ed]<br>
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college campuses can be superspreaders? [https://academictimes.com/college-campuses-can-be-superspreaders-but-safe-reopening-possible-study/ academic times]<br>
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are college campuses COVID-19 superspreaders? [https://newsroom.taylorandfrancisgroup.com/new-study-suggests-that-college-campuses-are-covid-19-superspreaders/ t&f press release], [https://www.upi.com/Health_News/2021/01/13/College-campuses-may-be-COVID-19-super-spreaders-study-finds/5661610548574/ united press international]<br>
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new study suggests that campuses are COVID-19 superspreaders [https://www.eurekalert.org/pub_releases/2021-01/tfg-nss011121.php eurekalert!], [https://consumer.healthday.com/b-1-13-study-confirms-college-campuses-as-super-spreader-centers-2649875013.html healthday]<br>
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les campus universitaires sont des super-epandeurs [https://www.crumpi.com/2021/01/13/les-campus-universitaires-sont-des-super-epandeurs-de-covid-19-les-epidemies-sur-les-campus-locaux-se-propagent-rapidement-dans-tout-le-comte/ crumpi]<br>
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reopening college campuses could initiate superspreading [https://www.news-medical.net/news/20201224/Reopening-college-campuses-could-initiate-COVID-19-superspreading.aspx med life sciences]<br>
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a new class explores how to safely reopen a campus during covid-19 [https://engineering.stanford.edu/magazine/article/new-class-explores-how-safely-reopen-campus-during-covid-19 stanford report] [http://biomechanics.stanford.edu/paper/CMECH20b.pdf reopening paper]<br>
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data-driven modeling of covid-19-lessons learned
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[http://biomechanics.stanford.edu/paper/EML081220.jpg webinar announcement] 
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[https://www.youtube.com/watch?v=lBMPfltcDqs&feature=youtu.be webinar]
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[http://biomechanics.stanford.edu/paper/EML20.pdf paper] <br>
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how COVID-19 spread has been contained by travel bans [https://www.sciencedaily.com/releases/2020/05/200504191018.htm science daily] [https://infosurhoy.com/news-summary/how-covid-19-spread-has-been-contained-by-travel-bans/ infosurhoy] [http://biomechanics.stanford.edu/paper/CMBBE20.pdf cmbbe paper] <br>
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covid-19 travel restrictions have saved millions of people [https://www.health24.com/Medical/Infectious-diseases/Coronavirus/covid-19-travel-restrictions-have-saved-millions-of-people-from-being-infected-mathematical-modelling-shows-20200507-2 health24 ]  [https://medrxiv.org/cgi/content/short/2020.05.01.20088047v1 medRxiv Rvalues]<br>
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how COVID-19 spread has been contained by travel bans [https://newsroom.taylorandfrancisgroup.com/how-covid-19-spread-has-been-contained-by-travel-bans/# press release] [http://biomechanics.stanford.edu/paper/CMBBE20.pdf cmbbe paper] [http://biomechanics.stanford.edu/paper/CMECH20a.pdf mobility paper]<br>
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was haben die grenzschliessungen tatsachlich gebracht? [https://www.srf.ch/news/schweiz/kampf-gegen-das-coronavirus-was-haben-die-grenzschliessungen-tatsaechlich-gebracht swiss public radio] <br>
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wie sinnvoll sind reisebeschrankungen wirklich? [https://www.welt.de/vermischtes/article207810451/Corona-Krise-und-Grenzen-Wie-sinnvoll-sind-Reisebeschraenkungen-wirklich.html welt] [http://biomechanics.stanford.edu/paper/CMBBE20.pdf cmbbe paper] <br>
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so bremsen reisebeschrankungen das coronavirus aus [https://www.mdr.de/wissen/corona-reise-verbot-eindaemmung-covid-modell-100.html mdr wissen] [https://medrxiv.org/cgi/content/short/2020.05.01.20088047v1 medRxiv Rvalues]<br>
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using math to understand COVID-19 outbreak dynamics [https://med.stanford.edu/cvi/mission/news_center/articles_announcements/using-math-to-understand-covid-19-outbreak-dynamics.html stanford medicine] [http://biomechanics.stanford.edu/paper/BMMB20.pdf bmmb paper]
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[https://www.medrxiv.org/content/10.1101/2020.05.23.20111419v1 asymptomatic]<br>
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predict covid's spread and recovery [https://engineering.stanford.edu/magazine/article/brain-inspired-model-can-help-predict-covid-s-spread-and-recovery?sf120699572=1 stanford engineering] [https://www.medrxiv.org/content/10.1101/2020.04.06.20055863v2 medRxiv in the us] [https://medrxiv.org/cgi/content/short/2020.04.18.20071035v1 medRxiv in europe]<br>
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[[Image:research_us.jpg|720px]]
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<div class="publicationheader">... and the other cool stuff we do</div>
  
 
growth is a distinguishing feature of all living things. throughout the past century, the growth of living systems has fascinated physiologists, biologists, and clinical scientists alike. yet, most of their efforts remain exploratory and mainly qualitative.  
 
growth is a distinguishing feature of all living things. throughout the past century, the growth of living systems has fascinated physiologists, biologists, and clinical scientists alike. yet, most of their efforts remain exploratory and mainly qualitative.  
<b>in the living matter lab, we use the fundamental laws of physics and create interactive simulation tools to predict the physiology and pathology of living systems.</b> we strive to understand the mechanisms by which living systems grow, develop, evolve, and adapt. this is not always straightforward: living systems can undergo extreme deformations, change their mass, generate active contraction, and develop prestrain and residual stress.  these phenomena are non-intuitive to traditional engineers and often difficult to grasp. they require us to advance the classical field theories of mechanics towards living matter physics, design our own mathematical models, and create our own simulation tools. in addition to a fundamental knowledge in biology and medicine, this demands a theoretical background in tensor calculus, continuum mechanics, and thermodynamics, paired with the ability to design efficient, stable, and robust computational tools.
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<b>in the living matter lab, we use the fundamental laws of physics and create interactive simulation tools to predict the physiology and pathology of living systems.</b> we strive to understand the mechanisms by which living systems grow, develop, evolve, and adapt. this is not always straightforward: living systems can undergo extreme deformations, change their mass, generate active contraction, and develop prestrain and residual stress.  these phenomena are non-intuitive to traditional engineers and often difficult to grasp. they require us to advance the classical field theories of mechanics towards living matter physics, design our own mathematical models, and create our own simulation tools. here are some examples of projects that we are currently addressing:
  
 
<div class="publicationheader">the living heart project</div>
 
<div class="publicationheader">the living heart project</div>
  
our heart is not only our most vital, but also our most complex organ: precisely controlled by the interplay of electrical and mechanical fields, it consists of four chambers and four valves, which act in concert to regulate its filling, ejection, and overall pump function. while numerous computational models exist to study either the electrical or the mechanical response of its individual chambers, the integrative electro-mechanical response of the whole heart remains poorly understood. with support of the nsf career award, our lab has designed the first fully coupled electro-mechanical model for excitation-contraction coupling within a single, unified finite element framework. our heart model has become a true success story: since may 2013, we have worked with the largest commercial finite element company, abaqus/dassault systemes, towards implementing our core algorithms into the abaqus infrastructure. together with the living heart team at dassault systemes, we have established the first four-chamber heart simulator for human heart function. the living heart project was officially launched in may 2014. since then, our work has received broad media attention and was featured in several scientific publications. to date, the living heart ecosystem has grown to 32 contributing member organizations, with more than 150 cardiovascular specialists from research, industry, and medicine, who have free access to our heart simulator to test and accelerate the development of the living heart via crowdsourcing.  
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our heart is not only our most vital, but also our most complex organ: precisely controlled by the interplay of electrical and mechanical fields, it consists of four chambers and four valves, which act in concert to regulate its filling, ejection, and overall pump function. while numerous computational models exist to study either the electrical or the mechanical response of its individual chambers, the integrative electro-mechanical response of the whole heart remains poorly understood. with support of the nsf career award, our lab has designed the first fully coupled electro-mechanical model for excitation-contraction coupling within a single, unified finite element framework. [http://biomechanics.stanford.edu/paper/LivingHeartEK.mp4 our heart model] has become a true success story: since may 2013, we have worked with the largest commercial finite element company, abaqus/dassault systemes, towards implementing our core algorithms into the abaqus infrastructure. together with the living heart team at dassault systemes, we have established the first four-chamber heart simulator for human heart function. the [http://www.3ds.com/heart living heart project] was officially launched in may 2014. since then, our work has received broad media attention and was featured in several  
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[http://www.sciencedirect.com/science/article/pii/S0997753814000564 scientific publications]. to date, the living heart ecosystem has grown to 32 contributing member organizations, with more than 150 cardiovascular specialists from research, industry, and medicine, who have free access to our heart simulator to test and accelerate the development of the living heart via crowdsourcing.  
  
 
[[Image:research01.jpg|720px]]
 
[[Image:research01.jpg|720px]]
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<b>figure 1.</b> the living heart project. in collaboration with abaqus/dassault systemes, we have created the first fully finite-element based whole heart model for realistic human heart simulations of excitation-contraction coupling.
 
<b>figure 1.</b> the living heart project. in collaboration with abaqus/dassault systemes, we have created the first fully finite-element based whole heart model for realistic human heart simulations of excitation-contraction coupling.
  
figure 1 illustrates our first prototype of the living heart model, which allows us to explore and understand the key features, physics, and technologies required to create an integrative, predictive model of the living human heart. ultimately, the living heart project will unite leading cardiovascular researchers, medical device manufacturers, regulatory agencies, and practicing cardiologists on the shared mission to develop and validate personalized digital human heart models and establish a unified foundation for in silico cardiovascular medicine, see http://www.3ds.com/heart. our computational models, which form the core of these efforts are documented in more than 20 peer-reviewed journal publications.
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figure 1 illustrates our first prototype of the living heart model, which allows us to explore and understand the key features, physics, and technologies required to create an integrative, predictive model of the living human heart. ultimately, the living heart project will unite leading cardiovascular researchers, medical device manufacturers, regulatory agencies, and practicing cardiologists on the shared mission to develop and validate personalized digital human heart models and establish a unified foundation for in silico cardiovascular medicine. our computational models, which form the core of these efforts are documented in more than 20 peer-reviewed journal publications and in several [http://biomechanics.stanford.edu/paper/MEheart.pdf featured articles] and
 
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[https://www.youtube.com/watch?v=6hsx_da1vVs animations].
<div class="publicationheader">from generic to patient specific - anatomic models of the human heart</div>
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to calibrate and validate our model against clinical data, one of our students volunteered to have his EKG recording taken, see figure 1. to generate patient-specific anatomic models of the heart, we collaborate with professor michael mc connell in cardiovascular medicine. he took a series of MRI scans from which we generated a finite element mesh. figure 2 illustrates the time sequence of cardiac excitation simulated on the resulting patient-specific geometry. 
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for the first time, we were able to generate an <em>in silico</em> EKG
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from the integration of all flux vectors projected onto six characteristic directions in space, see figure 1
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[[http://biomechanics.stanford.edu/paper/CNME09.pdf 51]]. we are excited about the incredible agreement between the <em>in vivo</em> recorded EKG, left, and the <em>in silico</em> predicted EKG, right. together with our collaborators in cardiac medicine, we plan to use our algorithms for both student education and new therapy design.
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[[Image:vision02.jpg|720px]]
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<b>figure 2.</b>
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patient-specific simulation of cardiac electrophysiology. MRI scan of human heart (left), simulated time sequence of cardiac excitation (middle), and diagnostic MRI images to generate anatomic human heart model (right).
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<div class="publicationheader">from excitation to contraction - simulation tools for the beating heart</div>
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electric excitation induces an increased calcium concentration within the cell, which, in turn, initiates cellular contraction through actin-myosin filament sliding. to simulate these effects, existing simulation tools combine a finite-difference based excitation model with a finite-element based contraction model, having to pass information back and forth between both models at every instant in time. to reduce the risk of inherent instabilities associated with this explicit approach, existing simulation tools require an extremely fine spatial and temporal discretization.
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taking advantage of our core competence in multi-physics modeling,
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we have developed a fully coupled multi-field finite element approach to monolithically solve
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the electrical excitation problem and
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the mechanical equilibrium problem. this model can directly incorporate experimentally measured tension-length relations by mapping them onto patient-specific fiber orientations determined non-invasively through diffusion tensor MRI, see figure 3. for the first time, we have demonstrated a unified, fully coupled, extremely efficient, and robust solution technique that can reliably predict excitation-contraction patterns on single desktop computers with simulation times on the order of minutes.
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[[Image:vision03.jpg|720px]]
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<b>figure 3.</b>  
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<div class="publicationheader">cardiac optogenetics</div>
fiber orientation map from diffusion tensor MRI adopted from zhukov & barr [2003] (left), actin-myosin based filament sliding model with characteristic tension-length relation (middle), and simulation of excitation-contraction coupling in terms of bi-ventricular heart model with generic fiber orientation (right).
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<div class="publicationheader">from cells to tissues - heart failure characterized through continuum growth</div>
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heart disease is the primary cause of death in industrialized  nations, claiming more than 16 million lives worldwide every year. in the united states alone, almost half a million people die each year as a result of heart rhythm disorders. despite its invasive nature, electrical stimulation remains the gold standard treatment to control rhythm disturbances through direct contact stimulation. together with our clinical collaborators, we have pioneered a novel technology to control heart rhythm disorders at a distance by means of light using a new concept known as [http://biomechanics.stanford.edu/paper/BIOPJ11.pdf optogenetics]. we have created mathematical models and computational tools to decipher the mechanisms by which optogenetics can regulate cardiac function with the ultimate goal to create a biological pacemaker of genetically engineered cardiac cells.
  
a leading cause of heart failure is myocardial infarction caused by the local death of heart muscle cells due to insufficient blood supply.
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[[File:research02.jpg|720px]]
as a result, the functional units of the myocardium, the cardiomyocytes, lose their contractile property and die. recently, stem cell therapy has emerged as a promising methodology for cardiac repair by injecting cells into the damaged tissue.
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in close collaboration with professors chris zarins in vascular surgery and sarah heilshorn in material sciences, we have developed computational tools to simulate the progression of infarct-induced heart failure to predict optimal cell injection sites.
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the underlying continuum model is based on the multiplicative decomposition of the deformation gradient into an elastic part and a growth part [[http://biomechanics.stanford.edu/paper/CMES05.pdf 25],[http://biomechanics.stanford.edu/paper/JMPS09.pdf 54]]. in the past, we have successfully applied this model 
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in the context of open system thermodynamics [[http://biomechanics.stanford.edu/paper/ROYAL03.pdf 12],[http://biomechanics.stanford.edu/paper/ACTA03.pdf 13],[http://biomechanics.stanford.edu/paper/IJNME03a.pdf 14],[http://biomechanics.stanford.edu/paper/CMECH03.pdf 15]]
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to simulate progressive plaque growth in arteries
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[[http://biomechanics.stanford.edu/paper/BMMB06.pdf 34]]. together with
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professor andreas menzel from the tu dortmund, germany
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[[http://biomechanics.stanford.edu/paper/IJNME07a.pdf 41]],
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professor gerhard holzapfel from the tu graz, austria, and professors krishna garikipati and ellen arruda from the university of michigan, we have also developed algorithms to predict remodeling in arteries
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[[http://biomechanics.stanford.edu/paper/JMS07.pdf 36]]
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and tendons
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[[http://biomechanics.stanford.edu/paper/JMPS05.pdf 27],[http://biomechanics.stanford.edu/paper/PHILMAG06.pdf 29]]. we have now developed a new macroscopic growth and remodeling law for cardiac tissue
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motivated by microscopic changes in cardiomyocyte geometry that can be quantified experimentally through tissue histology.
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figure 4 shows our simulation of infarct-induced growth motivated by micro-ct images of mouse infarct models provided by our collaborator joe wu in radiology.
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[[Image:vision04.jpg|720px]]
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<b>figure 2.</b> cardiac optogenetics. optical stimulation opens a cation channel to initiate a photocurrent, which increases the sodium concentration. this triggers an increase in the electric potential and initiates mechanical contraction.
  
<b>figure 4.</b>
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we prototyped a [http://biomechanics.stanford.edu/paper/JMPS12.pdf multiscale computational model] for the optogenetic control of human hearts, which we have calibrated across four biological scales as illustrated in figure 2. we used this model to make patient-specific predictions of ion channel dynamics, virtually probe landscapes of process parameters, and identify optimal photostimulation sequences in silico before testing them in vivo. this work is documented in five journal articles and has initiated a broad interest in the general media including several
virtual injection of stem-cell derived cardiomyocytes into the damaged myocardium (left). micro-ct images of infarct-induced growth in mouse model adopted from doyle et al. [2007] (middle). finite element simulation of infarct-induced growth (right).
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[http://www.nsf.gov/discoveries/disc_summ.jsp?cntn_id=129057 featured stories],
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[http://www.scienceupdate.com/?powerpress_pinw=8660-podcast podcasts], and
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[http://biomechanics.stanford.edu/paper/Deutschlandfunk.mp3 radio interviews].  
  
<div class="publicationheader">from passive to active - tissue engineered solutions to prevent heart failure</div>
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<div class="publicationheader">characterizing living skin</div>
  
recent studies in the wu lab have shown that stem cells
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skin is our interface with the outside world. in its natural environment, it displays unique mechanical characteristics including prestrain and growth. while there is a general agreement on the physiological importance of these features, they remain poorly characterized mainly because they are difficult to access with standard laboratory techniques. our lab has established a novel, inexpensive technique to [http://biomechanics.stanford.edu/paper/ABM14.pdf characterize living skin] using multi-view stereo and isogeometric analysis. based on easy-to-create hand-held camera images, we quantify prestretch, deformation, and growth in a controlled porcine model of chronic skin expansion. over a period of five weeks, we gradually inflate subcutaneouly implanted balloons, take weekly photographs of the experimental scene, reconstruct the geometry from a tattooed surface grid, and create parametric representations of the skin surface.
may offer regenerative potential in infarct-induced heart failure. however, randomly injected cells lack the organization and physical structure required to create a cohesive, uniform tissue with continuous, synchronized beating.
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through a multidisciplinary collaboration with professors joe wu in radiology, chris zarins in vascular surgery, sarah heilshorn in material sciences, and beth pruitt in mechanical engineering,
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we are investigating the potential to engineer actively contracting stem-cell based tissue grafts to re-establish cardiac contraction and prevent heart failure. figure 5 displays our multi-scale finite element model of actively contracting cardiomyocytes seeded on a polymeric base layer derived in a collaboration with professor markus boel from the tu braunschweig, germany
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[[http://biomechanics.stanford.edu/paper/CMECH08a.pdf 48]]. the <em>in silico</em> designed tissue constructs were calibrated, validated, and verified against <em>in vitro</em> engineered muscular thin films cultured by our collaborator professor kit parker at harvard university.  
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our model is used to optimize the functional integration of a multi-layered tissue patch upon its implantation onto the ventricular wall.
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[[Image:vision05.jpg|720px]]
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[[Image:research04.jpg|720px]]
  
<b>figure 5.</b>  
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<b>figure 3.</b> skin expansion in pediatric forehead reconstruction.
virtual implantation of tissue engineered vascular grafts onto the damaged myocardium (left).
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actively contracting cardiomyocytes seeded on polymeric base layer, experiment (top) vs. finite element simulation (bottom).
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<div class="publicationheader">from empirical to predictive - choice of optimal medical devices</div>
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we analyzed these representations and quantified the average area prestretch to 1.44 and the average area growth to 2.25. we used these data to calibrate our skin growth model to simulate clinical cases of skin expansion in [http://biomechanics.stanford.edu/paper/JTBIO12.pdf pediatric forehead reconstruction]. our simulations accurately predict the clinically observed mechanical and structural response of living skin both acutely and chronically. our living skin model can easily be generalized to arbitrary biological membranes and serve as a valuable tool to virtually manipulate living systems, simply by means of changes in their mechanical environment. our skin research was initially motivated by a [http://biomechanics.stanford.edu/paper/JMPS11a.pdf class project] in fall 2010 and has, to date, inspired twelve conference papers and eleven [http://biomechanics.stanford.edu/paper/JTBIO12.pdf  peer-reviewed journal articles].
  
mitral regurgitation is a progressive, valvular disorder
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<div class="publicationheader">physical biology of brain development</div>
affecting 4 million people in the united states alone.
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the most common surgical approach to repair a leaking valve is to
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bring the leaflets closer together using annuloplasty rings. annuloplasty rings come in different shapes, materials, and sizes.
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choosing the optimal ring type largely depends on the surgeon's experience and personal preference. it is hypothesized that annuloplasty rings influence leaflet curvature, which in turn may considerably impact repair durability. in an attempt to guide the optimal ring choice and improve repair devices, we have quantified leaflet curvature in beating ovine hearts using <em>in vivo</em> acquired videofluoroscopic marker data provided by our collaborator professor craig miller in cardiothoracic surgery
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[[http://biomechanics.stanford.edu/paper/BMMB09.pdf 56]].
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figure 6 documents the acute impact of annuloplasty ring implantation on the maximum principal leaflet curvature determined with our custom-made subdivision surface algorithm. using the same data set in an inverse finite element analysis has allowed us, for the first time, to identify the material parameters of the mitral valve in the beating heart
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[[http://biomechanics.stanford.edu/paper/AJPHC08.pdf 46]].
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a co-advised student in the lab of professor craig miller and professor neil ingels from the palo alto medical foundation  identified the <em>in vivo</em> stiffness to be an order of magnitude larger than the <em>in vitro</em> measured tissue stiffness
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[[http://biomechanics.stanford.edu/paper/AJPHC09.pdf 50],[http://biomechanics.stanford.edu/paper/JBIOM09.pdf 52]].
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the developing human brain remains one of the few unsolved mysteries of science. advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. however, the precise role of mechanics throughout this process remains under appreciated and poorly understood. we have recently shown that mechanical stretch plays a crucial role in [http://biomechanics.stanford.edu/paper/SREP14.pdf brain development].
  
[[Image:vision06.jpg|720px]]
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[[Image:research03.jpg|720px]]
  
<b>figure 6.</b>  
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<b>figure 4.</b> variety of mammalian brains. caitlin, adrian, ellen, james, moritz, mona, rijk, maria.
intraoperative photograph showing 23 tantalium markers sewn on the mitral valve leaflet (left), annuloplasty ring (middle), and maximum principal curvature distribution in the leaflet with ring (top) and without ring (bottom).
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<b>our vision is to revolutionize thinking
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using the nonlinear field theories of mechanics, supplemented by the theory of finite growth, we have modeled the human brain as a living system with a morphogenetically growing gray matter surface and a growing white matter core. this approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. to characterize the stiffness of gray and white matter tissue, we have designed new protocols for [http://biomechanics.stanford.edu/paper/JMBBM15.pdf indentation testing] and demonstrated that white matter, with an average modulus of 1.9kpa, is stiffer than gray matter, with an average modulus of 1.4kpa. our simulations suggest that anisotropic white matter growth, as an emergent property from [http://biomechanics.stanford.edu/paper/ABME15a.pdf chronic axon elongation], intrinsically induces symmetry breaking, and predicts surface morphologies in agreement with magnetic resonance images from very preterm neonates. our model predicts that deviations in cortical thickness, elasticity, and growth induce morphological abnormalities. using the gyrification index, the ratio between the total and exposed surface area, we have shown that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. understanding the mechanisms of human brain development has direct implications on the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism. In the past year, we have published six peer reviewed
in regenerative medicine and induce a paradigm shift from empirical to predictive therapy
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[http://biomechanics.stanford.edu/paper/JMPS14b.pdf journal articles] and edited a  
design using multi-scale, multi-physics models derived from first principles.</b>
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[http://link.springer.com/article/10.1007/s10237-015-0662-4 multi-author review] on brain mechanics.
  
 
[[previous research accomplishments 02]]<br>
 
[[previous research accomplishments 02]]<br>
 
[[previous research accomplishments 01]]<br>
 
[[previous research accomplishments 01]]<br>

Latest revision as of 13:38, 13 January 2021

check out our latest COVID-19 outbreak predictions...

college campuses are COVID-19 superspreaders forbes, US news & world report
are colleges superspreaders inside higher ed
college campuses can be superspreaders? academic times
are college campuses COVID-19 superspreaders? t&f press release, united press international
new study suggests that campuses are COVID-19 superspreaders eurekalert!, healthday
les campus universitaires sont des super-epandeurs crumpi
reopening college campuses could initiate superspreading med life sciences
a new class explores how to safely reopen a campus during covid-19 stanford report reopening paper
data-driven modeling of covid-19-lessons learned webinar announcement webinar paper
how COVID-19 spread has been contained by travel bans science daily infosurhoy cmbbe paper
covid-19 travel restrictions have saved millions of people health24 medRxiv Rvalues
how COVID-19 spread has been contained by travel bans press release cmbbe paper mobility paper
was haben die grenzschliessungen tatsachlich gebracht? swiss public radio
wie sinnvoll sind reisebeschrankungen wirklich? welt cmbbe paper
so bremsen reisebeschrankungen das coronavirus aus mdr wissen medRxiv Rvalues
using math to understand COVID-19 outbreak dynamics stanford medicine bmmb paper asymptomatic
predict covid's spread and recovery stanford engineering medRxiv in the us medRxiv in europe

Research us.jpg

... and the other cool stuff we do

growth is a distinguishing feature of all living things. throughout the past century, the growth of living systems has fascinated physiologists, biologists, and clinical scientists alike. yet, most of their efforts remain exploratory and mainly qualitative. in the living matter lab, we use the fundamental laws of physics and create interactive simulation tools to predict the physiology and pathology of living systems. we strive to understand the mechanisms by which living systems grow, develop, evolve, and adapt. this is not always straightforward: living systems can undergo extreme deformations, change their mass, generate active contraction, and develop prestrain and residual stress. these phenomena are non-intuitive to traditional engineers and often difficult to grasp. they require us to advance the classical field theories of mechanics towards living matter physics, design our own mathematical models, and create our own simulation tools. here are some examples of projects that we are currently addressing:

the living heart project

our heart is not only our most vital, but also our most complex organ: precisely controlled by the interplay of electrical and mechanical fields, it consists of four chambers and four valves, which act in concert to regulate its filling, ejection, and overall pump function. while numerous computational models exist to study either the electrical or the mechanical response of its individual chambers, the integrative electro-mechanical response of the whole heart remains poorly understood. with support of the nsf career award, our lab has designed the first fully coupled electro-mechanical model for excitation-contraction coupling within a single, unified finite element framework. our heart model has become a true success story: since may 2013, we have worked with the largest commercial finite element company, abaqus/dassault systemes, towards implementing our core algorithms into the abaqus infrastructure. together with the living heart team at dassault systemes, we have established the first four-chamber heart simulator for human heart function. the living heart project was officially launched in may 2014. since then, our work has received broad media attention and was featured in several scientific publications. to date, the living heart ecosystem has grown to 32 contributing member organizations, with more than 150 cardiovascular specialists from research, industry, and medicine, who have free access to our heart simulator to test and accelerate the development of the living heart via crowdsourcing.

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figure 1. the living heart project. in collaboration with abaqus/dassault systemes, we have created the first fully finite-element based whole heart model for realistic human heart simulations of excitation-contraction coupling.

figure 1 illustrates our first prototype of the living heart model, which allows us to explore and understand the key features, physics, and technologies required to create an integrative, predictive model of the living human heart. ultimately, the living heart project will unite leading cardiovascular researchers, medical device manufacturers, regulatory agencies, and practicing cardiologists on the shared mission to develop and validate personalized digital human heart models and establish a unified foundation for in silico cardiovascular medicine. our computational models, which form the core of these efforts are documented in more than 20 peer-reviewed journal publications and in several featured articles and animations.

cardiac optogenetics

heart disease is the primary cause of death in industrialized nations, claiming more than 16 million lives worldwide every year. in the united states alone, almost half a million people die each year as a result of heart rhythm disorders. despite its invasive nature, electrical stimulation remains the gold standard treatment to control rhythm disturbances through direct contact stimulation. together with our clinical collaborators, we have pioneered a novel technology to control heart rhythm disorders at a distance by means of light using a new concept known as optogenetics. we have created mathematical models and computational tools to decipher the mechanisms by which optogenetics can regulate cardiac function with the ultimate goal to create a biological pacemaker of genetically engineered cardiac cells.

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figure 2. cardiac optogenetics. optical stimulation opens a cation channel to initiate a photocurrent, which increases the sodium concentration. this triggers an increase in the electric potential and initiates mechanical contraction.

we prototyped a multiscale computational model for the optogenetic control of human hearts, which we have calibrated across four biological scales as illustrated in figure 2. we used this model to make patient-specific predictions of ion channel dynamics, virtually probe landscapes of process parameters, and identify optimal photostimulation sequences in silico before testing them in vivo. this work is documented in five journal articles and has initiated a broad interest in the general media including several featured stories, podcasts, and radio interviews.

characterizing living skin

skin is our interface with the outside world. in its natural environment, it displays unique mechanical characteristics including prestrain and growth. while there is a general agreement on the physiological importance of these features, they remain poorly characterized mainly because they are difficult to access with standard laboratory techniques. our lab has established a novel, inexpensive technique to characterize living skin using multi-view stereo and isogeometric analysis. based on easy-to-create hand-held camera images, we quantify prestretch, deformation, and growth in a controlled porcine model of chronic skin expansion. over a period of five weeks, we gradually inflate subcutaneouly implanted balloons, take weekly photographs of the experimental scene, reconstruct the geometry from a tattooed surface grid, and create parametric representations of the skin surface.

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figure 3. skin expansion in pediatric forehead reconstruction.

we analyzed these representations and quantified the average area prestretch to 1.44 and the average area growth to 2.25. we used these data to calibrate our skin growth model to simulate clinical cases of skin expansion in pediatric forehead reconstruction. our simulations accurately predict the clinically observed mechanical and structural response of living skin both acutely and chronically. our living skin model can easily be generalized to arbitrary biological membranes and serve as a valuable tool to virtually manipulate living systems, simply by means of changes in their mechanical environment. our skin research was initially motivated by a class project in fall 2010 and has, to date, inspired twelve conference papers and eleven peer-reviewed journal articles.

physical biology of brain development

the developing human brain remains one of the few unsolved mysteries of science. advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. however, the precise role of mechanics throughout this process remains under appreciated and poorly understood. we have recently shown that mechanical stretch plays a crucial role in brain development.

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figure 4. variety of mammalian brains. caitlin, adrian, ellen, james, moritz, mona, rijk, maria.

using the nonlinear field theories of mechanics, supplemented by the theory of finite growth, we have modeled the human brain as a living system with a morphogenetically growing gray matter surface and a growing white matter core. this approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. to characterize the stiffness of gray and white matter tissue, we have designed new protocols for indentation testing and demonstrated that white matter, with an average modulus of 1.9kpa, is stiffer than gray matter, with an average modulus of 1.4kpa. our simulations suggest that anisotropic white matter growth, as an emergent property from chronic axon elongation, intrinsically induces symmetry breaking, and predicts surface morphologies in agreement with magnetic resonance images from very preterm neonates. our model predicts that deviations in cortical thickness, elasticity, and growth induce morphological abnormalities. using the gyrification index, the ratio between the total and exposed surface area, we have shown that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. understanding the mechanisms of human brain development has direct implications on the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism. In the past year, we have published six peer reviewed journal articles and edited a multi-author review on brain mechanics.

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