UNMC_Acronym_Vert_sm_4c
University of Nebraska Medical Center

Cardiovascular Biology and Biomechanics Laboratory

Our laboratory is a venue of active collaboration among biomedical engineers, vascular biologists and medical doctors. We apply a unique translational approach that integrates mathematics, computational simulations, artificial intelligence, physiology and molecular biology to understand the role of local biomechanical factors in vascular biology of atherosclerosis, stent restenosis and thrombosis.

Our multi-scale investigations extend from in-vitro cell cultures to small and large animal studies, as well as clinical trials. The process:

  1. Basic science research
  2. Proof-of-concept studies
  3. Confirmatory studies
  4. Clinical studies.

Emphasis

  • Biomechanics: Fluid shear stresses and solid stresses
  • Multi-modality imaging: Invasive (OCT, IVUS) and non-invasive (CCTA, MRI, PET)
  • Multidisciplinary: Biomedical and chemical engineering; molecular and vascular biology; and medicine
  • Cardiovascular Disease: Pathophysiology and theranostics

 

Projects

3D cell co-culture model of atherosclerosis 

We developed a novel 3D co-culture model of atherosclerosis, a systematic and cheap experimental approach on comprehending and reversing the atherosclerotic process. In this model, endothelial cells, smooth muscle cells and monocytes are cultured and interact together, simulating accurately the vascular milieu of atherosclerosis.

 

 

 

 

 





 

 

 

Mechanobiology
To examine the histological and molecular impact of shear stress on the initiation and progression of atherosclerosis, we expose our 3D co-culture model to different flows and measure the pertinent molecular markers for potential therapeutic solutions.
Local treatment for atherosclerosis

To reduce the side effects and increase the efficacy of anti-atherosclerotic medications, we are experimenting with a local approach against atherosclerotic plaques. Nanotechnology promotes the specific delivery of therapeutic compounds and offers significant advantages over more traditional therapies, both in terms of efficacy and safety. One drawback of conventional drug delivery nanotechniques is the lack of site targeting.

To answer that problem, we have developed lipid nanoparticles that can be loaded with anti-atherosclerotic drugs to specifically attach to the plaque, or inflamed endothelium, and interact with it. To manipulate those drug-loaded lipid nanoparticles, we have designed a novel atraumatic micro-catheter capable of local delivery. Both the design scheme and feasibility of the catheter, as well as the efficacy of the lipid nanoparticles are being tested in vitro and ex vivo in a custom-designed bioreactor, to be eventually studied in vivo (rabbits).

Computational simulations of coronary bifurcation

Percutaneous cardiovascular interventions are still associated with major technical challenges and require extensive planning and intra-procedural precise visualization methods. Advances in computational modeling and simulation science allow patient-specific rehearsal of endovascular stenting procedures.

Patient-specific rehearsal constitutes a unique tool that may help plan the endovascular material choice and navigation, optimize the preoperative preparation and predict the outcome.

This is how precision medicine along with pre-procedural planning can help optimize bifurcation stenting and improve clinical outcomes. Patient-specific computational stenting simulations may shift the management paradigm of coronary bifurcation interventions and provide a new dimension on how to improve the stenting and post-dilatation techniques.

Flow ISR clinical study

For the first time in humans, we are conducting a randomized, multi-national, multi-centered clinical study – Effect of Local Biomechanical Factors on Bifurcation Stent Restenosis and Thrombosis, or the FLOW ISR study – to investigate the role of fluid stresses on stent restenosis.

We use a validated subject-specific finite element analysis of arterial bifurcations rooted in clinical and experimental data to faithfully predict stent restenosis. The overall objective of this study is to use an individualized approach to identify, for a specific bifurcation, the optimal bifurcation stenting technique that creates a favorable local biomechanical environment and reduces stent restenosis.

Our study brings together extensive expertise, infrastructure and preliminary work in fluid and solid mechanics, computational simulations and vascular biology. These findings will establish clinically-relevant hypotheses that will serve as basis for our long-term goal: a large, randomized controlled trial to show improved clinical outcomes with patient-specific bifurcation stenting strategies.

Renal denervation

Whether arterial and venous innervation regulates renal blood flow is still disputed.
In collaboration with Dr. Zucker’s group, we block the renal nervous system in pigs, in anticipation of renal blood flow modification.

Using top-notch intravascular imaging modalities, we measure the arterial renal flow as well as the size of the renal artery, before and after the denervation.

Education and training

Virtual reality simulation of cardiovascular procedures can contribute to interventional training and improve the educational experience without putting patients at risk, raising ethical conflicts nor requiring expensive animal or cadaver facilities. The ability to demonstrate complex anatomic relationships and the capacity to collect great amounts of data lets us meet the needs of training and assessing interventional skills. Using 3-D  printing of soft materials, such as coronaries, with embedded electronics and sensors is one other way we use to study our data and reflect patient-specific rehearsal before stenting.

Guidance with augmented and virtual reality can help achieve this goal, by visualizing the plaque and facilitating alignment of the stent graft with the artery of interest. Our division has an active collaboration with the iEXCEL – UNMC's state-of-the-art program and infrastructure on medical simulations.

Through iEXCEL, we provide a unique training and education on cardiovascular imaging and interventions to our faculty, fellows and staff. We are building simulation models that will form an essential component of the fellows’ experience in a step towards migrating the education out of the conventional lecture rooms to a whole new world that allows the learners to dive within and relate to the educational materials. 

Join our lab
Email  Dr. Yiannis Chatzizisis about research opportunities with in the Cardiovascular Biology and Biomechanics Laboratory.

Patents