RECENT PROJECTS

RECENT PROJECTS

We work on a diverse range of projects, from understanding the biomechanics of vascular pathologies to biomedical device development.

 In-Vitro model of arterial thrombosis


Background

  • Arterial thrombosis leading to heart attack and stroke forms at very high shear rates (3500 to >100 000 s-1)
  • Clots composed primarily of platelets
  • Our Findings (Para 2011, Bark 2012)
  • Utilizing coronary-sized stenotic glass test section coated with collagen
  • Three stages of thrombus formation: lag time, rapid platelet accumulation (RPA), occlusion
  • Dependence on shear rate
  • Lag time decreases with increasing shear
  • RPA rate increases with increasing shear up to ~6000 s-1

Current Objectives

  • Quantify effects of flow pulsatility, surface functionalization, stenosis shape, and platelet transport (see right)
  • Miniaturization of assay using microfluidics à point-of-care
  • Evaluate diagnostic capabilities in  bleeding and thrombotic disorders

Biomechanics of platelet aggregation under high shear


Background

  • Myocardial infarction occurs as a results of platelet thrombosis formation within an atherosclerotic, stenosed artery
  • Very high shear stress conditions within stenoses, shear rates up to 500,000 s-1
  • High shear adhesion is modulated by the A1 domain of von Willebrand factor (vWF-A1) binding to glycoprotein IBα (GPIbα) on platelets

Modeling

  • Suggests several biomechanical parameters that may be required for platelet aggregation under high shear (Wellings 2012)
  • Multivalent bonding of platelets to vWF to balance shear force
  • vWF unfolding to expose sufficient binding sites
  • vWF overlapping to form concave nets to maximize contact with platelets
  • Bond time on the order of 1-10 μs (on-rate on the order of 108 M-1s-1) à 1000 times faster than any previously reported intercellular bonds

Current Objectives

  • Experimentally demonstrate the proposed requirements
  • Translate results to clinical applications

Fluid mechanics of in-vitro aortic dissection model


Background

  • Descending aortic dissection can lead to malperfusion of visceral organs, aneurysmal degeneration, and rupture of the aorta
  • False lumen thrombosis correlated with improved patient outcomes
  • Larger diameter tears associated with worse patient outcomes
  • Silicone model of dissection allows for in vitro testing of flow conditions and endovascular interventions

Our Findings

  • Pulsatile flow introduces arterial wall and dissection flap motion not seen with steady flow, as well as changes to flap orifice geometry

Current Objectives

  • Determine computationally dominant geometric factors contributing to increased false lumen flow and shear rate
  • Demonstrate different shear and flow rates among variant dissection geometries and normal aorta model
  • Calculate flow and shear rates in dissected aorta following deployment of endovascular stent-grafts
  • Correlate results with clinical studies

Thrombosis in pediatric ECMO


Background

  • Extracorporeal membrane oxygenation (ECMO)
  • Life support for patients that require long-term heart-lung support
  • Used in congenital defects or other diseases that cause low cardiac output, hypoxemia, or arrhythmias
  • Challenges: Thromboembolism, hemorrhage

Our Findings

  • Clots were found at  tubing junctions  in 100% of the patient circuits examined
  • Local regions with low shear rate (<100 s-1)
  • Histological analysis indicates clots  are fibrin-rich, consistent with low shear regimes.

Current Objectives

  • In vitro system to replicate ECMO clotting
  • Test thrombosis prevention methods such as modification of local geometries, blood chemistry, and surface chemistry

PVA composed medical implants


Polyvinyl alcohol (PVA) exhibits good biocompatibility and holds promise for medical implants

Prosthetic Venous Valve

Background

  • Chronic Venous Insufficiency
  • Leg pain, varicose veins, fatigue, induration, and ulceration
  • Affects 1.4 million Americans
  • Existing treatments (compression stockings, vein stripping, and others) are not fully effective and do not restore normal venous functions

Current Objectives

  • Design, analyze, and evaluate a prosthetic venous valve capable of percutaneous delivery
  • In vitro and in silico studies show low reflux, short closing times, and favorable shear rates to reduce thrombosis risk
  • Currently pursuing in vivo animal studies