BioManufacturing and Vascular Device Laboratory
Department of Industrial Engineering at the University of Pittsburgh
1. Transcatheter-Based Tissue-Engineered Biohybrid Medical Devices
2. Real-Time Diagnostic Micro Implants for Monitoring Vascular Diseases in Heart and Brain
3. Endovascular Devices for Treating Cardiovascular Diseases
4. Development of A Novel Vascular Total Analysis System
Dr. Youngjae Chun's past research involves an interdisciplinary study on design and manufacturing of several endovascular devices containing a novel smart material (e.g., thin film Nickel-Titanium: TFN) and investigating the in-vivo/in-vitro behaviors for vascular repair. This research focuses on entire the process (i.e., from fabricating TFN to in-vivo studies) for developing TFN based medical devices for treating vascular diseases with interventional procedures. Research works and contributions are briefly described below.
 Thin Film NiTi (TFN) Covered Microstent for Intracranial Aneurysm Occlusion
The current gold standard to treat intracranial aneurysms is endovascular therapy using platinum coils to fill the aneurysm sac. While coils are beneficial, they are only useful for aneurysms with "necks" narrow enough to hold coils in place. To address this issue, a novel approach, namely "Thin Film NiTi (TFN) Covered Microstent" was attempted to occlude the neck of the intracranial aneurysm using a micro-patterned hyper-elastic ultra-thin film NiTi (i.e., thickness <6micrometer). This work includes developing TFN materials with specific properties, designing hyper-elastic (i.e., >700% strain without mechanical failure) micro patterns using finite element modeling, developing innovative microfabrication techniques (i.e., a novel lift-off method) to create robust micro features, and conducting in-vitro/in-vivo testings. Recent results showed 4 week patency in the arteries without thrombogenic complications and undesirable excessive neointimal hyperplasia. Something that was previously not thought possible in small diameter vessels.
 Superhydrophilic Surface Treatment and In Vitro Evaluation on Hemocompatibility
One of the dominant concerns of thin film NiTi (TFN) material (or for that matter any vascular device) is thrombosis when a device is used in small vessels (e.g., <4mm diameter). For many artificial materials thrombosis is directly related to hydrophilic and negatively charged surfaces on the materials. A new thin film NiTi's superhydrophilic surface has been developed by chemical treatment. An additional benefit is that the surface is negatively charged, a feature that prevents thrombosis from occurring in small diameter vessels. The approach is a chemical method with 30% hydrogen peroxide at room temperature that produces a superhydrophilic and negatively charged surface. Superhydrophilic TFN (S-TFN) has significantly decreased platelet adhesion and aggregation compared to commercially available covering such as expanded polytetrafluroethylene (ePTFE). In addition, the potential infectivity of S-TFN was investigated and compared with currently available endograft materials used for indwelling medical devices. This study has been demonstrated that S-TFN is more resistant than ePTFE to E. Coli, S. Aureus, and S. Epidermidis adherence and that surface treatment to create a super hydrophilic layer further decreases adherence. These findings suggest that S-TFN may represent a superior material to resist both thrombosis and infection in endografts.
 A Novel Thin Film NiTi (TFN) Endograft to Treat Peripheral Arterial Disease
One of the major problems in the current treatment of peripheral arterial disease (PAD) is endograft thrombosis. The thrombogenicity of superhydrophilic thin film NiTi (S-TFN) to ePTFE covered stent grafts was compared under in vitro whole blood circulation. Results revealed ePTFE has a substantially larger total blood deposition as compared to S-TFN. Similar trends are observed in both fibrin deposition (measured by ELISA assays) and protein deposition (quantified by mass spectrometry). In addition, several in vitro studies were conducted to determine the potential to seed and grow endothelial cells on S-TFN scaffold. This research focused on the relationship between S-TFN fenestration size and endothelial cell migration. The fenestrations of 20x40µm showed nearly confluent cell layers and the fenestrations of 30x60µm showed robust, confluent cell growth. This information produced a geometric design pattern that will limit smooth muscle cell migration through the thickness of the S-TFN covered endograft while promoting endothelial cell migration along the length of the S-TFN covered endograft. Based on this study, a S-TFN covered endograft that improves upon the current "gold standard" ePTFE covered grafts would have a major impact on the lives of a large group of individuals suffering from peripheral arterial disease.
 In-vitro Studies on Hemodynamics Alteration using Particle Image Velocimetry
Hemodynamics and its relationship with indwelling medical devices in the vascular system are a critical step to demonstrate a device's function in the body. In vitro hemodynamic changes have been demonstrated that significant flow alterations occur after deployment of an ultra-high porous (i.e., 88~94%) TFN covered stent in cerebral aneurysm models. TFN covered stents significantly reduce flow velocity and alter flow patterns in both wide-neck and fusiform aneurysm sacs after deployment. The intra-aneurysmal RMS velocity magnitudes were reduced by 97% for wide-neck and 67% for fusiform models compared to the nonstented model, respectively. In addition, the local wall shear rates in the sac was experimented and high porous devices reduced these values more than 99% for a wide-neck and more than 66% for a fusiform model compared to the nonstented model, respectively. These significant reductions have great potential to promote occlusion of the aneurysm sac and may represent a more effective way to treat cerebral aneurysms.
 In-vivo Swine Tests for Evaluating TFN Device Functions and Biocompatibility
In-vivo swine test represents an important and critical component before entering human trials. I have helped conduct in-vivo swine test to evaluate TFN device functions in a small diameter artery (3.5~5.0mm). I successfully showed an S-TFN covered stent remained patent and rapidly endothelialized after 4 weeks. The neointimal growth suggests that there is some small amount of platelet deposition on the S-TFN that aids in the healing process. More recently, a survival animal study has been conducted and histophathology results (SEM and H&E staining) confirmed stent patency with minimal neointimal reaction. A more ambitious effort has recently demonstrated rapid isolation of intra-aneurysmal blood flow from parent arteries after placing an ultra-porous hyper-elastic S-TFN covered stent. In-vivo studies have shown a 100% success rate at occluding surgically created aneurysms in as little as 5 minutes. This result is significantly superior to other flow diverting devices. I have also extended research into the biology of aneurysm thrombosis in small artery and used results as a feedback mechanism to modify device manufacturing processes.
 Thin Film Nitinol (NiTi): A Feasibility Study For A Novel Aortic Stent Graft Material
Although technological improvements continue to advance the designs of aortic stent grafts, miniaturization of the required delivery systems would allow their application to a wider range of patients and potentially decrease the access difficulties that are encountered. This feasibility study to determine if thin-film NiTi (Nitinol) could be used as a covering for stent grafts ranging from 16 mm to 40 mm in diameter. Various devices were successfully created and deployed via delivery systems half the size of fabric-covered stent grafts (i.e. the 16 mm stent graft that originally was delivered via a 16 F system was reduced to 8F and the 40 mm stent graft delivered via a 24 F system was reduced to 12 F). No migration of the devices was observed with deployment in both straight and curved tubing, which was sized so that the stent-grafts were oversized by 20%. Both forms of the thin-film were noted to be more flexible than the same sized ePTFE stent graft, and the patterned graft had an additional 15-30% flexibility versus the non-patterned film. These in vitro results demonstrate the feasibility of TFN for covering stent grafts designed for placement in the aorta. The delivery profile can be significantly reduced across a wide range of sizes, while the material remained more flexible than ePTFE. This material may lead to a new generation of low profile stent grafts for the treatment of aortic disease.
Updated Feb. 07 2014