BME PhD Dissertation Defense - Peijiang Wang

  • Starts: 11:00 am on Thursday, August 9, 2018
Title: “Bioresorbable Scaffold: An Integrated Approach” Committee: Prof. Elazer R. Edelman, MIT IMES (Co-Advisor) Prof. Bela Suki, BU BME (Co-Advisor) Prof. Joe Tien, BU BME (Chair) Prof. Dimitrije Stamenovic, BU BME Prof. Jeffrey C. Grossman, MIT MSE Prof. Nicola Ferralis, MIT MSE Abstract: Bioresorbable scaffolds (BRS) were thought to represent the next cardiovascular interventional revolution in relief of obstructive coronary atherosclerosis yet they failed in comparison to metal stents. They were expected to provide mechanical support non-inferior to metal stents in short-term and gradually degrade to eliminate long-term complications associated with permanent implants. However, their clinical performance at all times were inferior to metal stents, including increased rate of thrombosis and myocardial infraction. These problems evaded detection emerging only in clinical trials leading one to wonder if BRS were appropriately characterized during the preclinical testing. We specifically questioned whether methods designed for metal stents could detect issues with BRS or hide potential areas of concerns. This work sought to determine how to define mechanical failure modes of BRS distinct from metal stents, and if such definition might have predicted clinical failure of the 1st generation BRS and if implemented now enable optimization of the design of next generation scaffolds. We developed a BRS-specific integrated approach involving benchtop mechanical testing, computational modelling, material characterization, and animal model validation evaluating de novo intact devices or those in which control defects were introduced. We performed mechanical characterizations with variable working environments and parameters. Micro-cracks and localized deformations were identified as a form of accelerated wear and challenge to structural integrity. We designed and built a high-throughput multimodal fatigue tester to generate deformation modes evident in arterial deformations in vivo, and test scaffold durability during acute and subacute timeframes. We reproduced fracture rates and locations seen in animal models, and revealed the relationship between loading modes, scaffold design, and fracture initiation and propagation. Finally, we utilized Raman spectroscopy to identify heterogeneities in material microstructures, which induced non-uniform degradation and severe localized deformations that could explain early structural failures and late clinical complications. Failure modes of BRS are distinct from those of bare metal stents and techniques designed to detect the one are not readily appropriate for the other. Characterization of device performance matched to device design might enable more appropriate device design.
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