3D-Nanoprinted Soft Robotic Microcatheters with Integrated Microfluidic Circuitry for Cerebrovascular Surgery - Project Summary: Cerebral aneurysms are estimated to be prevalent in 3–7% of the general population—with cases increasing by more than 5% each year—resulting in ~500,000 deaths annually. Minimally invasive neurosurgery typically represents the best surgical option for treating unruptured aneurysms due to benefits including reduced length of stay and complications compared to invasive surgical clipping. Endovascular neurointerventions rely on microcatheters to traverse cerebral anatomy safely to deliver embolic devices or stents for aneurysm treatment. In many cases, however, tortuous vasculature and geometrically complex aneurysms pose substantial navigation challenges for neurointerventionalists due to an inability to maneuver conventional microcatheters safely. These difficulties in navigating such cerebrovascular anatomies contribute to longer procedural times, unsuccessful catheterization attempts, and increased risks of complications. To address the clinical need for neurosurgical microcatheters that overcome these maneuverability-associated barriers, we propose to engineer and evaluate 3D-nanoprinted soft robotic microcatheters with integrated microfluidic circuitry as a means to enable on-demand, multi-directional steering and navigation control during endovascular neurointerventions. Our overarching hypothesis is that, by leveraging and extending recent advances at the intersection of machine learning-based design, additive nanomanufacturing, integrated microfluidic circuitry, and soft microrobotics, novel classes of remotely steerable neurosurgical microcatheters can be realized at unprecedented scales to surmount current maneuverability-based deficits, and ultimately, improve catheterization efficacy, safety, and outcomes in the treatment of cerebral aneurysms. We will investigate the clinical feasibility of this hypothesis through four specific aims. In Aim 1, we will create machine learning-based design techniques for predicting and informing the operational performance of the soft robotic microcatheter. In Aim 2, we will examine the manu- facturing efficacy for 3D nanoprinting multi-actuator tips and integrated microfluidic circuits both independently and as fully unified soft robotic microcatheters capable of on-demand, multi-directional deformations with minimal infrastructure and external control scheme-associated requirements. In Aim 3, we will develop a handheld controller for the neurointerventionalist and compare the maneuverability efficacy of the soft robotic micro- catheter to that of standard clinical microcatheters using in vitro models of cerebrovascular anatomy based on patient-specific clinical 3D angiography images. In Aim 4, we will assess the feasibility and safety of the soft robotic microcatheter (i.e., with respect to standard clinical microcatheters) by performing minimally invasive endovascular neurointerventions in animal models (canine, n=8). If successful, the proposed 3D-nanoprinted soft robotic microcatheters hold unique promise to be transformative not only for treating cerebral aneurysms, but also for wide-ranging endovascular interventions currently considered challenging or high risk due to small, complex, tortuous, and/or delicate vasculature, such as for the treatment of pediatric congenital heart defects.
