Project Title: Engineering 3D Human Cardiac Muscle Using Induced Pluripotent Stem Cells Participating Labs/Departments: Feinberg lab, Biomedical Engineering, Materials Science and Engineering Location: Scott Hall Primary Investigator: Adam Feinberg Research Description: The goal of this project is to develop an improved 3D engineered cardiac muscle tissue using human induced pluripotent stem cells. The eventual application of this tissue is to create an in vitro model of human heart muscle for drug discovery and toxicity screening. Previous work in the Feinberg lab has developed technologies to engineer 3D cardiac muscle and also has established human iPS culture and differentiation into cardiomyocytes. The proposed research will combine these technologies in order to tissue engineer human heart muscle with defined structural and functional properties. To do this we will use 3D printed molds to cast collagen gels embedded with these cells and culture them for defined periods to form muscle tissue. Students will fix these tissues, label the cytoskeletal and then image in 3D using the confocal and multiphoton microscopes. Contractility experiments will also be performed where students measure the force generation of these engineered tissues. The anticipated endpoint is to have produced a function human cardiac tissue over the summer research period. The undergraduate student will work in close collaboration with graduate students to learn how to culture human iPS cells and will be trained in the required tissue engineering techniques. Clinical Exposure: Research rotations as required by the Carnegie Heart Program Major/Course/Skill Prerequisites: Cell culture, microcontact printing, immunofluorescent staining, confocal imaging, image analysis

Project Title: Flexible Electronic Biosensors to Monitor Cardiac Output Participating Departments: Biomedical Engineering and Materials Science & Engineering Location: Carnegie Mellon & Allegheny General Hospital Primary Investigators: C. J. Bettinger, PhD (CMU) and M. Scott Halbreiner, M.D. (AGH) Research Description: The overall goal of this project is to design, fabricate, characterize, and deploy flexible sensors that can be affixed to the surface of structures in the heart (Fig. 1). These tethered sensor arrays will record pressure and flow waveforms, data that can be used to calculate cardiac output after major operations such as heart transplants. The current standard-of-care for monitoring cardiac output is a wire-based device that dwells within the aorta. Indwelling sensors have many risks and complications including infection and clotting. Flexible sensors affixed to the exterior of the heart could provide the same information about cardiac output with much less risk to the patient. Furthermore, the novel materials and fabrication techniques in this project (Fig. 2) could underpin future sensing technologies including chemical, optical, or electrophysiological transducers that can provide additional insight into cardiac function. Towards this end, the student will work with graduate students in the Bettinger Group to:

• Design, calibrate, and fabricate strain sensors • Integrate strain sensors with flexible adhesive

polymers • Measure the electronic properties of flexible strain

sensors in vitro • Test flexible strain sensors in animal subjects

through collaborations with AGH Clinical Exposure: The student will work with Dr. M. Scott Halbreiner, M. D. to learn more about the technology and practice related to the following areas: heart transplantation, complex aortic diseases, and minimally invasive cardiac surgery. These objectives will be completed by activities including shadowing and observation of clinical procedures as appropriate. Major/Course/Skill Prerequisites: Interest in polymers, solid mechanics, and microfabrication. Experience with SolidWorks and ANSYS a plus, but not required. MSE, ECE, MechE, and BME majors encouraged to apply.

Fig. 1 (a) Proposed in vivo deployment of flexible sensors to monitor cardiac output. (b) Two sets of sensor arrays will monitor cardiac output in vivo.

Fig. 2 Design and processing of polymer-based strain sensors. (a) Schematic and (b) pictures of transfer printing of microelectronic sensors. c) Optical and scanning electron micrographs showing top and side views of device. (d) Sensors can adhere to tissues such as pulmonary arteries.

Project Title: Comparing Cardiovascular Strain between MRI and Echocardiography Participating Labs/Departments: Cardiology Location: AGH Cardiac MRI Lab Primary Investigator: Robert W.W. Biederman, MD Research Description: Cardiovascular strain is emerging as a clinically important variable to assess diastolic function in patients with suspected heart disease. There are two major imaging modalities that can be utilized to assess myocardial strain: cardiovascular MRI and echocardiography. MRI has long been recognized as a modality that can assess both systolic, and more recently, diastolic cardiac function. However, more contemporary assessments of diastolic function have moved away from flow-based to myocardial-base approaches. While echocardiography has incorporated this new strategy into current clinical practice, MRI has not, but we believe, has the requisite physiological ability to surpass echo if suitable focus is directed. This project involves performing measurements on patient image data obtained with each imaging modality and assessing conditions under which results are similar or different. Clinical Exposure: The student will have exposure to the clinical cardiovascular magnetic resonance imaging suite as well as clinical echocardiography, as well as research rotations as required by the Carnegie Heart Program

Major/Course/Skill Prerequisites: Matlab or similar preferred but not essential

Project Title Microfluidic Study of Clot in an Artificial Lung Participating Labs and Departments: Cook Cardiopulmonary Bioengineering Lab in the Biomedical Engineering Department Location: Scott Hall, 3rd Floor Primary Investigator: Keith Cook Research Description: Medical devices have encountered the problem of clot formation on blood contacting artificial surfaces for decades. As clot covers the functional surface of medical devices, it increases risk for the patient and reduces the efficacy of the device. This project studies the formation of clot inside the complex geometry of an artificial lung or oxygenator and how different variables affect coagulation in order to best inform the design of future artificial lungs. Students on this project will learn to work with blood in vitro and learn basic benchtop wet-lab techniques. They will also gain an understanding of blood coagulation and some clinical applications of the work that they will work on. Clinical Exposure (Required for SURP in BME at CMU): Research rotations as required by the Carnegie Heart Program Major/Course/Skill Prerequisites: None, Interest in STEM preferred

Project Title: Synthesis and Evaluation of a Drug Eluting Degradable Polymer for Use in Artificial Oxygenators Participating Labs/Departments:

Cook lab (CMU BME) and the Allegheny Singer Research Institute

Location:

Scott Hall and Allegheny General Hospital

Primary Investigator:

Keith Cook

Research Description:

Our lab is developing biocompatible materials to replace weaving fibers incorporated in artificial lung manufacturing to secure woven hollow fiber mats for oxygenators. During this project, students will learn to synthesize fibroin from raw silk, characterize the material to manipulate the structure for drug loading, release, and manufacturing stability. The student will be expected to develop research protocols with the graduate student, and cultivate skills required for materials characterization, manipulation, drug release evaluation and blood incubation testing. The student will be expected to organize, analyze, and present all collected data.

Clinical Exposure (Required for SURP in BME at CMU):

Research rotations as required by the Carnegie Heart Program

Major/Course/Skill Prerequisites:

The ideal student will study BME as well as either material science, biology, biochemistry or chemical engineering. This project is ideal for a pre-med student, as they will learn about advancement in medical technology, pulmonologist, biocompatibility for medical technologies, and blood dynamics for incubation testing.

Project Title: Testing a Pulmonary Assist Device for Destination Therapy

Participating Labs/Departments:

Cook lab (CMU BME) and the Allegheny Singer Research Institute

Location:

Scott Hall and Allegheny General Hospital

Primary Investigator:

Keith Cook

Research Description:

Our lab is developing an artificial lung for destination therapy. This summer we will be evaluating its long-term in vivo use. The pulmonary assist device (PAD) will be surgically attached and will be used for a period of up to 60 days. During this time, students will take data on the function of the PAD and animal physiology. The student will run a variety of hematological tests (blood gases, cell counts, various ELISAs), give and monitor medications, care for the sheep, and troubleshoot any problems that arise. Lastly, the student will be expected to organize and analyze data for presentation.

Clinical Exposure (Required for SURP in BME at CMU):

Research rotations as required by the Carnegie Heart Program

Major/Course/Skill Prerequisites:

The ideal student will study BME as well as either mechanical engineering, material science, or chemical engineering. This project is ideal for a pre-med student, as they will learn about surgery, anesthesia, pulmonology, and critical care.

Project Title: Soft Robotic Sleeve for Muscle-powered Cardiac Support Participating Labs/Departments:

1. Circulatory Support Lab, Biomedical Engineering Dept., Carnegie Mellon Univ. (CMU) 2. Cardiothoracic Surgery Dept., Allegheny General Hospital (AGH)

Location: Carnegie Mellon University & Allegheny General Hospital, Pittsburgh, PA Course Instructors: Dennis R. Trumble, PhD (Asst. Research Professor, CMU) Walter E. McGregor, MD (Director, Robotic & Minimally Invasive Heart Surgery, AGH) Research Description: A fundamental breakthrough in long-term circulatory support technology is needed to drive the field forward. The reasons for this are two-fold. First, despite decades of research extracorporeal drive systems for long-term ventricular assist devices (VADs) continue to be extremely problematic in terms of infection risk and patient quality of life. Second, bleeding and thrombosis associated with exposure to blood-contacting surfaces are life-threatening complications that have yet to be resolved in the setting of long-term circulatory support. Together, these problems have proven difficult, if not impossible, to overcome using traditional blood pump technologies and there is no indication that the latest generation of rotary devices will prove to be any more successful in the long run. Given the persistent difficulties encountered with existing blood pump technologies used in the chronic setting, the promise of safe, reliable long-term circulatory support is likely to remain unfulfilled unless and until there is a fundamental change in the way we approach this problem. Research by our laboratory suggests that the best way to deal with longstanding problems created by drivelines and blood contacting surfaces is to avoid them altogether by harnessing the body’s own endogenous energy stores (i.e., skeletal muscle) and applying this power to the external surface of the heart. The primary enabling technology behind this work is an implantable muscle energy converter (MEC) developed by Dr. Trumble (see figure). The MEC is, in essence, an internal energy transfer mechanism that utilizes electrically stimulated skeletal muscle as an endogenous power source and transmits this energy in hydraulic form. Through numerous iterative design improvements implemented over several years, this device has been refined and shown to exhibit excellent anatomic fit, extreme mechanical durability and high energy transfer efficiency with the capacity to transmit up to 1.25 joules of contractile work per actuation cycle. The primary objective of the research project is to design, build and test a cardiac compression mechanism that can be actuated by the MEC device as illustrated in the accompanying figure. This can be accomplished, in principle, using an array of flexible tubular elements wrapped around both ventricles of the heart. By affixing a series of inflatable tubes side-by-side, a functional array can be constructed that will actively shorten when inflated and re-expand with fluid evacuation. This approach is similar in concept to the pneumatic AbioBooster device (Abiomed, Inc., Danvers, MA), which operates on the same principle and is specifically designed for low-volume actuation. Because the ratio of hydraulic to physiologic stroke volume for this device rises with the number of tubes used to form the compressive sleeve, such a ‘compressive sleeve’ could be tuned to operate in accordance with low MEC stroke volumes (either 5 or 20 mL, depending on the model used).

Laboratory / Clinical Exposure During the course of this work the student will have the opportunity to participate in the following clinical activities:

1. Open heart surgery observation to develop a technical appreciation of surgical methods, application of cardiopulmonary bypass, echo technology for cardiac imaging, and anesthesia technology for patient monitoring.

2. Patient rounds in the ICU to gain exposure to critical care technologies and also up-close encounters with ventricular assist devices, extracorporeal membrane oxygenation (ECMO), and cardiac transplantation.

3. Patient rounds on the floor to reinforce the human side of surgical medicine and medical device development.

Course Prerequisites: Students must have a firm understanding of global cardiac mechanics, a working knowledge of biomaterials (to address the tissue/device interface aspects of the project), and a strong background in Computer Aided Design (CAD).

Project Title: Monitoring of brain hemodynamics in traumatic brain injured patients and healthy volunteers Participating Labs/Departments: Kainerstorfer Lab, BME Location: Scott Hall Primary Investigator: Jana Kainerstorfer Research Description: We have developed a non-invasive method for monitoring intracranial pressure (ICP) by measuring cerebral hemodynamic changes via an optical technique called near-infrared spectroscopy. Non-invasive ICP monitoring is important in many diseases, where an invasive probe cannot be placed, including stroke. Our method is based on transfer function analysis of measured hemodynamic changes to obtain ICP traces. We are starting data collection to validate our methods in traumatic brain injured children. The student working on this project will help analyze data from patients but will dominantly perform control measurements on healthy volunteers. Data collection on healthy volunteers will include optical recording from the brain while subjects perform a variety of exercises. The student will be trained in optical data collection as well as signal processing methods. At the end of the summer, the student will have finished data collection and will have developed signal processing methods to quantify hemodynamic differences between patients and healthy subjects. Clinical Exposure Data collection will be done by the graduate students; if clinical routines allow it, the student will be able to observe data collection in the neuro-intensive care unit of the Children’s Hospital. Major/Course/Skill Prerequisites: Basic knowledge of Matlab and signal processing