PI: Stephen Badylak Title: REPAIR: Regenerative Electronic Platform through Advanced Intelligent Regulation Description: We will engineer the Regenerative Electronic Platform through Advanced Intelligent Regulation (REPAIR) Patch, which will dramatically improve the speed and functional outcome of wound healing. The technologic basis of our approach is the use of a novel array of sensors and actuators, designed and controlled through the use of computational models and embedded within an inductive cytocompatible extracellular matrix (ECM) hydrogel. The REPAIR Patch will be developed and tested in a dog model of volumetric muscle loss (VML). The REPAIR platform, which is flexible with regard to geometry, [...]

PI: Mohammad Eslami and David Vorp Title: Endovascular Orifice Detection (EOrD) Device for In Situ Fenestration of Abdominal Aortic Aneurysm Description: Abdominal aortic aneurysm (AAA) is a localized dilatation of the aorta and if left untreated may go on to rupture which is associated with a 90% mortality rate. This is the 15th leading cause of death in the United States with more than 15,000 deaths reported annually. When an aneurysm reaches the maximum diameter criteria (greater than 5.0 – 5.5 cm), clinicians will intervene with either open surgery or endovascular repair (EVAR). For complex AAA cases, a minimally invasive [...]

PI: Eric Lagasse Title: Cell Therapy for Patients with End Stage Liver Disease Description: Obesity is a complex medical condition caused by dysregulation of systemic metabolism, excessive accumulation of body fat, insulin resistance and a variety of additional health issues.  Hepatocytes produce bile acids, which are recognized as key regulators of systemic metabolism, particularly systemic energy expenditure. In this pilot study, we propose experiments to transplant hepatocytes into lymph nodes of mice under fat-induced diet and compare to transplant of brown fat tissue into lymph nodes for an effective treatment of metabolic syndrome. Statement of Work: Cell-based therapy is a promising approach [...]

PI: Donghun Shin Title: Delineating the molecular mechanisms of hepatocyte-to-cholangiocyte reprogramming Description: Biliary epithelial cells (BECs; also called as cholangiocytes) that line the hepatic biliary tree control bile composition and flow. Injury to the BECs leads to cholestasis, which can progress to fibrosis, cirrhosis, and liver failure. Cholestatic liver diseases are associated with high morbidity and mortality; however, few effective therapies are available. In fact, liver transplantation is the only life-extending treatment for end-stage cholestatic liver diseases, but the shortage of donor livers makes this therapy extremely limited. In the injured liver with biliary damage, hepatocytes (HCs) can contribute to [...]

PI: Sruti Shiva Co-PI: Anthony J. Molina Title: The relationship between blood based bioenergetics and muscle function, mobility, and aging Description: As people age, they experience declining physical performance, which is associated with diminished quality of life, augmented health care costs, and is a strong predictor of morbidity and mortality. Thus, uncovering mechanisms that underlie age-associated mobility decline and identifying reliable biomarkers to predict this decline is imperative for the development of interventions to maintain physical ability with age. Mitochondria generate chemical energy to support homeostatic function of most cells in the body, and mitochondrial dysfunction is linked to age-associated [...]

PI: Kang Kim Title: Super Resolution Ultrasound Imaging of Vasa Vasorum to Characterize the Progression of Atherosclerotic Plaques and Predict Rupture Vulnerability Description: Acute coronary syndromes and strokes together constitute a leading cause of morbidity and mortality in the United States and Europe, approximately 80% of which are caused by atherosclerotic plaque (AP) rupture. Over the past decade, extensive efforts have been made to identify a rupture-prone AP. Among others, infiltration of dense neovascularization arising from vasa vasorum (VV) into the AP core plays a critical role in AP rupture. Postmortem studies revealed key involvement of VV in AP. However, a [...]

PI: Jonathan Vande Geest Title: Preclinical Assessment of a Compliance Matched Biopolymer Vascular Graft Description: There are approximately 250,000 coronary artery bypass graft (CABG) procedures performed annually to treat coronary heart disease (CHD) with graft failure rates reported to be as high as 42.8%. A major cause of graft failure in CABG has been attributed to graft compliance mismatch leading to subsequent intimal hyperplasia and graft thrombosis. The development of a compliance matched functional small diameter vascular graft will therefore significantly improve the treatment of those with CHD. Tissue engineering has shown promise in achieving some but not all of [...]

PIs: Pamela Moalli, Kyle Orwig, and Caroline Gargett Title: Vaginal Stem Cells: The Missing Link in Vaginal Reconstruction Description: An increasing number of women are seeking vaginal reconstruction surgery to repair tissue loss after surgery for pelvic cancers or following ovariectomy, chemotherapy and radiation, which can result in the vagina becoming contracted, thinned and painful. After noticing the limited range of biomaterials for these procedures, Moalli was inspired to develop better solutions. This project seeks to identify stem cell populations that restore vaginal structure and function and isolate the cellular ecosystems needed for stem cell survival, proliferation and engraftment. The [...]