Author: Zamora R, Barclay D, Yin J, Alonso EM, Leonis MA, Mi Q, Billiar TR, Simmons RL, Squires RH, Vodovotz Y
Grant of the Month
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2019 | July 30, 2019
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2019 | June 26, 2019
PI: Ron Poropatich
PI (Pitt): Michael Pinsky
PI (CMU): Artur Dubrawski
Title: TRAuma Care In a Rucksack: TRACIR
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2019 | May 29, 2019
PI: Pamela Moalli
Co-PI: Steven Abramowitch
Title: Overcoming Complications of Polypropylene Prolapse Meshes: Development of Novel Elastomeric Auxetic Devices
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2019 | April 29, 2019
PI: Michael Boninger
Title: A Biomimetic Approach towards a Dexterous Neuroprosthesis
Description: Cervical spinal cord injury results in the loss of arm and hand function, which significantly limits independence and results in costs over the person’s lifespan. A brain-computer interface (BCI) can be used to bypass the injured tissue to enable control of a robotic arm and to provide somatosensory feedback. Two primary limitations of current state-of-the-art BCIs for arm and hand control are: (1) the inability to control the forces exerted by the prosthetic hand and (2) the lack of somatosensory feedback from the hand. In the proposed study, we seek to considerably improve dexterous control of prosthetic limbs by implementing decoding strategies that enable the user to not only control the movements of the arm and hand, but also the forces transmitted through the hand. We anticipate that our biomimetic approach to decoding will yield intuitive, dexterous control of the prosthetic hand. Tactile sensations will be conveyed to the user through intracortical microstimulation (ICMS) of somatosensory cortex. The spatiotemporal patterns of stimulation will be based on our basic scientific understanding of how tactile information is encoded in somatosensory cortex, which we expect will result in more natural and intuitive sensations. In order to achieve our goal of developing a dexterous neuroprosthesis, we have brought together a team with human BCI experience from the University of Pittsburgh along with the basic science expertise at both Pitt and the University of Chicago. We will collaborate with experts in implantable neurotechnology (Blackrock Microsystems) and robotics (The Biorobotics Institute) to ensure that the device hardware allows us to take a biomimetic approach for control and feedback with an eye toward clinical translation. A total of 4 participants will be tested in a multisite study to accomplish the following three specific aims. Aim 1: Evoke natural and intuitive tactile sensations through ICMS of somatosensory cortex. We expect that biomimetic ICMS will evoke sensations that more closely resemble everyday tactile sensations and intuitively convey information about contacted objects than does standard fixed-frequency ICMS. Aim 2: Derive kinematic and kinetic signals from motor cortex for hand control. We will assess the degree to which motor cortical neurons encode forces exerted on objects. Based on these observations, we will develop hybrid decoders that enable controlling both the movement and force using a synergy-based approach. Aim 3: Demonstrate improved arm and hand function with a biomimetic sensorimotor BCI that combines the sensory feedback developed in Aim 1 with the hybrid decoding developed in Aim 2. A battery of functional assessments will be used including novel metrics designed specifically for sensorimotor prosthetics along with well-established tests identified in the NIH Common Data Elements. We anticipate that subjects will substantially improve their dexterity using a biomimetic BCI as compared to non-biomimetic BCIs or BCIs without somatosensory feedback.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2019 | April 10, 2019
PI: Marc Simon
Title: A Phase II Trial of Metformin for Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2019 | February 26, 2019
PI: George Gittes
Title: Alpha Cells Conversion to Beta Cells in Non-Human Primates
Description: An ideal solution to the treatment or cure of type 1 diabetes mellitus would be the formation of new functioning β-cells from the patient’s own tissues that are not attacked by the autoimmunity, thereby avoiding the need for any immunosuppression. Abundant recent data have suggested that α-cells are a viable potential source for endogenous transdifferentiation into β-cells. Here, we describe a pancreatic intraductal viral delivery system in the mouse, wherein a single infusion of an adeno-associated virus (AAV), carrying a pdx1/mafA expression vector, is given to a toxin-induced (alloxan) diabetic mouse. This AAV gene therapy induced robust and durable α-cell transdifferentiation into β-cell-like cells through neogenesis, with recovery of over 60% of the β-cell mass within 4 weeks, and with persistent, durable euglycemia. Serendipitously, when this β-cell-like cell neogenesis was similarly induced in the autoimmune NOD mouse model, the mice became euglycemic for 4 months or more, without any additional therapy or immunosuppression. To our knowledge, no clinically applicable β-cell replacement therapy in NOD mice has been successful without immunosuppression. We suspect that the neogenic β-cell-like cells may not be attacked by the autoimmunity because they are “imperfect” β-cells by RNA-seq analysis. Since pancreatic duct injection is routinely performed in humans as a relatively simple, non-surgical procedure, and since numerous viral gene therapy trials are currently ongoing for several diseases, we feel that our approach may be rapidly translatable to humans with type 1 diabetes mellitus. In this proposal, we will perform important proof-of-principle studies in non-human primates as last steps in preparation for human gene therapy clinical trials. The primate pancreas has a very different texture and consistency than the mouse pancreas (and is very similar to the human pancreas). Thus, the mechanics of the viral delivery will likely require substantial alterations. In addition, a glucagon promoter is preferable to the CMV promoter for expression of pdx1 and mafA, so we will strive to develop and optimize a glucagon promoter vector that is effective in primates. Further studies will investigate this pancreatic ductal infusion approach in the context of AAV neutralizing antibodies. We will also perform detailed analyses of the new β-cell-like cells, including physiology, gene expression phenotype, and anatomy. In summary, we feel that the proposed studies, if successful, should position us well in preparation for clinical trials in humans with type 1 diabetes mellitus.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2019 | January 28, 2019
PI: Michael Boninger
Title: A Biomimetic Approach Towards a Dexterous Neuroprosthesis
Description: Cervical spinal cord injury results in the loss of arm and hand function, which significantly limits independence and results in costs over the person’s lifespan. A brain-computer interface (BCI) can be used to bypass the injured tissue to enable control of a robotic arm and to provide somatosensory feedback. Two primary limitations of current state-of-the-art BCIs for arm and hand control are: (1) the inability to control the forces exerted by the prosthetic hand and (2) the lack of somatosensory feedback from the hand. In the proposed study, we seek to considerably improve dexterous control of prosthetic limbs by implementing decoding strategies that enable the user to not only control the movements of the arm and hand, but also the forces transmitted through the hand. We anticipate that our biomimetic approach to decoding will yield intuitive, dexterous control of the prosthetic hand. Tactile sensations will be conveyed to the user through intracortical microstimulation (ICMS) of somatosensory cortex. The spatiotemporal patterns of stimulation will be based on our basic scientific understanding of how tactile information is encoded in somatosensory cortex, which we expect will result in more natural and intuitive sensations. In order to achieve our goal of developing a dexterous neuroprosthesis, we have brought together a team with human BCI experience from the University of Pittsburgh along with the basic science expertise at both Pitt and the University of Chicago. We will collaborate with experts in implantable neurotechnology (Blackrock Microsystems) and robotics (The Biorobotics Institute) to ensure that the device hardware allows us to take a biomimetic approach for control and feedback with an eye toward clinical translation. A total of 4 participants will be tested in a multisite study to accomplish the following three specific aims. Aim 1: Evoke natural and intuitive tactile sensations through ICMS of somatosensory cortex. We expect that biomimetic ICMS will evoke sensations that more closely resemble everyday tactile sensations and intuitively convey information about contacted objects than does standard fixed-frequency ICMS. Aim 2: Derive kinematic and kinetic signals from motor cortex for hand control. We will assess the degree to which motor cortical neurons encode forces exerted on objects. Based on these observations, we will develop hybrid decoders that enable controlling both the movement and force using a synergy-based approach. Aim 3: Demonstrate improved arm and hand function with a biomimetic sensorimotor BCI that combines the sensory feedback developed in Aim 1 with the hybrid decoding developed in Aim 2. A battery of functional assessments will be used including novel metrics designed specifically for sensorimotor prosthetics along with well-established tests identified in the NIH Common Data Elements. We anticipate that subjects will substantially improve their dexterity using a biomimetic BCI as compared to non-biomimetic BCIs or BCIs without somatosensory feedback.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2018 | January 16, 2019
PI: Moni K. Datta
Co-PI: Prashant Kumta and Robert Kormos
Title: Novel Aptamer-Based Biosensor Platforms for Detection of Cardiomyopathy Conditions
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2018 | November 30, 2018
PI: Piervincenzo Rizzo (Principal Investigator), Ian Conner (Co-Principal Investigator), Samuel Dickerson (Co-Principal Investigator)
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2018 | October 26, 2018
PI: William R, Wagner, PhD Co-investigator, Donald Taylor, PhD, MBA Co-investigator
Title: Philadelphia-Pittsburgh Pediatric Medical Device Consortium
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2018 | September 28, 2018
PI: J. Peter Rubin
Title: Integrated Clilnical and Research Systems for Diabetic Foot Wound Care
Description: Diabetes is a common, complex, and costly disease affecting 9.4% (30.3 millions) of Americans. It remains the 7th leading cause of death in the United States, contributing to over 250,000 deaths annually. Diabetic foot ulcers (DFU) are the most frequently recognized complication in diabetics with an incidence of 6% in the diabetic global population, 6% among Medicare diabetic beneficiaries, 5% among diabetic U.S. veterans and a lifetime incidence of foot ulcers between 19% and 34% in diabetics. The natural history of a diabetes-related foot ulcer is devastating. More than half of ulcers become infected and approximately 20% of moderate or severe diabetic foot infections lead to amputation. Mortality after diabetes-related amputations is greater than 70% at 5 years for all patients with diabetes, which is 2.5 times higher than in diabetic patients without a foot ulcer. This proposal is designed to establish a clinical research unit (CRU) at the University of Pittsburgh Medical Center that integrates high quality care delivery seamlessly with outstanding clinical research. The CRU will then be a participating site in the NIH consortium studying biomarkers for diabetic foot ulcer healing. Our central hypothesis is that we can address the major challenges of diabetic foot ulcer clinical research through the seamless integration of wound center clinical operations with research operations. Our specific aims are: Aim 1: Establish a unified recruiting and retention system integrated with the clinical operations of our wound care service line, and linked to our EPIC scheduling system and electronic medical record (EMR). Aim 2: Establish integrated research quality systems, linked to highly standardized clinical pathways, and supported by a wound Informatics and Data Core connecting our 8 wound care centers.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2018 | August 28, 2018
PI: Joseph Glorioso and Gary Cohen, PhD
Title: Cancer Vaccine for Melanoma
Description: Drs. Glorioso and Cohen will share a two-year ACGT grant to support a study to develop a cancer vaccine for melanoma. Their research builds on previously successful results using a tumor-targeted, actively replicating herpes virus to infiltrate cancers and stimulate an immune system assault. Dr. Glorioso calls the methodology a “heat-seeking missile that targets metastatic cancer for destruction.” The treatment doesn’t stop there. Once the cancer is eliminated, the vaccine inserts an immunity barrier to protect against recurrence. Melanoma is among the most deadly cancers and this treatment offers new hope.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2018 | July 30, 2018
PI: Shilpa Sant
Title: Three-dimensional organoid models to study breast cancer progression
Description: Approximately 20% of breast cancers detected through mammography are pre-invasive Ductal Carcinoma in situ (DCIS). If left untreated, approximately 20-50% of DCIS will progress to more deadly Invasive Ductal Carcinoma (IDC). No prognostic biomarkers can reliably predict the risk of progression from DCIS to IDC. Similar genomic profiles of matched pre-invasive DCIS and IDC suggests that the progression is not driven by genetic aberrations in DCIS cells, but microenvironmental factors, such as hypoxia and metabolic stress prevalent in DCIS, may drive the transition. We need innovative models to investigate how to halt steps of DCIS progression to invasive phenotypes and subsequent metastasis from the primary site. This proposal directly addresses this unmet need by developing a novel three-dimensional in vitro organoid model that recapitulates key hallmarks of DCIS to IDC progression: tumor-size induced hypoxia and metabolic stress, tumor heterogeneity and spontaneous emergence of migratory phenotype in the same parent cells without any additional stimulus. A tangible advantage of the proposed organoid models is the ability to precisely and reproducibly study how the hypoxic microenvironment induces tumor migration in real time and in isolation from non-tumor cells present in vivo, providing unique opportunity to define tumor-intrinsic mechanisms of DCIS to IDC progression. Our preliminary observations lead to central hypothesis that tumor size-induced hypoxia establishes a “hypoxic secretome”, which initiates the migratory phenotype; the hypoxic secretome then cooperate with intracellular signaling networks to independently maintain cell migration. We propose three independent but inter-related aims to link hypoxic secretome with the initiation, maintenance and spatial distribution of migratory phenotypes. Aim 1 will engineer size-controlled DCIS organoids (150-600 µm) with controlled hypoxic microenvironments to identify and examine how hypoxic secretome initiates migratory phenotype. We will combine experimental organoid models with time-lapse imaging and computational approaches to study organoid migration. Aim 2 will demonstrate that migratory cells can re-establish the secretome and maintain migratory phenotype independent of hypoxia. We will reconstruct an intracellular signaling network activated by the hypoxic secretome using microarray data. We will verify these gene expression signatures in sorted migratory and non-migratory cells, and validate them using secretome inhibition studies. Aim 3 will investigate, for the first time, the spatial distribution and origin of the migratory phenotype. We will use CRISPR-based gene knock-in (FP-labeling), automated image analyses, and a deep-learning algorithm to track and visualize the emergence of migratory phenotypes from the hypoxic core outward to the periphery or from the migratory front. The successful development of this 3D organoid model and completion of the proposed work will provide answers to two fundamental questions in the progression of invasive breast cancer: 1) What causes some DCIS cells to become migratory and develop into invasive tumors? 2) How and where does the migratory phenotype (IDC) emerge? The mechanistic understanding gained from these studies will improve diagnosis, lead to the development of treatment strategies to arrest invasion at the pre-malignant stage, and thus prevent patient overtreatment. It is straightforward to generalize our system to other tumor types, development of tumor/stromal co-culture, and drug screening.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2018 | June 26, 2018
PI: Eric Lagasse
Title: A New Molecular Mechanism to Bioengineering a Liver
Description: Hepatocyte transplantation has many potential applications. Extensive animal experiments have shown that hepatocytes transplanted in the liver or at ectopic sites survive, function, and actively participate in the regenerative process. However, our understanding of hepatocyte engraftment and their remarkable proliferative and regenerative potential is limited, even if primary hepatocyte transplantation is at the doorstep of applications in the treatment of inherited and acquired human diseases. We previously made a serendipitous observation that normal hepatocytes transplanted in the peritoneal cavity of an animal with lethal liver disease migrate into the lymphatic system and engineer ectopic liver-like organoids that rescue an animal model from a fatal metabolic disorder. How hepatocytes enter the lymphatics and what molecular mechanism is responsible for the generation of ectopic mass is not known. We hypothesized that hepatocytes must borrow some of the molecular mechanism lymphocytes use to migrate into the lymphatics. Our interest will be to study ectopic cell transplantation and our central objective of our application is to translate a highly interesting observation, the generation of ectopic liver, to a potential clinical application for patients with liver diseases.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2018 | May 24, 2018
PI: Dietrich Stephan
Title: LifeX
Description: The facility at 2124 Penn Ave. in Pittsburgh’s Strip District includes office and laboratory space where biotechnology companies can collaborate. In addition to the physical space, the LifeX platform brings together experts with proven track records of building new pharmaceuticals, medical devices, molecular diagnostics and population-health solutions to support entrepreneurs with deep industry knowledge. LifeX’s initial cohort of companies will focus on unmet health needs related to cancer, Alzheimer’s disease, multidrug-resistant bacterial infections, obesity and diabetes and rare genetic diseases.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2018 | April 27, 2018
PI: Lee Fisher and Douglas J Weber
Title: Spinal root stimulation for restoration of function in lower-limb amputees
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2018 | March 28, 2018
PI: David Brienza
Title: Rehabilitation Engineering Research Center
Description: Researchers plan to spend the first few years of the grant improving or adding to existing standards, particularly related to cushion load-bearing performance, cushion durability, caster durability, and wheel rolling resistance, and the remaining few years applying those standards to different products. Ultimately, the researchers envision their work being used in several ways, including helping funding sources make reimbursement decisions, and clinicians, providers, and users make product decisions.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2018 | February 27, 2018
PI: Jonathan Vande Geest
Title: Preclinical assessment of a compliance matched biopolymer vascular graft
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2018 | January 25, 2018
PI: Mike Schneider, DC, PhD
Co-PI: Anthony Delitto, PhD
Description: The researchers will compare spinal manipulation and supported self-management to usual medical care, which includes prescription medications for the care of acute lower back pain in adult patients at increased risk of becoming chronic.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2017 | December 15, 2017
PI: Warren C. Ruder
Title: Creating Smart Biomaterials using Engineered Bacteria that Cooperatively Reprogram Mammalian Cells
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2017 | November 29, 2017
PI: Bryan Tillman
Co-I: Young Jae Chun
Title: An Organ Perfusion Stent as an Alternative to Surgery in Donor Organ Recovery
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2017 | October 30, 2017
PI: Lance Davidson
Title: Biomechanics of Morphogenesis
Description: Physical mechanical processes are central to the morphogenesis of embryos and their organs. The goal of this proposal is to apply a multi-scale analysis of the mechanics of convergent extension, identifying biomechanical mechanisms that establish passive tissue properties such as stiffness as well as active processes that generate forces of extension, regulate cell behaviors and tissue deformation, and how passive mechanics and active force generating processes are coordinated within the frog embryo. Studies outlined in this proposal will answer: (1) How are cell-scale structures and tissue mechanics are integrated during elongation? Early development is marked by dramatic changes in the mechanical properties of embryos. To understand how and why these properties change we test simple models of tissue mechanics based on synthetic closed-cell foams using bioengineering and biophysical methods to disrupt features from large scale architecture to the subcellular actomyosin-dependent cortex. (2) What single-cell mechanical processes contribute to convergent extension? We extend our analysis of cell behaviors to an unbiased approach that combines wide-field confocal microscopy with descriptive biomechanical analyses from the level of the cell, to the local neighborhood, to the strain fields of the entire embryo. Combining analyses of neural plate and paraxial somitic mesoderm we describe the dependence of these movements on planar polarity signaling. Using systems approaches we seek to test the dependencies of specific cell behaviors on both upstream signaling systems and their targeted downstream effectors. (3) How are tissue polarity cues transduced into polarized cell behaviors? We hypothesize that polarized cell behaviors and the oriented forces they generate are the result of cues produced by anisotropic strain. To test the roles of polarized intracellular factors and mechanical strain in organizing cell behaviors we use magnetogenetics and micro-scale tissue stretchers. Results from this project will complement ongoing efforts to identify the molecular regulators of morphogenesis by providing a conceptual framework developing new hypotheses of morphogenesis and bioengineering tools to test them. The significance of our work provides researchers a more complete understanding of the contribution of cell- and tissue-mechanics to development, to understand the role of tissue mechanics in oncogenesis, and to provide fundamental physical principles for future functional tissue engineers.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2017 | September 29, 2017
PI: Rocky Tuan
Title: Tissue Chip Modeling of Synovial Joint Pathologies: Effects of Inflammation and Adipose-Mediated Diabetic Complications
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2017 | August 30, 2017
PI: Julie Phillippi
Co-PI: Thomas Gleason, Marie Billaud, Vera Donnenberg, Stephen Badylak
Title: Matrix mediated vasa vasorum dysfunction in thoracic aortic disease
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2017 | July 31, 2017
PI: Christopher Hughes, MD
Co-PI: Paulo Fontes, MD
Title: Whole Organ Sonothrombolysis
Description: This technology is a new ex-vivo application for sonothrombolysis (SNT), which combines the use of ultrasound (US) probes and microbubbles timely infused through the arterial port of liver allografts being preserved by a machine perfusion (MP) system. The US probe pulses induces microbubble oscillation and bursting in a process called cavitation. This ex-vivo technology is intended to remove red blood cells (RBCs) plugs and cellular debris from the hepatic arterial peri-biliary plexus (PBP) prior to liver allograft implantation from organs obtained from donors after cardiac death (“DCD”) These patients experience extended periods of hypoperfusion under anoxic conditions prior to organ recovery. The use of DCD livers poses a significant risk for the subsequent development of ischemic cholangiopathy (IC) by the recipient in the post-operative period. IC is an irreversible complication stemming from prolonged ischemia to the PBP leading into recurrent biliary sepsis and subsequent liver allograft failure. This lethal condition requires mandatory retransplantation while yielding prolonged hospital stays and excessive post-operative costs. Previous attempts to prevent IC after DCD liver transplantation using different technologies have failed. IC is caused by progressive clotting of the small blood vessels supplying the PBP, which prevents blood and oxygen from reaching the biliary tree effectively once the liver is transplanted. The ex-vivo SNT technology was designed to remove the clots ex-vivo while enhancing the oxygenation of the bile duct system before the liver is transplanted. It can be used with all current MP systems currently being evaluated for liver preservation.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2017 | July 6, 2017
PI: Stephen Badylak
Title: 3D Bioprinted Human Trachea for Pediatric Patients
Description: The overall goal of this project is the development and preclinical testing of a tissue engineered trachea for use in pediatric patients. The natural growth of pediatric patients requires that an engineered tissue or organ vital to life must “grow” with the patient. The present project will design, develop, and test in preclinical models, a bioengineered trachea consisting of naturally occurring extracellular matrix (ECM), as a scaffold, that is custom manufactured by 3D printing (Feinberg Laboratory, Carnegie Mellon University). The combined expertise of the Badylak Laboratory, which will acquire and prepare the matrix materials, with the Feinberg Laboratory that has expertise in 3D printing, will produce engineered tracheas that will be tested in a rapidly growing porcine model at the McGowan Institute for Regenerative Medicine. The project is milestone driven and consists of two years of development followed by three years of testing.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2017 | May 24, 2017
PI: Anna Balazs
Title: Adaptive Self‐Assembled Systems: Exploiting Multifunctionality for Bottom‐up Large Scale Engineering
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2017 | April 26, 2017
PI: Bryan Brown
Title: Assessing the Impacts of Aging upon the Macropahge Response to Implantable Materials
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2017 | March 29, 2017
PI: David H. Kohn, William V. Giannobile, David J. Mooney, Charles Sfeir, and William R. Wagner
Title: Michigan-Pittsburgh-Wyss Resource Center: Supporting Regenerative Medicine in Dental, Oral and Craniofacial Technologies
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2017 | February 28, 2017
PI: Bryan Brown
Co-I: Pamela Moalli and Stephen Badylak
Title: Assessing the Impact of Macrophage Polarization Upon the Success of Biomaterial Implants
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2017 | January 30, 2017
PI: William Federspiel, William Wagner, Peter Wearden
Title: Ambulatory Assist Lung for Children
Description: Acute and chronic lung diseases remain the most life threatening causes of death and hospitalization in the pediatric population. Cystic fibrosis (CF), pulmonary hypertension and pulmonary fibrosis have been observed to be the most frequent causes of lung failure in pediatric patients. Mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) have been used to bridge sick kids to transplant. These procedures can lead to poor post-transplant outcomes by their very restrictive nature on mobility. This project will develop a compact respiratory assist device for pediatric patients, the Pittsburgh Pediatric Ambulatory Lung (P-PAL) to replace ECMO as a bridge to transplant or recovery in kids with acute and chronic lung failure. The P-PAL is a wearable and fully integrated blood pump and gas exchange module that will be designed for implantation of inflow cannula and outflow cannula/grafts in the right atrium and pulmonary artery, respectively. The P-PAL will be designed for longer-term respiratory support (1-3 months before cartridge change-out) at 70-90% of normal metabolic oxygenation requirements, while pumping blood from 1 to 2.5 Liters/min. The specific aims of project are 1) To modify the design and operational parameters of the P-PAL to meet requirements for blood pumping, gas exchange, priming volume, and form factor, 2) To build P-PAL prototypes along the design development pathway for bench characterization studies of pumping performance, gas exchange, and hemolysis, 3) To improve the hemocompatibility of the P-PAL by exploiting novel polymeric zwitterionic coatings that we have already begun to develop for our adult wearable assist lung, and 4) To perform acute and chronic studies in healthy lambs to demonstrate the in-vivo performance and hemocompatibility of the PAAL device and to study its interaction with the cardiopulmonary system.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2016 | December 16, 2016
PI: Jennifer Collinger and Michael Boninger
Title: Neural Control of Dexterous Manipulation and Translation to a Portable System
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2016 | November 28, 2016
PI: Anne Robertson
Title: Improving cerebral aneurysm risk assessment through understanding wall vulnerability and failure modes
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2016 | October 28, 2016
PI: Andrew Schwartz
Title: Enhanced Neural Prosthetics Using Shared-Mode Control
Description: This project builds on the world’s most advanced program in brain-controlled robotic arms and hands for paralyzed individuals. A group of Pittsburgh scientists and engineers will enhance the performance of neural prosthetics, allowing a paralyzed person to manipulate an object. A prosthetic limb will operate under an individual’s brain control, with a boost from an artificial intelligence component designed to predict what the individual intends to do. This shared-mode control will enable people who have quadriplegia to dexterously handle objects with a robotic arm and hand, and thus increase their independence in daily life.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2016 | September 28, 2016
PI: Timothy Corcoran and Robert Parker
Title: Building Multilevel Models of Therapeutic Response in the Lungs
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2016 | August 30, 2016
PI: Amanda Gillespie
Co-I: Jackie L. Gartner-Schmidt, Clark Rosen, Jonathan Yabes
Title: Efficacy of Conversation Training Therapy
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2016 | July 25, 2016
PI: Robert Parker and Gilles Clermont
Title: Endotypes of thrombocytopenia in the critically ill
Description: Thrombocytopenia is extremely frequent in critically ill patients. However, the role of acute platelet responses in critically ill patients is not well studied, and the multifactorial etiology of thrombocytopenia in the ICU makes it difficult to understand, or understand whether or not to treat it. In several situations such as traumatic injury or sepsis, very low platelet counts have been to bleeding, thrombosis and end-organ injury. Platelets have been extensively studied as a key component of hemostasis, but a rapidly emerging concept is that platelets are also key effector cells in systemic inflammatory processes as both instigators of local and systemic inflammatory reactions and also participants in the inflammation that contributes to tissue injury. The link between platelets and inflammation is complex and bidirectional, as inflammatory ligands have been shown to regulate platelet function and activated platelets induce inflammatory responses in other cell types. The overarching theme of this proposal is to study platelet dynamics in critically ill patients, construct clinical endotypes of thrombocytopenia in this population, and to relate these endotypes to underlying mesoscale mechanisms through computational modeling. We will use a large electronic health record-based database and a tri-state trauma database as source data to construct these endotypes. We define endotype as clinical patterns defined along four dimensions: (1) baseline information (demographic, chronic disease burden, severity of illness and admitting diagnosis), (2) features of the platelet count time series (rate of decrease, nadir, etc.), (3) concurrent interventions, and (4) outcome. The computational approach will attempt to root clinical endotypes in mechanistic interpretations (or collections of alternative interpretations), contributing to focus basic science investiagtions, and to close key knowledge gaps preventing the design and use of targeted anti-platelet-inflammatory therapies in the critically ill. Computational models will be developed at different levels of complexity, with a specific attention to tie underlying mechanisms to functional assays routinely performed in thrombocytopenic patients, such as prothrombin time, activated coagulation time, and thromboelastogram.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2016 | June 27, 2016
PI: Rocky S. Tuan
Co-I: Peter Alexander and Riccardo Gottardi
Title: A Microphysiological 3D Organotypic Culture System for Studying Degradation and Repair of Composite Skeletal Tissues in a Microgravity Environment
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2016 | May 23, 2016
PI: Fabrisia Ambrosio, Bennett Van Houten
Co-I: Aaron Barchowsky, Mauricio Rojas, Donna Stolz
Title: The Anti-Aging Effect of Klotho on Skeletal Muscle Regeneration
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2016 | May 3, 2016
PI: J. Peter Rubin, MD
Titles: PUMP
Description: PUMP is a solution aimed at reducing hospital-acquired pressure ulcers, affecting an estimated 3 million patients annually. The monitoring and alert solutions, using wearable devices and hospital bed sensors, will provide real-time documentation of patient repositioning and a process to improve compliance with these preventative measures.