In response to: PAR-04-023, we are proposing a Bioengineering Research Partnership to design and test an extracorporeal device for the treatment of severe sepsis, based on the principle of hemoadsorption. Our multidisciplinary team comprises basic science and clinical researchers, bioengineering and biomaterials experts, and experts in complex systems modeling. Our proposal will carefully integrate this diverse group of researchers from both technical and biomedical fields, crossing the boundaries of multiple scientific disciplines and leveraging the capabilities of both industry and academia. Our project is entitled Systems Engineering of a Pheresis Intervention for Sepsis (SEPsIS). Severe sepsis (acute onset organ failure in the setting of infection) is a major health problem that kills nearly 250,000 Americans each year and costs billions of dollars. Available therapies for sepsis, including those recently approved, are suboptimal and new therapies are urgently needed. However, the complexities of the inflammatory response network and the high cost of clinical trials, particularly in the critically ill, renders the traditional drug/device development paradigm obsolete. We have previously developed and tested an extracorporeal blood purification device for treatment in chronic renal disease and have adapted this device for the treatment of acute inflammatory diseases. We have also developed and partially calibrated-in both rodents and humans-a mathematical model of sepsis. This project proposes to integrate these two achievements and, through an iterative design process, develop a device that can be used to treat severe sepsis. The goal of this proposal is to design an extracorporeal blood purification device for the treatment of severe sepsis. This proposal will bring together investigators from the following departments at the University of Pittsburgh: Bioengineering, Chemical Engineering, Critical Care Medicine, Surgery, Medicine, and Mathematics. We will also call on the expertise of two companies, one specializing in adsorbent polymer technology (MedaSorb Technologies, LLC) and the other in complex systems modeling (Immunetrics, Inc.).

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL080926-01
Application #
6942868
Study Section
Special Emphasis Panel (ZRG1-SBIB-G (50))
Program Officer
Mitchell, Phyllis
Project Start
2005-09-28
Project End
2010-08-31
Budget Start
2005-09-28
Budget End
2006-08-31
Support Year
1
Fiscal Year
2005
Total Cost
$1,218,030
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Singbartl, Kai; Miller, Lauren; Ruiz-Velasco, Victor et al. (2016) Reversal of Acute Kidney Injury-Induced Neutrophil Dysfunction: A Critical Role for Resistin. Crit Care Med 44:e492-501
Namas, Rami A; Mi, Qi; Namas, Rajaie et al. (2015) Insights into the Role of Chemokines, Damage-Associated Molecular Patterns, and Lymphocyte-Derived Mediators from Computational Models of Trauma-Induced Inflammation. Antioxid Redox Signal 23:1370-87
Morrell, Eric D; Kellum, John A; Hallows, Kenneth R et al. (2014) Epithelial transport during septic acute kidney injury. Nephrol Dial Transplant 29:1312-9
Azhar, Nabil; Vodovotz, Yoram (2014) Innate immunity in disease: insights from mathematical modeling and analysis. Adv Exp Med Biol 844:227-43
Morrell, Eric D; Kellum, John A; Pastor-Soler, Núria M et al. (2014) Septic acute kidney injury: molecular mechanisms and the importance of stratification and targeting therapy. Crit Care 18:501
Peng, Zhi-Yong; Bishop, Jeffery V; Wen, Xiao-Yan et al. (2014) Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model. Crit Care 18:R141
Aerts, Jean-Marie; Haddad, Wassim M; An, Gary et al. (2014) From data patterns to mechanistic models in acute critical illness. J Crit Care 29:604-10
Rimmelé, Thomas; Kaynar, Ata Murat; McLaughlin, Joseph N et al. (2013) Leukocyte capture and modulation of cell-mediated immunity during human sepsis: an ex vivo study. Crit Care 17:R59
Peng, Zhi-Yong; Zhou, Feihu; Wang, Hong-Zhi et al. (2013) The anti-oxidant effects are not the main mechanism for glutamine's protective effects on acute kidney injury in mice. Eur J Pharmacol 705:11-9
Peng, Zhi-Yong; Zhang, Jicheng; Rimmelé, Thomas et al. (2013) Development of venovenous extracorporeal blood purification circuits in rodents for sepsis. J Surg Res 185:790-6

Showing the most recent 10 out of 53 publications