Nosocomial infections are the fourth leading cause of death in the U.S. with >2 million cases annually (or ~10% of American hospital patients). About 60% of these infections are associated with an implanted medical device causing >$4.5 billion medical costs in 1992 and ~80,000 deaths annually. It is estimated that over 5 million artificial or prosthetic parts are implanted per annum in the U.S. alone. Our goal, with NIH support, is to engineer biomaterials that will solicit a short- and long-term immune response to specific bacterial colonization. For short-term immediate defense, model biomaterials will release fusion protein complexes - artificial opsonins - designed to enhance the coupling of invading bacteria to monocyte/macrophage (MO);thus promoting phagocytosis. For long-term protection, the biomaterial will transfect antigen-presenting cells (specifically dendritic cells - DCs) to produce T- and B-cell memory and antibody expression, and potentially stimulate direct native killer T-cell responses.

Public Health Relevance

It is estimated that over 5 million artificial or prosthetic devices are implanted per annum in the U.S. alone. However, 70% of hospital-acquired infections are associated with implants or indwelling medical devices, with the case-to-fatality ratio between 5-50%. In this 5-yr NIH RO1 research grant, we will develop a novel class of biomaterials that promote healing while preventing bacterial colonization and subsequent infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI074661-05
Application #
8282948
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Gondre-Lewis, Timothy A
Project Start
2008-06-07
Project End
2014-04-30
Budget Start
2012-06-01
Budget End
2014-04-30
Support Year
5
Fiscal Year
2012
Total Cost
$512,806
Indirect Cost
$184,084
Name
University of Washington
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Yan, Lin; Zhang, Lei; Ma, Hongyan et al. (2014) A Single B-repeat of Staphylococcus epidermidis accumulation-associated protein induces protective immune responses in an experimental biomaterial-associated infection mouse model. Clin Vaccine Immunol 21:1206-14
Wilson, John T; Keller, Salka; Manganiello, Matthew J et al. (2013) pH-Responsive nanoparticle vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides. ACS Nano 7:3912-25
Park, Jaehyung; Wu, Cindy T; Bryers, James D (2013) Chemokine programming dendritic cell antigen response: part I - select chemokine programming of antigen uptake even after maturation. Immunology 139:72-87
Park, Jaehyung; Bryers, James D (2013) Chemokine programming dendritic cell antigen response: part II - programming antigen presentation to T lymphocytes by partially maintaining immature dendritic cell phenotype. Immunology 139:88-99
Manganiello, Matthew J; Cheng, Connie; Convertine, Anthony J et al. (2012) Diblock copolymers with tunable pH transitions for gene delivery. Biomaterials 33:2301-9
Katzenmeyer, Kristy N; Bryers, James D (2011) Multivalent artificial opsonin for the recognition and phagocytosis of Gram-positive bacteria by human phagocytes. Biomaterials 32:4042-51
Novak, Matthew T; Bryers, James D; Reichert, William M (2009) Biomimetic strategies based on viruses and bacteria for the development of immune evasive biomaterials. Biomaterials 30:1989-2005
Bryers, James D (2008) Medical biofilms. Biotechnol Bioeng 100:1-18