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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Biomaterials and Biointerfaces Study Section (BMBI)
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Gondre-Lewis, Timothy A
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University of Washington
Biomedical Engineering
Schools of Engineering
United States
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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