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.
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.
|Maris, Nathan L; Shea, Dylan; Bleem, Alissa et al. (2017) Chemical and Physical Variability in Structural Isomers of an l/d ?-Sheet Peptide Designed To Inhibit Amyloidogenesis. Biochemistry :|
|Chen, Ruying; Ma, Hongyan; Zhang, Lei et al. (2017) Precision-porous templated scaffolds of varying pore size drive dendritic cell activation. Biotechnol Bioeng :|
|Hopping, Gene; Kellock, Jackson; Barnwal, Ravi Pratap et al. (2014) Designed ?-sheet peptides inhibit amyloid formation by targeting toxic oligomers. Elife 3:e01681|
|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|
|Galperin, Anna; Long, Thomas J; Garty, Shai et al. (2013) Synthesis and fabrication of a degradable poly(N-isopropyl acrylamide) scaffold for tissue engineering applications. J Biomed Mater Res A 101:775-86|
|Cheng, Connie; Convertine, Anthony J; Stayton, Patrick S et al. (2012) Multifunctional triblock copolymers for intracellular messenger RNA delivery. Biomaterials 33:6868-76|
|Manganiello, Matthew J; Cheng, Connie; Convertine, Anthony J et al. (2012) Diblock copolymers with tunable pH transitions for gene delivery. Biomaterials 33:2301-9|
Showing the most recent 10 out of 15 publications