Biomaterial-associated infections account for over one million nosocomial infections per year, and their prevention is a critical component to successful regenerative medicine strategies. Bacterial infection of biomaterial implants frequently results in complete removal of the implant despite aggressive antibiotic therapy. Staphylococcus aureus and Pseudomonas aeruginosa are the most clinically relevant gram positive and gram negative pathogens associated with medical device failure. Bacteriophages are bacteria-specific viruses that have the ability to infect and lyse host bacteria. We have recently engineered a poly (ethylene glycol) (PEG)-based hydrogel system for controlled delivery of therapeutic proteins that facilitates bone repair in a murine radial segmental defect model. Contamination of these hydrogels with bacteria leads to complete inhibition of bone healing, persistence of bacteria, and bone resorption. The objective of this project is to engineer PEG- based hydrogels that are infection resistant. The central hypothesis is that delivery of bacteriophage using a PEG-hydrogel will reduce infection in a mouse model for bone repair.
Aim 1 : Engineer hydrogels for controlled delivery of active bacteriophage to eliminate bacteria.
Aim 2 : Examine the ability of phage presenting hydrogels to reduce infection and improve bone repair.
Aim 3 : Characterize the in vivo inflammatory response to bacteriophage containing hydrogels. The proposed research is innovative because it focuses on developing biomaterials that resistant infection without the use of antibiotics, thereby reducing the development of antibiotic resistant bacteria while minimizing implanted device failure. As outcomes of this research, we will establish the feasibility of controlled bacteriophage release hydrogels to reduce infection and promote bone repair. This research will establish a strategy for infection-resistant biomaterials that is applicable to various biomedical devices.

Public Health Relevance

Biomaterials play an important role in assisting in the bone healing process. When these materials are infected with bacteria, they are no longer capable of aiding in the bone regenerative process and need to be surgically removed. We will engineer implants to be resistant to bacterial infection by incorporating bacteria specific viruses called bacteriophages.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30AR069472-03
Application #
9419167
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Washabaugh, Charles H
Project Start
2016-02-22
Project End
2020-02-21
Budget Start
2018-02-22
Budget End
2019-02-21
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Georgia Institute of Technology
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30318
Weaver, Jessica D; Headen, Devon M; Aquart, Jahizreal et al. (2017) Vasculogenic hydrogel enhances islet survival, engraftment, and function in leading extrahepatic sites. Sci Adv 3:e1700184