The treatment of open fractures often requires grafting in order for union to occur. Despite meticulous surgical care and antibiotic administration, small amounts of bacteria often survive within a biofilm in the bone defect. When the fracture is grafted, the avascular bone graft provides the residual bacteria with an ideal environment to thrive, which increases the likelihood of infection. Injectable, settable lysine-derived polyurethane composite bone grafts augmented with a biofilm dispersal agent can overcome both the biological challenges for healing and the microbiological challenges associated with infection. Release of a biofilm dispersal agent for an extended period of time is anticipated to protect the graft from bacterial colonization and subsequent infection. Recently, naturally occurring biofilm dispersal agents, such as D-amino acids, have been discovered that both prevent bacteria from forming a biofilm and also signal bacteria that are in a biofilm to disperse. Bacteria released from the biofilm revert to the antibiotic-susceptible planktonic phenotype, thereby potentiating the effects of systemic antibiotics. We hypothesize that injectable, settable biofilm-dispersive bone grafts will allow healing to occur in contaminated open fractures, thereby improving patient outcomes and reducing rates of complications, including infection and non-union.

Public Health Relevance

Currently available bone grafts for treatment of open fractures increase the likelihood of infection. Incorporating a biofilm dispersal agent that prevents bacteria from adhering to the graft is anticipated to improve the standard of care for treatment of open fractures and reduce complications such as infection and nonunion.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR064772-01A1
Application #
8695891
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Panagis, James S
Project Start
2014-04-01
Project End
2019-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
1
Fiscal Year
2014
Total Cost
$314,319
Indirect Cost
$86,932
Name
Vanderbilt University Medical Center
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212