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.
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.
| Lockhart, Jacob N; Spoonmore, Thomas J; McCurdy, Michael W et al. (2018) Poly(glycidol) Coating on Ultrahigh Molecular Weight Polyethylene for Reduced Biofilm Growth. ACS Appl Mater Interfaces 10:4050-4056 |
| Kwakwa, Kristin A; Vanderburgh, Joseph P; Guelcher, Scott A et al. (2017) Engineering 3D Models of Tumors and Bone to Understand Tumor-Induced Bone Disease and Improve Treatments. Curr Osteoporos Rep 15:247-254 |
| Hendrix, Andrew S; Spoonmore, Thomas J; Wilde, Aimee D et al. (2016) Repurposing the Nonsteroidal Anti-inflammatory Drug Diflunisal as an Osteoprotective, Antivirulence Therapy for Staphylococcus aureus Osteomyelitis. Antimicrob Agents Chemother 60:5322-30 |
| Harmata, Andrew J; Ma, Yun; Sanchez, Carlos J et al. (2015) D-amino acid inhibits biofilm but not new bone formation in an ovine model. Clin Orthop Relat Res 473:3951-61 |
