BME PhD Proposal Seminar: Jason Inzana
Design of 3D Printed Antibiotic Bone Graft Substitutes for Treatment of Implant-Associated Osteomyelitis in a Segmental Bone Defect
Supervised by Dr. Hani Awad
Implant-associated bacterial infection of bone (osteomyelitis; OM) is extremely difficult to treat. One hundred thousand fracture fixation cases become infected annually in the U.S. and cost an average of $15,000 per incident. Treating chronic OM requires extensive debridement to remove infected bone, implant exchange, and often placement of an antibiotic-laden poly-methyl methacrylate (PMMA) block or beads to deliver high, local doses of antibiotics. However, PMMA cements are poor materials for drug delivery considering that their non-degradability and low porosity inhibit antibiotic diffusion. Impaired bone healing and reinfection still occur in 10-20% of treated cases, so there is a critical need for improved treatments of chronic, implant-associated OM. I propose to develop an antibiotic-loaded, calcium phosphate cement-collagen (Ab-CPC-Col) composite for treatment of implant-associated OM with segmental bone loss. 3D printing is an additive manufacturing process where objects are built layer-by-layer using a powder substrate and a binding solution that is delivered from non-contact inkjets. Employing 3D printing as the fabrication technique will enable precise and reproducible control of antibiotic deposition, patient-specific geometries, and good material porosity for cellular and vascular invasion during bone healing.
Further, the Ab-CPC-Col composite is fully biodegradable, which will allow complete antibiotic release and eliminate the need for an explant surgery. These antimicrobial, bone-mimetic scaffolds will be designed through three specific aims:
- Demonstrate the feasibility of 3D printing dual-antibiotic, collagen-embedded calcium phosphate cements that are biocompatible, antimicrobial, and osteoconductive.
- Optimize the antibiotic dose, cement binder composition, and collagen density through in vitro evaluation of antibiotic release and scaffold mechanical properties.
- Evaluate the effects of antibiotic dose and collagen on infection management and bone healing in a novel murine model of implant-associated OM with a critical size bone defect.
These Ab-CPC-Col scaffolds are expected to reliably treat implant-associated OM and improve subsequent bone healing through efficacious local delivery of antibiotics from a bone-mimetic, osteoconductive scaffold.