OsteneTM is a soft moldable adhesive material that sticks well to bleeding bone surfaces. It was invented by researchers at USC and CHLA as a replacement for standard bone wax, a beeswax-based material that causes local inflammation and is known to increase the risk of infection after surgery. In contrast, Ostene is a combination of biocompatible water-soluble polymers which is absorbed completely within 2-3 days of implantation;it is non-inflammatory and also has an intrinsic anti-infective effect due to its ability to prevent bacterial adhesion to surfaces. This combination of properties makes Ostene an ideal material for delivery of antibiotics directly to the wound during any surgical procedure that involves the cutting of bone. The objective of this project is to develop a formulation of Ostene with Gentamicin which retains its hemostatic properties but also releases gentamicin during the immediate post-operative period to prevent infection of the bone (osteomyelitis) or the rest of the wound. This application describes the initial formulation development, in vitro validations, biocompatibility testing and in vivo animal pharmacokinetic studies. These pre-clinical studies will form the basis for a 510(k) / IND submission, to be followed by a clinical study in phase II, which will examine whether the interoperative use of Ostene+Gentamicin in cardiothoracic surgery can reduce the incidence of sternal wound infections (SWIs). SWIs are relatively common (6-9%), cause significant morbidity and mortality (1-2%) and have a high cost of treatment (average >$20,000 per case). By extension from previous studies, successful development and deployment of Ostene+Gentamicin could potentially reduce the incidence of SWIs by 50%, which would have a major impact on SWI related deaths, disability and treatment costs.
Sternal wound infections (SWIs) are a relatively common complication of cardiac surgery. In recent studies, the reported incidence of SWI after sternotomy was 6-9%, of which about two- thirds were classified as superficial, and one-third of (2-3% in total) as deep SWI or mediastinitis, which are associated with significant morbidity, often require prolonged inpatient treatment, and have a mortality rate between 10 and 20%. In the US, cost estimates for treatment of an SWI range from $20,000 to $40,000. These numbers are consistent with studies from other countries, e.g., $16,600 in the Netherlands, $18,500 (Sweden) and $23,250 (Australia). Assuming a current average treatment cost of one SWI in the US to be $25,000, with 646,000 cardiac operations per year and an SWI incidence of 5%, the total additional health care cost due to this one potentially preventable complication amounts to $800,000,000 annually. Local delivery of Gentamicin to the surgical site via a collagen sponge implant has been shown to reduce the incidence of SWI by about 50%. The product to be developed under this proposal Ostene+Gentamicin, is expected to be at least as effective for prevention of SWI as the collagen-based implant, but will also be considerably less expensive and much easier to use during surgery. Ostene is fully resorbed within 1-3 days, a more appropriate time frame for antibiotic prophylaxis compared to the collagen sponge, which remains at the site for 2-3 weeks. Ostene is increasingly used for hemostasis in cardiac surgery as a preferred alternative to bonewax or other hemostatic materials (e.g., Avitene). Thus, once developed, the Ostene+ Gentamicin combination would be not expected to meet any major barrier to acceptance.
