The long-term goal of Carmell Therapeutics for this proposal is to develop a blood plasma-based biomaterial bone filler product that will elute antimicrobials to inhibit infection. Bacterial contamination is present perioperatively in 48-68% o all open wounds and 100% of severe open injuries. Per year in the U.S. ~ 123,000 open tibia fractures are contaminated, requiring an added patient treatment cost of $29,000. Additional indirect costs (Worker's Compensation, lost wages, productivity, etc.) are enormous but harder to quantify. Current standard of care involves systemic antibiotics, early debridement, and the off-label, prophylactic use of local antibiotic delivery via impregnated poly(methyl methacrylate) (PMMA) beads, which have unknown release kinetics and must be removed from the defect prior to bone reduction procedures. Clinicians need a product that enhances bone repair as well as controls infection through local antibiotic delivery. Carmell believes that combining antimicrobial delivery with its blood plasma-based biomaterials (PBMs) (which elute regenerative factors as they degrade) have the potential to meet this need. The Phase I hypothesis is that the product, the REPAIR Plus" Bone Putty, can locally deliver antimicrobials to control infection. To test the hypothesis antimicrobials will be incorporated into PBMs and their release and activity will be verified using disk diffusion-based in vitro assays. The products biological activity and biocompatibility will then be established in vitro using a metabolic assay and electron microscopy. The product's antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus and their biofilms will be demonstrated in vitro using 3D fluorescence staining and cell culture techniques. Finally, clearance of S. aureus infection in vivo in a pilot feasibility study using a rat tibia model will be established, where bacteria added to a bone defect will be challenged with the product to determine the product's ability to clear the bacteria over 14 days. Following the demonstration of feasibility in Phase I, Phase II will build on the infection control data to examine enhanced bone repair (with infection control) in vivo as well as conduct regulatory-focused studies to demonstrate biocompatibility and safety, all to prepare for a first-in-man clinical study. Carmell will additionally recruit an antibiotic supplier as a partner for supply and regulatory documentation as well as for potential licensing opportunities. Overall, an effective, off-the-shelf, and easy to use product that could improve patient outcome and reduce treatment complications as well as costs will have enormous marketing potential for the treatment of open tibia fractures and other open bone fracture applications.
Bacterial infection is a major clinical concern, particularly in bone fractures where such infections can lead to non-unions, additional surgeries, and protracted antibiotic treatments, all at high cost. Ideally, a clinical product could locally contrl infection and at the same time augment the healing of fractures, but currently no such product is available for clinical use. Carmell has developed plasma-based biomaterials made from human blood plasma that have the potential to be safe, cost-effective, and ready-to-use products that accelerate bone healing and additionally elute antimicrobials that inhibit local infection.