Bone repair is a highly coordinated process that involves numerous cell types, growth factors and extracellular matrix (ECM) components. Osteoblasts recruited to the fracture site from surrounding tissues have a central role in new bone formation. They are responsible for the synthesis and deposition of a collagen-rich ECM that is subsequently mineralised. The early recruitment of inflammatory cells is critical for normal bone healing. These cells release peroxidase enzymes, whose functional involvement in bone repair has mainly been studied in the context of providing oxidative defence against invading microorganisms. Our laboratory has recently made a new discovery showing the ability of peroxidases to directly stimulate collagen biosynthesis and generate a mineralised ECM in-vitro. Therefore, the objective of this study was to assess the potential of peroxidases to promote bone repair in-vivo using a calvarial critical size defect (CSD) mouse model. To assess the ability of peroxidases to promote bone regeneration, a 3mm defect was created on the right parietal bone of mice (n=14). The defect was filled with a biodegradable scaffold loaded with peroxidases or saline. Live microCT imaging was used to monitor bone regeneration over time. We showed that scaffolds pre-loaded with peroxidases significantly inhibited bone regeneration within the defect site, compared to the vehicle treated scaffolds after 8 weeks. We concluded that the CSD model, which heals by intramembranous ossification, is not a suitable model for testing the bone regenerative potential of peroxidases. A recent pilot study was conducted on sheep using a fracture repair model, which heals via endochondral ossification in the presence of an inflammatory response. Considering their role in inflammation, we hypothesise that peroxidases will promote bone regeneration in a fracture repair model. Further studies will be conducted to validate the fracture repair model to confirm the therapeutic potential of peroxidases in bone repair.