Synthetic Nanoparticle Antibodies as an Immunomodulatory Strategy for Musculoskeletal Trauma

Abstract

Approximately 6 million bone fractures are reported annually within the US, 10% of which may experience complications, such as nonunion (permanent failure to heal) or delayed healing. These complications often result in prolonged hospital visits and/or increased financial burden on the patients. To expedite bone healing, researchers have explored implanting biomaterial scaffolds for critical breaks, delivery of bone morphogenic proteins (BMPs), and improving vascularization of damaged regions. Recent studies, however, have shed light on the role of inflammatory cells in the bone repair process. Furthermore, studies have shown scenarios involving chronic inflammation, such as bone fractures, stimulate the proliferation and activation of myeloid-derived immunosuppressor cells (MDSCs). MDSCs are a heterogeneous population of immature myeloid cells that are categorized into two subsets: Ly6G(+) Ly6C(low) granulocytic (G-MDSC) and Ly6G(-) Ly6C(high) monocytic cells (M-MDSC). Differences between these two groups primarily lies in their respectively low/high production of nitric oxide (NO) and reactive oxidative species (ROS). Both subsets have been found to inhibit inflammatory cell activity during the bone repair process, indicating that these cells may be a potential target for immunomodulatory strategies. One such strategy, synthetic nanoparticle antibodies (SNAb), was previously developed in our lab to specifically deplete MDSCs while restoring effector cell activity. Here we explore the optimization of SNAb fabrication, and the effect of SNAbs on the presence of certain cell types in musculoskeletal tissue.