UNLABELLED: Traditionally, the orthopaedic trauma literature has been dominated by small studies that were largely single-center initiatives. More recently, there has been a paradigm shift toward larger, multicenter studies because the orthopaedic community embraced the concepts of evidence-based medicine and the need for high-quality research to guide clinical practice. The International Orthopaedic Multicenter Study in Fracture Care is a large multicenter international cohort study in musculoskeletal trauma in Africa, Asia, and Latin America. This is the first study of this magnitude within the global orthopaedic trauma community. The International Orthopaedic Multicenter Study in Fracture Care study has provided an opportunity to form new international collaborative relationships and to develop new research capacity and global collaborative relationships that will provide the foundation for future studies in injury prevention and management. LEVELS OF EVIDENCE: IV.

Beta-2 microglobulin (B2M) is an immune system protein that is found on the surface of all nucleated human cells. B2M is naturally shed from cell surfaces into the plasma, followed by renal excretion. In patients with impaired renal function, B2M will accumulate in organs and tissues leading to significantly reduced life expectancy and quality of life. While current hemodialysis methods have been successful in managing electrolyte as well as small and large molecule disturbances arising in chronic renal failure, they have shown only modest success in managing plasma levels of B2M and similar sized proteins, while sparing important proteins such as albumin. We describe a systematic protein design effort aimed at adding the ability to selectively remove specific, undesired waste proteins such as B2M from the plasma of chronic renal failure patients. A novel nanoparticle built using a tetrahedral protein assembly as a scaffold that presents 12 copies of a B2M-binding nanobody is described. The designed nanoparticle binds specifically to B2M through protein-protein interactions with nanomolar binding affinity (~4.2 nM). Notably, binding to the nanoparticle increases the effective size of B2M by over 50-fold, offering a potential selective avenue for separation based on size. We present data to support the potential utility of such a nanoparticle for removing B2M from plasma by either size-based filtration or by polyvalent binding to a stationary matrix under blood flow conditions. Such applications could address current shortcomings in the management of problematic mid-sized proteins in chronic renal failure patients.