Selective patterning of netrin-1 as a novel guiding cue for anisotropic dendrogenesis in osteocytes

Although protein patterning approaches have found widespread applications in tuning surface characteristics of biomaterials, selective control of growth in cell body and dendrites utilizing such platforms remains difficult. The functional roles assumed by cell body and dendrites in a physiological milieu have extremely high specificity. In particular, osteocytes embedded inside the mineralized bone matrix are interconnected via dendritic cell processes characterized by an anisotropic arrangement of the lacunar-canalicular system, where the fluid-flow inside the canaliculi system regulates the mechanoresponsive functionalization of bone. Control of cellular networks connected by dendritic cell processes is, therefore, imperative for constructing artificially controlled bone-mimetic structures and as an extension, for gaining insights into the molecular mechanisms underlying dendrogenesis inside the mineralized bone matrix. Here, we report an innovative strategy to induce controlled elongation of cell body or dendritic process structures in selective directions by using the inkjet printing technique. Artificial runways employing netrin-1, inspired by neural architecture, were utilized to trigger controlled elongation in the osteocyte dendritic processes in desired directions. This is the first report, to the best of our knowledge, demonstrating that anisotropic dendrogenesis of osteocytes can be controlled with selective patterning of extracellular proteins, specifically via the axon guidance ligand netrin-1.