A nanotopography-based strategy to precisely manipulate the osteoimmune environment for bone regeneration.

A barrier membrane is a major component of guided bone regeneration (GBR), which is traditionally viewed as a physical barrier. Due to its “foreign body” nature, the implantation of a barrier membrane would inevitably modulate immune response and subsequently affect bone dynamics, which has long been neglected. To bridge this knowledge gap, we investigated the osteoimmunomodulatory effects of barrier collagen membranes. It is found that barrier collagen membranes elicit significant effects on modulating the osteoimmune response of macrophages, by upregulating the expression of pro-inflammatory cytokines (TNFα, IL-1β, IL-6, and IL-18) and osteogenic factors (BMP2/6, WNT10b, OSM). The modulated-osteoimmune environment was beneficial for the osteogenic differentiation of BMSCs, due to the activation of BMP, canonical WNT/β-catenin, and OSM signalling pathways. The membrane-mediated osteoimmunomodulation was further modulated to show whether osteogenesis could be enhanced via manipulating the membrane-mediated osteoimmunomodulation. The membrane-mediated osteoimmune response was successfully tuned through coating the collagen membranes with nanometer-sized bioactive glass Ca₂ZnSi₂O₇ by pulsed laser deposition, which is indicated from the change in the expression profile of inflammatory cytokines and the upregulated expression of osteogenic factors. The modulated osteoimmune environment enhanced the osteogenic differentiation of BMSCs, suggesting that collagen membranes with nanometer-sized Ca₂ZnSi₂O₇ coating can be promising for GBR applications. These results collectively imply that barrier membranes are bioactive barriers with an osteoimmunomodulatory effect and not just physical barriers. New generation barrier membranes should be designed with a favourable osteoimmunomodulatory property.

The paradoxical effect of cobalt on biological processes has aroused controversy regarding the application of cobalt-based biomaterials in bone regeneration. Tuning the dose range of cobalt ions may be a valid strategy to resolve the controversies about cobalt use for orthopedic applications. Recent progress in bone biology has highlighted the effects of multisystem cooperation (especially of osteoimmune, skeletal, and vascular systems) on bone dynamics. Before the application of this dose-tuning strategy, a deeper understanding of its dose-dependent effect on the cooperation of osteoimmune, skeletal, and vascular systems is needed. However, due to the difficulties with investigating the interaction of multiple systems in vitro, the multimodal effects of cobalt on bone homeostasis were investigated here, in an in vivo scenario.