Guided Bone Regeneration with a Nitric‐Oxide Releasing Polymer Inducing Angiogenesis and Osteogenesis in Critical‐Sized Bone Defects

Synthetic scaffolds, as bone grafts, provide a favorable environment for the repair and growth of new bone tissue at defect sites. However, the lack of angio- and osteo-induction limits the usefulness of artificial scaffolds for bone regeneration. Nitric oxide (NO) performs essential roles in healing processes, such as regulating inflammation and addressing incomplete revascularization. In this study, a polymer capable of controlled NO release is developed to promote the osteogenic capacity in artificial scaffolds. The biological efficiency of the NO compound is assessed by its effect on pre-osteoblasts and macrophages in vitro and the extent of vascularization and bone formation in the calvaria defect model in vivo. The compound does not inhibit cell adhesion or proliferation. NO treatment significantly increases both alkaline phosphatase activity and mineralization in pre-osteoblasts. Macrophages treated with NO secrete high levels of anti-inflammatory factors and adopt the pro-regenerative phenotype. In the critical-sized defect model, the collagen scaffold containing the NO compound enhances neovascularization and bone formation. The developed NO-releasing system promotes osteogenesis and regeneration of damaged bone tissue. As the multiple functions of NO involve macrophage modulation and angiogenesis, such release systems may be valuable for guiding bone regeneration in critical-sized defects.