Institute for Clinical Dental Research, Department of Dentistry, Korea University Guro Hospital, Seoul, 08308, Republic of Korea.
Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang-si, 37673, Republic of Korea.
Macromol Biosci. 2022 Oct;22(10):e2200162. doi: 10.1002/mabi.202200162. Epub 2022 Aug 3.
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.
合成支架作为骨移植物，为缺损部位新骨组织的修复和生长提供了有利的环境。然而，缺乏血管生成和成骨诱导作用限制了人工支架在骨再生中的应用。一氧化氮（NO）在愈合过程中发挥着重要作用，如调节炎症和解决不完全再血管化。在这项研究中，开发了一种能够控制 NO 释放的聚合物，以促进人工支架的成骨能力。通过体外对成骨前体细胞和巨噬细胞的作用以及体内颅骨缺损模型中的血管生成和骨形成程度来评估 NO 化合物的生物学效率。该化合物不会抑制细胞黏附或增殖。NO 处理可显著增加成骨前体细胞的碱性磷酸酶活性和矿化。用 NO 处理的巨噬细胞分泌高水平的抗炎因子，并呈现出促进再生的表型。在临界尺寸缺陷模型中，含有 NO 化合物的胶原支架增强了新血管生成和骨形成。开发的 NO 释放系统可促进受损骨组织的成骨和再生。由于 NO 的多种功能涉及巨噬细胞调节和血管生成，因此这种释放系统可能对指导临界尺寸缺陷中的骨再生具有重要价值。
