Achieving bone fracture union after trauma represents a major challenge for the orthopedic surgeon. Fracture non-healing has a multifactorial etiology and there are many risk factors for non-fusion. Environmental factors such as wound contamination, infection, and open fractures can contribute to non-healing, as can patient specific factors such as poor vascular status and improper immunologic response to fracture. Nitric oxide (NO) is a small, neutral, hydrophobic, highly reactive free radical that can diffuse across local cell membranes and exert paracrine functions in the vascular wall. This molecule plays a role in many biologic pathways, and participates in wound healing through decontamination, mediating inflammation, angiogenesis, and tissue remodeling. Additionally, NO is thought to play a role in fighting wound infection by mitigating growth of both Gram negative and Gram positive pathogens. Herein, we discuss recent developments in NO delivery mechanisms and potential implications for patients with bone fractures. NO donors are functional groups that store and release NO, independent of the enzymatic actions of NOS. Donor molecules include organic nitrates/nitrites, metal-NO complexes, and low molecular weight NO donors such as NONOates. Numerous advancements have also been made in developing mechanisms for localized nanomaterial delivery of nitric oxide to bone. NO-releasing aerogels, sol- gel derived nanomaterials, dendrimers, NO-releasing micelles, and core cross linked star (CCS) polymers are all discussed as potential avenues of NO delivery to bone. As a further target for improved fracture healing, 3d bone scaffolds have been developed to include potential for nanoparticulated NO release. These advancements are discussed in detail, and their potential therapeutic advantages are explored. This review aims to provide valuable insight for translational researchers who wish to improve the armamentarium of the feature trauma surgeon through use of NO mediated augmentation of bone healing.

中文翻译：

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创伤骨科再生医学中的纳米材料一氧化氮递送

外伤后实现骨折愈合对骨科医生来说是一项重大挑战。骨折不愈合的病因是多方面的，不融合的危险因素很多。环境因素，如伤口污染、感染和开放性骨折，以及患者的特定因素，如血管状况不佳和对骨折的不当免疫反应，都可能导致不愈合。一氧化氮 (NO) 是一种小的、中性的、疏水的、高反应性的自由基，可以扩散穿过局部细胞膜并在血管壁中发挥旁分泌功能。该分子在许多生物途径中发挥作用，并通过去污、介导炎症、血管生成和组织重塑参与伤口愈合。此外，NO 被认为通过减缓革兰氏阴性和革兰氏阳性病原体的生长在抵抗伤口感染中发挥作用。在此，我们讨论了 NO 输送机制的最新进展以及对骨折患者的潜在影响。NO 供体是储存和释放 NO 的官能团，与 NOS 的酶促作用无关。供体分子包括有机硝酸盐/亚硝酸盐、金属-NO 复合物和低分子量 NO 供体，例如 NONOates。在开发将一氧化氮局部纳米材料输送到骨骼的机制方面也取得了许多进展。NO 释放气凝胶、溶胶-凝胶衍生的纳米材料、树枝状大分子、NO 释放胶束和核心交联星形 (CCS) 聚合物都被讨论为 NO 输送到骨骼的潜在途径。作为改善骨折愈合的进一步目标，已经开发出 3d 骨支架以包括纳米颗粒 NO 释放的潜力。详细讨论了这些进展，并探讨了它们的潜在治疗优势。本综述旨在为希望通过使用 NO 介导的骨愈合增强来改善特征创伤外科医生的医疗设备的转化研究人员提供有价值的见解。