Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus.
Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus.
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DOI：
10.1021/acsami.7b18458
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发表时间：
2018-01-24
影响因子：
9.5
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Hu Z;Ma C;Rong X;Zou S;Liu X
糖尿病（DM）影响着全世界数亿人的骨修复和再生过程。作为一种慢性炎症性疾病，DM在缺陷部位产生促炎微环境。然而，大多数关于DM相关骨再生的研究忽视了DM条件下免疫调节的重要性，并采用与正常骨愈合相同的方法，导致骨愈合有限。在这项研究中，我们开发了一种独特的生物启发可注射微球作为骨免疫调节生物材料，调节巨噬细胞在DM条件下创造一个促进愈合的微环境。该微球与肝素修饰的明胶纳米纤维自组装，并将白细胞介素4（IL 4）掺入纳米纤维肝素修饰的明胶微球（NHG-MS）。IL 4具有与肝素的结合结构域，并且IL 4与肝素的结合稳定该细胞因子，保护其免于变性和降解，并且随后抑制其持续释放以调节巨噬细胞极化。负载IL 4的NHG-MS将促炎性M1巨噬细胞转化为促愈合的M2表型，将M2/M1比率恢复到正常水平，有效地解决炎症，并最终增强成骨细胞分化和骨再生。因此，开发利用巨噬细胞的免疫调节能力的骨免疫调节生物材料是一种新的和有前途的策略，以增强糖尿病条件下的骨再生。
Bone repair and regeneration process is markedly impaired in diabetes mellitus (DM) that affects hundreds of millions of people worldwide. As a chronic inflammatory disease, DM creates a proinflammatory microenvironment in defective sites. Most of the studies on DM-associated bone regeneration, however, neglect the importance of immunomodulation under the DM condition and adopt the same approaches to normal bone healing, leading to limited bone healing. In this study, we developed a unique bioinspired injectable microsphere as an osteoimmunomodulatory biomaterial that modulates macrophages to create a prohealing microenvironment under the DM condition. The microsphere was self-assembled with heparin-modified gelatin nanofibers, and interleukin 4 (IL4) was incorporated into the nanofibrous heparin-modified gelatin microsphere (NHG-MS). IL4 has binding domains with heparin, and the binding of IL4 to heparin stabilizes this cytokine, protects it from denaturation and degradation, and subsequently prolongs its sustained release to modulate macrophage polarization. The IL4-loaded NHG-MS switched the proinflammatory M1 macrophage into a prohealing M2 phenotype, recovered the M2/M1 ratio to a normal level, efficiently resolved the inflammation, and ultimately enhanced osteoblastic differentiation and bone regeneration. The development of osteoimmunomodulatory biomaterials that harness the power of macrophages for immunomodulation, therefore, is a novel and promising strategy to enhance bone regeneration under DM condition.
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影响因子：
12.7
作者：
Rubin MR;Patsch JM
通讯作者：
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影响因子：
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作者：
Guariguata, L.;Whiting, D. R.;Shaw, J. E.
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通讯作者：
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影响因子：
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作者：
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