Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong, 999077, China.
Department of Materials Science and Engineering, Korea University, Seoul, 02841, Republic of Korea.
Nat Commun. 2019 Apr 12;10(1):1696. doi: 10.1038/s41467-019-09733-6.
Macrophages regulate host responses to implants through their dynamic adhesion, release, and activation. Herein, we employ bisphosphonate (BP)-coated gold nanoparticle template (BNP) to direct the swift and convertible formation of Mg-functional Mg-BP nanoparticle (NP) on the BP-AuNP surface via reversible Mg-BP coordination, thus producing (Mg-BP)-Au dimer (MgBNP). Ethylenediaminetetraacetic acid-based Mg chelation facilitates the dissolution of Mg-BP NP, thus enabling the reversion of the MgBNP to the BNP. This convertible nanoassembly incorporating cell-adhesive Mg moieties directs reversible attachment and detachment of macrophages by BP and EDTA, without physical scraping or trypsin that could damage cells. The swift formation of RGD ligand- and Mg-bifunctional RGD-Mg-BP NP that yields (RGD-Mg-BP)-Au dimer (RGDBNP) further stimulates the adhesion and pro-regenerative M2-type polarization of macrophages, both in vitro and in vivo, including rho-associated protein kinase. This swift and non-toxic dimer formation can include diverse bio-functional moieties to regulate host responses to implants.
巨噬细胞通过其动态黏附、释放和激活来调节宿主对植入物的反应。在此，我们采用双膦酸盐（BP）涂层金纳米粒子模板（BNP），通过可逆的 Mg-BP 配位，在 BP-AuNP 表面上快速且可转换地形成 Mg 功能化的 Mg-BP 纳米粒子（NP），从而生成（Mg-BP）-Au 二聚体（MgBNP）。基于乙二胺四乙酸（EDTA）的 Mg 螯合促进了 Mg-BP NP 的溶解，从而使 MgBNP 恢复为 BNP。这种包含细胞黏附性 Mg 部分的可转换纳米组装体通过 BP 和 EDTA 引导巨噬细胞的可逆附着和分离，而无需物理刮除或可能损伤细胞的胰蛋白酶。快速形成 RGD 配体和 Mg 双功能 RGD-Mg-BP NP，生成（RGD-Mg-BP）-Au 二聚体（RGDBNP），进一步刺激了体外和体内巨噬细胞的黏附和促再生 M2 型极化，包括 rho 相关蛋白激酶。这种快速且无毒的二聚体形成可以包含各种生物功能基团来调节宿主对植入物的反应。
