Self-Assembled Human Adipose-Derived Stem Cell-Derived Extracellular Vesicle-Functionalized Biotin-Doped Polypyrrole Titanium with Long-Term Stability and Potential Osteoinductive Ability
Self-Assembled Human Adipose-Derived Stem Cell-Derived Extracellular Vesicle-Functionalized Biotin-Doped Polypyrrole Titanium with Long-Term Stability and Potential Osteoinductive Ability
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自组装人体脂肪干细胞衍生的细胞外囊泡功能化生物素掺杂聚吡咯钛，具有长期稳定性和潜在的骨诱导能力
DOI：
10.1021/acsami.9b17015
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发表时间：
2019-12-11
影响因子：
9.5
通讯作者：
Sun, Jiaming
中科院分区：
文献类型：
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作者：
Chen, Lifeng;Mou, Shan;Sun, Jiaming
间充质干细胞衍生的细胞外囊泡（MSC-EVs）含有蛋白质或microRNA（miRNAs），具有多种生物活性和低免疫原性，被认为是骨移植物表面修饰的理想材料。然而，改性效率还不令人满意，导致治疗效果受损。在这里，我们报告了一种新的固定方法，通过自组装生物素化MSCEVs到生物素掺杂的聚吡咯钛（Bio-Ppy-Ti）的表面，以提高其在体外和体内的生物功能。使用这种方法，在超声震荡30 s后，锚定在Bio-Ppy-Ti表面上的人脂肪来源的干细胞-EV（hASC-EV）的量是纯Ti的185倍，并且在4 ℃下在Bio-Ppy-Ti表面上保持稳定14天。与纯钛相比，EV-Bio-Ppy-Ti在体外表现出更强的细胞相容性和成骨诱导性，并在异位成骨模式下表现出抗凋亡能力。基因芯片分析进一步证明了几种骨诱导miRNAs被封装在hASC-EV中，这可以解释EV-Bio-Ppy-Ti的高骨再生能力。因此，这种MSC-EV生物素固定化方法似乎是高效和长期稳定的，以证明其用于临床金属植入物的潜力。
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), containing proteins or microRNAs (miRNAs), possessing various biological activity and low immunogenicity, are considered promising for surface modification of bone grafts. However, the modification efficiency is not satisfied yet, resulting in compromised therapy effects. Here, we report a novel immobilized method by self-assembling biotinylated MSCEVs onto the surface of biotin-doped polypyrrole titanium (Bio-Ppy-Ti) to improve its biofunctions in vitro and in vivo. Using this method, the amount of human adipose derived stem cell-EVs (hASC-EVs) anchored onto the Bio-Ppy-Ti surface was 185-fold higher than that of pure Ti after ultrasonic concussion for 30 s and it remained stable on the Bio-Ppy-Ti surface for 14 days at 4 degrees C. Compared to pristine Ti, EV-Bio-Ppy-Ti exhibited enhanced cell compatibility and osteoinductivity for osteoblasts in vitro and antiapoptosis ability in the ectopic bone formation mode. Gene chip analysis further demonstrated that several osteoinductive miRNAs were encapsulated in hASC-EVs, which may explain the high bone regeneration ability of EV-Bio-Ppy-Ti. Thus, this MSC-EV biotin-immobilized method appears to be highly efficient and long-term stable for demonstrating its potential for clinical metal implants.