Bone-Targeting Exosome Mimetics Engineered by Bioorthogonal Surface Functionalization for Bone Tissue Engineering.
Bone-Targeting Exosome Mimetics Engineered by Bioorthogonal Surface Functionalization for Bone Tissue Engineering.
复制标题
通过生物正交表面功能化设计的骨靶向外泌体模拟物，用于骨组织工程。
DOI：
10.1021/acs.nanolett.2c04159
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发表时间：
2023
期刊：
影响因子：
10.8
通讯作者：
Lee,Min
中科院分区：
文献类型：
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作者：
Lee,Chung-Sung;Fan,Jiabing;Hwang,HeeSook;Kim,Soyon;Chen,Chen;Kang,Minjee;Aghaloo,Tara;James,AaronW;Lee,Min
细胞外囊泡作为一种安全的生物载体在生物医学工程中引起了人们极大的兴趣。需要开发更有效的递送策略以改善局部治疗功效并使脱靶副作用最小化。在这里，外泌体模拟物（EM）的报告骨靶向涉及通过生物正交功能化的羟基磷灰石结合部分的引入。工程化EM的骨结合能力用羟基磷灰石涂覆的支架和离体骨结合测定来验证。EM结合的构建体提供了用于细胞粘附、增殖和成骨分化的生物相容性基底。特别地，Smoothened激动剂（SAG）掺入EM中通过激活hedgehog信号传导大大增加了成骨能力。此外，与EM/SAG整合的支架显著改善了体内再骨化。最后，生物分布研究证实了全身给药的EM在骨组织中的蓄积。这种简单的工程策略可能是一种促进骨再生的通用工具，为骨骼疾病的复杂治疗提供了一种有前途的纳米医学方法。
Extracellular vesicles have received a great interest as safe biocarriers in biomedical engineering. There is a need to develop more efficient delivery strategies to improve localized therapeutic efficacy and minimize off-target adverse effects. Here, exosome mimetics (EMs) are reported for bone targeting involving the introduction of hydroxyapatite-binding moieties through bioorthogonal functionalization. Bone-binding ability of the engineered EMs is verified with hydroxyapatite-coated scaffolds and an ex vivo bone-binding assay. The EM-bound construct provided a biocompatible substrate for cell adhesion, proliferation, and osteogenic differentiation. Particularly, the incorporation of Smoothened agonist (SAG) into EMs greatly increased the osteogenic capacity through the activation of hedgehog signaling. Furthermore, the scaffold integrated with EM/SAG significantly improved in vivo reossification. Lastly, biodistribution studies confirmed the accumulation of systemically administered EMs in bone tissue. This facile engineering strategy could be a versatile tool to promote bone regeneration, offering a promising nanomedicine approach to the sophisticated treatment of bone diseases.