한빛사논문
Chung-Sung Lee 1, Jiabing Fan 1, Hee Sook Hwang 1, Soyon Kim 1, Chen Chen 1, Minjee Kang 1, Tara Aghaloo 2, Aaron W James 3,4, Min Lee 1,5
1Division of Advanced Prosthodontics, University of California, Los Angeles, California 90095, United States.
2Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles, California 90095, United States.
3Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, United States.
4Orthopedic Hospital Research Center, University of California, Los Angeles, California 90095, United States.
5Department of Bioengineering, University of California, Los Angeles, California 90095, United States.
Corresponding Authors : Aaron W. James, Min Lee
C.-S.L. and J.F. contributed equally to this work.
Abstract
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.
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