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Biomaterials, Volume 302, November 2023, 122342 | https://doi.org/10.1016/j.biomaterials.2023.122342 Efficient drug supply in stem cell cytosol via pore-forming saponin nanoparticles promotes in vivo osteogenesis and bone regeneration.

Ji Sun Park ¹, Chaehyun Lee ¹, Seo Young Cheon, Yeeun Lee, Hayoung Jeon, Donghyun Lee, Se Hee Kim, Seong Gi Lim, Heebeom Koo

Department of Medical Life Sciences, Department of Biomedicine & Health Sciences, and Catholic Photomedicine Research Institute, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea

¹These authors contributed equally to this work.

Corresponding author: Heebeom Koo

Abstract

Directional differentiation of stem cells is a key step in stem cell therapy. In this study, we developed saponin-based nanoparticles (Ad-SNPs) containing dexamethasone (Dex) and alpha-lipoic acid (ALA) to promote osteogenic differentiation of human mesenchymal stem cells (hMSCs) and bone regeneration. The Ad-SNPs can achieve rapid cellular uptake through a pore-forming effect without cytotoxic cationic charges. They also provide extended retention in cell cytosol due to their uptake route. These properties are advantageous in efficiently supplying drugs to the hMSCs. The combination of Dex and ALA facilitated mitochondrial fusion and prevented reactive oxygen species-induced DNA damage. It also helped to preserve mitochondrial dynamics, and the efficient supply of it provided by the Ad-SNPs induced differentiation of hMSCs into osteoblasts. The Ad-SNPs showed outstanding performance in osteoblast differentiation, maturation, and mineralization in 3D culture compared with NPs without saponin and with free drugs. When Ad-SNP-treated hMSCs were tested in a rat femoral bone defect model, they showed the fastest regeneration of bones and complete repair in the shortest period among all groups. To the best of our knowledge, this study is the first application of pore-forming saponin-based NPs with rapid cellular uptake and extended retention to stem cell therapy, and we demonstrated their promising potential in bone regeneration and efficient delivery of Dex and ALA.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-10-10)
연구진국내 연구진
분야 바이오·의료융합 > 바이오소재

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