title: Mussel Adhesion-Inspired Reverse Transfection Platform Enhances Osteogenic Differentiation and Bone Formation of Human Adipose-Derived Stem Cells.
abstract: Using small interfering RNA (siRNA) to regulate gene expression is an emerging strategy for stem cell manipulation to improve stem cell therapy. However, conventional methods of siRNA delivery into stem cells based on solution-mediated transfection are limited due to low transfection efficiency and insufficient duration of cell-siRNA contact during lengthy culturing protocols. To overcome these limitations, a bio-inspired polymer-mediated reverse transfection system is developed consisting of implantable poly(lactic-co-glycolic acid) (PLGA) scaffolds functionalized with siRNA-lipidoid nanoparticle (sLNP) complexes via polydopamine (pDA) coating. Immobilized sLNP complexes are stably maintained without any loss of siRNA on the pDA-coated scaffolds for 2 weeks, likely due to the formation of strong covalent bonds between amine groups of sLNP and catechol group of pDA. siRNA reverse transfection with the pDA-sLNP-PLGA system does not exhibit cytotoxicity and induces efficient silencing of an osteogenesis inhibitor gene in human adipose-derived stem cells (hADSCs), resulting in enhanced osteogenic differentiation of hADSCs. Finally, hADSCs osteogenically committed on the pDA-sLNP-PLGA scaffolds enhanced bone formation in a mouse model of critical-sized bone defect. Therefore, the bio-inspired reverse transfection system can provide an all-in-one platform for genetic modification, differentiation, and transplantation of stem cells, simultaneously enabling both stem cell manipulation and tissue engineering.
authors.affiliation: Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, Republic of Korea.
authors.forename: Jisoo
authors.initials: J
authors.lastname: Shin
authors.affiliation: Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, Republic of Korea.
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, Republic of Korea.
authors.forename: Yoonhee
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, Republic of Korea.
authors.forename: Kisuk
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, Republic of Korea.
authors.forename: Jong Seung
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, Republic of Korea.
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology, Seoul, 136-650, Republic of Korea.|Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7LD, U.K.
authors.forename: Hyung-Seop
authors.initials: HS
authors.lastname: Han
authors.affiliation: Department of Bioengineering, Hanyang University, Seoul, 133-791, Republic of Korea.
authors.forename: Jinkyu
authors.initials: J
authors.lastname: Lee
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology, Seoul, 136-650, Republic of Korea.
authors.forename: Hojeong
authors.initials: H
authors.lastname: Jeon
authors.affiliation: Department of Bioengineering, Hanyang University, Seoul, 133-791, Republic of Korea.
authors.forename: Heungsoo
authors.initials: H
authors.lastname: Shin
authors.affiliation: Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, Republic of Korea.
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Cho
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D001861:Bone Regeneration / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D034741:RNA, Small Interfering / Q000737:chemistry; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D034741:RNA, Small Interfering; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: lipidoid nanoparticles; osteogenic differentiation; polydopamine; siRNA reverse transfection; stem cells