Light-triggered RNA release and induction of hMSC osteogenesis via photodegradable, dual-crosslinked hydrogels

被引:33
作者
Cong Truc Huynh [1 ]
Minh Khanh Nguyen [1 ]
Naris, Mantas [1 ]
Tonga, Gulen Yesilbag [2 ]
Rotello, Vincent M. [2 ]
Alsberg, Eben [1 ,3 ]
机构
[1] Case Western Reserve Univ, Dept Biomed Engn, 10900 Euclid Ave, Cleveland, OH 44106 USA
[2] Univ Massachusetts, Dept Chem, 710 North Pleasant St, Amherst, MA 01003 USA
[3] Case Western Reserve Univ, Dept Orthopaed Surg, 10900 Euclid Ave, Cleveland, OH 44106 USA
基金
美国国家卫生研究院;
关键词
bone tissue engineering; in situ forming hydrogel; miRNA; on-demand release; photolabile hydrogels; siRNA; stem cell differentiation; UV-controllable release; MESENCHYMAL STEM-CELLS; PH/TEMPERATURE-SENSITIVE HYDROGEL; SIRNA DELIVERY; POTENTIAL APPLICATION; SUSTAINED DELIVERY; IN-VIVO; SIGNALING PATHWAY; BLOCK-COPOLYMER; DIFFERENTIATION; MIRNA;
D O I
10.2217/nnm-2016-0088
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aim: To engineer a photodegradable hydrogel system for actively controlled release of bioactive unmodified RNA at designated time points to induce hMSC osteogenesis. Materials & methods: RNA/polyethylenimine complexes were loaded into dual-crosslinked photodegradable hydrogels to examine the capacity of UV light application to trigger their release. The ability of released RNA to drive hMSC osteogenic differentiation was also investigated. Results & conclusion: RNA release from photodegradable hydrogels was accelerated upon UV application, which was not observed in non-photodegradable hydrogels. Regardless of the presence of UV light, released siGFP exhibited high bioactivity by silencing GFP expression in HeLa cells. Importantly, siNoggin or miRNA-20a released from the hydrogels induced hMSC osteogenesis. This system provides a potentially valuable physician/patient-controlled 'on-demand' RNA delivery platform for biomedical applications.
引用
收藏
页码:1535 / 1550
页数:16
相关论文
共 79 条
[1]   RNAi therapeutics: Principles, prospects and challenges [J].
Aagaard, Lars ;
Rossi, John J. .
ADVANCED DRUG DELIVERY REVIEWS, 2007, 59 (2-3) :75-86
[2]   RNA interference: Biology, mechanism, and applications [J].
Agrawal, N ;
Dasaradhi, PVN ;
Mohmmed, A ;
Malhotra, P ;
Bhatnagar, RK ;
Mukherjee, SK .
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 2003, 67 (04) :657-+
[3]   siRNA Nanoparticle Functionalization of Nanostructured Scaffolds Enables Controlled Multilineage Differentiation of Stem Cells [J].
Andersen, Morten O. ;
Nygaard, Jens V. ;
Burns, Jorge S. ;
Raarup, Merete K. ;
Nyengaard, Jens R. ;
Bunger, Cody ;
Besenbacher, Flemming ;
Howard, Kenneth A. ;
Kassem, Moustapha ;
Kjems, Jorgen .
MOLECULAR THERAPY, 2010, 18 (11) :2018-2027
[4]  
Bassit ACF, 2015, J NANOMED NANOTECHNO, V6, P257
[5]   MiRNA inhibition in tissue engineering and regenerative medicine [J].
Beavers, Kelsey R. ;
Nelson, Christopher E. ;
Duvall, Craig L. .
ADVANCED DRUG DELIVERY REVIEWS, 2015, 88 :123-137
[6]   Tissue Engineering and Regenerative Medicine: History, Progress, and Challenges [J].
Berthiaume, Francois ;
Maguire, Timothy J. ;
Yarmush, Martin L. .
ANNUAL REVIEW OF CHEMICAL AND BIOMOLECULAR ENGINEERING, VOL 2, 2011, 2 :403-430
[7]   Interactions between silica surfaces coated by polyelectrolyte multilayers in aqueous environment: comparison between precursor and multilayer regime [J].
Bosio, V ;
Dubreuil, F ;
Bogdanovic, G ;
Fery, A .
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, 2004, 243 (1-3) :147-155
[8]   Mesenchymal Stem Cells in the Human Corneal Limbal Stroma [J].
Branch, Matthew James ;
Hashmani, Khurram ;
Dhillon, Permesh ;
Jones, D. Rhodri E. ;
Dua, Harminder Singh ;
Hopkinson, Andrew .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2012, 53 (09) :5109-5116
[9]   RNAi therapeutics: a potential new class of pharmaceutical drugs [J].
Bumcrot, David ;
Manoharan, Muthiah ;
Koteliansky, Victor ;
Sah, Dinah W. Y. .
NATURE CHEMICAL BIOLOGY, 2006, 2 (12) :711-719
[10]   Fidgetin-Like 2: A Microtubule-Based Regulator of Wound Healing [J].
Charafeddine, Rabab A. ;
Makdisi, Joy ;
Schairer, David ;
O'Rourke, Brian P. ;
Diaz-Valencia, Juan D. ;
Chouake, Jason ;
Kutner, Allison ;
Krausz, Aimee ;
Adler, Brandon ;
Nacharaju, Parimala ;
Liang, Hongying ;
Mukherjee, Suranjana ;
Friedman, Joel M. ;
Friedman, Adam ;
Nosanchuk, Joshua D. ;
Sharp, David J. .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2015, 135 (09) :2309-2318