Biomimicking Fiber Scaffold as an Effective In Vitro and In Vivo MicroRNA Screening Platform for Directing Tissue Regeneration

Na Zhang, Ulla Milbreta, Jiah Shin Chin, Coline Pinese, Junquan Lin, Hitomi Shirahama, Wei Jiang, Hang Liu, Ruifa Mi, Ahmet Hoke, Wutian Wu, Sing Yian Chew

Research output: Contribution to journalArticlepeer-review

Abstract

MicroRNAs effectively modulate protein expression and cellular response. Unfortunately, the lack of robust nonviral delivery platforms has limited the therapeutic application of microRNAs. Additionally, there is a shortage of drug-screening platforms that are directly translatable from in vitro to in vivo. Here, a fiber substrate that provides nonviral delivery of microRNAs for in vitro and in vivo microRNA screening is introduced. As a proof of concept, difficult-to-transfect primary neurons are targeted and the efficacy of this system is evaluated in a rat spinal cord injury model. With this platform, enhanced gene-silencing is achieved in neurons as compared to conventional bolus delivery (p < 0.05). Thereafter, four well-recognized microRNAs (miR-21, miR-222, miR-132, and miR-431) and their cocktails are screened systematically. Regardless of age and origin of the neurons, similar trends are observed. Next, this fiber substrate is translated into a 3D system for direct in vivo microRNA screening. Robust nerve ingrowth is observed as early as two weeks after scaffold implantation. Nerve regeneration in response to the microRNA cocktails is similar to in vitro experiments. Altogether, the potential of the fiber platform is demonstrated in providing effective microRNA screening and direct translation into in vivo applications.

Original languageEnglish (US)
Article number1800808
JournalAdvanced Science
Volume6
Issue number9
DOIs
StatePublished - May 3 2019

Keywords

  • RNA interference
  • contact guidance
  • electrospinning
  • gene silencing
  • neural tissue engineering

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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