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

Adv. Sci., 2019 · DOI: 10.1002/advs.201800808 · Published: February 27, 2019

Genetics Biomedical Regenerative Medicine & Stem Cells

Simple Explanation

MicroRNAs effectively modulate protein expression and cellular response. Unfortunately, the lack of robust nonviral delivery platforms has limited the therapeutic application of microRNAs. 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. Altogether, the potential of the fiber platform is demonstrated in providing effective microRNA screening and direct translation into in vivo applications.

Study Duration

2 weeks in vivo

Participants

Sprague-Dawley rats (7–9 weeks, 200–250 g)

Evidence Level

Not specified

Key Findings

1
Enhanced gene-silencing is achieved in neurons as compared to conventional bolus delivery (p < 0.05).
2
Robust nerve ingrowth is observed as early as two weeks after scaffold implantation.
3
Nerve regeneration in response to the microRNA cocktails is similar to in vitro experiments.

Research Summary

Here, we introduce a biomimicking aligned fiber platform which allows the delivery of miRs both in vitro and in vivo in a sustained and nonviral manner. The easy incorporation of different miRs into this platform also makes it possible to conduct extensive miR screening. Consequently, the development of effective miR therapeutics, particularly targeting tissue regeneration, remains slow.

Practical Implications

Effective microRNA Delivery

The biomimicking aligned fiber platform enables sustained and nonviral delivery of microRNAs (miRs) both in vitro and in vivo, addressing a significant bottleneck in miR therapy.

Enhanced Nerve Regeneration

Incorporating miRs into biomimicking PCL fiber constructs enhances gene silencing and promotes nerve regeneration, offering a promising approach for treating spinal cord injuries.

Drug Screening Platform

The fiber-mediated miR delivery platform serves as an effective in vitro and in vivo drug testing system, facilitating the development of miR therapeutics for tissue regeneration.

Study Limitations

1
The study did not illustrate related pathways that may have been affected by these miR combinations and their possible antagonistic effects.
2
In-depth studies such as tracing and functional evaluations will be conducted to further investigate the efficacy of our platform and the effects of these miRs on promoting functional recovery in the long term.
3
This work did not illustrate related pathways that may have been affected by these miR combinations and their possible antagonistic effects.

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