A 3D Fiber‐Hydrogel Based Non‐Viral Gene Delivery Platform Reveals that microRNAs Promote Axon Regeneration and Enhance Functional Recovery Following Spinal Cord Injury. Issue 15 (29th May 2021)

• Record Type: Journal Article
• Authors: Zhang, Na; Lin, Junquan; Lin, Vincent Po Hen; Milbreta, Ulla; Chin, Jiah Shin; Chew, Elaine Guo Yan; Lian, Michelle Mulan; Foo, Jia Nee; Zhang, Kunyu; Wu, Wutian; Chew, Sing Yian
• Is Part Of: Advanced science. Volume 8:Issue 15(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-05-29
• Subjects: electrospinning -- hydrogel -- neural tissue engineering -- RNA interference -- RNA sequencing; Science -- Periodicals; 505
• DOI: 10.1002/advs.202100805
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: Current treatment approaches toward spinal cord injuries (SCI) have mainly focused on overcoming the inhibitory microenvironment that surrounds lesion sites. Unfortunately, the mere modulation of the cell/tissue microenvironment is often insufficient to achieve desired functional recovery. Therefore, stimulating the intrinsic growth ability of injured neurons becomes crucial. MicroRNAs (miRs) play significant roles during axon regeneration by regulating local protein synthesis at growth cones. However, one challenge of using miRs to treat SCI is the lack of efficient delivery approaches. Here, a 3D fiber‐hydrogel scaffold is introduced which can be directly implanted into a spinal cord transected rat. This 3D scaffold consists of aligned electrospun fibers which provide topographical cues to direct axon regeneration, and collagen matrix which enables a sustained delivery of miRs. Correspondingly, treatment with Axon miRs (i.e., a cocktail of miR‐132/miR‐222/miR‐431) significantly enhances axon regeneration. Moreover, administration of Axon miRs along with anti‐inflammatory drug, methylprednisolone, synergistically enhances functional recovery. Additionally, this combined treatment also decreases the expression of pro‐inflammatory genes and enhance gene expressions related to extracellular matrix deposition. Finally, increased Axon miRs dosage with methylprednisolone, significantly promotes functional recovery and remyelination. Altogether, scaffold‐mediated Axon miR treatment with methylprednisolone is a promising therapeutic approach for SCI. Abstract : A novel approach of targeting axon local protein synthesis to promote the intrinsic growth ability of neurons by scaffold‐mediated microRNA delivery is introduced. The biofunctional 3D fiber‐hydrogel scaffold provides topographical cues that direct axon regrowth and a novel microRNA cocktail (miR‐132/miR‐222/miR‐431), which in the presence of methylprednisolone, enhances both nerve regeneration and functional recovery after spinal cord injury.