Sustained and Bioresponsive Two‐Stage Delivery of Therapeutic miRNA via Polyplex Micelle‐Loaded Injectable Hydrogels for Inhibition of Intervertebral Disc Fibrosis

Feng, Ganjun; Zha, Zengshi; Huang, Yong; Li, Junjie; Wang, Yuheng; Ke, Wei; Hong-ying, Chen; Liu, Limin; Song, Yueming; Ge, Zhishen

doi:10.1002/adhm.201800623

Cited by 65 publications

(61 citation statements)

References 65 publications

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“…Most of the efforts on musculoskeletal tissue repair have been concentrated on bone and cartilage tissues via delivery of pDNA encoding for osteogenic (BMP-2, OSX) or chondrogenic (TGF-β3, SOX9) factors [ 33 , 35 , 36 , 37 , 38 , 40 , 41 , 42 , 70 , 83 , 90 ], osteogenic siRNA [ 44 , 49 , 71 , 78 , 81 ], mechanosensitive osteogenic/angiogenic miRNA [ 78 , 80 , 82 , 84 ], and chondrogenic mRNA molecules [ 17 ] using alginate [ 33 , 34 , 35 , 36 , 37 , 38 ], fibrin [ 17 , 49 ], chitosan [ 41 , 42 , 44 ], gelatin [ 82 , 90 ], or PEG-based hydrogels [ 70 , 71 , 78 , 80 , 81 , 83 , 84 ].…”

Section: Discussionmentioning

confidence: 99%

“…For in situ formation of polyplex micelle-encapsulated hydrogels, these systems were comprised of cationic block copolymers designed to complex mir-29a mixed with PEG gelation precursors and MMP-cleavable peptide crosslinkers. These GAM resulted in an effective MMP-2 inhibition in IDD tissues inhibiting the fibrosis process and reversing IDD in a rabbit animal model [ 84 ] ( Figure 3 ; Table 2 ).…”

Section: Hydrogel-mediated Gene Delivery In Regenerative Medicinementioning

confidence: 99%

“…Similarly, controlled delivery of RNA molecules from hydrogels networks may enhance local and sustained siRNA [ 43 , 44 , 48 , 49 , 56 , 59 , 71 , 75 , 76 , 78 , 79 , 85 , 86 ] and miRNA [ 46 , 47 , 60 , 62 , 63 , 80 , 81 , 82 , 84 , 92 ] delivery limiting undesired targets [ 14 ], and protect mRNA nanoparticles from the biological environment improving their cellular access [ 17 , 58 ].…”

Section: Introductionmentioning

confidence: 99%

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Hydrogel-Based Localized Nonviral Gene Delivery in Regenerative Medicine Approaches—An Overview

et al. 2020

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Hydrogel-based nonviral gene delivery constitutes a powerful strategy in various regenerative medicine scenarios, as those concerning the treatment of musculoskeletal, cardiovascular, or neural tissues disorders as well as wound healing. By a minimally invasive administration, these systems can provide a spatially and temporarily defined supply of specific gene sequences into the target tissue cells that are overexpressing or silencing the original gene, which can promote natural repairing mechanisms to achieve the desired effect. In the present work, we provide an overview of the most avant-garde approaches using various hydrogels systems for controlled delivery of therapeutic nucleic acid molecules in different regenerative medicine approaches.

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Section: Discussionmentioning

confidence: 99%

Section: Hydrogel-mediated Gene Delivery In Regenerative Medicinementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hydrogel-Based Localized Nonviral Gene Delivery in Regenerative Medicine Approaches—An Overview

et al. 2020

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“…Another gene delivery method recently applied for the inter-vertebral disc is the polyplex micelle which forms a corona of hydrophilic segments surrounding the core of water-incompatible segments. 57 Feng et al 58 reported a sustained and bioresponsive 2-stage microRNA (miRNA) delivery system into disc NP cells with injectable MMP-degradable hydrogels encapsulating MMP-responsive polyplex micelles. In this study, miR-NA-29 (miR-29) was focused on.…”

Section: ) Polyplex Micellementioning

confidence: 99%

Gene Therapy Approach for Intervertebral Disc Degeneration: An Update

2020

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Intervertebral disc degeneration is the primary cause of back pain and associated with neurological disorders including radiculopathy, myelopathy, and paralysis. The currently available surgical treatments predominantly include the excision of pathological discs, resulting in the function loss, immobilization, and potential additional complications due to the altered biomechanics. Gene therapy approach involves gene transfer into cells, affects RNA and protein synthesis of the encoded genes in the recipient cells, and facilitates biological treatment. Relatively long-exerting therapeutic effects by gene therapy are potentially advantageous to treat slow progressive degenerative disc disease. In gene therapy, the delivery method and selection of target gene(s) are essential. Although gene therapy was first mediated by viral vectors, technological progress has enabled to apply nonviral vectors and polyplex micelles for the disc. While RNA interference successfully provides specific downregulation of multiple genes in the disc, clustered regularly interspaced short palindromic repeats (CRISPR) system has increased attention to alter the process of intervertebral disc degeneration. Then, more recent findings of our studies have suggested autophagy, the intracellular self-digestion, and recycling system under the negative regulation by the mammalian target of rapamycin (mTOR), as a gene therapy target in the disc. Here we briefly review backgrounds and applications of gene therapy for the disc, introducing strategies of autophagy and mTOR signaling modulation through selective RNA interference.

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“…The results of this study support that the increase in miR-31-5p level is consistent with the decrease in SDF-1 protein level through Western blot detection. [54][55][56][57][58][59][60] . It is worth emphasizing that the level of miRNAs may be regulated by the methylation of the promoter region, which may affect certain phenotypes 61,62 .…”

Section: Microarray Detection Of Idd Np Was Executed To Analyze the Dmentioning

confidence: 99%

The role of miR-31-5p in the development of intervertebral disc degeneration and its therapeutic potential

Zhou

Deng

et al. 2020

Preprint

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Intervertebral disc degeneration (IDD) refers to the abnormal response of cell-mediated progressive structural failure. In order to understand the molecular mechanism of the maintenance and destruction of the intervertebral disc, new IDD treatment methods are developed. Here, we first analyzed the key regulators of IDD through miRNA microarrays. The cell structure and morphology were discovered by Histological and radiographic. Then, the level of miR-31-5p was disclosed by qRT-PCR. The association between miR-31-5p and SDF-1/CXCR7 axis was discovered by 3’-Untranslated region (UTR) cloning and luciferase assay. The apoptosis of cells under different treatments was disclosed by Flow cytometer. The cell proliferation was discovered by EdU assay. Finally, the protein levels of SDF-1, CXCR7, ADAMTS-5, Col II, Aggrecan and MMP13 were discovered by Western blot. The results show that miR-31-5p is a key regulator of IDD and its level is down-regulated in IDD. Overexpression of miR-31-5p facilitates NP cell proliferation, inhibits apoptosis, facilitates ECM formation and inhibits the level of matrix degrading enzymes in NP cells. The SDF-1/CXCR7 axis is the direct target of miR-31-5p. miR-31-5p acts on IDD by regulating SDF-1/CXCR7. In vitro experiments further verified that the up-regulation of miR-31-5p prevented the development of IDD. In conclusion, overexpression of miR-31-5p can inhibit IDD by regulating SDF-1/CXCR7.HighlightsThe level of miR-31-5p decreased in NP;The increase in methylation status is consistent with the decrease in miR-31-5p levels;Upregulation of miR-31-5p stimulated NP cell proliferation, restrained apoptosis, promoted ECM;SDF-1/CXCR7 axis is the target of miR-31-5p;Overexpression of miR-31-5p inhibits IDD through SDF-1/CXCR7;In vitro experiments proved up-regulation of miR-31-5p prevented the development of IDD.

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Sustained and Bioresponsive Two‐Stage Delivery of Therapeutic miRNA via Polyplex Micelle‐Loaded Injectable Hydrogels for Inhibition of Intervertebral Disc Fibrosis

Cited by 65 publications

References 65 publications

Hydrogel-Based Localized Nonviral Gene Delivery in Regenerative Medicine Approaches—An Overview

Hydrogel-Based Localized Nonviral Gene Delivery in Regenerative Medicine Approaches—An Overview

Gene Therapy Approach for Intervertebral Disc Degeneration: An Update

The role of miR-31-5p in the development of intervertebral disc degeneration and its therapeutic potential

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