Evidence map›Paper›PMID 28376367›Full record

ArticleBiomaterials2017

Injectable nanofibrous spongy microspheres for NR4A1 plasmid DNA transfection to reverse fibrotic degeneration and support disc regeneration.

Ganjun Feng, Zhanpeng Zhang, Ming Dang, Xiaojin Zhang, Yasmine Doleyres, Yueming Song, Di Chen, Peter X Ma

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 79 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Ganjun FengDepartment of Biologic and Materials Science, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Zhanpeng ZhangDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
Ming DangMacromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109, USA.
Xiaojin ZhangDepartment of Biologic and Materials Science, University of Michigan, Ann Arbor, MI, 48109, USA.
Yasmine DoleyresMacromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109, USA.
Yueming SongDepartment of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Di ChenDepartment of Biochemistry, Rush University, Chicago, IL, 60612, USA.
Peter X MaDepartment of Biologic and Materials Science, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA; Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address: mapx@umich.edu.
University of Michigan–Ann Arbor · USWest China Hospital of Sichuan University · CNRush University · US

Funding

Tissue Engineering and RegenerationT32DE007057 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID H. KOHN · 1985 to 2026
$17.3M
Periodontal Engineering Using Biomimetic Nano ScaffoldsR01DE015384 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MA, PETER X · 2003 to 2011
$2.9M
Orchestrating Bone Regeneration on Multiple ScalesR01DE017689 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MA, PETER X · 2007 to 2010
$1.4M
NIDCR NIH HHS R01 DE015384NIDCR NIH HHS R01 DE017689NIDCR NIH HHS T32 DE007057
6 · The paper itself

Abstract

Safe and efficient gene therapy is highly desired for controlling pathogenic fibrosis of nucleus pulposus (NP) tissue, which would result in intervertebral disc (IVD) degeneration and disability if left untreated. In this work, a hyperbranched polymer (HP) with high plasmid DNA (pDNA) binding affinity and negligible cytotoxicity is synthesized, which can self-assemble into nano-sized polyplexes with a "double shell" structure that can transfect pDNA into NP cells with very high efficiency. These polyplexes are then encapsulated in biodegradable nanospheres (NS) to enable two-stage delivery: 1) temporally-controlled release of pDNA-carrying polyplexes and 2) highly efficient delivery of pDNA into cells by the released polyplexes. These biodegradable NS are co-injected with nanofibrous spongy microspheres (NF-SMS) to localize the cellular transfection of the pDNA encoding orphan nuclear receptor 4A1 (NR4A1), which was recently reported as a therapeutic agent to delay pathogenic fibrosis. It is shown that HP can transfect human NP cells efficiently in vitro with low cytotoxicity. The two-stage delivery system is able to present the polyplexes over a sustained time period (more than 30 days) in the tail of a rat. The NR4A1 pDNA carried by the HP polyplexes is found to therapeutically reduce the pathogenic fibrosis of NP tissue in a rat-tail degeneration model. In conclusion, the combination of the two-stage NR4A1 pDNA delivery NS and NF-SMS is able to repress fibrosis and to support IVD regeneration.

Indexed as

AgedAnimalsCells, CulturedDNAFibrosisGenetic TherapyHumansInjectionsIntervertebral DiscIntervertebral Disc DegenerationNanofibersNuclear Receptor Subfamily 4, Group A, Member 1PlasmidsRats, Sprague-DawleyRegenerationTransfectionDNANR4A1 protein, humanNuclear Receptor Subfamily 4, Group A, Member 1FibrosisGene therapyHyperbranched polymerNonviral gene carrierNuclear receptorNucleus pulposus regeneration

Identifiers

PMID28376367
PMCPMC5448136
OpenAlexW2603203808

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.