Evidence map›Paper›PMID 29885529›Full record

ArticleActa biomaterialia2018

RNA interfering molecule delivery from in situ forming biodegradable hydrogels for enhancement of bone formation in rat calvarial bone defects.

Minh K Nguyen, Oju Jeon, Phuong N Dang, Cong T Huynh, Davood Varghai, Hooman Riazi, Alexandra McMillan, Samuel Herberg, Eben Alsberg

Abstract read
In one paragraph

Article in Acta biomaterialia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

50 citing papers in PubMed, 109 citations in OpenAlex.

  1. Millimeter-Scale Dual-Opposing RNA-Gradient Hydrogel for Interfacial Gene Silencing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  10. Bioactive materials forBioactive materials · 2024
    Review
  11. 3D Bioprinting in Otolaryngology: A Review.Advanced healthcare materials · 2023
    Review
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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

9 authors at 2 institutions in 1 country.

Minh K NguyenDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States.
Oju JeonDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States.
Phuong N DangDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States.
Cong T HuynhDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States.
Davood VarghaiDepartment of Neurological Surgery, Case Western Reserve University, Cleveland, OH 44106, United States.
Hooman RiaziDepartment of Neurological Surgery, Case Western Reserve University, Cleveland, OH 44106, United States.
Alexandra McMillanDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States.
Samuel HerbergDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States.
Eben AlsbergDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States; Department of Orthopaedic Surgery, Case Western Reserve University, Cleveland, OH 44106, United States. Electronic address: eben.alsberg@case.edu.
Case Western Reserve University · USNeurological Surgery · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
TRAINING PROGRAM IN MUSCULOSKELETAL RESEARCHT32AR007505 · NIAMS · CASE WESTERN RESERVE UNIVERSITY · PI TRIOLO, RONALD J · 1986 to 2023
$6.3M
Clinical and Translational Science Collaborative of ClevelandTL1TR000441 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$2.8M
High-Throughput Microenvironment Regulation for ChondrogenesisR01AR066193 · NIAMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI ALSBERG, EBEN, KHADEMHOSSEINI, ALI · 2015 to 2020
$2.1M
Opposing RNAi Molecule Gradient Constructs to Repair Osteochondral DefectsR01AR069564 · NIAMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI ALSBERG, EBEN · 2016 to 2021
$1.8M
Controlled, Sustained Delivery of siRNA to hMSCs for Enhanced Bone RegenerationR56DE022376 · NIDCR · CASE WESTERN RESERVE UNIVERSITY · PI ALSBERG, EBEN · 2012 to 2012
$346k
Blockade of miR-29b-1-5p promotes MSC-mediated bone regeneration during agingF32DE024712 · NIDCR · CASE WESTERN RESERVE UNIVERSITY · PI HERBERG, SAMUEL · 2014 to 2016
$166k
NIAMS NIH HHS R01 AR066193NIAMS NIH HHS R01 AR069564NIAMS NIH HHS T32 AR007505NIDCR NIH HHS F32 DE024712NIDCR NIH HHS R56 DE022376NIGMS NIH HHS T32 GM007250
6 · The paper itself

Abstract

RNA interference (RNAi) may be an effective and valuable tool for promoting the growth of functional tissue, as short interfering RNA (siRNA) and microRNA (miRNA) can block the expression of genes that have negative effects on tissue regeneration. Our group has recently reported that the localized and sustained presentation of siRNA against noggin (siNoggin) and miRNA-20a from in situ forming poly(ethylene glycol) (PEG) hydrogels enhanced osteogenic differentiation of encapsulated human bone marrow-derived mesenchymal stem cells (hMSCs). Here, the capacity of the hydrogel system to accelerate bone formation in a rat calvarial bone defect model is presented. After 12 weeks post-implantation, the hydrogels containing encapsulated hMSCs and miRNA-20a resulted in more bone formation in the defects than the hydrogels containing hMSCs without siRNA or with negative control siRNA. This localized and sustained RNA interfering molecule delivery system may provide an excellent platform for healing bony defects and other tissues. STATEMENT OF SIGNIFICANCE: Delivery of RNAi molecules may be a valuable strategy to guide cell behavior for tissue engineering applications, but to date there have been no reports of a biomaterial system capable of both encapsulation of cells and controlled delivery of incorporated RNA. Here, we present PEG hydrogels that form in situ via Michael type reaction, and that permit encapsulation of hMSCs and the concomitant controlled delivery of siNoggin and/or miRNA-20a. These RNAs were chosen to suppress noggin, a BMP-2 antagonist, and/or PPAR-γ, a negative regulator of BMP-2-mediated osteogenesis, and therefore promote osteogenic differentiation of hMSCs and subsequent bone repair in critical-sized rat calvarial defects. Simultaneous delivery of hMSCs and miRNA-20a enhanced repair of these defects compared to hydrogels containing hMSCs without siRNA or with negative control siRNA. This in situ forming PEG hydrogel system offers an exciting platform for healing critical-sized bone defects by localized, controlled delivery of RNAi molecules to encapsulated hMSCs and surrounding cells.

Indexed as

Absorbable ImplantsBone RegenerationCells, ImmobilizedDrug Delivery SystemsRNA, Small InterferingSkullAnimalsCarrier ProteinsHeterograftsHumansHydrogelsMaleMesenchymal Stem CellsMesenchymal Stem Cell TransplantationNoggin ProteinRatsCarrier ProteinsHydrogelsNoggin ProteinRNA, Small InterferingBone regenerationhMSCHydrogelRNAi

Identifiers

PMID29885529
PMCPMC6119505
OpenAlexW2806854794

What OpenQuestion holds

Textmetadata
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.