Evidence map›Paper›PMID 35171668›Full record

ArticleScience advances2022

Efficient healing of large osseous segmental defects using optimized chemically modified messenger RNA encoding BMP-2.

Rodolfo E De La Vega, Martijn van Griensven, Wen Zhang, Michael J Coenen, Christopher V Nagelli, Joseph A Panos, Carlos J Peniche Silva, Johannes Geiger, Christian Plank, Christopher H Evans and 1 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
17.9field-weighted citation impact, top 1% 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

56 citing papers in PubMed, 87 citations in OpenAlex.

  1. Article
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  5. Development-based In Vivo Bioreactor Strategy for Challenging Senescent Bone Reconstruction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  15. What's New in Musculoskeletal Basic Science.The Journal of bone and joint surgery. American volume · 2025
    Article
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  17. Article
  18. 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

11 authors at 3 institutions in 3 countries.

Rodolfo E De La VegaRehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-2196-8729
Martijn van GriensvenRehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-5104-9881
Wen ZhangEthris GmbH, Planegg, Germany.
Michael J CoenenRehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA.
Christopher V NagelliRehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-2582-8387
Joseph A PanosRehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA.
Carlos J Peniche SilvacBITE, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands.ORCID 0000-0002-2290-8269
Johannes GeigerEthris GmbH, Planegg, Germany.
Christian PlankEthris GmbH, Planegg, Germany.ORCID 0000-0002-6072-4903
Christopher H EvansRehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-5532-2347
Elizabeth R BalmayorRehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-0484-4847
Maastricht University · NLMayo Clinic in Arizona · USEthris (Germany) · DE

Funding

Technology Development P2CHD086843 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AMBROSIO, FABRISIA · 2015 to 2024
$10.5M
Musculoskeletal Research Training ProgramT32AR056950 · NIAMS · MAYO CLINIC ROCHESTER · PI Jennifer J Westendorf · 2009 to 2026
$7.0M
Use of Chemically Modified RNA to Enhance Bone HealingR01AR074395 · NIAMS · MAYO CLINIC ROCHESTER · PI EVANS, CHRISTOPHER HOWARD · 2019 to 2023
$2.5M
NIAMS NIH HHS R01 AR074395NIAMS NIH HHS T32 AR056950NICHD NIH HHS P2C HD086843
6 · The paper itself

Abstract

Large segmental osseous defects heal poorly. Recombinant, human bone morphogenetic protein-2 (rhBMP-2) is used clinically to promote bone healing, but it is applied at very high doses that cause adverse side effects and raise costs while providing only incremental benefit. We describe a previously unexplored, alternative approach to bone regeneration using chemically modified messenger RNA (cmRNA). An optimized cmRNA encoding BMP-2 was delivered to critical-sized femoral osteotomies in rats. The cmRNA remained orthotopically localized and generated BMP locally for several days. Defects healed at doses ≥25 μg of BMP-2 cmRNA. By 4 weeks, all animals treated with 50 μg of BMP-2 cmRNA had bridged bone defects without forming the massive callus seen with rhBMP-2. Moreover, such defects recovered normal mechanical strength quicker and initiated bone remodeling faster. cmRNA regenerated bone via endochondral ossification, whereas rhBMP-2 drove intramembranous osteogenesis; cmRNA provides an innovative, safe, and highly translatable technology for bone healing.

Indexed as

Bone Morphogenetic Protein 2Bone RegenerationAnimalsFemurOsteogenesisRatsRecombinant ProteinsRNA, MessengerWound HealingBone Morphogenetic Protein 2Recombinant ProteinsRNA, Messenger

Identifiers

PMID35171668
PMCPMC8849297
OpenAlexW4213050397

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.