Evidence map›Paper›PMID 31391536›Full record

ArticleScientific reports2019

Electrical stimulation shifts healing/scarring towards regeneration in a rat limb amputation model.

K M C Oliveira, J H Barker, E Berezikov, L Pindur, S Kynigopoulos, M Eischen-Loges, Z Han, M B Bhavsar, D Henrich, L Leppik

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

29 citing papers in PubMed, 53 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Elucidation ofFrontiers in microbiology · 2026
    Article
  6. Accelerated Bone Healing via Electrical Stimulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  7. ISSLS Prize in Basic Science 2025: Structural changes of muscle spindles in the multifidus muscle after intervertebral disk injury are resolved by targeted activation of the muscle.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2025
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. The bioelectrical properties of bone tissue.Animal models and experimental medicine · 2023
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Come together: On-chip bioelectric wound closure.Biosensors & bioelectronics · 2021
    Article
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

10 authors at 2 institutions in 2 countries.

K M C OliveiraFrankfurt Initiative for Regenerative Medicine, Experimental Orthopedics & Trauma Surgery, J.W. Goethe University, Frankfurt am Main, Germany.ORCID http://orcid.org/0000-0002-3338-793X
J H BarkerFrankfurt Initiative for Regenerative Medicine, Experimental Orthopedics & Trauma Surgery, J.W. Goethe University, Frankfurt am Main, Germany.
E BerezikovEuropean Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0002-1145-2884
L PindurFrankfurt Initiative for Regenerative Medicine, Experimental Orthopedics & Trauma Surgery, J.W. Goethe University, Frankfurt am Main, Germany.
S KynigopoulosFrankfurt Initiative for Regenerative Medicine, Experimental Orthopedics & Trauma Surgery, J.W. Goethe University, Frankfurt am Main, Germany.
M Eischen-LogesFrankfurt Initiative for Regenerative Medicine, Experimental Orthopedics & Trauma Surgery, J.W. Goethe University, Frankfurt am Main, Germany.
Z HanFrankfurt Initiative for Regenerative Medicine, Experimental Orthopedics & Trauma Surgery, J.W. Goethe University, Frankfurt am Main, Germany.ORCID http://orcid.org/0000-0003-3128-3077
M B BhavsarFrankfurt Initiative for Regenerative Medicine, Experimental Orthopedics & Trauma Surgery, J.W. Goethe University, Frankfurt am Main, Germany.
D HenrichDepartment of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, Frankfurt am Main, Germany.
L LeppikFrankfurt Initiative for Regenerative Medicine, Experimental Orthopedics & Trauma Surgery, J.W. Goethe University, Frankfurt am Main, Germany. Liudmila.Leppik@kgu.de.
Goethe University Frankfurt · DEUniversity Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Different species respond differently to severe injury, such as limb loss. In species that regenerate, limb loss is met with complete restoration of the limbs' form and function, whereas in mammals the amputated limb's stump heals and scars. In in vitro studies, electrical stimulation (EStim) has been shown to promote cell migration, and osteo- and chondrogenesis. In in vivo studies, after limb amputation, EStim causes significant new bone, cartilage and vessel growth. Here, in a rat model, the stumps of amputated rat limbs were exposed to EStim, and we measured extracellular matrix (ECM) deposition, macrophage distribution, cell proliferation and gene expression changes at early (3 and 7 days) and later stages (28 days). We found that EStim caused differences in ECM deposition, with less condensed collagen fibrils, and modified macrophage response by changing M1 to M2 macrophage ratio. The number of proliferating cells was increased in EStim treated stumps 7 days after amputation, and transcriptome data strongly supported our histological findings, with activated gene pathways known to play key roles in embryonic development and regeneration. In conclusion, our findings support the hypothesis that EStim shifts injury response from healing/scarring towards regeneration. A better understanding of if and how EStim controls these changes, could lead to strategies that replace scarring with regeneration.

Indexed as

Electric Stimulation TherapyAmputation StumpsAmputation, SurgicalAnimalsCell ProliferationCicatrixDisease Models, AnimalGene Expression RegulationHumansMaleNeovascularization, PhysiologicRatsTreatment OutcomeWound Healing

Identifiers

PMID31391536
PMCPMC6685943
OpenAlexW2966087142

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.