Evidence map›Paper›PMID 40447668›Full record

ArticleScientific reports2025

Inflammatory factors released by ACL reconstruction tendon grafts and their potential for macrophage polarization.

Janne Spierings, Marina van Doeselaar, Mads Buenen, Florencia Abinzano, Marieke van der Steen, Rob Janssen, Keita Ito, Jasper Foolen

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PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Trial
  2. Review
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.

Janne SpieringsOrthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Marina van DoeselaarOrthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Mads BuenenOrthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Florencia AbinzanoOrthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Marieke van der SteenDepartment of Orthopaedic Surgery & Trauma, Máxima Medical Centre Eindhoven/Veldhoven, Eindhoven, The Netherlands.
Rob JanssenOrthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Keita ItoOrthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. K.Ito@tue.nl.
Jasper FoolenOrthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.

Funding

Horizon 2020 952981
6 · The paper itself

Abstract

Anterior cruciate ligament (ACL) rupture requires reconstruction (ACLR), often using tendon autografts, to restore joint stability. However, postoperative issues persist, especially in younger patients, with the primary cause still unclear. These issues are believed to result from a detrimental in vivo remodeling response, characterized by macrophage-involving inflammation that is driven by dead and dying graft resident cells. This research aimed to (1) analyze factors secreted by different tendon grafts, (2) investigate how these factors influence macrophage polarization, and (3) explore the influence of patients' age on these secreted factors. An ex vivo set-up was used to provide new insights into the role of tendon grafts in the inflammatory response observed after ACLR in a patient-specific way. It was found that the dying cells in fresh autografts released a mixture of pro- and anti-inflammatory cytokines and matrix metalloproteinases. This release was reduced in grafts where the cells were already dead (frozen) or in grafts from which the cells were removed (decellularized). The release of pro-inflammatory cytokines by fresh grafts may contribute to the inflammatory response after ACLR. However, secreted factors did not polarize (THP-1) macrophages in our in vitro setup. A key finding of this study was the observed patient-specific response, which was not age-related in the used cohort, which emphasizes the need for personalized rehabilitation. In the future, correlating these findings with clinical patients' outcomes can enhance understanding of patient-specific recovery and aid in finding a biomarker for personalized rehabilitation.

Indexed as

Anterior Cruciate Ligament InjuriesAnterior Cruciate Ligament ReconstructionInflammation MediatorsMacrophagesTendonsAdultAnterior Cruciate LigamentCytokinesFemaleHumansInflammationMaleMiddle AgedTHP-1 CellsYoung AdultCytokinesInflammation MediatorsACL reconstructionAnterior cruciate ligamentDecellularizationMacrophage polarizationTendon grafts

Identifiers

PMID40447668
PMCPMC12125384

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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.