Cited by 213Bone Tissue Engineering MaterialsBone Metabolism and DiseasesWound Healing and Treatments

Modulating macrophage activities to promote endogenous bone regeneration: Biological mechanisms and engineering approaches

Open access
Niu, Yiming, Wang, Zhenzhen, Shi, Yuchen, Dong, Lei, Wang, Chunming·2021·Bioactive Materials

Abstract

A coordinated interaction between osteogenesis and osteoimmune microenvironment is essential for successful bone healing. In particular, macrophages play a central regulatory role in all stages of bone repair. Depending on the signals they sense, these highly plastic cells can mediate the host immune response against the exterior signals of molecular stimuli and implanted scaffolds, to exert regenerative potency to a varying extent. In this article, we first encapsulate the immunomodulatory functions of macrophages during bone regeneration into three aspects, as sweeper, mediator and instructor. We introduce the phagocytic role of macrophages in different bone healing periods ('sweeper') and overview a variety of paracrine cytokines released by macrophages either mediating cell mobilisation, vascularisation and matrix remodelling ('mediator'), or directly driving the osteogenic differentiation of bone progenitors and bone repair ('instructor'). Then, we systematically classify and discuss the emerging engineering strategies to recruit, activate and modulate the phenotype transition of macrophages, to exploit the power of endogenous macrophages to enhance the performance of engineered bone tissue.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.bioactmat.2020.08.012

Cites

179 of 179 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 5

  1. [40]Cavalli L. Brandi M.L. Periprosthetic Bone Loss: Diagnostic and Therapeutic Approaches 2013 F1000Research 2 PMC4304431 25642325
  2. [51]Schlundt C. El Khassawna T. Serra A. Dienelt A. Wendler S. Schell H. van Rooijen N. Radbruch A. Lucius R. Hartmann S. Duda G.N. Schmidt-Bleek K. Macrophages in bone fracture healing: their essential role in endochondral ossification Bone 106 2018 78 89 26529389
  3. [111]Guihard P. Danger Y. Brounais B. David E. Brion R. Delecrin J. Richards C.D. Chevalier S. Redini F. Heymann D. Gascan H. Blanchard F. Induction of osteogenesis in mesenchymal stem cells by activated monocytes/macrophages depends on oncostatin M signaling Stem Cell. 30 4 2012 762 772 22267310
  4. [112]Wu A.C. Raggatt L.J. Alexander K.A. Pettit A.R. Unraveling macrophage contributions to bone repair BoneKEy Rep. 2 2013 373 PMC4098570 25035807
  5. [126]Pajarinen J. Lin T. Gibon E. Kohno Y. Maruyama M. Nathan K. Lu L. Yao Z. Goodman S.B. Mesenchymal stem cell-macrophage crosstalk and bone healing Biomaterials 196 2019 80 89 29329642 PMC6028312

Cited by

Sorted by citations

Authors
Niu, Y., Wang, Z., Shi, Y., Dong, L., & Wang, C.
Affiliations
  • University of Macau (MO)
  • State Key Laboratory of Pharmaceutical Biotechnology (CN)
Corresponding author
Wang, Chunming
Venue
Bioactive Materials
Publisher
Elsevier BV
Published
2021-01
Volume
6
Issue
1
Pages
244-261
ISSN
  • 2097-1192 (ISSN-L)
  • 2452-199X
OpenAlex
W3080282321
Cited by
213
References
179
Citations by year
2026: 16 · 2025: 35 · 2024: 51 · 2023: 53 · 2022: 35 · 2021: 23
FWCI
2.32
Type
journal article
Language
en
Open access
Locations
  • Bioactive Materials (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Fundo para o Desenvolvimento das Ciências e da Tecnologia (0018/2019/AFJ)
  • University of Macau (MYRG2019-00080-ICMS)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
Keywords
macrophages, bone regeneration, bone formation, osteoimmunology, phagocytosis, macrophage recruitment, vascularization, matrix remodeling, osteogenic differentiation, bone scaffolds

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review