Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration
Open accessAbstract
It has been proven that the mechanical microenvironment can impact the differentiation of mesenchymal stem cells (MSCs). However, the effect of mechanical stimuli in biofabricating hydroxyapatite scaffolds on the inflammatory response of MSCs remains unclear. This study aimed to investigate the effect of mechanical loading on the inflammatory response of MSCs seeded on scaffolds. Cyclic mechanical loading was applied to biofabricate the cell-scaffold composite for 15 min/day over 7, 14, or 21 days. At the predetermined time points, culture supernatant was collected for inflammatory mediator detection, and gene expression was analyzed by qRT-PCR. The results showed that the expression of inflammatory mediators ( IL1B and IL8) was downregulated ( p < 0.05) and the expression of ALP ( p < 0.01) and COL1A1 ( p < 0.05) was upregulated under mechanical loading. The cell-scaffold composites biofabricated with or without mechanical loading were freeze-dried to prepare extracellular matrix-based scaffolds (ECM-based scaffolds). Murine macrophages were seeded on the ECM-based scaffolds to evaluate their polarization. The ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying enhanced the expression of M2 polarization-related biomarkers ( Arginase 1 and Mrc1 , p < 0.05) of macrophages in vitro and increased bone volume/total volume ratio in vivo. Overall, these findings demonstrated that mechanical loading could dually modulate the inflammatory responses and osteogenic differentiation of MSCs. Besides, the ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying facilitated the M2 polarization of macrophages in vitro and bone regeneration in vivo. Mechanical loading may be a promising biofabrication strategy for bone biomaterials.
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.
Integrity signals
Registry
Cites
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.
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?
It is also crucial to control degradation kinetics, mechanical stimuli, and oxygen concentrations in the transplanted site.
“It is also crucial to control degradation kinetics, mechanical stimuli, and oxygen concentrations in the transplanted site [210].”
From Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review (2023) · cites this paper as [210]
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
Veiseh, O., Doloff, J. C., Ma, M., Vegas, A. J., Tam, H. H., Bader, A. R., Li, J., Langan, E., Wyckoff, J., Loo, W. S., et al. (2015) · Nature Materials · doi:10.1038/nmat4290 · Cited by 897 · see citing works
Evaluation of phenotypic and functional stability of RAW 264.7 cell line through serial passages
Taciak, B., Białasek, M., Braniewska, A., Sas, Z., Sawicka, P., Kiraga, Ł., Rygiel, T., & Król, M. (2018) · PLOS ONE · doi:10.1371/journal.pone.0198943 · Cited by 377 · see citing works
Chen, M., Zhang, Y., Zhou, P., Liu, X., Zhao, H., Zhou, X., Gu, Q., Li, B., Zhu, X., & Shi, Q. (2020) · Bioactive Materials · doi:10.1016/j.bioactmat.2020.05.004 · Cited by 229 · cited 1× · see citing works
“It is an important strategy to use the functional phenotypes of macrophages activated by biomaterials to assess the regenerative and immunoregulatory potential of biomaterials [7,61,62].”
BackgroundSelf-citation
Flagged first, then by citations
Research works printed but not linked: 63
- [1]O'Keefe R.J. Bone tissue engineering and regeneration: from discovery to the clinic--an overview Tissue Eng. B Rev. 17 2011 389 392 10.1089/ten.TEB.2011.0475 PMC3223012 21902614 · DOI
- [2]Ho-Shui-Ling A. Bone regeneration strategies: engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives Biomaterials 180 2018 143 162 10.1016/j.biomaterials.2018.07.017 30036727 PMC6710094 · DOI
- [3]Putters T.F. Morbidity of anterior iliac crest and calvarial bone donor graft sites: a 1-year randomized controlled trial Int. J. Oral Maxillofac. Surg. 47 2018 1474 1480 10.1016/j.ijom.2018.06.002 29935790 · DOI
- [4]Boehm K.S. Donor site morbidities of iliac crest bone graft in craniofacial surgery: a systematic review Ann. Plast. Surg. 83 2019 352 358 10.1097/SAP.0000000000001682 30562201 · DOI
- [5]Parikh S.N. Bone graft substitutes: past, present, future J. Postgrad. Med. 48 2002 142 148 12215702
- [7]Chen Z. Tuning chemistry and topography of nanoengineered surfaces to manipulate immune response for bone regeneration applications ACS Nano 11 2017 4494 4506 10.1021/acsnano.6b07808 28414902 · DOI
- [8]Sadowska J.M. Effect of nano-structural properties of biomimetic hydroxyapatite on osteoimmunomodulation Biomaterials 181 2018 318 332 10.1016/j.biomaterials.2018.07.058 30098568 · DOI
- [9]Lee J.Y. Design of a 3D BMP-2-delivering tannylated PCL scaffold and its anti-oxidant, anti-inflammatory, and osteogenic effects in vitro Int. J. Mol. Sci. 19 2018 10.3390/ijms19113602 PMC6274927 30445673 · DOI
- [10]Lourenco A.H. Osteogenic, anti-osteoclastogenic and immunomodulatory properties of a strontium-releasing hybrid scaffold for bone repair Mater Sci Eng C Mater Biol Appl 99 2019 1289 1303 10.1016/j.msec.2019.02.053 30889663 · DOI
- [11]Dai C. Three-dimensional high-porosity chitosan/honeycomb porous carbon/hydroxyapatite scaffold with enhanced osteoinductivity for bone regeneration ACS Biomater Sci Eng 6 2019 575 586 33463242
- [12]Zhang X. Novel hierarchical nitrogen-doped multiwalled carbon nanotubes/cellulose/nanohydroxyapatite nanocomposite as an osteoinductive scaffold for enhancing bone regeneration ACS Biomater Sci Eng 5 2018 294 307 33405875
- [13]Kim I.G. Bioactive cell-derived matrices combined with polymer mesh scaffold for osteogenesis and bone healing Biomaterials 50 2015 75 86 10.1016/j.biomaterials.2015.01.054 25736498 · DOI
- [14]Huang G. Functional and biomimetic materials for engineering of the three-dimensional cell microenvironment Chem. Rev. 117 2017 12764 12850 10.1021/acs.chemrev.7b00094 28991456 PMC6494624 · DOI · Paper page
- [15]Lu H. Cultured cell-derived extracellular matrix scaffolds for tissue engineering Biomaterials 32 2011 9658 9666 10.1016/j.biomaterials.2011.08.091 21937104 · DOI
- [16]Long T. Fabrication of three-dimensional porous scaffold based on collagen fiber and bioglass for bone tissue engineering J. Biomed. Mater. Res. B Appl. Biomater. 103 2015 1455 1464 10.1002/jbm.b.33328 25430707 · DOI
- [17]Wu R.X. Modulating macrophage responses to promote tissue regeneration by changing the formulation of bone extracellular matrix from filler particles to gel bioscaffolds Mater Sci Eng C Mater Biol Appl 101 2019 330 340 10.1016/j.msec.2019.03.107 31029326 · DOI
- [18]Carvalho M.S. Co-culture cell-derived extracellular matrix loaded electrospun microfibrous scaffolds for bone tissue engineering Mater Sci Eng C Mater Biol Appl 99 2019 479 490 10.1016/j.msec.2019.01.127 30889723 PMC6452855 · DOI
- [19]Kim I.G. Mechanotransduction of human pluripotent stem cells cultivated on tunable cell-derived extracellular matrix Biomaterials 150 2018 100 111 10.1016/j.biomaterials.2017.10.016 29035736 · DOI
- [20]Ma J. Biomimetic matrix fabricated by LMP-1 gene-transduced MC3T3-E1 cells for bone regeneration Biofabrication 9 2017 045010 10.1088/1758-5090/aa8dd1 28930090 · DOI
- [21]Milan J.L. Computational modelling of the mechanical environment of osteogenesis within a polylactic acid-calcium phosphate glass scaffold Biomaterials 30 2009 4219 4226 10.1016/j.biomaterials.2009.04.026 19477510 · DOI
- [22]Skerry T.M. The response of bone to mechanical loading and disuse: fundamental principles and influences on osteoblast/osteocyte homeostasis Arch. Biochem. Biophys. 473 2008 117 123 10.1016/j.abb.2008.02.028 18334226 · DOI
- [23]Kimelman-Bleich N. The effect of ex vivo dynamic loading on the osteogenic differentiation of genetically engineered mesenchymal stem cell model J Tissue Eng Regen Med 5 2011 384 393 10.1002/term.324 20740691 · DOI
- [24]Jagodzinski M. Influence of perfusion and cyclic compression on proliferation and differentiation of bone marrow stromal cells in 3-dimensional culture J. Biomech. 41 2008 1885 1891 10.1016/j.jbiomech.2008.04.001 18495131 · DOI
- [25]Ravichandran A. In v Itro cyclic compressive loads potentiate early osteogenic events in engineered bone tissue J. Biomed. Mater. Res. B Appl. Biomater. 105 2017 2366 2375 10.1002/jbm.b.33772 27527120 · DOI
- [26]Kong Z. Dynamic compression promotes proliferation and neovascular networks of endothelial progenitor cells in demineralized bone matrix scaffold seed J. Appl. Physiol. 113 1985 619 626 10.1152/japplphysiol.00378.2011 22723630 · DOI
- [27]Ruggiu A. Bone mechanobiology, gravity and tissue engineering: effects and insights J Tissue Eng Regen Med 9 2015 1339 1351 10.1002/term.1942 25052837 · DOI
- [28]Guilak F. Biomechanics and mechanobiology in functional tissue engineering J. Biomech. 47 2014 1933 1940 10.1016/j.jbiomech.2014.04.019 24818797 PMC4051419 · DOI
- [29]David V. Ex Vivo bone formation in bovine trabecular bone cultured in a dynamic 3D bioreactor is enhanced by compressive mechanical strain Tissue Eng. 14 2008 117 126 10.1089/ten.a.2007.0051 18333810 · DOI
- [30]Pfannkuche J.J. Intervertebral disc organ culture for the investigation of disc pathology and regeneration - benefits, limitations, and future directions of bioreactors Connect. Tissue Res. 61 2020 304 321 10.1080/03008207.2019.1665652 31556329 · DOI
- [31]Williams D.F. On the mechanisms of biocompatibility Biomaterials 29 2008 2941 2953 10.1016/j.biomaterials.2008.04.023 18440630 · DOI · Paper page
- [32]Liu Y. Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-gamma and TNF-alpha Nat. Med. 17 2011 1594 1601 10.1038/nm.2542 22101767 PMC3233650 · DOI
- [33]Solis A.G. Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity Nature 573 2019 69 74 10.1038/s41586-019-1485-8 31435009 PMC6939392 · DOI · Paper page
- [34]Albarran-Juarez J. Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation J. Exp. Med. 215 2018 2655 2672 10.1084/jem.20180483 30194266 PMC6170174 · DOI
- [35]Qiao C. Human mesenchymal stem cells isolated from the umbilical cord Cell Biol. Int. 32 2008 8 15 10.1016/j.cellbi.2007.08.002 17904875 · DOI
- [36]Gantenbein B. An in vitro organ culturing system for intervertebral disc explants with vertebral endplates: a feasibility study with ovine caudal discs Spine (Phila Pa 31 1976 2665 2673 10.1097/01.brs.0000244620.15386.df 17077734 · DOI
- [37]Illien-Junger S. The combined effects of limited nutrition and high-frequency loading on intervertebral discs with endplates Spine (Phila Pa 35 1976 1744 1752 10.1097/BRS.0b013e3181c48019 20395884 · DOI
- [38]Brunelli M. Short bursts of cyclic mechanical compression modulate tissue formation in a 3D hybrid scaffold J Mech Behav Biomed Mater 71 2017 165 174 10.1016/j.jmbbm.2017.03.008 28342324 · DOI
- [39]Shariatzadeh M. Effect of mechanical loading on osteogenesis of human embryonic stem cell-derived mesenchymal progenitors within collagen microspheres J. Cell Sci. Ther. 9 2018 10.4172/2157-7013.1000282 · DOI
- [40]Hu K. Long noncoding RNA ZBED3-AS1 induces the differentiation of mesenchymal stem cells and enhances bone regeneration by repressing IL-1beta via Wnt/beta-catenin signaling pathway J. Cell. Physiol. 234 2019 17863 17875 10.1002/jcp.28416 30919957 · DOI
- [41]Lacey D.C. Proinflammatory cytokines inhibit osteogenic differentiation from stem cells: implications for bone repair during inflammation Osteoarthritis Cartilage 17 2009 735 742 10.1016/j.joca.2008.11.011 19136283 · DOI
- [42]Martino M.M. Inhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration Nat. Commun. 7 2016 11051 10.1038/ncomms11051 27001940 PMC4804175 · DOI
- [43]Huang R.L. Opposing TNF-alpha/IL-1beta- and BMP-2-activated MAPK signaling pathways converge on Runx2 to regulate BMP-2-induced osteoblastic differentiation Cell Death Dis. 5 2014 e1187 10.1038/cddis.2014.101 24743742 PMC4001295 · DOI
- [44]Glaeser J.D. Anti-inflammatory peptide attenuates edema and promotes BMP-2-induced bone formation in spine fusion Tissue Eng. 24 2018 1641 1651 10.1089/ten.TEA.2017.0512 PMC7063562 29766758 · DOI
- [45]Barbalho S.M. The potential role of medicinal plants in bone regeneration Alternative Ther. Health Med. 25 2019 32 39 31202209
- [46]Fasolino I. Osteoinductive and anti-inflammatory properties of chitosan-based scaffolds for bone regeneration Mater Sci Eng C Mater Biol Appl 105 2019 110046 10.1016/j.msec.2019.110046 31546343 · DOI
- [47]Gao L. Decellularized aortic scaffold alleviates H2O2-induced inflammation and apoptosis in CD34+ progenitor cells while driving neovasculogenesis BioMed Res. Int. 2020 6782072 10.1155/2020/6782072 32104703 PMC7035506 · DOI
- [48]Bakogiannis C. Platelet-derived chemokines in inflammation and atherosclerosis Cytokine 122 2019 154157 10.1016/j.cyto.2017.09.013 29198385 · DOI
- [49]Broxmeyer H.E. Comparative analysis of the human macrophage inflammatory protein family of cytokines (chemokines) on proliferation of human myeloid progenitor cells. Interacting effects involving suppression, synergistic suppression, and blocking of suppression J. Immunol. 150 1993 3448 3458 7682242
- [50]Ruehle M.A. Extracellular matrix compression temporally regulates microvascular angiogenesis Sci. Adv. 6 2020 eabb6351 10.1126/sciadv.abb6351 32937368 PMC7442478 · DOI
- [51]Diaz M.F. Biomechanical forces promote immune regulatory function of bone marrow mesenchymal stromal cells Stem Cell. 35 2017 1259 1272 10.1002/stem.2587 PMC5405000 28181347 · DOI
- [52]Schoenenberger A.D. Macromechanics and polycaprolactone fiber organization drive macrophage polarization and regulate inflammatory activation of tendon in vitro and in vivo Biomaterials 249 2020 120034 10.1016/j.biomaterials.2020.120034 32315865 · DOI · Paper page
- [53]Ji J. The effect of mechanical loading on osteogenesis of human dental pulp stromal cells in a novel in vitro model Cell Tissue Res. 358 2014 123 133 10.1007/s00441-014-1907-8 24916612 · DOI
- [54]Shalumon K.T. Rational design of gelatin/nanohydroxyapatite cryogel scaffolds for bone regeneration by introducing chemical and physical cues to enhance osteogenesis of bone marrow mesenchymal stem cells Mater Sci Eng C Mater Biol Appl 104 2019 109855 10.1016/j.msec.2019.109855 31500067 · DOI
- [55]Horner C.B. Spatially regulated multiphenotypic differentiation of stem cells in 3D via engineered mechanical gradient ACS Appl. Mater. Interfaces 11 2019 45479 45488 10.1021/acsami.9b17266 31714732 · DOI
- [56]Haugh M.G. Temporal and spatial changes in cartilage-matrix-specific gene expression in mesenchymal stem cells in response to dynamic compression Tissue Eng. 17 2011 3085 3093 10.1089/ten.tea.2011.0198 21870950 · DOI
- [57]Sawatjui N. Biomimetic scaffolds and dynamic compression enhance the properties of chondrocyte- and MSC-based tissue-engineered cartilage J Tissue Eng Regen Med 12 2018 1220 1229 10.1002/term.2653 29489056 · DOI
- [58]Schreivogel S. Load-induced osteogenic differentiation of mesenchymal stromal cells is caused by mechano-regulated autocrine signaling J Tissue Eng Regen Med 13 2019 1992 2008 10.1002/term.2948 31359634 · DOI
- [59]Zhang Z.Y. A comparison of bioreactors for culture of fetal mesenchymal stem cells for bone tissue engineering Biomaterials 31 2010 8684 8695 10.1016/j.biomaterials.2010.07.097 20739062 · DOI
- [60]Yang D. The immune reaction and degradation fate of scaffold in cartilage/bone tissue engineering Mater Sci Eng C Mater Biol Appl 104 2019 109927 10.1016/j.msec.2019.109927 31500038 · DOI · Paper page
- [61]Chung L. Key players in the immune response to biomaterial scaffolds for regenerative medicine Adv. Drug Deliv. Rev. 114 2017 184 192 10.1016/j.addr.2017.07.006 28712923 · DOI
- [64]Hartley J.W. Expression of infectious murine leukemia viruses by RAW264. 7 cells, a potential complication for studies with a widely used mouse macrophage cell line Retrovirology 5 2008 1 18177500 PMC2253558
- [65]Hulsart-Billstrom G. A surprisingly poor correlation between in vitro and in vivo testing of biomaterials for bone regeneration: results of a multicentre analysis Eur. Cell. Mater. 31 2016 312 322 10.22203/ecm.v031a20 27215739 · DOI
- [66]Luo L. The effects of dynamic compression on the development of cartilage grafts engineered using bone marrow and infrapatellar fat pad derived stem cells Biomed. Mater. 10 2015 055011 10.1088/1748-6041/10/5/055011 26391756 · DOI
Cited by
Sorted by citations
Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review
Vach Agocsova, S., Culenova, M., Birova, I., Omanikova, L., Moncmanova, B., Danisovic, L., Ziaran, S., Bakos, D., & Alexy, P. (2023) · Materials · doi:10.3390/ma16124267 · Cited by 98 · see citing works
- Authors
- Zhang, P., Liu, X., Guo, P., Li, X., He, Z., Li, Z., Stoddart, M. J., Grad, S., Tian, W., Chen, D., Zou, X., Zhou, Z., & Liu, S.
- Affiliations
- Sun Yat-sen University (CN)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- AO Foundation (CH)
- Beijing Jishuitan Hospital (CN)
- Corresponding author
- Chen, Dafu
- Zou, Xuenong
- Zhou, Zhiyu
- ORCID
- Venue
- Bioactive Materials
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 6
- Issue
- 10
- Pages
- 3097-3108
- ISSN
- 2097-1192 (ISSN-L)
- 2452-199X
- PMC
- PMC7960680
- OpenAlex
- W3150254463
- Cited by
- 54
- References
- 3
- Citations by year
- 2025: 13 · 2024: 12 · 2023: 12 · 2022: 12 · 2021: 5
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- 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
- National Natural Science Foundation of China (31900583, 32071341, 32071351, 81772400)
- Sanming Project of Medicine in Shenzhen (SZSM201911002)
- Fundamental Research Funds for the Central Universities (19ykzd05)
- Natural Science Foundation of Guangzhou City (201704030082, 201807010031)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- cyclic loading, hydroxyapatite scaffolds, bone regeneration, mesenchymal stem cells, osteogenic differentiation, macrophage polarization, M2 macrophages, freeze-drying, IL1B, interleukin-8, Alps, COL1A1, bone biomaterials
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