Multimodal mechanoregulation strategies towards tissue regeneration
Open accessAbstract
Mechanical microenvironment of each tissue plays an important role in regulating its special cellular behaviors, such as morphology, proliferation, differentiation, and migration. Mechanical signals can direct lineage specification or promote cell migration towards injury sites and facilitate tissue repair. During tissue regeneration, mechanoregulation is also important due to the ability of providing an extracellular microenvironment that closely resembles the physiological state for cells. Currently, mechanoregulation strategies have been usually applied to promote tissue regeneration. However, the in vivo mechanical environment is highly complex, these single mechanical conditioning strategies cannot comprehensively replicate the mechanical microenvironment experienced by cells or tissues in the body, thereby hindering the achievement of efficient tissue regeneration. The proposal of multimodal mechanoregulation strategies offers promising avenues to address this limitation. Herein, we summarize the critical role of mechanical factors in promoting tissue regeneration and the current development of different multimodal mechanoregulation approaches. Furthermore, the complex mechanical microenvironment of various tissues such as bone, intervertebral disc and cardiac. Afterwards, the recent successful applications of multimodal mechanical strategies in regenerative therapies were reviewed. And we delineate the persisting challenges, potential resolutions, and emerging translational prospects for multimodal mechanoregulation strategies in regenerative medicine, providing a reference for further development of multimodal mechanoregulation approaches.
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An optimal biodegradable implant should degrade substantially only after fulfilling its mechanical role during fracture healing, necessitating a degradation rate that aligns with the bone healing process.
“Actually, an optimal biodegradable implant should degrade substantially only after fulfilling its mechanical role during the fracture healing period, necessitating a degradation rate that aligns with the bone healing process42–44.”
From Intelligence-responsive wettability switch coating on magnesium implants for treating osteoporotic fracture (2026) · cites this paper as [44]
The Clinical translation section discusses degradation of a PLLA scaffold and its acidic byproducts, but not when a fracture-fixation implant should lose mechanical support. Searches for fracture healing, implant degradation rate, and mechanical support found no passage linking degradation timing to bone healing. (LLM, conf=0.76)
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Ma, Y., Liu, N., Shao, X., Shi, T., Lin, J., Liu, B., Shen, T., Guo, B., & Jiang, Q. Y. (2024) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2024.06.012 · Cited by 11 · see citing works
Baxter, A. L., Thrasher, A., Etnoyer-Slaski, J. L., & Cohen, L. L. (2023) · Frontiers in Pain Research · doi:10.3389/fpain.2023.1114633 · Cited by 10 · see citing works
The effects of matrix stiffness on immune cells in bone biology
Jiang, T., Zheng, M.-T., Li, R.-M., & Ouyang, N. (2024) · Mechanobiology in Medicine · doi:10.1016/j.mbm.2024.100046 · Cited by 10 · see citing works
Zhou, Z., Suo, Y., Bai, J., Lin, F., Gao, X. Y., Shan, H., Ni, Y., Zhou, X., Sheng, L., & Dai, J. (2023) · Aging and Disease · doi:10.14336/ad.2023.00205 · Cited by 10 · see citing works
Cimmino, C., Netti, P. A., & Ventre, M. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.933410 · Cited by 9 · see citing works
Atashipour, S. R., & Baqersad, J. (2023) · Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials · doi:10.1016/j.jmbbm.2023.106266 · Cited by 8 · see citing works
Zhang, Z., Han, R., Liu, Y., Yu, X., Wang, G., Bai, Y., Yang, R., Jin, T., & Zhang, X. (2025) · Chemical Engineering Journal · doi:10.1016/j.cej.2025.164550 · Cited by 8 · see citing works
Garrido, C. A., Garske, D. S., Bucher, C. H., Amini, S., Duda, G. N., Schmidt‐Bleek, K., & Cipitria, A. (2025) · Acta Biomaterialia · doi:10.1016/j.actbio.2025.07.063 · Cited by 8 · see citing works
Zhou, J., Wang, J., Li, J., et al. (2024) · JOR Spine · doi:10.1002/jsp2.1314 · Cited by 7 · see citing works
Mechanical environment for in vitro cartilage tissue engineering assisted by in silico models.
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Zhang, W., Wang, H., Chu, G., Yu, L., Han, F., Yu, Q., Wang, Y., & Li, B. (2023) · Applied Materials Today · doi:10.1016/j.apmt.2023.101751 · Cited by 7 · see citing works
Self-citationLiu, B., Song, G., Wang, Y., Song, C., Cao, Y., Tong, J., Wang, Y., Fan, X., Shi, N., Zhao, H., et al. (2025) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2025.05.004 · Cited by 6 · see citing works
Prolonged cyclical loading induces Haversian remodeling in mandibles of growing rabbits
Lad, S. E., Kowalkowski, H., Liggio, D. F., Ding, H., & Ravosa, M. J. (2023) · Journal of Experimental Biology · doi:10.1242/jeb.245942 · Cited by 5 · see citing works
Harnessing mechanobiology to enhance cell therapy
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Mechanical forces pattern endocardial Notch activation via mTORC2-PKC pathwayPreprint
Mu, Y., Hu, S., Liu, X., Tang, X., Lin, J., & Shi, H. (2024) · eLife · doi:10.7554/elife.97268 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Qi, G., Ma, T., Wang, Y., Chen, K., Yan, Y., Li, Z., Deng, N., Tseng, C., Li, B., Zheng, Y., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-72683-3 · Cited by 2 · see citing works
Self-citation
- Authors
- Yu, Q., Duan, Y., Zhu, Z., Ji, W., Zhu, C., & Li, B.
- Affiliations
- Soochow University (CN)
- Corresponding author
- Zhu, Caihong
- Li, Bin
- Venue
- Mechanobiology in Medicine
- Publisher
- Elsevier BV
- Published
- 2025-12
- Volume
- 3
- Issue
- 4
- Pages
- 100159
- ISSN
- 2949-9070 (ISSN-L)
- PMC
- PMC12552545
- OpenAlex
- W4415614737
- Cited by
- 8
- References
- 112
- Citations by year
- 2026: 8
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Mechanobiology in Medicine (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- National Natural Science Foundation of China (824B2075, U24A20670, 81925027, 32371414, 32130059)
- Graduate Research and Innovation Projects of Jiangsu Province (KYCX25_3488)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- mechanoregulation, tissue regeneration, mechanical microenvironment, mechanobiology, bone regeneration, intervertebral disc regeneration, cardiac regeneration, cell migration, lineage specification, regenerative medicine
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 ›
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