Tailoring the multiscale mechanics of tunable decellularized extracellular matrix (dECM) for wound healing through immunomodulation
Open accessAbstract
With the discovery of the pivotal role of macrophages in tissue regeneration through shaping the tissue immune microenvironment, various immunomodulatory strategies have been proposed to modify traditional biomaterials. Decellularized extracellular matrix (dECM) has been extensively used in the clinical treatment of tissue injury due to its favorable biocompatibility and similarity to the native tissue environment. However, most reported decellularization protocols may cause damage to the native structure of dECM, which undermines its inherent advantages and potential clinical applications. Here, we introduce a mechanically tunable dECM prepared by optimizing the freeze-thaw cycles. We demonstrated that the alteration in micromechanical properties of dECM resulting from the cyclic freeze-thaw process contributes to distinct macrophage-mediated host immune responses to the materials, which are recently recognized to play a pivotal role in determining the outcome of tissue regeneration. Our sequencing data further revealed that the immunomodulatory effect of dECM was induced via the mechnotrasduction pathways in macrophages. Next, we tested the dECM in a rat skin injury model and found an enhanced micromechanical property of dECM achieved with three freeze-thaw cycles significantly promoted the M2 polarization of macrophages, leading to superior wound healing. These findings suggest that the immunomodulatory property of dECM can be efficiently manipulated by tailoring its inherent micromechanical properties during the decellularization process. Therefore, our mechanics-immunomodulation-based strategy provides new insights into the development of advanced biomaterials for wound healing.
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The decellularized extracellular matrix (dECM) helps prevent adhesions by acting as a biocompatible physical barrier between healing tissues, minimizing direct contact and reducing fibroblast proliferation.
“The decellularized extracellular matrix (dECM) helps prevent adhesions by acting as a biocompatible physical barrier between healing tissues, minimizing direct contact and reducing fibroblast proliferation [101].”
From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [101]
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Decellularization of tissues and organs
Gilbert, T. W., Sellaro, T. L., & Badylak, S. F. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.02.014 · Cited by 2,222 · see citing works
Ellis, S., Lin, E. J., & Tartar, D. (2018) · Current Dermatology Reports · doi:10.1007/s13671-018-0234-9 · Cited by 625 · cited 1× · see citing works
“Impaired wound healing may lead to functional disorders and aesthetic complications, reducing the patients’ quality of life and increasing the global disease burden [1].”
BackgroundExtracellular matrix-derived biomaterials in engineering cell function
Xing, H., Lee, H., Luo, L., & Kyriakides, T. R. (2020) · Biotechnology Advances · doi:10.1016/j.biotechadv.2019.107421 · Cited by 302 · see citing works
Regulation of decellularized matrix mediated immune response
Chakraborty, J., Roy, S., & Ghosh, S. (2020) · Biomaterials Science · doi:10.1039/c9bm01780a · Cited by 130 · see citing works
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Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering
Fazel Anvari-Yazdi, A., Badea, I., & Chen, X. (2025) · Gels · doi:10.3390/gels11060441 · Cited by 20 · see citing works
- Authors
- Luo, P., Huang, R., Wu, Y., Liu, X., Shan, Z., Gong, L., Deng, S., Liu, H., Fang, J., Wu, S., Wu, X., Liu, Q., Chen, Z., Yeung, K. W. K., Qiao, W., Chen, S., & Chen, Z.
- Affiliations
- Sun Yat-sen University (CN)
- University of Hong Kong - Shenzhen Hospital (CN)
- University of Hong Kong (HK)
- Corresponding author
- Qiao, Wei
- Chen, Shoucheng
- Chen, Zhuofan
- ORCID
- Venue
- Bioactive Materials
- Publisher
- Elsevier BV
- Published
- 2023-10
- Volume
- 28
- Pages
- 95-111
- ISSN
- 2097-1192 (ISSN-L)
- 2452-199X
- PMC
- PMC10209339
- OpenAlex
- W4376881528
- Cited by
- 36
- References
- 4
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 18 · 2023: 1
- FWCI
- 9.07
- 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 (82201119, 82071167, 82201124, 82001095, 81970975, 81901055)
- Health and Medical Research Fund (09201466)
- Basic and Applied Basic Research Foundation of Guangdong Province (2021A1515110380, 2023A1515011963)
- Food and Health Bureau
- China Postdoctoral Science Foundation (2021TQ0379, 2022M713575)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
- Keywords
- decellularized extracellular matrix, wound healing, immunomodulation, macrophage polarization, M2 macrophages, micromechanical properties, mechanotransduction, skin damage, tissue regeneration, 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 ›
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