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Cited by 48Tissue Engineering and Regenerative MedicineElectrospun Nanofibers in Biomedical Applications3D Printing in Biomedical Research

A step towards clinical application of acellular matrix: A clue from macrophage polarization

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Petrosyan, Astgik, Da Sacco, Stefano, Tripuraneni, Nikita, Kreuser, Ursula, Lavarreda-Pearce, Maria, Tamburrini, Riccardo, De Filippo, Roger E., Orlando, Giuseppe +2 more·2017·Matrix Biology
DOI 10.1016/j.matbio.2016.08.009PMC PMC6717660
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Abstract

The outcome of tissue engineered organ transplants depends on the capacity of the biomaterial to promote a pro-healing response once implanted in vivo. Multiple studies, including ours, have demonstrated the possibility of using the extracellular matrix (ECM) of animal organs as platform for tissue engineering and more recently, discarded human organs have also been proposed as scaffold source. In contrast to artificial biomaterials, natural ECM has the advantage of undergoing continuous remodeling which allows adaptation to diverse conditions. It is known that natural matrices present diverse immune properties when compared to artificial biomaterials. However, how these properties compare between diseased and healthy ECM and artificial scaffolds has not yet been defined. To answer this question, we used decellularized renal ECM derived from WT mice and from mice affected by Alport Syndrome at different time-points of disease progression as a model of renal failure with extensive fibrosis. We characterized the morphology and composition of these ECMs and compared their in vitro effects on macrophage activation with that of synthetic scaffolds commonly used in the clinic (collagen type I and poly-L-(lactic) acid, PLLA). We showed that ECM derived from Alport kidneys differed in fibrous protein deposition and cytokine content when compared to ECM derived from WT kidneys. Yet, both WT and Alport renal ECM induced macrophage differentiation mainly towards a reparative (M2) phenotype, while artificial biomaterials towards an inflammatory (M1) phenotype. Anti-inflammatory properties of natural ECMs were lost when homogenized, hence three-dimensional structure of ECM seems crucial for generating an anti-inflammatory response. Together, these data support the notion that natural ECM, even if derived from diseased kidneys promote a M2 protolerogenic macrophage polarization, thus providing novel insights on the applicability of ECM obtained from discarded organs as ideal scaffold for tissue engineering.

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  • Preparation techniques such as homogenization, which compromise the mechanical integrity of the dECM scaffold, may result in excessive release of inherent cytokines and trigger more intense inflammatory responses.

    “The application of preparation techniques such as homogenization, which compromise the mechanical integrity of the dECM scaffold, may result in the excessive release of inherent cytokines and trigger more intense inflammatory responses [194].”

    From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [194]

    The Results and Discussion (page numbers unavailable) report that homogenized renal ECM favored pro-inflammatory M1 macrophage polarization compared with intact ECM. The Discussion proposes greater access to embedded cytokines as a possible explanation, but the paper does not establish excessive cytokine release or measure a broader inflammatory response. (LLM, conf=0.84)

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Authors
Petrosyan, A., Da Sacco, S., Tripuraneni, N., Kreuser, U., Lavarreda-Pearce, M., Tamburrini, R., De Filippo, R. E., Orlando, G., Cravedi, P., & Perin, L.
Affiliations
  • University of Southern California (US)
  • Radboud Institute for Molecular Life Sciences (NL)
  • Atrium Health Wake Forest Baptist (US)
  • Icahn School of Medicine at Mount Sinai (US)
Corresponding author
Perin, Laura
ORCID
Venue
Matrix Biology
Publisher
Elsevier BV
Published
2017-01
Volume
57-58
Pages
334-346
ISSN
0945-053X (ISSN-L)
DOI
10.1016/j.matbio.2016.08.009
PMC
PMC6717660
OpenAlex
W2515444928
Cited by
48
References
8
Citations by year
2025: 1 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 8 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 5
FWCI
5.91
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Matrix Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • GOFFAR Foundation
  • California Institute for Regenerative Medicine
  • Nora Baart Foundation
  • Dutch Kidney Foundation
Topics
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Keywords
acellular matrix, extracellular matrix, macrophage polarization, M2 macrophages, Alport syndrome, renal fibrosis, tissue engineering scaffolds, type I collagen, poly(L-lactic acid), anti-inflammatory response, organ transplantation
MeSH terms
Animals, Anti-Inflammatory Agents, Disease Models, Animal, Extracellular Matrix, Humans, Immunohistochemistry, Kidney, Macrophage Activation, Macrophages, Mice, Inbred C57BL, Nephritis, Hereditary, Phenotype, Polyesters, Immunophenotyping, Cytokines, Tissue Engineering, Collagen Type I, Mice, Tissue Scaffolds, Primary Cell Culture

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