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Cited by 140Hydrogels: synthesis, properties, applicationsTissue Engineering and Regenerative Medicine3D Printing in Biomedical Research

Genipin and EDC crosslinking of extracellular matrix hydrogel derived from human umbilical cord for neural tissue repair

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Výborný, Karel, Vallová, Jana, Kočí, Zuzana, Kekulová, Kristýna, Jiráková, Klára, Jendelová, Pavla, Hodan, Jiří, Kubinová, Šárka·2019·Scientific Reports
DOI 10.1038/s41598-019-47059-xPMC PMC6650505
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Abstract

Extracellular matrix (ECM) hydrogels, produced by tissue decellularization are natural injectable materials suitable for neural tissue repair. However, the rapid biodegradation of these materials may disrupt neural tissue reconstruction in vivo. The aim of this study was to improve the stability of the previously described ECM hydrogel derived from human umbilical cord using genipin and N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC), crosslinking at concentration of 0.5–10 mM. The hydrogels, crosslinked by genipin (ECM/G) or EDC (ECM/D), were evaluated in vitro in terms of their mechanical properties, degradation stability and biocompatibility. ECM/G, unlike ECM/D, crosslinked hydrogels revealed improved rheological properties when compared to uncrosslinked ECM. Both ECM/G and ECM/D slowed down the gelation time and increased the resistance against in vitro enzymatic degradation, while genipin crosslinking was more effective than EDC. Crosslinkers concentration of 1 mM enhanced the in vitro bio-stability of both ECM/G and ECM/D without affecting mesenchymal stem cell proliferation, axonal sprouting or neural stem cell growth and differentiation. Moreover, when injected into cortical photochemical lesion, genipin allowed in situ gelation and improved the retention of ECM for up to 2 weeks without any adverse tissue response or enhanced inflammatory reaction. In summary, we demonstrated that genipin, rather than EDC, improved the bio-stability of injectable ECM hydrogel in biocompatible concentration, and that ECM/G has potential as a scaffold for neural tissue application.

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  • Comparative studies have scrutinized various crosslinking techniques, evaluating mechanical strength, degradation resistance, and biocompatibility, all of which are crucial for successful tissue repair and regeneration.

    “Comparative studies have scrutinized various crosslinking techniques, evaluating mechanical strength, degradation resistance, and biocompatibility, all of which are crucial for successful tissue repair and regeneration.[ 155 ]”

    From Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations (2025) · cites this paper as [155]

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References 44 · Cited by 140

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Authors
Výborný, K., Vallová, J., Kočí, Z., Kekulová, K., Jiráková, K., Jendelová, P., Hodan, J., & Kubinová, Š.
Affiliations
  • Charles University (CZ)
  • Czech Academy of Sciences, Institute of Experimental Medicine (CZ)
  • Czech Academy of Sciences (CZ)
Corresponding author
Kubinová, Šárka
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2019-07-23
Volume
9
Issue
1
Pages
10674-10674
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-019-47059-x
PMC
PMC6650505
OpenAlex
W2962966292
Cited by
140
References
44
Citations by year
2026: 17 · 2025: 15 · 2024: 24 · 2023: 25 · 2022: 21 · 2021: 27 · 2020: 9 · 2019: 2
FWCI
5.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Keywords
extracellular matrix hydrogel, genipin crosslinking, EDC crosslinking, human umbilical cord, neural repair, injectable scaffolds, hydrogel stability, enzymatic degradation, rheological properties, mesenchymal stem cells, neural stem cells, axonal sprouting, in situ gelation, biocompatibility
MeSH terms
Carbodiimides, Extracellular Matrix, Humans, Nerve Regeneration, Umbilical Cord, Hydrogels, Tissue Engineering, Iridoids, Cell Proliferation, Tissue Scaffolds, Mesenchymal Stem Cells

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