Crosslinking strategies for silk fibroin hydrogels: promising biomedical materials
Open accessAbstract
Due to their strong biomimetic potential, silk fibroin (SF) hydrogels are impressive candidates for tissue engineering, due to their tunable mechanical properties, biocompatibility, low immunotoxicity, controllable biodegradability, and a remarkable capacity for biomaterial modification and the realization of a specific molecular structure. The fundamental chemical and physical structure of SF allows its structure to be altered using various crosslinking strategies. The established crosslinking methods enable the formation of three-dimensional (3D) networks under physiological conditions. There are different chemical and physical crosslinking mechanisms available for the generation of SF hydrogels (SFHs). These methods, either chemical or physical, change the structure of SF and improve its mechanical stability, although each method has its advantages and disadvantages. While chemical crosslinking agents guarantee the mechanical strength of SFH through the generation of covalent bonds, they could cause some toxicity, and their usage is not compatible with a cell-friendly technology. On the other hand, physical crosslinking approaches have been implemented in the absence of chemical solvents by the induction of β-sheet conformation in the SF structure. Unfortunately, it is not easy to control the shape and properties of SFHs when using this method. The current review discusses the different crosslinking mechanisms of SFH in detail, in order to support the development of engineered SFHs for biomedical applications.
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Sonication induces β-sheet conformation in silk fibroin by increasing local temperature, pressure, and strain.
“Various concentrations of SF and G compositions were developed to determine their crosslinking time after sonication, which induces β-sheet conformation in SF [35] by increasing the local temperature, pressure, and strain [36].”
From Development of silk microfiber-reinforced bioink for muscle tissue engineering and in situ printing by a handheld 3D printer (2025) · cites this paper as [35]
Section 4.1.4 (Ultrasonication) says sonication induces physical β-sheet crosslinks in silk fibroin and that changes in temperature and pressure, with applied strain, lead to self-assembly and gelation. It does not specify that temperature and pressure increase locally, so the claimed direction of those changes is not fully supported. (LLM, conf=0.84)
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References 264 · Cited by 95
Research works printed but not linked: 3
- Guillaume O et al 2015 Optimization of silk mesh for soft tissue reinforcements: preliminary in vitro investigations toward cell-based therapy Eur. Cells Mater. 30 16 (www.researchgate.net/profile/Olivier_Guillaume3/ publication/289893674_Optimization_of_silk_ mesh_for_soft_tissue_reinforcements_preliminary_ in_vitro_investigations_toward_cell-based_ therapy/links/5693533708aee91f69a73f6a.pdf)
- Teuschl A H et al 2015 Silk fibroin for peripheral nerve regeneration: a novel preparation method improved mechanical characteristics and supports regeneration in rat sciatic nerves Tissue Eng. Part A 21 S36-S36 (www.researchgate.net/publication/296096531_ Silk_Fibroin_for_Peripheral_Nerve_ Regeneration_A_Novel_Preparation_Method_Improved_ Mechanical_Characteristics_and_Supports_ Regeneration_in_Rat_Sciatic_Nerves)
- Mason T J and Peters D 2002 Practical Sonochemistry: Power Ultrasound Uses and Applications (Cambridge: Woodhead Publishing) 166 (www.sciencedirect.com/book/ 9781898563839/practical-sonochemistry#book- description)
- Authors
- Farokhi, M., Aleemardani, M., Solouk, A., Mirzadeh, H., Teuschl, A. H., & Redl, H.
- Affiliations
- Amirkabir University of Technology (IR)
- University of Applied Sciences Technikum Wien (AT)
- Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA (AT)
- Corresponding author
- Solouk, Atefeh
- Mirzadeh, Hamid
- ORCID
- Venue
- Biomedical Materials
- Publisher
- IOP Publishing
- Published
- 2021-02-12
- Volume
- 16
- Issue
- 2
- Pages
- 022004
- ISSN
- 1748-6041 (ISSN-L)
- 1748-605X
- OpenAlex
- W3083999658
- Cited by
- 95
- References
- 264
- Citations by year
- 2026: 17 · 2025: 25 · 2024: 19 · 2023: 17 · 2022: 14 · 2021: 3
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biomedical Materials (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Silk-based biomaterials and applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
- Keywords
- silk fibroin, silk fibroin hydrogel, crosslinking, chemical crosslinking, physical crosslinking, β-sheet conformation, three-dimensional network, mechanical properties, biodegradability, tissue engineering scaffolds, biocompatibility
- MeSH terms
- Animals, Biocompatible Materials, Carbon Dioxide, Cross-Linking Reagents, Fibroins, Glutaral, Humans, Hydrogen-Ion Concentration, Materials Testing, Models, Theoretical, Osmosis, Polymers, Bombyx, Stress, Mechanical, Surface-Active Agents, Temperature, Crystallography, X-Ray, Hydrogels, Tissue Engineering, Iridoids, Silk, Chemical Phenomena
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