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  • Review Article
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Silk chemistry and biomedical material designs

Abstract

Silk fibroin has applications in different medical fields such as tissue engineering, regenerative medicine, drug delivery and medical devices. Advances in silk chemistry and biomaterial designs have yielded exciting tools for generating new silk-based materials and technologies. Selective chemistries can enhance or tune the features of silk, such as mechanics, biodegradability, processability and biological interactions, to address challenges in medically relevant materials (hydrogels, films, sponges and fibres). This Review details the design and utility of silk biomaterials for different applications, with particular focus on chemistry. This Review consists of three segments: silk protein fundamentals, silk chemistries and functionalization mechanisms. This is followed by a description of different crosslinking chemistries facilitating network formation, including the formation of composite biomaterials. Utility in the fields of tissue engineering, drug delivery, 3D printing, cell coatings, microfluidics and biosensors are highlighted. Looking to the future, we discuss silk biomaterial design strategies to continue to improve medical outcomes.

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Fig. 1: Hierarchical structures, amino acid composition and processing conditions of silk fibroin.
Fig. 2: Different chemical modification methods to functionalize silk.
Fig. 3: Silk gelation and different crosslinking approaches.
Fig. 4: Role of chemistry in silk materials and devices towards biological applications.
Fig. 5: Illustration of different chemistries and biomedical applications.

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Acknowledgements

The authors gratefully acknowledge NIH, the National Science Foundation, the Air Force Office of Scientific Research and the Army Research Office for funding that led to some of the research cited here. The authors thank Y.-T. L. Dingle of Pipette and Stylus LLC for her assistance with some of the figure preparations.

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J.K.S. and D.L.K. conceived the topic and designed the structure and content of the Review. J.K.S. wrote the first draft with contributions from O.H. and T.F. All authors contributed to the discussion, reviewing and editing of the manuscript.

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Correspondence to Jugal Kishore Sahoo or David L. Kaplan.

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Nature Reviews Chemistry thanks Philipp Seib, Saphia Matthew, Yingying Zhang and Keiji Numata for their contribution to the peer review of this work.

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Glossary

3D printing

Three-dimensional deposition, construction and solidification of biomaterials with a predefined geometry and composition.

β-Sheet

Secondary structure of proteins formed by hydrogen bonds between silk chains.

Biocompatibility

One of the most important properties while designing a biomaterial for biomedical application in which a material is compatible with the host microenvironment without inducing any inflammatory or cytotoxic effect.

Bioinks

Materials used in the 3D bioprinting process for deposition and fabrication of 3D structures.

Carbodiimide coupling

Chemical conjugation reaction between a carboxylic acid and amine residue that leads to the formation of an amide bond.

Crosslinking

Specific bond formation that initiates and facilitates network formation and gelation.

Hydrogels

Crosslinked polymeric networks, formed by entanglement of polymer chains in aqueous environment.

Sacrificial networks

Weak, reversible networks present within a stronger network and broken before the stronger, backbone network.

Silk fibroin

Structural, fibrous protein polymer, extracted from the cocoons of Bombyx mori silkworm.

Stiffness

Measured by elastic modulus, stiffness is the ability of hydrogel to resist deformation.

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Sahoo, J.K., Hasturk, O., Falcucci, T. et al. Silk chemistry and biomedical material designs. Nat Rev Chem 7, 302–318 (2023). https://doi.org/10.1038/s41570-023-00486-x

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