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Towards constructing extracellular matrix-mimetic hydrogels: An elastic hydrogel constructed from tandem modular proteins containing tenascin FnIII domains

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引用

Lv, S., Bu, T., Kayser, J., Bausch, A., & Li, H. (2013). Towards constructing extracellular matrix-mimetic hydrogels: An elastic hydrogel constructed from tandem modular proteins containing tenascin FnIII domains. ACTA BIOMATERIALIA, 9(5), 6481-6491. doi:10.1016/j.actbio.2013.01.002.


引用: https://hdl.handle.net/21.11116/0000-000F-2E5A-A
要旨
Protein-based hydrogels have been developed for various biomedical
applications where they provide artificial extracellular
microenvironments that mimic the physical and biochemical
characteristics of natural extracellular matrices (ECMs). In natural
ECMs, a large number of proteins are tandem modular proteins consisting
of many individually folded functional domains that confer structural
and biological functionalities. Such tandem modular proteins are
promising building blocks for constructing ECM-mimetic biomaterials.
However, their use for such purposes has not been explored extensively.
Tenascin-C (TNC) is an ECM tandem modular protein and plays an important
role in mechanotransduction by regulating important cell matrix
interactions. The third FnIII domain of TNC (TNfn3) contains an RGD
sequence and is known to bind integrins. Here we use the TNfn3 domain
and resilin sequence-based tandem modular protein FRF4RF4R (F represents
the TNfn3 domain and R represents the resilin sequence, respectively) as
a building block to construct protein-based ECM-mimetic hydrogels. The
tandem modular protein-based building block FRF4RF4R closely mimics the
architecture of the naturally occurring tandem modular ECM protein TNC
and incorporates intact RGD-containing FnIII domains. Our results
demonstrate that tandem modular proteins containing TNfn3 can be readily
photochemically crosslinked into elastic hydrogels, whose Young's
modulus can be tuned by the concentration of the tandem modular protein
solution. In vitro studies demonstrate that none of the photochemical
crosslinking reaction components are cytotoxic at the level tested, and
the hydrogel supports the spread of human lung fibroblast cells. Our
results demonstrate that FRF4RF4R-based hydrogel is a novel ECM-mimetic
hydrogel. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All
rights reserved.