(Keynote) Strategical Design and Applications of Responsive Gels with Dynamic Crosslinks
Authors: Miyata Takashi 
Published: February 2020

Stimuli-responsive gels are useful soft materials for developing sensors, drug delivery systems and cell cultures. We proposed a novel strategy for designing biomolecularly stimuli-responsive gels that undergo changes in the volume in response to a target biomolecule. Our strategy uses molecular complexes as dynamic crosslinks that dissociate and associate in the presence and absence of a target biomolecule [1]. Using the strategy, we have prepared a variety of responsive gels that exhibit swelling/shrinking behaviors or sol-gel phase transition in response to a target biomolecule. These studies demonstrated that dynamic crosslinks are useful tools for designing stimuli-responsive gels. This paper focuses on strategical design of stimuli-responsive gels using dynamic crosslinks and their applications to drug delivery, sensors and cell cultures.
Biomolecularly stimuli-responsive gels that can swell in response to a target biomolecule have been designed as biomolecule-crosslinked gels using biomolecular complex crosslinks such as antigen-antibody complexes and DNA duplexes [2]. As biomolecularly stimuli-responsive gels that can shrink in the presence of a target biomolecule, we have prepared biomolecule-imprinted gels by molecular imprinting that uses cyclodextrin (CD), lectin, antibody and DNA as ligands [3, 4]. In addition, polypeptides with inherent secondary structures such as α-helix and random coil were utilized for designing molecularly imprinted gels with molecular recognition sites [5]. The binding capacity of molecularly imprinted polypeptides gels was regulated by pH-dependent conformational changes. The fascinating properties of the molecularly imprinted polypeptide gels suggest that they exhibit potential as smart drug carriers.
We prepared micro- and nano-sized molecularly stimuli-responsive gels such as particles, thin films and microvalves. For example, molecularly imprinted gel layers with molecular recognition sites were prepared on surface plasmon resonance (SPR) sensor chips by surface-initiated atom transfer radical polymerization (SI-ATRP) [6]. The molecularly imprinted gel layer chips exhibited a large SPR signal and binding constant, compared to nonimprinted gel layer chips. To fabricate self-regulated micro-total analysis systems (μ-TAS), we prepared various micro-sized gels that exhibited quick swelling or shrinkage in response to a target molecule in a microchannel by photopolymerization using a ﬂuorescence microscope [7]. The flow rate of a microchannel was autonomously regulated by the molecularly stimuli-responsive swelling or shrinking of their micro-gels as smart microvalves.
Biotin-conjugated four-armed poly(ethylene glycol) (biotinylated Tetra-PEG) was designed as molecularly stimuli-responsive sol–gel transition polymers that underwent the phase transition from a sol to a gel state in response to avidin as a target molecule [8]. When avidin was added to a buffer solution containing biotinylated Tetra-PEG, the solution transformed to a gel state immediately. The addition of free biotin to the resulting gel induced its dissociation to a sol state. In addition, to design DDS reservoirs and cell culture scaffolds, we designed dual stimuli-responsive sol–gel transition polymers that responded to photo/temperature- and photo/molecule-stimuli.

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