大澤　重仁    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position
Article types	Original article
Language	English
Peer review	Peer reviewed
Presence of invitation	Invited paper
Title	N-Hydroxysuccinimide Bifunctionalized Triblock Cross-Linker Having Hydrolysis Property for a Biodegradable and Injectable Hydrogel System
Journal	Formal name：ACS Biomaterials Science & Engineering ISSN code：23739878
Domestic / Foregin	Foregin
Volume, Issue, Page	5(11),pp.5759-5769
Total page number	11
Author and coauthor	Shohei Ishikawa, Daisuke Matsukuma, Kazutoshi Iijima, Michihiro Iijima, Shigehito Osawa, and Hidenori Otsuka
Authorship	Corresponding author
Publication date	2019/04/18
Summary	Herein, we designed a N-hydroxysuccinimide (NHS) ester-terminated ABA triblock copolymer composed of poly(ethylene glycol) (PEG) as hydrophilic A segments and poly(dl-lactide) (PLA) as B segment having hydrolysis property (NHS-PEG-b-PLA-b-PEG-NHS) to be a cross-linker of polymer segments having amine groups for facile construction of injectable and degradable hydrogel. The PLA domain, which is widely accepted hydrolyzable segments, is inherently hydrophobic and simple introduction of the NHS group on the ends of PLA would not have high reactivity in aqueous milieu to construct injectable hydrogel. Thus, in this design, hydrophilic PEG was introduced as A segments to increase the reactivity of NHS groups at the ends of linkers by increasing the mobility. To demonstrate the property as a cross-linker for constructing degradable and injectable hydrogel, carboxylmethyl chitosan (CH), which is a polymer segment having amine groups, and NHS-PEG-b-PLA-b-PEG-NHS solutions were mixed to form the hydrogel (CH/PEG–PLA-PEG) under physiological condition. The formation of CH/PEG–PLA-PEG hydrogel proceeded within minute-order period after mixing the solutions, suggesting NHS-PEG-b-PLA-b-PEG-NHS is applicable to the cross-linker for construction of injectable hydrogel system with time-dependent gelation property. Degradation of the obtained CH/PEG-PLA-PEG hydrogel was observed, whereas that of CH/PEG, which was prepared from NHS-PEG-NHS and CH, was not observed, appealing the degradation property of the CH/PEG-PLA-PEG hydrogel based on hydrolysis of the PLA domain. Furthermore, chondrocytes embedded in CH/PEG-PLA-PEG hydrogels promoted collagen synthesis compared to CH/PEG. These demonstrations indicate the designed NHS-PEG-b-PLA-b-PEG-NHS is a promising cross-linker to construct the injectable and degradable hydrogel and eventually promote hydrogel performance as a tissue regeneration scaffold.
DOI	10.1021/acsbiomaterials.9b00218