Journal
ACS APPLIED BIO MATERIALS
Volume 2, Issue 10, Pages 4545-4556Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.9b00668
Keywords
polypeptide; polypeptoid; dynamic bonds; in situ forming hydrogel; pH responsiveness; cell culture
Funding
- National Natural Science Foundation of China [21674037]
- Natural Science Foundation of Shanghai [18ZR1410200]
- National Key Research and Development Program [2016YFC1100703]
- Science and Technology Commission of Shanghai Municipality [18JC1410802]
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The emerging tide of hydrogels in biomedical fields drives them to possess good biocompatibility, tunable mechanical properties, and fast gelation process. Herein, a composite hydrogel containing copolypept(o)ides and functional polysaccharides was constructed through dynamic acylhydrazone linkages. First, a series of peptide-peptoid copolymers were synthesized by ring-opening polymerization of sarcosine (Sar) and L-glutamic acid.-benzyl ester (BLG) N-carboxyanhydrides (NCAs). The benzyl groups of BLG units were substituted with hydrazide groups through ester-amide exchange aminolysis reaction. The statistical copolymer of poly(sarcosine-co-glutamate-hydrazide) (P(Sar-co-GH)) was chosen as an optimized precursor due to its excellent water solubility and gel-forming ability with aldehyde-modified sodium alginate (OSA). Moreover, cellulose nanocrystals (CNCs) were prepared as nanofillers to reinforce the P(Sar-co-GH)-OSA hydrogel. We demonstrated that the copolymer sequences and composition contents made a difference to the properties of the formed hydrogels by variation of the cross-linking density. The dynamic acylhydrazone bonds endowed hydrogels with pH responsiveness and reversible networks. The NIH/3T3 cells encapsulated in the hydrogels maintained high viability and proliferation abilities, indicating that the nanocomposite hydrogels could be explored to fabricate a customized responsive drug delivery system or cell scaffolds for tissue engineering.
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