Citation: Zhang Zhen, He Chao-liang, Xu Qing-hua, Zhuang Xiu-li, Chen Xue-si. Preparation of Poly(L-glutamic acid)-based Hydrogels via Diels-Alder Reaction and Study on Their Biomolecule-responsive Properties[J]. Acta Polymerica Sinica, ;2018, (1): 99-108. doi: 10.11777/j.issn1000-3304.2018.17221 shu

Preparation of Poly(L-glutamic acid)-based Hydrogels via Diels-Alder Reaction and Study on Their Biomolecule-responsive Properties

1.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022
2.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026

Corresponding author: He Chao-liang, clhe@ciac.ac.cn Chen Xue-si, xschen@ciac.ac.cn
Received Date: 6 August 2017
Revised Date: 2 September 2017

A novel type of biomolecule-responsive polypeptide hydrogels were fabricated by inverse electron demand Diels-Alder reaction between disulfide-linked, norbornene-conjugated poly(L-glutamic acid) (PLG-SS-Norb) and tetrazine-teminated 4-armed poly(ethylene glycol) (PEG-T). Mono-norbornene group modified cystamine (Norb-SS-NH₂) was synthesized and then introduced into the side chains of PLG through EDC/NHS chemistry. The obtained polymer was mixed with PEG-T to form the hydrogels in phosphate buffer saline (PBS) at various polymer concentrations and PLG-SS-Norb/PEG-T mass ratio. The gelation was accomplished in several minutes via inverse electron demand Diels-Alder reaction between the norbornene and tetrazine groupswith nitrogen as the byproduct. The mechanical properties were investigated by dynamic mechanical analysis, which indicated that the storage moduli of the hydrogels were influenced by polymer concentration and the molar ratio of two functional groups. Due to the peptide linkage in poly(L-glutamic acid) (PLG) backbone and disulfide bonds in the crosslinking points, the hydrogels were sensitive to proteolitic enzymes and thiol-containing reductive biomolecules. The degradation of the hydrogel was markedly accelerated in the presence of glutathione (GSH) or elastase in vitro. Particularly, dynamic mechanical analysis revealed a remarkabe decrease in the storage moduli from 3.3 kPa to 0.51 kPa within 12 h in the presence of 0.8 mmol/L GSH, and the influence of GSH treatment on the hydrogel was also clearly demonstrated by changing pore structure in scanning electron microscopy (SEM) images. After subcutaneous injection into rats, PLG/PEG hydrogel linked with disulfide bonds completely degraded in 6 days and displayed obviously enhanced degradation rate compared to the counterpart without disulfide bonds. Moreover, MTT assay showed that nearly 90% of L929 cells remained viable after incubation with PLG-SS-Norb or PEG-T at concentrations up to 1 g/L. The live/dead cell staining assay and the histology analysis showed that the polypeptide hydrogel exhibited good cytocompatibility in vitro and histocompatibility in vivo.
- Injectable hydrogel,
- Poly(amino acid),
- Diels-Alder reaction,
- Biomolecule-sensitivity,
- Polypeptid
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