Citation: Xiao-ya Ding, Yu Wang, Gao Li, Chun-sheng Xiao, Xue-si Chen. Iminoboronate Ester Cross-linked Hydrogels with Injectable, Self-healing and Multi-responsive Properties[J]. Acta Polymerica Sinica, ;2019, 50(5): 505-515. doi: 10.11777/j.issn1000-3304.2019.19015 shu

Iminoboronate Ester Cross-linked Hydrogels with Injectable, Self-healing and Multi-responsive Properties

Xiao-ya Ding ^1,2 ,
Yu Wang ¹ ,
Gao Li ^1,2,3 ,
Chun-sheng Xiao ^1,3,, ,
Xue-si Chen ^1,2,3

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
3.
Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022

Corresponding author: Chun-sheng Xiao, xiaocs@ciac.ac.cn
Received Date: 22 January 2019
Revised Date: 27 February 2019
Available Online: 4 April 2019

Injectable self-healing hydrogels are fancy candidates for biomedical applications, especially in such areas as minimally invasive surgical procedures, interventional therapy, and 3D bio-printing. Herein, a general and robust synthetic route to injectable self-healing hydrogels was developed based on a facile three-component reaction between the primary amine groups in hyperbranched poly(ethylenimine) (PEI), 2-formylphenylboronic acid (2-FPBA), and the cis-diols in sodium alginate (SA). Briefly, 2-FPBA reacted with PEI at first to generate a PEI/2-FPBA conjugate through forming iminoboronate bonds. The residual boronic acid groups in PEI/2-FPBA conjugate further reacted with cis-diols in the sugar unite of SA to generate iminoboronate ester linkages, thereby yielding the target product of hydrogels. The formation of iminoboronate and boronic acid ester bonds in iminoboronate ester linkages was confirmed by ¹H- and ¹¹B-NMR spectra. Dynamic rheological measurements revealed that the storage modulus (G′) of hydrogels was dependent on the feeding molar ratios of primary amine groups in PEI, 2-FPBA, and sugar units in SA. Moreover, the resulting hydrogels exhibited excellent self-healing and shear-thinning properties, given that both iminoboronate and boronic acid ester bonds are well known as dynamic covalent bonds. Based on these attributes, the hydrogels prepared were expected to have successful application in 3D printing by serving as a hydrogel " ink”. In addition, their responsiveness towards pH, H₂O₂, cysteine (Cys), glutathione (GSH), and fructose allowed an accelerated degradation process in acidic medium or in the presence of H₂O₂, Cys, GSH, or fructose; Scanning electron microscopy (SEM) observation further suggested a significant destruction of their porous structure after a period of degradation. As a result, these hydrogels proved quite applicable for the delivery of protein therapeutics with multi-responsive drug release properties. Their minimal cytotoxicity towards A549, HeLa, and L929 cells was also confirmed by the MTT assay. It is worth mentioning that with 2-FPBA functioning as the cross-linker, many other amine groups-rich polymers, even natural proteins, can be used to fabricate dynamic hydrogels with injectable, seal-healing, and multi-responsive properties. Therefore, hydrogels prepared from the strategy proposed in this study may hold tremendous potentials in tissue engineering, drug delivery, and 3D bio-printing.
- Iminoboronate,
- Boronic acid ester,
- Self-healing hydrogel,
- Injectability,
- Multi-responsiveness
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