ISSN 1000-3304CN 11-1857/O6

基于亚胺硼酸盐和硼酸酯键的可注射自修复水凝胶及其多重响应性能研究

丁晓亚 王宇 李杲 肖春生 陈学思

引用本文: 丁晓亚, 王宇, 李杲, 肖春生, 陈学思. 基于亚胺硼酸盐和硼酸酯键的可注射自修复水凝胶及其多重响应性能研究[J]. 高分子学报, 2019, 50(5): 505-515. doi: 10.11777/j.issn1000-3304.2019.19015 shu
Citation1:  Xiao-ya Ding, Yu Wang, Gao Li, Chun-sheng Xiao and 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

基于亚胺硼酸盐和硼酸酯键的可注射自修复水凝胶及其多重响应性能研究

    通讯作者: 肖春生, E-mail: xiaocs@ciac.ac.cn
  • 基金项目: 国家自然科学基金(基金号 51773196,51833010)和中国科学院青年创新促进会(项目号 2017266)资助项目

摘要: 报道了一种基于亚胺硼酸盐和硼酸酯键的动态共价交联水凝胶. 该水凝胶是通过2-甲酰基苯基硼酸(2-FPBA)与超支化聚乙烯亚胺(PEI)末端的伯胺基团和海藻酸钠(SA)糖单元上的顺式二醇反应形成亚胺硼酸盐-硼酸酯交联结构制得. 该水凝胶制备过程简单,所需高分子材料无需事先进行化学修饰;成胶条件温和,在室温下混合即可快速形成水凝胶. 流变学实验表明,水凝胶力学强度随PEI、2-FPBA和SA中反应基团比例的变化而变化. 同时,由于成胶所用化学键—亚胺硼酸盐和硼酸酯键—均为动态共价键,所得水凝胶还具有良好的自修复和可注射性能,可用作3D打印的水凝胶“墨水”. 体外降解实验结果表明,水凝胶对pH值、H2O2以及多种生物分子(如半胱氨酸、谷胱甘肽以及果糖等)都具有响应性,可用作蛋白药物响应性释放的载体. 进一步体外细胞毒性实验表明,水凝胶对细胞没有明显的毒性,具有良好的生物相容性.

English

    1. [1]

      Hoffman A S. Adv Drug Delivery Rev, 2002, 54: 3 − 12 doi: 10.1016/S0169-409X(01)00239-3

    2. [2]

      Drury J L, Mooney D J. Biomaterials, 2003, 24: 4337 − 4351 doi: 10.1016/S0142-9612(03)00340-5

    3. [3]

      Peppas N A, Hilt J Z, Khademhosseini A, Langer R. Adv Mater, 2006, 18: 1345 − 1360 doi: 10.1002/(ISSN)1521-4095

    4. [4]

      Yu L, Ding J. Chem Soc Rev, 2008, 37: 1473 − 1481 doi: 10.1039/b713009k

    5. [5]

      Duan J J, Zhang L N. Chinese J Polym Sci, 2017, 35: 1165 − 1180 doi: 10.1007/s10118-017-1983-9

    6. [6]

      Wang H, Heilshorn S C. Adv Mater, 2015, 27: 3717 − 3736 doi: 10.1002/adma.v27.25

    7. [7]

      Rosales A M, Anseth K S. Nat Rev Mater, 2016: 1 − 15

    8. [8]

      Rowan S J, Cantrill S J, Cousins, G R L, Sanders J K M, Stoddart J F. Angew Chem Int Ed, 2002, 41: 898 − 952 doi: 10.1002/1521-3773(20020315)41:6<>1.0.CO;2-R

    9. [9]

      Lehn J M. Chem Soc Rev, 2007, 36: 151 − 60 doi: 10.1039/B616752G

    10. [10]

      Jin Y, Yu C, Denman R J, Zhang W. Chem Soc Rev, 2013, 42: 6634 − 54 doi: 10.1039/c3cs60044k

    11. [11]

      Ji S, Xia J, Xu H. ACS Macro Lett, 2015, 5: 78 − 82

    12. [12]

      Zhang Yaling(张亚玲), Yang Bin(杨斌), Xu Liang(徐亮), Zhang Xiaoyong(张小勇), Tao Lei(陶磊), Wei Yen(危岩). Acta Chimica Sinica(化学学报), 2013, 71: 485 − 492

    13. [13]

      Wei Z, Yang J H, Zhou J, Xu F, Zrinyi M, Dussault P H, Osada Y, Chen Y M. Chem Soc Rev, 2014, 43: 8114 − 31 doi: 10.1039/C4CS00219A

    14. [14]

      Li Q, Liu C, Wen J, Wu Y, Shan Y, Liao J. Chin Chem Lett, 2017, 28: 1857 − 1874 doi: 10.1016/j.cclet.2017.05.007

    15. [15]

      Liu M, Zeng X, Ma C, Yi H, Ali Z, Mou X, Li S, Deng Y, He N. Bone Res, 2017, 5: 17014 doi: 10.1038/boneres.2017.14

    16. [16]

      Ye Bihua(叶碧华), Meng Lu(孟璐), Li Lihua(李立华), Li Na(李娜), Li Zhiwen(李志文), Li Riwang(李日旺), Cai Zhengwei(蔡正伟), Zhou Changren(周长忍). Acta Polymerica Sinica(高分子学报), 2016, (2): 134 − 148

    17. [17]

      Zhang Y, Tao L, Li S, Wei Y. Biomacromolecules, 2011, 12: 2894 − 2901 doi: 10.1021/bm200423f

    18. [18]

      Yang B, Zhang Y, Zhang X, Tao L, Li S, Wei Y. Polym Chem, 2012, 3: 3235 − 3238 doi: 10.1039/c2py20627g

    19. [19]

      Li Y, Wang X, Wei Y, Tao L. Chin Chem Lett, 2017, 28: 2053 − 2057 doi: 10.1016/j.cclet.2017.09.004

    20. [20]

      Zhang Y, Fu C, Li Y, Wang K, Wang X, Wei Y, Tao L. Polym Chem, 2017, 8: 537 − 544 doi: 10.1039/C6PY01704E

    21. [21]

      Qu J, Zhao X, Ma P X, Guo B. Acta Biomater, 2017, 58: 168 − 180 doi: 10.1016/j.actbio.2017.06.001

    22. [22]

      Qu J, Zhao X, Liang Y, Zhang T, Ma P X, Guo B. Biomaterials, 2018, 183: 185 − 199 doi: 10.1016/j.biomaterials.2018.08.044

    23. [23]

      Guo B, Qu J, Zhao X, Zhang M. Acta Biomater, 2019, 84: 180 − 193 doi: 10.1016/j.actbio.2018.12.008

    24. [24]

      Yesilyurt V, Webber M J, Appel E A, Godwin C, Langer R, Anderson D G. Adv Mater, 2016, 28: 86 − 91 doi: 10.1002/adma.201502902

    25. [25]

      Ding X, Li G, Xiao C, Chen X. Macromol Chem Phys, 2019, 220: 1800484 doi: 10.1002/macp.v220.3

    26. [26]

      Cao L, Cao B, Lu C, Wang G, Yu L, Ding J. J Mater Chem B, 2015, 3: 1268 − 1280 doi: 10.1039/C4TB01705F

    27. [27]

      Tseng T C, Tao L, Hsieh F Y, Wei Y, Chiu I M, Hsu S H. Adv Mater, 2015, 27: 3518 − 3524 doi: 10.1002/adma.v27.23

    28. [28]

      Wu X, He C, Wu Y, Chen X. Biomaterials, 2016, 75: 148 − 62 doi: 10.1016/j.biomaterials.2015.10.016

    29. [29]

      Deng G, Li F, Yu H, Liu F, Liu C, Sun W, Jiang H, Chen Y. ACS Macro Lett, 2012, 1: 275 − 279 doi: 10.1021/mz200195n

    30. [30]

      Grover G N, Lam J, Nguyen T H, Segura T, Maynard H D. Biomacromolecules, 2012, 13: 3013 − 3017 doi: 10.1021/bm301346e

    31. [31]

      Lou J, Liu F, Lindsay C D, Chaudhuri O, Heilshorn S C, Xia Y. Adv Mater, 2018: 1705215

    32. [32]

      Wei Z, Yang J H, Liu Z Q, Xu F, Zhou J X, Zrínyi M, Osada Y, Chen Y M. Adv Funct Mater, 2015, 25: 1352 − 1359 doi: 10.1002/adfm.v25.9

    33. [33]

      Otsuka H, Nagano S, Kobashi Y, Maeda T, Takahara A A. Chem Commun, 2010, 46: 1150 − 1152 doi: 10.1039/B916128G

    34. [34]

      Bandyopadhyay A, Gao J. J Am Chem Soc, 2016, 138: 2098 − 2101 doi: 10.1021/jacs.5b12301

    35. [35]

      Li Y, Liu Y, Ma R, Xu Y, Zhang Y, Li B, An Y, S hi, L. ACS Appl Mater Interfaces, 2017, 9: 13056 − 13067 doi: 10.1021/acsami.7b00957

    36. [36]

      Yan B, Huang J, Han L, Gong L, Li L, Israelachvili J N, Zeng H. ACS Nano, 2017, 11: 11074 − 11081 doi: 10.1021/acsnano.7b05109

    37. [37]

      Jungst T, Smolan W, Schacht K, Scheibel T, Groll J. Chem Rev, 2016, 116: 1496 − 1539 doi: 10.1021/acs.chemrev.5b00303

    38. [38]

      Wei Q, Xu M, Liao C, Wu Q, Liu M, Zhang Y, Wu C, Cheng L, Wang Q. Chem Sci, 2016, 7: 2748 − 2752 doi: 10.1039/C5SC02234G

    39. [39]

      Cal P M, Vicente J B, Pires E, Coelho A V, Veiros L F, Cordeiro C, Gois P M. J Am Chem Soc, 2016, 2012, 134: 10299 − 10305

    40. [40]

      Cambray S, Gao J. Accounts Chem Res, 2018, 51: 2198 − 2206 doi: 10.1021/acs.accounts.8b00154

    41. [41]

      Pettignano A, Grijalvo S, Haring M, Eritja R, Tanchoux N, Quignard F, Diaz Diaz D. Chem Commun, 2017, 53: 3350 − 3353 doi: 10.1039/C7CC00765E

    42. [42]

      Zhang Zhen(张震), He Chaoliang(贺超良), Xu Qinghua(徐清华), Zhuang Xiuli(庄秀丽), Chen Xuesi(陈学思). Acta Polymerica Sinica(高分子学报), 2018, (1): 99 − 108

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  • Figure 1.  Schematic illustration of the formation of hydrogel through iminoboronate ester-mediated cross-linking

    Figure 2.  (a) Formation of hydrogel by mixing SA solution with PEI+2-FPBA solution; (b) Unsuccessful gelation when simply mixing PEI and SA solution; (c) 1H-NMR and (d) 11B-NMR spectra of 2-FPBA, PEI+2-FPBA mixture, and PEI+2-FPBA+SA mixture in D2O;. (e, f) Time sweep rheological tests of hydrogels formed by PEI, 2-FPBA, and SA at different feeding ratios (X denotes the relative molar amount of primary amino groups in PEI; Y denotes the relative molar amount of 2-FPBA; Z denotes the relative molar amount of monosaccharide unite in SA.)

    Figure 3.  (a) Strain sweep rheological test of the hydrogel; (b) Time sweep rheological test of the hydrogel when the strain was switched back to 1%; (c) Time sweep rheological test of hydrogel when alternated step strain was applied (The small strain was 1%, and the large strain was 500%.); (d) Self-healing process of a heart-shaped hydrogel sample at room temperature

    Figure 4.  (a) Viscosity measurement of the hydrogel; (b) Oscillatory stress sweep test of the hydrogel; (c) Angular frequency sweep test of the hydrogel; (d) Schematic and photograph of 3D printing

    Figure 5.  Degradation behaviors of the hydrogel at different pHs (a) or in the presence of H2O2 (b), Cys (c) GSH (d), or fructose (e) at different concentrations; (f) Photographs of the hydrogels before and after degradation; (g) Mechanisms of hydrogel degradation at low pH (g1) or in the presence of H2O2 (g2), Cys (g3), GSH (g3), or fructose (g4); (h) SEM images of the hydrogels before (h1) and after degradation at low pH (h2) or in the presence of H2O2 (h3), Cys (h4), GSH (h5), or fructose (h6)

    Figure 6.  (a) In vitro drug release behaviors of BSA-FITC-loaded hydrogels in the absence or presence of 1 mmol L−1 H2O2, GSH, Cys, or fructose (Data are presented as mean ± SD with n = 3); (b) CD spectra of the BSA-FITC samples obtained after release from the hydrogels

    Figure 7.  Cytotoxicity of the hydrogel towards different cell lines

    Table 1.  Preparation and swelling properties of the hydrogels

    Sample X:Y:Z a Weight of PEI b
    (mg)
    Weight of 2-FPBAb
    (mg)
    Volume of 3 wt% SA
    solution b (μL)
    Swelling ratio
    1 1.5:0.3:1.0 7.20 1.25 200 15.4 ± 2.5
    2 1.2:0.3:1.0 5.70 1.25 200 12.9 ± 1.5
    3 1.0:0.3:1.0 4.79 1.25 200 17.0 ± 0.3
    4 0.8:0.3:1.0 3.83 1.25 200 10.9 ± 0.5
    5 0.5:0.3:1.0 2.40 1.25 200 8.0 ± 0.5
    6 1.0:0.8:1.0 4.79 3.34 200 10.4 ± 1.9
    7 1.0:0.5:1.0 4.79 2.08 200 14.2 ± 0.8
    a X denotes the relative molar amount of primary amino groups in PEI, Y denotes the relative molar amount of 2-FPBA, and Z denotes the relative molar amount of monosaccharide unite in SA; b The final concentration of PEI, 2-FPBA and SA in each sample was keep at about 5 wt%.
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  • 通讯作者:  肖春生, xiaocs@ciac.ac.cn
  • 收稿日期:  2019-01-22
  • 修稿日期:  2019-02-27
  • 网络出版日期:  2019-04-04
  • 刊出日期:  2019-05-01
通讯作者: 陈斌, bchen63@163.com
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