可持续抗非特异性蛋白质吸附的凝血酶响应型水凝胶涂层

黄佳磊; 郁李胤; 王境鸿; 李翔; 唐增超; 李丹; 陈红

doi:10.11777/j.issn1000-3304.2021.21017

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可持续抗非特异性蛋白质吸附的凝血酶响应型水凝胶涂层

研究论文 | 更新时间：2023-05-22

- 可持续抗非特异性蛋白质吸附的凝血酶响应型水凝胶涂层
- Thrombin-responsive Hydrogel Coating with Sustainable Resistance to Nonspecific Protein Adsorption
- 高分子学报 2021年52卷第9期页码：1118-1128
- 作者机构：
  
  1.苏州大学材料与化学化工学部
  2.江苏百赛飞生物科技有限公司苏州 215123
- 作者简介：
  
  E-mail: lidan@suda.edu.cn
- 基金信息：
  
  国家重点研发计划(2016YFC1100402);国家自然科学基金(基金号 ┣22075192);21905191┫
- DOI：10.11777/j.issn1000-3304.2021.21017
  中图分类号：
- 纸质出版日期：2021-09-20，
  
  网络出版日期：2021-07-25，
  
  收稿日期：2021-01-19，
  
  修回日期：2021-03-13，
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黄佳磊,郁李胤,王境鸿等.可持续抗非特异性蛋白质吸附的凝血酶响应型水凝胶涂层[J].高分子学报,2021,52(09):1118-1128.

Huang Jia-lei,Yu Li-yin,Wang Jing-hong,et al.Thrombin-responsive Hydrogel Coating with Sustainable Resistance to Nonspecific Protein Adsorption[J].ACTA POLYMERICA SINICA,2021,52(09):1118-1128.
黄佳磊,郁李胤,王境鸿等.可持续抗非特异性蛋白质吸附的凝血酶响应型水凝胶涂层[J].高分子学报,2021,52(09):1118-1128. DOI： 10.11777/j.issn1000-3304.2021.21017.

Huang Jia-lei,Yu Li-yin,Wang Jing-hong,et al.Thrombin-responsive Hydrogel Coating with Sustainable Resistance to Nonspecific Protein Adsorption[J].ACTA POLYMERICA SINICA,2021,52(09):1118-1128. DOI： 10.11777/j.issn1000-3304.2021.21017.

摘要

仿生人体血液系统抗凝机制，在异体材料表面构建兼具生物惰性和响应性抗凝活性的涂层，是解决血液接触类器械在应用过程中引发血栓生成的理想路径. 为此，本研究设计了一种能够持续性抗非特异性蛋白吸附并可特异性抑制血栓形成的凝血酶响应性水凝胶涂层. 该涂层以聚乙二醇二丙烯酸酯(PEGDA)为主要骨架成分，结合凝血酶底物多肽交联剂(Pep)和纤溶活性分子——组织型纤溶酶原激活剂(t-PA)，经光致交联固定在基材表面. 在血液环境中，涂层能够有效保持抗非特异性蛋白吸附的性能. 而在血栓形成条件下，凝血酶触发水凝胶缓慢降解，释放t-PA分子，从而激发血液系统的纤溶功能溶解初生血栓. 更有意义的是，降解后的水凝胶涂层能够保持基本骨架并仍具有抗蛋白吸附性能. 本研究为优化和完善植介入器械抗血栓策略提供了新的思路.

Abstract

Constructing the surface coating with both biological inertness and responsive antithrombotic activity is an ideal way to solve the problem of foreign-material induced thrombosis in the applications of blood-contact medical devices. In this work

a thrombin-responsive hydrogel coating is designed and prepared based on one-step photocuring. The coating can sustainably resist non-specific protein adsorption and specifically inhibit thrombus formation in a thrombosis responsible way. Poly(ethylene glycol diacrylate) (PEGDA) and a thrombin-cleavable peptide (Pep) were used in the photo-initiated polymerization system. PEGDA worked as the main skeleton component as well as crosslinker

and the peptide mainly as the thrombin-cleavable crosslinker. The fibrinolytic molecule

tissue plasminogen activator (t-PA)

was loaded during the hydrogel forming. The results showed that the coating could keep resistance to non-specific protein adsorption in normal blood environment and specifically trigger the release of t-PA in the presence of thrombin so that the nascent clot can be lysed. Moreover

the hydrogel coating could maintain the basic skeleton and thus the resistance to protein adsorption could be kept even after degradation by thrombin. In general

this research provides new ideas for optimizing the anti-thrombotic properties of blood contacting medical devices.

关键词

抗蛋白吸附水凝胶涂层抗血栓表面纤溶

Keywords

Anti-protein adsorptionHydrogel coatingAnti-thrombotic surfaceFibrinolysis

references

Sukavaneshvar S. Adv Drug Deliv Rev, 2017, 112: 24-34. doi:10.1016/j.addr.2016.07.009http://dx.doi.org/10.1016/j.addr.2016.07.009

Reviakine I, Jung F, Braune S, Brash J L, Latour R, Gorbet M, van Oeveren W. Blood Rev, 2017, 31(1): 11-21. doi:10.1016/j.blre.2016.07.003http://dx.doi.org/10.1016/j.blre.2016.07.003

Mackman N. Nature, 2008, 451(7181): 914-918. doi:10.1038/nature06797http://dx.doi.org/10.1038/nature06797

Stricker R B, Wong D, Shiu D T, Reyes P T, Shuman M A. Blood, 1986, 68(1): 275-280. doi:10.1182/blood.v68.1.275.bloodjournal681275http://dx.doi.org/10.1182/blood.v68.1.275.bloodjournal681275

Liu X, Yuan L, Li D, Tang Z, Wang Y, Chen G, Chen H, Brash J L. J Mater Chem B, 2014, 2(35): 5718-5738. doi:10.1039/c4tb00881bhttp://dx.doi.org/10.1039/c4tb00881b

Qi P, Maitz M F, Huang N. Surf Coat Technol, 2013, 233: 80-90. doi:10.1016/j.surfcoat.2013.02.008http://dx.doi.org/10.1016/j.surfcoat.2013.02.008

Gorbet M B, Sefton M V. Biomaterials, 2004, 25(26): 5681-5703. doi:10.1016/j.biomaterials.2004.01.023http://dx.doi.org/10.1016/j.biomaterials.2004.01.023

Liu S, Feng X, Jin R, Li G. Expert Opin Drug Del, 2018, 15(2): 173-184. doi:10.1080/17425247.2018.1384464http://dx.doi.org/10.1080/17425247.2018.1384464

Biran R, Pond D. Adv Drug Deliv Rev, 2017, 112: 12-23. doi:10.1016/j.addr.2016.12.002http://dx.doi.org/10.1016/j.addr.2016.12.002

Drozdov A S, Vinogradov V V, Dudanov I P, Vinogradov V V. Sci Rep, 2016, 6(1): 28119. doi:10.1038/srep28119http://dx.doi.org/10.1038/srep28119

Wu C, Zhou Y, Wang H, Hu J, Wang X. J Saudi Chem Soc, 2019, 23(8): 1080-1089. doi:10.1016/j.jscs.2019.05.011http://dx.doi.org/10.1016/j.jscs.2019.05.011

Lowe S, O'Brien-Simpson N M, Connal L A. Polym Chem, 2015, 6(2): 198-212. doi:10.1039/c4py01356ehttp://dx.doi.org/10.1039/c4py01356e

Zhang G, Lu S, Zhang L, Meng Q, Shen C, Zhang J. J Membr Sci, 2013, 436: 163-173. doi:10.1016/j.memsci.2013.02.009http://dx.doi.org/10.1016/j.memsci.2013.02.009

Kostina N Y, Sharifi S, de Los Santos Pereira A, Michalek J, Grijpma D W, Rodriguez-Emmenegger C. J Mater Chem B, 2013, 1(41): 5644-5650. doi:10.1039/c3tb20704hhttp://dx.doi.org/10.1039/c3tb20704h

Irfan M, Basri H, Irfan M, Lau W J. RSC Adv, 2015, 5(116): 95421-95432. doi:10.1039/c5ra11344jhttp://dx.doi.org/10.1039/c5ra11344j

Sun M, Su Y, Mu C, Jiang Z. Ind Eng Chem Res, 2010, 49(2): 790-796. doi:10.1021/ie900560ehttp://dx.doi.org/10.1021/ie900560e

Vales T P, Jee J P, Lee W Y, Cho S, Lee G M, Kim H J, Kim J S. Materials, 2020, 13(4):943-955. doi:10.3390/ma13040943http://dx.doi.org/10.3390/ma13040943

Sin M C, Sun Y M, Chang Y. ACS Appl Mater Interfaces, 2014, 6(2): 861-873. doi:10.1021/am4041256http://dx.doi.org/10.1021/am4041256

Chen S, Li L, Zhao C, Zheng J. Polymer, 2010, 51(23): 5283-5293. doi:10.1016/j.polymer.2010.08.022http://dx.doi.org/10.1016/j.polymer.2010.08.022

Vinogradov V V, Drozdov A S, Mingabudinova L R, Shabanova E M, Kolchina N O, Anastasova E I, Markova A A, Shtil A A, Milichko V A, Starova G L, Precker R L M, Vinogradov A V, Hey-Hawkins E, Pidko E A. J Mater Chem B, 2018, 6(16): 2450-2459. doi:10.1039/c8tb00072ghttp://dx.doi.org/10.1039/c8tb00072g

Alibeik S, Zhu S, Brash J L. Colloids Surf B, 2010, 81(2): 389-396. doi:10.1016/j.colsurfb.2010.07.024http://dx.doi.org/10.1016/j.colsurfb.2010.07.024

Nilsson P H, Engberg A E, Back J, Faxalv L, Lindahl T L, Nilsson B, Ekdahl K N. Biomaterials, 2010, 31(16): 4484-4491. doi:10.1016/j.biomaterials.2010.02.036http://dx.doi.org/10.1016/j.biomaterials.2010.02.036

Senatore F, Bernath F, Meisner K. J Biomed Mater Res, 1986, 20(2): 177-188. doi:10.1002/jbm.820200207http://dx.doi.org/10.1002/jbm.820200207

Chapurina Y, Vinogradov V V, Vinogradov A V, Sobolev V E, Dudanov I P, Vinogradov V V. J Med Chem, 2015, 58(15): 6313-6317. doi:10.1021/acs.jmedchem.5b00654http://dx.doi.org/10.1021/acs.jmedchem.5b00654

Wu Z, Chen H, Li D, Brash J L. Acta Biomater, 2011, 7(5): 1993-1998. doi:10.1016/j.actbio.2011.01.026http://dx.doi.org/10.1016/j.actbio.2011.01.026

Mackman N, Bergmeier W, Stouffer G A, Weitz J I. Nat Rev Drug Discov, 2020, 19(5): 333-352. doi:10.1038/s41573-020-0061-0http://dx.doi.org/10.1038/s41573-020-0061-0

Gunawan S T, Kempe K, Bonnard T, Cui J, Alt K, Law L S, Wang X, Westein E, Such G K, Peter K, Hagemeyer C E, Caruso F. Adv Mater Technol, 2015, 27(35): 5153-5157. doi:10.1002/adma.201502243http://dx.doi.org/10.1002/adma.201502243

Li C, Du H, Yang A, Jiang S, Li Z, Li D, Brash J L, Chen H. Adv Funct Mater, 2017, 27(45): 1703931-1703934. doi:10.1002/adfm.201703934http://dx.doi.org/10.1002/adfm.201703934

Gao Y, Hou M, Yang R, Zhang L, Xu Z, Kang Y, Xue P. Macromol Mater Eng, 2018, 303(12): 1800233. doi:10.1002/mame.201800233http://dx.doi.org/10.1002/mame.201800233

Nemir S, Hayenga H N, West J L. Biotechnol Bioeng, 2010, 105(3): 636-644. doi:10.1002/bit.22574http://dx.doi.org/10.1002/bit.22574

Ayhan F, Ozkan S. Drug Deliv, 2007, 14(7): 433-439. doi:10.1080/10717540701202911http://dx.doi.org/10.1080/10717540701202911

Gombotz W R, Wang G H, Horbett T A, Hoffman A S. J Biomed Mater Res, 1991, 25(12): 1547-1562. doi:10.1002/jbm.820251211http://dx.doi.org/10.1002/jbm.820251211

Jeon S I, Andrade J D. J Colloid Interface Sci, 1991, 142(1): 159-166. doi:10.1016/0021-9797(91)90044-9http://dx.doi.org/10.1016/0021-9797(91)90044-9

Gombotz W R, Guanghui W, Hoffman A S. J Appl Polym Sci, 1989, 37(1): 91-107. doi:10.1002/app.1989.070370108http://dx.doi.org/10.1002/app.1989.070370108

Li D, Chen H, Wang S, Wu Z, Brash J L. Acta Biomater, 2011, 7(3): 954-958. doi:10.1016/j.actbio.2010.10.021http://dx.doi.org/10.1016/j.actbio.2010.10.021

Li D, Wang S, Wu Z, Chen H, Brash J L. Soft Matter, 2013, 9(7): 2321-2328. doi:10.1039/c2sm27306chttp://dx.doi.org/10.1039/c2sm27306c

Chen H, Chen Y, Sheardown H, Brook M A. Biomaterials, 2005, 26(35): 7418-7424. doi:10.1016/j.biomaterials.2005.05.053http://dx.doi.org/10.1016/j.biomaterials.2005.05.053

Zheng J, Song W, Huang H, Chen H. Colloid Surface B, 2010, 77(2): 234-239. doi:10.1016/j.colsurfb.2010.01.032http://dx.doi.org/10.1016/j.colsurfb.2010.01.032

Du H, Li C, Luan Y, Liu Q, Yang W, Yu Q, Li D, Brash J L, Chen H. Mater Horiz, 2016, 3(6): 556-562. doi:10.1039/c6mh00307ahttp://dx.doi.org/10.1039/c6mh00307a

Huang D, Wu K, Zhang Y, Ni Z, Zhu X, Zhu C, Yang J, ZhuGe Q, Hu J. Rev Adv Mater Sci, 2019, 58(1): 159-170. doi:10.1515/rams-2019-0024http://dx.doi.org/10.1515/rams-2019-0024

Chang M, Lin Y H, Gabayno J L, Li Q, Liu X. Bioengineered, 2017, 8(1): 29-35. doi:10.1080/21655979.2016.1227145http://dx.doi.org/10.1080/21655979.2016.1227145

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血液接触材料表面抗血栓改性新策略:构建纤溶活性表面