Chitosan-based multifunctional flexible hemostatic bio-hydrogel

被引:127
作者
Song, Fuyu [1 ]
Kong, Yue [1 ]
Shao, Changyou [1 ]
Cheng, Yi [1 ]
Lu, Jie [1 ]
Tao, Yehan [1 ]
Du, Jian [1 ]
Wang, Haisong [1 ]
机构
[1] Dalian Polytech Univ, Liaoning Key Lab Lignocellulose Chem & BioMat, Sch Light Ind & Chem Engn, Dalian 116034, Peoples R China
基金
国家重点研发计划;
关键词
Modified chitosan; Self-adhesive; Self-healing; Degradability; Stretchability; Biocompatibility; Hemostatic bio-hydrogel; TISSUE-ADHESIVE HYDROGEL; IN-VIVO; NETWORK; POLYMER; TOUGH; SCAFFOLD; GELATION; FUCOIDAN; BACTERIA; SURFACE;
D O I
10.1016/j.actbio.2021.09.056
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Realizing the potential application of chitosan as an effective biomedical hemostatic agent has become an emerging research hotspot. However, fabricating a flexible chitosan-based hemostatic bio-hydrogel with self-adhesion feature in humid conditions and rapid hemostasis capability remains a challenge. Herein, we reported the development of chitosan-based hydrogels (DCS-PEGSH gels) with typical multilevel pore structures, which were cross-linked by 3-(3,4-dihydroxyphenyl) propionic acid-modified chitosan (DCS) and sebacic acid-terminated polyethylene glycol modified by p-hydroxybenzaldehyde (PEGSH). By precisely regulating the proportion of PEGSH, the fabricated bio-hydrogels displayed favorable cytocompatibility, suitable stretchability (similar to 780%), and blood absorbability (1300% +/- 50%). Moreover, the strong adhesion (similar to 68.5 kPa) of the assembled bio-hydrogel ensured its firm adherence on pigskin and on bleeding wound in both static and dynamic humid environments without shedding, thus providing a long service life. The fabricated hydrogels exhibited shorter blood clotting time (50 s) and lower blood clotting index (BCI, 41) than the commercial chitosan sponge (288 s, BCI 65). Notably, the amount of blood loss from the liver in mice was reduced by almost 90% as compared to that for the control group. This study paves a solid way for developing a chitosan-based hydrogel with self-adhesive, self-healing, stretchability, biocompatibility, and antibacterial and antioxidant properties through molecular design and structural regulation, which will enable the biomedical application of chitosan in emergency hemostasis, particularly in joints and extremities. Statement of significance The design and preparation of multifunctional integrated green adhesive bio-hydrogels while avoiding the use of organic solvents and toxic chemical reagents has been an emerging challenge. Herein, a flexible chitosan-based hemostatic bio-hydrogel that integrates multifunctional properties was successfully synthesized. The bio-hydrogel displayed suitable stretchability (780%) and blood absorbability (1300% +/- 50%). Moreover, the strong adhesion (68.5 kPa) ensured firm adherence of the assembled hydrogel on pigskin and on the bleeding wound site in both static and dynamic humid environments without shedding, thus providing a long service life. In addition, the designed hydrogel showed good compatibility and antibacterial performance. The dynamic Schiff base endowed the bio-hydrogel with excellent self-healing performance without any external stimuli. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:170 / 183
页数:14
相关论文
共 61 条
[1]   Synthesis and Properties of Hemostatic and Bacteria-Responsive in Situ Hydrogels for Emergency Treatment in Critical Situations [J].
Bu, Yazhong ;
Zhang, Licheng ;
Liu, Jianheng ;
Zhang, Lihai ;
Li, Tongtong ;
Shen, Hong ;
Wang, Xing ;
Yang, Fei ;
Tang, Peifu ;
Wu, Decheng .
ACS APPLIED MATERIALS & INTERFACES, 2016, 8 (20) :12674-12683
[2]   Injectable drug-loaded polysaccharide hybrid hydrogels for hemostasis [J].
Cao, Jinying ;
Xiao, Ling ;
Shi, Xiaowen .
RSC ADVANCES, 2019, 9 (63) :36858-36866
[3]   High-Strength, Self-Adhesive, and Strain-Sensitive Chitosan/Poly(acrylic acid) Double-Network Nanocomposite Hydrogels Fabricated by Salt-Soaking Strategy for Flexible Sensors [J].
Cui, Chen ;
Shao, Changyou ;
Meng, Lei ;
Yang, Jun .
ACS APPLIED MATERIALS & INTERFACES, 2019, 11 (42) :39228-39237
[4]   An Autolytic High Strength Instant Adhesive Hydrogel for Emergency Self-Rescue [J].
Cui, Chunyan ;
Wu, Tengling ;
Gao, Fei ;
Fan, Chuanchuan ;
Xu, Ziyang ;
Wang, Hongbo ;
Liu, Bo ;
Liu, Wenguang .
ADVANCED FUNCTIONAL MATERIALS, 2018, 28 (42)
[5]   Chitosan-A versatile semi-synthetic polymer in biomedical applications [J].
Dash, M. ;
Chiellini, F. ;
Ottenbrite, R. M. ;
Chiellini, E. .
PROGRESS IN POLYMER SCIENCE, 2011, 36 (08) :981-1014
[6]   Electrical bioadhesive interface for bioelectronics [J].
Deng, Jue ;
Yuk, Hyunwoo ;
Wu, Jingjing ;
Varela, Claudia E. ;
Chen, Xiaoyu ;
Roche, Ellen T. ;
Guo, Chuan Fei ;
Zhao, Xuanhe .
NATURE MATERIALS, 2021, 20 (02) :229-+
[7]   A Novel Wound Dressing Based on Ag/Graphene Polymer Hydrogel: Effectively Kill Bacteria and Accelerate Wound Healing [J].
Fan, Zengjie ;
Liu, Bin ;
Wang, Jinqing ;
Zhang, Songying ;
Lin, Qianqian ;
Gong, Peiwei ;
Ma, Limin ;
Yang, Shengrong .
ADVANCED FUNCTIONAL MATERIALS, 2014, 24 (25) :3933-3943
[8]   Biodegradable poly(ester urethane)urea elastomers with variable amino content for subsequent functionalization with phosphorylcholine [J].
Fang, Jun ;
Ye, Sang-Ho ;
Shankarraman, Venkat ;
Huang, Yixian ;
Mo, Xiumei ;
Wagner, William R. .
ACTA BIOMATERIALIA, 2014, 10 (11) :4639-4649
[9]   Co-inspired hydroxyapatite-based scaffolds for vascularized bone regeneration [J].
Feng, Chun ;
Xue, Jianmin ;
Yu, Xiaopeng ;
Zhai, Dong ;
Lin, Rongcai ;
Zhang, Meng ;
Xia, Lunguo ;
Wang, Xiaoya ;
Yao, Qingqiang ;
Chang, Jiang ;
Wu, Chengtie .
ACTA BIOMATERIALIA, 2021, 119 :419-431
[10]   An intrinsically self-healing and biocompatible electroconductive hydrogel based on nanostructured nanocellulose-polyaniline complexes embedded in a viscoelastic polymer network towards flexible conductors and electrodes [J].
Han, Jingquan ;
Ding, Qinqin ;
Mei, Changtong ;
Wu, Qinglin ;
Yue, Yiying ;
Xu, Xinwu .
ELECTROCHIMICA ACTA, 2019, 318 :660-672