光响应智能生物粘附材料的设计与应用★

doi:10.6023/A23090402

化学学报 ›› 2023, Vol. 81 ›› Issue (12): 1739-1753.DOI: 10.6023/A23090402 上一篇下一篇

所属专题：庆祝《化学学报》创刊90周年合辑

综述

光响应智能生物粘附材料的设计与应用^★

张恒杰, 柳坤锐, 陈显春^*(), 顾志鹏^*(), 李乙文^*()

四川大学高分子科学与工程学院高分子材料工程国家重点实验室成都 610065

投稿日期:2023-09-03 发布日期:2023-10-22

作者简介:

张恒杰, 四川大学高分子科学与工程学院李乙文教授课题组在读博士生. 于2020年和2023年分别获得青岛科技大学工学学士和四川大学工学硕士学位, 主要研究方向为智能光响应生物粘附材料的制备及应用.

柳坤锐, 四川大学高分子科学与工程学院在读硕士生. 于2020年获得四川大学工学学士学位, 主要研究方向为基于天然高分子的生物粘附材料.

陈显春, 副教授, 博士生导师, 四川大学科研院重大项目与基地管理部副部长, 2010年6月获四川大学材料学博士学位. 主要研究兴趣包括无机/有机复合生物材料.

顾志鹏, 四川大学高分子科学与工程学院特聘副研究员, 2009年和2014年在四川大学高分子科学与工程学院分别获得学士、博士学位; 2014年~2016年在四川大学华西临床医学院从事博士后研究; 2016年~2019年在中山大学生物医学工程学院任特聘副研究员(合作带头人: 吴钧教授); 现在四川大学高分子科学与工程学院李乙文课题组, 目前研究领域主要集中在利用多酚化学在不同维度实现功能材料的构筑合成、材料加工及其在抗氧化领域的应用基础研究.

李乙文, 四川大学高分子科学与工程学院教授, 国家杰出青年科学基金获得者, 2008年在中国科学技术大学获得学士学位; 2013年在美国阿克伦大学获得博士学位; 2013年~2016年在美国加州大学圣地亚哥分校从事博士后研究. 自2016年起在四川大学开始独立教学与科研工作, 主要致力于人造黑色素和功能多酚等新概念大分子材料的基础与转化研究.

★庆祝《化学学报》创刊90周年.

基金资助:
项目受国家重点研发计划(2022YFB3804400); 国家自然科学基金(52173132)

Design and Application of Light Responsive Smart Bio-adhesive Materials^★

Hengjie Zhang, Kunrui Liu, Xianchun Chen(), Zhipeng Gu(), Yiwen Li()

State Key Laboratory of Polymer Materials Engineering, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065

Received:2023-09-03 Published:2023-10-22
Contact: *E-mail: ywli@scu.edu.cn;guzhipeng2019@scu.edu.cn;chenxianchun@scu.edu.cn; Tel.: 028-85401066
About author:
★Dedicated to the 90th anniversary of Acta Chimica Sinica.
Supported by:
National Key R&D Program of China(2022YFB3804400); National Natural Science Foundation of China(52173132)

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摘要/Abstract

智能生物粘附材料是一类通过生物粘附作用粘附于组织表面, 且对外界刺激具有特定响应的新型粘合剂. 因其止血快、生物相容性好、生物粘附性强且具有智能响应效果而在外科临床应用领域受到了极大的关注. 其中, 光响应生物粘附材料因具有无接触、时空调节、严格剪裁和远程控制等独特优势, 被广泛用于伤口止血及组织修复等领域. 除了广泛应用的紫外光, 可见光和近红外光因其优异的组织穿透深度、高稳定性和低能量特性而在这类光响应生物粘附材料中受到广泛关注. 本文总结了智能响应粘附材料的响应类型, 重点介绍了近年来光响应生物粘附材料的研究进展, 包括分类、性能及其在生物医学领域的具体应用等.

关键词: 智能响应, 生物粘附材料, 生物止血, 光控设计, 水凝胶

Smart bio-adhesive materials are a new type of adhesive that could adhere to tissue surface through bio-adhesion covalent and noncovalent interactions, including hydrogen bonding, electrostatic interactions, cation-π interactions, π-π interactions, Michael addition, Schiff base, amide bond and so on, which usually has a specific response to specific external and internal stimuli, such as in vivo (chemical components, pH, oxidants and enzymes) and in vitro (temperature, ultrasound, light) trigger types. Additionally, smart bio-adhesive materials have attracted great attention in clinical surgical applications due to its numerous advantages, including fast hemostasis, good biocompatibility, strong bio-adhesion, convenient use, simple preparation, excellent repair promoting performance and smart response effect. Among them, light responsive bio-adhesive materials, including ultraviolet (UV) light, visible and near infrared (NIR) light responsive bio-adhesive materials, have unique advantages such as non-contact, spatiotemporal regulation, strict tailoring, accurate positioning, simple operation and remote control, and which have been widely used in wound healing, tissue repair, antibacterial therapy, 3D printing, biomimetics and software devices, cell coating and culture, bio-production and patterning, and other applications. In addition to the widely used UV light responsive bio-adhesive materials, visible and NIR light bio-adhesive materials have received great attention in light responsive biomedical materials and bio-adhesive applications due to its unique features, including excellent and long tissue penetration depth, high stability, low damage to cells and human tissues, and low energy dosage. In this paper, response type of smart bio-adhesive materials is reviewed, and the research progress of UV light, visible and NIR light response bio-adhesive materials in recent years is mainly introduced, including classification, performance and specific application in biomedical field.

Key words: smart response, bio-adhesive material, biological hemostasis, light control design, hydrogel

引用此文

张恒杰, 柳坤锐, 陈显春, 顾志鹏, 李乙文. 光响应智能生物粘附材料的设计与应用^★[J]. 化学学报, 2023, 81(12): 1739-1753.

Hengjie Zhang, Kunrui Liu, Xianchun Chen, Zhipeng Gu, Yiwen Li. Design and Application of Light Responsive Smart Bio-adhesive Materials^★[J]. Acta Chimica Sinica, 2023, 81(12): 1739-1753.

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图/表 11

图1. (a)生物粘附材料的智能响应体内外触发开关类型[2]及(b)生物粘附材料的智能响应触发机制[6]

Figure 1. (a) Smart response of bio-adhesive materials in vivo and in vitro trigger types[2] and (b) the smart response triggering mechanism of bioadhesive materials[6]

图2. 光响应生物粘附材料的性能如可控性、组织穿透性、生物相容性以及其他性能(如抗氧化、抗菌等)[51?-53]

Figure 2. Performance of light responsive bio-adhesive materials such as controllability, tissue penetration, biocompatibility, and other properties (such as antioxidant, antibacterial, and so on)[51?-53]

图3. (a)紫外-近红外的能量以及生物组织穿透深度. (b)光化学调节的过程及类型: 光异构化、光笼作用以及光敏效应. (c)光化学粘附的应用, 如凝胶交联、药物释放和组织粘附等[7,64]

Figure 3. (a) Energy and the penetration depth of UV and NIR responsive bio-tissues. (b) The processes and types of photochemical regulation including photo isomerization, photocage effect and photosensitization effect. (c) Applications of photochemical adhesion, such as gel crosslinking, drug release, tissue adhesion and so on[7,64]

图4. (a)双键分子的紫外光粘附[66]、(b)偶氮苯分子的紫外光粘附[67]及(c)邻硝基苄基分子的紫外光粘附[74,80]

Figure 4. (a) UV responsive adhesion of double bond molecules[66], (b) UV responsive adhesion of azobenzene molecules[67] and (c) UV responsive adhesion of o-nitrobenzyl molecules[74,80]

图5. (a)二氯联吡啶钌可见光引发剂的种类及其作用机理[85?-87]、(b)基于钌引发剂的可见光响应粘附过程及(c)含水的吡啶钌可见光引发剂及其作用机理[45,88-89]

Figure 5. (a) Types and mechanism of visible light initiators of ruthenium dichlorobipyridine[85?-87], (b) visible light responsive adhesion process based on ruthenium initiator, and (c) visible light initiator and its action mechanism of hydrous pyridine ruthenium[45,88-89]

图6. (a)近红外光响应智能生物粘附胶水的制备和机理示意图、(b)上转换纳米粒子的透射电镜图像和上转换发射光谱、(c)无猪皮和猪皮覆盖的紫外光和近红外光触发水凝胶形成的实验结果图、(d)各组第0、1和3天伤口区域的代表性照片、(e)不同组的治疗后伤口面积的统计分析及(f)治疗3天后皮肤组织的免疫组织化学H&E染色[96]

Figure 6. (a) Preparation and mechanism of NIR responsive bio-glues, (b) transmission electron microscopy images and upconversion emission spectra of UCNPs, (c) experimental results of the formation of UV and NIR light triggered hydrogel covered without pig skin and with pig skin, (d) representative photos of wound areas on days 0, 1, and 3 of different group, (e) statistical analysis of wound area after different treatment, and (f) immunohistochemical H&E staining of skin tissue after 3 days[96]

图7. (a)红外光的分类、(b)基于红外光响应二硫化钼纳米片与丙烯酰胺的凝胶化过程[41]、(c)上转换纳米粒子的转换过程、(d) 980 nm上转换纳米粒子的双键分子响应用于3D打印[13]、(e) 980 nm上转换纳米粒子的红外光响应偶氮苯药物释放[97]及(f)近红外光照射下上转换纳米粒子的吡啶钌响应过程[98]

Figure 7. (a) Classification of NIR light, (b) NIR light responsive gel process of molybdenum disulfide nanosheets and acrylamide[41], (c) conversion process of UCNPs, (d) 3D printing based on double bond molecular and 980 nm UCNPs[13], (e) NIR responsive azobenzene drug release of 980 nm UCNPs[97], and (f) pyridine ruthenium response process of UCNPs under NIR light irradiation[98]

图8. (a)基于蛇毒提取物的用于肝脏止血的光响应凝血胶水[12]、(b)基于紫外光响应的用于猪的心脏止血的邻硝基苄醇粘附[102]及(c)受贻贝启发的抗氧化、抗菌、止血和粘附的紫外光响应水凝胶伤口敷料的制备及伤口止血愈合[103]

Figure 8. (a) Light responsive coagulation glues based on snake venom extract for liver hemostasis[12], (b) adhesion of o-nitrobenzyl alcohol based on UV light response for pig cardiac hemostasis[102], and (c) preparation of mussel inspired antioxidant, antibacterial, hemostatic, adhesive UV responsive hydrogel for wound dressing and hemostatic healing[103]

图9. (a)软组织再生修复: 基于聚谷氨酸的粘附贴片通过紫外光响应粘附促进心脏组织再生修复[105]及(b)硬组织再生修复: 基于光响应的磷酸钙纳米颗粒的可注射水凝胶用于骨质疏松症的骨再生修复[106]

Figure 9. (a) Soft tissue regeneration and repair: adhesive patches based on polyglutamic acid promote heart tissue regeneration and repair through UV responsive adhesion[105], and (b) hard tissue regeneration and repair: injectable hydrogel based on light response calcium phosphate nanoparticles used for bone regeneration and repair of osteoporosis[106]

图10. (a)用作多功能伤口敷料的具有可变粘附性和光热杀菌能力的近红外光响应水凝胶[110]以及(b)用于细菌感染伤口愈合的自愈、光热、抗菌且可注射的白光响应水凝胶粘合剂[111]

Figure 10. (a) NIR responsive hydrogels with variable adhesion and photothermal sterilization ability used for multifunctional wound dressing[110], and (b) self-healing, photothermal, antibacterial, injectable white light responsive hydrogels used for bacterial infection wound healing[111]

图11. 光响应生物粘附材料的其他应用: 3D打印、仿生和软体设备、细胞涂层及培养、水凝胶的生物制造和图案化

Figure 11. Other applications of light responsive bio-adhesive materials: 3D printing, biomimetics and software devices, cell coating and culture, biological production and patterning of hydrogels

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光响应智能生物粘附材料的设计与应用^★

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