中国组织工程研究

中国组织工程研究 ›› 2022, Vol. 26 ›› Issue (22): 3535-3542.doi: 10.12307/2022.282

• 纳米生物材料 nanobiomaterials • 上一篇    下一篇

细菌纳米纤维素/聚多巴胺复合管作为小口径人工血管的潜力

刘  亮1，2，3，胡高铨1，2，3，韦  昭1，2，3，陈  琳1，2，3，洪  枫1，2，3   

  1. 1东华大学化学化工与生物工程学院，上海市  201620；2上海纳米生物材料与再生医学工程技术研究中心，上海市  201620；3中国纺织工程学会，细菌纳米纤维制造与复合技术科研基地，上海市  201620
  • 收稿日期:2020-11-20 修回日期:2021-01-16 接受日期:2021-05-23 出版日期:2022-08-08 发布日期:2022-01-12
  • 通讯作者: 洪枫，教授，东华大学化学化工与生物工程学院，上海市 201620
  • 作者简介:刘亮，男，1997年生，湖北省武汉市人，汉族，2021年东华大学化学化工与生物工程学院毕业，硕士，主要从事生物医用材料研究。
  • 基金资助:
    国家重点研发计划课题(2018YFC1105501)，项目负责人：洪枫

Potential of bacterial nanocellulose/polydopamine composite tubes as small-diameter artificial blood vessel

Liu Liang1, 2, 3, Hu Gaoquan1, 2, 3, Wei Zhao1, 2, 3, Chen Lin1, 2, 3, Hong Feng1, 2, 3   

  1. 1College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China; 2Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai 201620, China; 3Scientific Research Base of Bacterial Nanofiber Manufacturing and Composite Technology, China Textile Engineering Society, Shanghai 201620, China
  • Received:2020-11-20 Revised:2021-01-16 Accepted:2021-05-23 Online:2022-08-08 Published:2022-01-12
  • Contact: Hong Feng, Professor, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China; Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai 201620, China; Scientific Research Base of Bacterial Nanofiber Manufacturing and Composite Technology, China Textile Engineering Society, Shanghai 201620, China
  • About author:Liu Liang, Master, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China; Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai 201620, China; Scientific Research Base of Bacterial Nanofiber Manufacturing and Composite Technology, China Textile Engineering Society, Shanghai 201620, China
  • Supported by:
    National Key Research and Development Program of China, No. 2018YFC1105501 (to HF)

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摘要：

文题释义：
细菌纳米纤维素管：由木葡糖酸醋杆菌在课题组自主设计的外硅胶管反应器中原位培养制备而来。虽然细菌纳米纤维素与植物纤维素具有相同的化学组成，但是细菌纳米纤维素具有更高的化学纯度和更好的生物相容性，因此近年来细菌纳米纤维素管在人工血管领域被广泛研究。
聚多巴胺：多巴胺在碱性溶液中可发生氧化自聚合，在材料表面形成具有超强黏性的聚多巴胺层，从而实现在各种材料表面的超强黏附，聚多巴胺涂层含有大量亲水的羟基和氨基官能团，可提高材料表面的亲水性和化学多功能性，其作为中间层可将功能分子牢固结合于基材表面，近年来常被应用于材料表面的改性。

背景：临床应用上缺乏小口径(<6 mm)人工血管。
目的：探究细菌纳米纤维素/聚多巴胺(bacterial nanocellulose/polydopamine，BNC/PDA)复合管用于小口径人工血管的潜力。
方法：通过外硅胶管反应器制备细菌纳米纤维素小口径人工血管，将经纯化的纤维素管浸渍在不同质量浓度(0.1，0.5，1.0，1.5，2.0 g/L)的多巴胺溶液中进行自聚合反应，制备BNC/PDA复合管，表征细菌纳米纤维素管与BNC/PDA复合管的微观结构、红外光谱、密度、持水量、水渗透量、爆破和缝合强度、轴向力学性能及血液和细胞相容性等性质。
结果与结论：①场发射扫描电镜显示，所有管的内表面是由纳米纤维搭建的3D网络结构，纤维分布均匀、结构致密，随着多巴胺质量浓度的增加，人工血管的纤维直径增大。②随着多巴胺质量浓度的增加，人工血管的密度、爆破和缝合强度及轴向力学性能增大，水渗透量和持水量减小。③溶血率与血小板黏附实验结果显示，细菌纳米纤维素管和BNC/PDA复合管的溶血率均为不溶血等级，复合管比细菌纳米纤维素管较少黏附血小板；全血凝固实验结果显示，复合管较细菌纳米纤维素管有较强的促凝血性能。④CCK-8实验结果显示，与单纯的细菌纳米纤维素相比，BNC/PDA-0.1复合管可促进人脐静脉内皮细胞的增殖，其余4种复合管抑制了细胞的增殖，并且BNC/PDA-1.5与BNC/PDA-2.0复合管表现出明显的细胞毒性；钙黄绿素荧光染色结果显示，细菌纳米纤维素管及BNC/PDA-0.1、BNC/PDA-0.5、BNC/PDA-1.0复合管表面的细胞可持续增殖，其中BNC/PDA-0.1复合管表面的细胞数量多于细菌纳米纤维素管。⑤结果表明，BNC/PDA复合管应用于小口径人工血管有一定的潜力，且后续可进一步接枝活性大分子实现功能化。
缩略语：细菌纳米纤维素/聚多巴胺：bacterial nanocellulose/polydopamine，BNC/PDA

https://orcid.org/0000-0003-0024-1413 (刘亮) 

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

关键词: 生物材料, 人工血管, 细菌纳米纤维素, 聚多巴胺, 血液相容性, 细胞相容性, 组织工程

Abstract: BACKGROUND: There is a lack of small-caliber artificial blood vessels (< 6 mm) in clinical application. 
OBJECTIVE: To explore the potential of bacterial nanocellulose/polydopamine (BNC/PDA) composite tubes for small-caliber artificial blood vessels. 
METHODS: Bacterial nanocellulose small-caliber artificial blood vessel was prepared through an external silicone tube reactor, and the purified cellulose tube was immersed in dopamine solutions of different mass concentrations (0.1, 0.5, 1.0, 1.5, 2.0 g/L) for self polymerization reaction. After preparation of BNC/PDA composite tubes, the microstructure, infrared spectrum, density, water holding capacity, water permeability, burst and suture strength, axial mechanical properties, and blood and cell compatibility of the bacterial nanocellulose tube and BNC/PDA composite tubes were characterized. 
RESULTS AND CONCLUSION: (1) The field emission scanning electron microscope showed that the inner surface of all tubes was a 3D network structure built by nanofibers, with uniform fiber distribution and compact structure. With the increase of dopamine mass concentration, the fiber diameter of artificial blood vessels increased. (2) As the mass concentration of dopamine increased, the density, burst and suture strength and axial mechanical properties of artificial blood vessels increased, and the water penetration and water holding capacity decreased. (3) The hemolysis rate and platelet adhesion test results showed that the hemolysis rate of the bacterial nanocellulose tube and the BNC/PDA composite tubes were both non-hemolytic grades. The composite tube adhered to platelets less than the bacterial nanocellulose tube. The whole blood coagulation test results showed that the composite tubes had stronger blood coagulation performance than the bacterial nanocellulose tube. (4) CCK-8 experiment results showed that compared with simple bacterial nanocellulose, the BNC/PDA-0.1 composite tubes could promote the proliferation of human umbilical vein endothelial cells; the other four composite tubes inhibited cell proliferation; and BNC/PDA-1.5 and BNC/PDA-2.0 composite tube showed obvious cytotoxicity. The results of calcein fluorescence staining showed that the cells on the surface of the simple bacterial nanocellulose, BNC/PDA-0.1, BNC/PDA-0.5, and BNC/PDA-1.0 composite tubes could continue to proliferate, among which the number of cells on the surface of the BNC/PDA-0.1 composite tubes was more than that on simple bacterial nanocellulose. (5) The results show that the BNC/PDA composite tubes have certain potential to be used in small-caliber artificial blood vessels, and it can be further grafted with active macromolecules to achieve functionalization.

Key words: biomaterials, artificial blood vessels, bacterial nanocellulose, polydopamine, blood compatibility, cell compatibility, tissue engineering

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