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化学进展 2022, Vol. 34 Issue (5): 1153-1165 DOI: 10.7536/PC210510 前一篇   后一篇

• 综述 •

材料表面性质调控细胞黏附

仲宣树1, 刘宗建2, 耿雪1, 叶霖1,*(), 冯增国1, 席家宁2,*()   

  1. 1.北京理工大学材料学院 北京 100081
    2.首都医科大学附属北京康复医院 北京 100044
  • 收稿日期:2021-05-07 修回日期:2021-07-06 出版日期:2022-05-24 发布日期:2021-07-29
  • 通讯作者: 叶霖, 席家宁
  • 作者简介:
    †These author contributed equally to this work
  • 基金资助:
    国家自然科学基金项目(2017YFC1104101)
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Regulating Cell Adhesion by Material Surface Properties

Xuanshu Zhong1, Zongjian Liu2, Xue Geng1, Lin Ye1(), Zengguo Feng1, Jianing Xi2()   

  1. 1. School of Materials, Beijing Institute of Technology,Beijing 100081, China
    2. Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100044, China
  • Received:2021-05-07 Revised:2021-07-06 Online:2022-05-24 Published:2021-07-29
  • Contact: Lin Ye, Jianing Xi
  • Supported by:
    National Natural Science Foundation of China(2017YFC1104101)

生物医用材料旨在通过调控材料和细胞之间的相互作用来实现组织的再生和修复。黏附过程直接决定了细胞是否能够充分发挥生物学性能,因此通过对材料表面的物理和化学改性来调控细胞黏附,对于生物材料具有至关重要的意义,也是非常活跃的研究热点。材料表面物理改性通常通过对包括表面粗糙度、形貌、模量和多孔结构等物理性质的调控,为细胞构建适合黏附的材料表面。而化学改性则借助于表面电荷及亲疏水性调控、促黏分子修饰等化学手段来提高材料表面与细胞间的相互作用力,进而促进细胞黏附。近年来,材料表面调控细胞黏附的研究取得了许多新的突破性进展。例如在传统的促黏分子表面修饰之外,人们逐步发现对促黏分子序构的精准调控也可以有效地提高材料表面的促黏性能。而刺激响应性表面则可以根据外界信号的刺激,使得材料表面在促黏和抗黏之间实现智能的转换。本文从物理改性、化学修饰、刺激响应性表面构建等角度出发,全面总结和讨论了材料表面性质对细胞黏附的调控作用,梳理了材料表面的设计思路,多种材料表面的修饰改性方法等最新进展,并展望了未来材料表面对细胞黏附的调控思路。

关键词： 细胞黏附, 生物医用材料, 表面修饰, 序构调控, 刺激响应性表面

Biomaterials aim to achieve tissue regeneration and repair by regulating the interaction between materials and cells. The adhesion determines whether cells could perform the expected biological functions absolutely. Therefore, it is critical for biomaterials to regulate cell adhesion by surface physical and chemical properties, which have aroused more and more attention recently. The physical modification on materials surface usually includes the regulation of surface roughness, morphology, modulus, and porous properties in order to build a suitable environment for cell adhesion. On the other hand, the chemical modifications such as surface charge and hydrophobicity regulation, covalently grafting and encapsulating adhesion-promoting molecules into the surface have made great effort to improve the interaction between the material surface and the cell, which will be capable of promoting cell adhesion. In recent years, a great number of breakthroughs have been accomplished in the field. In addition to covalently graft various adhesion-promoting molecules on the surface, it is reported that the adhesion performance would be significantly promoted by precise control of the sequence of the adhesion-promoting molecules. The sequence modulation represents a new strategy of surface modification, which can greatly enhance cell adhesion without the introduction of more powerful cell-promoting molecules or increasing their density. Besides, the intelligent change of adhesion-promoting and anti-adhesion surface can be accomplished according to the stimuli of external signals, which has been successfully applied in cell sheet tissue engineering and shows promising potential to be put into clinical application. Consequently, the review comprehensively summarizes the influences of material surface properties on cell adhesion by physical and chemical surface modification as well as the regulation of stimuli-responsive surface, the designs of adhesion-promoting surface, the technologies of adhesion-promoting surface preparation, and discusses their prospects.

Contents

1 Introduction

2 Cell adhesion regulated by surface physical properties

2.1 Surface roughness

2.2 Surface topography

2.3 Surface modulus and viscoelasticity

3 Cell adhesion regulated by surface chemical properties

3.1 Hydrophilicity and surface charge

3.2 Surface chemical modification by adhesion-promoting molecules and their sequence modulation

3.3 Surface encapsulation of adhesion-promoting molecules

4 Cell adhesion regulated by stimuli-responsive surface

4.1 Cell sheet tissue engineering

4.2 Supramolecular hydrogel with dynamic surface modulus

5 Conclusion and outlook

Key words: cell adhesion, biomedical materials, surface modification, sequence regulation, stimuli-responsive surface
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图1 细胞黏附的机理及影响因素
Fig. 1 The mechanism and influencing factors of cell adhesion
图2 表面粗糙度Sa对内皮细胞(EC)和平滑肌细胞(SMC)的选择性[22]
Fig. 2 The selective adhesion of endothelial cells (EC) and smooth muscle cells (SMC) by surface roughness Sa[22]. Copyright 2021, Elsevier Bioactive Materials
图3 促细胞黏附的多种材料表面形貌
Fig. 3 The various surface morphologies for cell adhesion
图4 肝素化学接枝改善材料表面亲水性的两种策略
Fig. 4 Two strategies of chemical grafting of heparin to improve the surface hydrophilicity of materials
图5 配体序构对细胞黏附的影响
Fig. 5 The effect of ligand sequence on cell adhesion
图6 聚轮烷的分子结构及其对细胞黏附的调控:(a)轮烷与聚轮烷的分子结构;(b)聚轮烷三嵌段共聚物与“聚轮烷环”[81];(c)“聚轮烷环”对整联蛋白的快速响应机制[84]
Fig. 6 The molecular structure of polyrotaxane and its modulation on cell adhesion: (a)Molecular structure of rotaxane and polyrotaxane; (b)Polyrotaxane triblock copolymer and "polyrotaxane loop"[81]. Copyright 2012 Elsevier Colloids & Surfaces B Biointerfaces; (c)The rapid response mechanism of "polyrotaxane loop" to integrins[84]. Copyright 2013 American Chemical Society
图7 利用多巴胺结构在各种材料表面构建功能化涂层
Fig. 7 Functional coatings on various substrates by dopamine
图8 羟基磷灰石薄膜(HAP)-TiO2-Ti复合结构
Fig. 8 Hydroxyapatite film (HAP)-TiO2 -Ti composite structure
图9 核壳结构纤维负载生物活性物质:(a)同轴电纺丝原理图;(b)核壳结构纤维的TEM照片;(c) 内皮细胞在核壳结构纤维支架上的黏附
Fig. 9 Core-shell structure fiber loading with collagen in the shell: (a) Schematic diagram of coaxial electrospinning; (b) TEM photograph of core-shell structure fiber; (c) Endothelial cells adhesion on the scaffold with core-shell structure fiber
图10 刺激响应性材料表面的构建策略
Fig. 10 Construction of stimuli-responsive materials surface for cell
图11 聚轮烷动态模量水凝胶
Fig. 11 Polyrotaxane hydrogel with dynamic modulus
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摘要

材料表面性质调控细胞黏附