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化学进展 2019, Vol. 31 Issue (11): 1576-1590 DOI: 10.7536/PC190432 前一篇   后一篇

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调控细胞迁移和组织再生的生物材料研究

左新钢, 张昊岚, 周同, 高长有**()   

  1. 浙江大学教育部高分子合成与功能构造重点实验室 高分子科学与工程学系 杭州 310027
  • 收稿日期:2019-04-23 出版日期:2019-11-15 发布日期:2019-10-23
  • 通讯作者: 高长有
  • 基金资助:
    国家自然科学基金项目(51873188); 国家自然科学基金项目(21434006)
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Biomaterials for Regulating Cell Migration and Tissue Regeneration

Xingang Zuo, Haolan Zhang, Tong Zhou, Changyou Gao**()   

  1. MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China
  • Received:2019-04-23 Online:2019-11-15 Published:2019-10-23
  • Contact: Changyou Gao
  • About author:
    ** E-mail:
  • Supported by:
    National Natural Science Foundation of China(51873188); National Natural Science Foundation of China(21434006)

组织再生材料为细胞、组织的生长提供必要的物质基础,维持再生组织的形状和力学性能,并实现与周围组织的有机整合。其中,材料-细胞的相互作用是组织再生材料的核心问题。组织再生材料表界面的物理结构和化学性能可以直接影响细胞的黏附、铺展、增殖、迁移和分化等行为,进而影响组织修复和再生的效果。多数组织和器官具有立体结构,并具有更为精细的微结构。因此,三维组织再生材料体系的构建及其微结构调控是另外一个重要问题。本文结合本课题组近年的工作,综合国内外最新研究成果,重点介绍了生物材料表界面物理结构和理化性质对微粒吞噬、细胞黏附的影响、梯度材料对细胞黏附和定向迁移的作用、3D水凝胶中的细胞迁移行为及特点,以及用于皮肤和软骨组织修复与再生的植入材料,最后对生物材料在组织再生中的研究与应用进行了展望。

关键词： 生物材料, 表界面, 细胞迁移, 水凝胶, 组织工程

Regenerative biomaterials provide the necessary substances to support the growth of cells and tissues, maintain the shape and mechanical properties of regenerated tissues, and promote the integration with surrounding tissues. The surfaces and interfaces of biomaterials interact directly with cells and tissues, and thus significantly influencing on many cellular behaviors such as adhesion, spreading, proliferation, migration and differentiation as well as the outcomes of tissue repair and regeneration. Moreover, most tissues and organs possess a 3 dimensional shape with specific microstructures. Therefore, the construction of regenerative biomaterials with a 3 D shape and control over their microstructures are key issues as well. In this review, the recent works on the factors affecting cellular uptake of colloidal particles and cell adhesion are introduced. The adhesion and directional migration of cells mediated by gradient biomaterials are summarized. The latest works on migration of cells into 3 D hydrogels are reviewed. The implantable biomaterials with 3D microstructures for skin and cartilage repair and regeneration are also introduced. Finally, the application and perspectives of biomaterials in tissue regenerative are discussed.

Key words: biomaterials, surface and interface, cell migration, hydrogels, tissue engineering
()
图1 (a)PAH-Py微胶囊的制备和表面1D-NT的形成过程,(b)PAH、Py-CHO和PAH-Py的化学结构[39]
Fig. 1 (a) Schematic illustration of PAH-Py microcapsule fabrication and 1D-NT protrusion, and(b) Chemical structures of PAH, Py-CHO, and PAH-Py [39]
图2 (a)卟啉微粒(MP)和表面具有纳米粒子的卟啉微粒(MP-NP)的制备示意图;(b)PAH-g-Por的形成和分解过程化学反应机理。(c~h)PAH-g-Por微粒表面形成的纳米颗粒凸起的代表性SEM图;在pH=1 盐酸中孵育不同时间后逐渐变成刺状纳米凸起。(c)0 min,(d)10 min,(e)30 min,(f)1 h,(g)3 h和(h)6 h。(c~h)中的标尺为1 μm[38]
Fig. 2 Schematic illustrations of(a) preparation of porphyrin micro-nano particles(MP-NPs) with nano-protrudent surface and the counterpart micro-particles(MPs), and(b) chemical reaction mechanism of formation and decomposition of PAH-g-Por.(c~h) Representative SEM images show the process of nanoparticles protruding on the surface of PAH-g-Por microparticles and the gradual turning into nano-spikes after being incubated in pH 1 HCl for 0 min(c), 10 min(d), 30 min(e), 1 h(f), 3 h(g), and 6 h(h), respectively. Scale bar in(c~h) is 1 μm[38]
图3 在不对称微粒表面,分步接种成纤维(Fibroblasts)和内皮细胞(endothelial cells)得到不对接结构细胞微粒[44]
Fig. 3 Stepwise seeding of fibroblasts and endothelial cells to obtain the anisotropic cell microspheres[44]
图4 通过点击化学在聚酯条带表面修饰CQAASIKVAV多肽,促进神经细胞的取向、迁移和轴突生长[18]
Fig. 4 Fabrication process of a CQAASIKVAV peptide-modified P(LLA-MTMC) film with stripe micropatterns, which promote the alignment and directional migration of Schwann cells as well as the neurite outgrowth of PC12 cells[18]
图5 具有温度开关性能的钛纳米管对包埋的S1P具有温度依赖的释放性能[58]
Fig. 5 Titanium nanotubes modified with thermal responsive polymers for stimuli-triggering release of loaded S1P[58]
图6 (a)在聚乙二醇阻黏层上形成的VAPG梯度表面。(b)相对于成纤维细胞,VAPG的密度梯度可对平滑肌细胞进行选择黏附并调控其定向迁移[19]
Fig. 6 (a) A density gradient of VAPG peptides generated on the uniform PEG layer.(b) Influence of the VAPG density gradient on selective adhesion and migration of SMCs over FIBs [19]
图7 PHEMA/YIGSR互补梯度的形成及其对内皮细胞特异性的诱导迁移作用[71]
Fig. 7 Formation of PHEMA/YIGSR complementary gradient and induced migration of endothelial cells[71]
图8 相对于成纤维细胞,KHI/PDMAPS互补梯度表面特异性促进血旺细胞黏附和定向迁移(a);(b)KHI/PDMAPS互补梯度其制备过程示意图[72]
Fig. 8 (a) Formation of PDMAPS/KHIFSDDSSEK complementary gradient and its induced migration to Schwann cells(SCs) over fibroblasts(FIBs),(b) Schematic illustration to show the fabrication of the complementary density gradient of KHI peptides and PDMAPS, whose densities are controlled by the precursory immobilized -N3 and -C(CH3)2Br derived from BCS and BES, respectively[72]
图9 (a)三维细胞迁移模型。(b)左边为Transwell,右边为负载胶原-壳聚糖支架的Transwell[75]
Fig. 9 (a) Schematic illustration to show the model of 3D cell migration.(b)(left) the Transwell mold, and(right) the Transwell mold loaded with an actual collagen-chitosan scaffold[75]
图10 MMP交联的细胞响应性MA-HA水凝胶的合成示意图,以及平滑肌细胞在U937细胞的诱导作用下向水凝胶中的迁移行为[76]
Fig. 10 Schematic illustrations of synthesis of MMP SP-crosslinked and cell-responsive MA-HA hydrogel, into which the migration behavior of SMCs is mediated by the cocultured U937 cells on the bottom well[76]
图11 3D打印微孔道结构中血管生成示意图,以及内皮细胞在水凝胶中的定向迁移行为[77]
Fig. 11 Schematic illustrations of angiogenic sprouting from 3D-printed microchannels and directed migration behaviors of endothelial cells in hydrogels[77]
图12 (a) PLGA径向孔支架制备示意图。(b, c) PLGA径向取向孔支架示意图和宏观图片。(d) PLGA径向取向孔支架原位促进组织软骨和软骨下骨再生示意图[95]
Fig. 12 Schematic illustration to show the preparation of(a,b,c) poly(lactide-co-glycolide) scaffold(O-PLGA) with radially oriented pores through unidirectional cooling.(d) O-PLGA scaffold used for regeneration of an osteochondral defect in a rabbit model[95]
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