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化学进展 2022, Vol. 34 Issue (3): 568-579 DOI: 10.7536/PC210613 前一篇   后一篇

• 综述 •

肽自组装水凝胶的制备及在生物医学中的应用

李红1, 史晓丹1, 李洁龄2,*()   

  1. 1 西安石油大学化学化工学院 西安 710065
    2 中国科学院过程工程研究所生化工程国家重点实验室 北京 100190
  • 收稿日期:2021-06-16 修回日期:2021-08-23 出版日期:2021-09-27 发布日期:2021-09-27
  • 通讯作者: 李洁龄
  • 基金资助:
    国家自然科学基金项目(22072155); 国家自然科学基金项目(21703169); 陕西省创新人才推进计划-青年科技新星项目(2021KJXX-39)

Self-Assembled Peptide Hydrogel for Biomedical Applications

Hong Li1, Xiaodan Shi1, Jieling Li2()   

  1. 1 College of Chemistry and Chemical Engineering, Xi'an Shiyou University,Xi'an 710065, China
    2 State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences,Beijing 100190, China
  • Received:2021-06-16 Revised:2021-08-23 Online:2021-09-27 Published:2021-09-27
  • Contact: Jieling Li
  • Supported by:
    National Natural Science Foundation of China(22072155); National Natural Science Foundation of China(21703169); Scientific Research Plan of Shaanxi Province of China(2021KJXX-39)

短肽自组装水凝胶作为一种新型的生物材料,具有生物相容性高、免疫原性低、含水量高、降解产物可被机体重吸收利用、结构与天然细胞外基质类似等优点,使其在材料科学、生物医药及临床医学等领域具有广阔的应用前景。在这篇综述中,我们主要介绍了常用的几种制备稳定的肽自组装水凝胶方法,包括酶催化的水凝胶化、化学/物理交联的水凝胶化以及光催化的水凝胶化。进一步,我们介绍一些关于肽自组装水凝胶在药物递送和抗肿瘤治疗、抗菌和伤口愈合以及3D生物打印和组织工程中的应用。我们希望通过本文的论述能引起更多的人对肽自组装水凝胶的关注,以推进其在生物医学领域应用的发展。

As a new type of biological material, short peptide self-assembled hydrogel holds the advantages of high biocompatibility, low immunogenicity, high water content, degradation products that can be absorbed by the body, and structure similar to natural extracellular matrix. It has broad application prospects in the fields of materials science, biomedicine and clinical medicine. In this review, we mainly introduce several commonly used methods for preparing stable and tough peptide self-assembled hydrogels, including enzyme-catalyzed hydrogelation and chemical/physical cross-linked hydrogelation and photocatalytic hydrogelation. Furthermore, some applications of peptide self-assembled hydrogels in drug delivery and anti-tumor therapy, antibacterial and wound healing, 3D bioprinting and tissue engineering are introduced. We hope that the discussion in this review can arouse more people's attention to peptide self-assembled hydrogels and promote the development of their applications in the biomedical field.

Contents

1 Introduction

2 Preparation of peptide self-assembled hydrogel

2.1 Enzyme-catalyzed hydrogelation

2.2 Chemical/physical cross-linked hydrogelation

2.3 Photocatalytic hydrogelation

3 Biomedical applications

3.1 Drug delivery and anti-tumor therapy

3.2 Antibacterial and wound healing

3.3 3D bioprinting and tissue engineering

4 Conclusion and perspective

()
图1 离子诱导酶网络结构的改变调控肽的组装结构示意图[49]
Fig.1 Schematic diagram of the regulation of peptide assembled structure by changing the structure of the ion-induced enzyme network[49]
图2 A) 肽分子结构式;B)水凝胶形貌表征图;C) 水凝胶可注射性表征;D) 3D打印水凝胶支架[54]
Fig.2 A) Peptide molecular structure; B) Morphology characterization of the hydrogel; C) Injectability characterization of the hydrogel; D) 3D printed hydrogel scaffold[54]
图3 Ru ( b p y ) 3 2 +介导的含酪氨酸短肽的光致化学交联以制备稳定性增强的肽基水凝胶示意图[59]
Fig.3 Schematic of Ru ( b p y ) 3 2 + mediated photocross-linking of tyrosine contained peptide for hydrogel formation with enhanced mechanical stability[59]
表1 肽自组装水凝胶制备方法汇总表
Table 1 Summary table of preparation methods for self-assembled peptide hydrogels
图4 A) 肽分子结构式;B) G3 (G(IIKK)3-NH2) 在含与不含MMP-2的Ac-I3SLGK-NH2凝胶中的释放情况;C) NIH 3T3 和 HeLa 细胞在负载和未负载 G3 的两种肽凝胶上孵育 24 h 后的存活率[65]
Fig.4 A) Molecular structures of the designed peptides; B) G3 (G(IIKK)3-NH2) release from the G3-loaded Ac-I3SLGK-NH2+MMP2 and Ac-I3SLGK-NH2 gels in the presence and absence of MMP-2; C) Viability of NIH 3T3 and HeLa cells on the two peptide gels with and without G3 loading. After incubation for 24 h, the cell viability was determined by MTT assays[65]
图5 A) 静电相互作用驱动的Fmoc-FF/PLL-SH共组装形成水凝胶的示意图; B) 在有或没有 Fmoc-FF/PLL-SH 水凝胶处理的情况下的肿瘤组织生长情况,其中插图为水凝胶植入12 天后切除的 B16 肿瘤组织的照片; C) 不同处理后 CD4+T/CD8+T 的比值[56]
Fig.5 A) Schematic diagram of the formation of Fmoc-FF/PLL-SH hydrogels based on electrostatic interaction-triggered co-assembly; B) Suppression of tumor growth with or without Fmoc-FF/PLL-SH hydrogel treatment. Images of the excised B16 tumor tissues at 12 days post implantation (inset); C) The ratio of CD4+T/CD8+T after different treatment[56]
图6 肽A9K2自组装水凝胶选择性抗菌示意图[88]
Fig.6 Schematic diagram of peptide A9K2 self-assembled hydrogel for antibacterial applications[88]
图7 全层烧伤模型示意图:A) 将预热的铝板涂在麻醉小鼠剃光的背上;然后去除受伤的皮肤并涂抹水凝胶; B) 水凝胶植入伤口部位的示意图[92]
Fig.7 Schematic representation of the full-thickness burn wound model: A) A pre-heated aluminum plaque was applied to the shaved dorsum of the anesthetized mouse; followed by the removal of the injured skin and the application of the hydrogel. B) A schematic of the hydrogel-implanted wound site[92]
图8 A) 脂肪族超短肽的分子结构; B)肽自组装水凝胶可连续注射性能表征; C)通过连续沉积肽溶液和含有细胞和/或小分子的 PBS 缓冲液打印的液滴阵列;D)在水凝胶中培养人胚胎干细胞H1[96]
Fig.8 A) Molecular structure of aliphatic ultrashort peptides; B) characterization of continuous injectable properties of peptide assembled hydrogel by extruding hydrogel into a concentrated salt bath; C) printed droplet arrays via sequential deposition of peptide and PBS containing cells and/or small molecules; D) Human H1 embryonic stem cells encapsulated in the hydrogels[96]
图9 肽组装水凝胶中碳纳米管的存在对细胞行为影响的示意图[98]
Fig.9 Effect of presence of SWNTs in the peptide assembled hydrogel on the cell behavior[98]
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