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化学进展 2022, Vol. 34 Issue (6): 1359-1368 DOI: 10.7536/PC210633 前一篇   后一篇

• 综述与评论 •

丝素蛋白3D打印在生物医学领域中的应用

古孝雪, 于晶, 杨明英, 帅亚俊*()   

  1. 浙江大学动物科学学院应用生物资源研究所 杭州 310058
  • 收稿日期:2021-06-29 修回日期:2021-08-19 出版日期:2021-12-02 发布日期:2021-12-02
  • 通讯作者: 帅亚俊
  • 基金资助:
    国家自然科学基金青年科学基金(31800807); 浙江省基础公益研究计划(LY22E030004); 中央高校基本科研业务费专项资金项目(2020QNA6028); 国家现代农业产业技术体系(CARS-18-ZJ0501)

Silk Fibroin-Based 3D Printing Strategies for Biomedical Applications

Xiaoxue Gu, Jing Yu, Mingying Yang, Yajun Shuai()   

  1. Research Institute of Applied Bioresources, College of Animal Science, Zhejiang University,Hangzhou 310058, China
  • Received:2021-06-29 Revised:2021-08-19 Online:2021-12-02 Published:2021-12-02
  • Contact: Yajun Shuai
  • Supported by:
    National Natural Science Foundation of China(31800807); Zhejiang Provincial Science and Technology Plans(LY22E030004); Fundamental Research Funds for the Central Universities(2020QNA6028); State of Sericulture Industry Technology System(CARS-18-ZJ0501)

增材制造,也称为三维(3D)打印,正推动制造、工程、医学等领域的全面创新升级。3D打印技术由于能够个性化定制生物的复杂3D微结构,构建仿生的功能化活组织或人工器官,近十年来在生物医学领域中取得了长足的发展。丝素蛋白(SF)是一种来源丰富、生物可降解、力学性能优良、细胞相容性极佳的天然有机高分子,为3D打印墨水的设计提供了一种有前景的选择。然而,作为结构蛋白,单一组分的SF具有的生理功能有限,且其经过打印后的稳定性较差,限制了SF在3D打印以及生物医药领域中的进一步发展。为此,研究人员通过化学改性技术和先进3D打印技术相结合,使得改性后的SF能够更适用于3D打印,并发展成为一种具有应用价值的生物材料。本文综述了SF的结构特征、SF的化学修饰策略、打印墨水的制备策略以及3D打印SF材料在生物医学领域的最新应用进展,并展望了3D打印SF生物材料的未来发展趋势,为其在更广阔领域的应用提供一定的借鉴。

Additive manufacturing, also known as three-dimensional (3D) printing, drives comprehensive innovations and upgrades in manufacturing, engineering, medicine, and other fields. 3D printing technology has made great progress in the biomedicine field in the past decade due to its ability to customize the complex 3D microstructures of organisms and construct biomimetic functional living tissues or artificial organs. In addition, silk fibroin (SF) is a natural organic polymer with abundant sources, biodegradable, excellent mechanical properties, and good cytocompatibility, which provides a promising choice for the design of 3D-printing inks. However, as a structural protein, single-component SF has limited physiological functions, and poor stability after printing, which limits the further development of SF in 3D printing and biomedical fields. For these reasons, researchers combined advanced 3D printing technologies with chemical modification methods to make the modified SF easy to be used for 3D printing and develop into a valuable biomaterial. Here, this article reviews the structural characteristics of SF, chemical modification strategies of SF, preparation strategies of printing inks and the latest application progress of 3D printed SF materials in the biomedical field. Meanwhile, we also look forward to the future development trend of 3D printed SF biomaterials, which provides a useful guideline for its application in a wider field.

Contents

1 Introduction

2 The structures and characteristics of SF

3 Preparation strategies of bio-inks

3.1 Compounding with polymers

3.2 Compounding with inorganics

3.3 Self cross-linking

3.4 Chemical modification

4 3D printing technologies

4.1 Inkjet

4.2 Extrusion

4.3 Photo-curing

5 Applications in the field of biomedical

5.1 Blood vessel regeneration

5.2 Cartilage repair

5.3 Bone repair

5.4 Skin healing

6 Conclusions and outlook

()
表1 SF基生物墨水的性能
Table 1 The properties of bio-inks based on SF
图1 SF-OBC支架在体外的细胞相容性和细胞反应[36]。(a)培养3天的细胞活死染色图,(b)和(c)为培养7天。(d)LESCs的激光共聚焦显微镜(LCSM)图像。(e)扫描电子显微镜(SEM)图。(f)为(e)的放大图。(g)和(h)为培养7天后的免疫荧光染色。(i)细胞活力
Fig. 1 Cytocompatibility and cellular response of SF-OBC scaffold[36]. (a) The live and dead staining images for 3 days, and (b) and (c) for 7 days. (d) LSCM of LESCs. (e) SEM of the cells/scaffold. (f) is the magnification of (e). (g) and (h) are the immunofluorescence staining of LESCs. (i) Cell viability. Copyright 2021, Springer Nature
图2 3D打印Sil-MA得到的复杂器官结构[40]
Fig. 2 3D printed products using Sil-MA ink showed complex organ structures[40]. Copyright 2018, Nature Communications
图3 水凝胶机械稳定性评价[60]。(a)高分子量SF酶促交联(SF-E5)支架和光交联(SF-P5)支架比较。(b)低分子量SF酶促交联(SF-E30)支架和光交联(SF-P30)支架比较
Fig. 3 Mechanical stability of hydrogel[60]. (a) Enzymatic reaction high molecular weight silk fibroin (SF-E5) and photocrosslinking reaction high molecular weight Silk fibroin (SF-P5). (b) Enzymatic reaction low molecular weight silk fibroin (SF-E30) and photocrosslinking reaction low molecular weight silk fibroin (SF-P30). Copyright 2019, Advanced Healthcare Materials
图4 喷墨、挤出式和数字光处理打印机介绍
Fig. 4 Introduction of inkjet, extrusion, and digit light processing bioprinters
表2 不同打印机性能的对比
Table 2 Comparison of bioprinter types
图5 用于全层皮肤伤口的3D打印支架[96]。(a)全层皮肤伤口。(b)覆盖打印支架的全层皮肤伤口。(c-h)新生组织的大体观察
Fig. 5 The 3D-printed scaffold material is used for full-thickness skin wounds[96]. (a) Full-thickness skin wounds. (b) A full-thickness skin wound covering the printing scaffold. (c-h) Gross observation of newly formed tissues. Copyright 2017, Springer Nature
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