基于丝素蛋白材料构建骨组织修复支架的三维多孔结构体系的研究进展

doi:10.12211/2096-8280.2022-026

合成生物学 ›› 2022, Vol. 3 ›› Issue (4): 795-809.DOI: 10.12211/2096-8280.2022-026

基于丝素蛋白材料构建骨组织修复支架的三维多孔结构体系的研究进展

邵云菲¹, 王卉¹, 朱怡然¹, 王树春¹, 姜雨淋¹, 胡建臣¹, 王晶², 张克勤¹

^1.苏州大学纺织与服装工程学院，现代丝绸国家工程实验室（苏州），纺织行业丝绸功能材料与技术重点实验室，江苏苏州 215123
^2.西安交通大学机械工程学院，陕西西安 710049

收稿日期:2022-04-28 修回日期:2022-07-12 出版日期:2022-08-31 发布日期:2022-09-08
通讯作者: 王卉,张克勤
作者简介:邵云菲（1995—），女，博士研究生。研究方向为丝素蛋白基骨组织工程支架制备及生物学应用。E-mail：361503687@qq.com
王卉（1980—），女，副教授，硕士生导师。研究方向：向自然学习，利用受生物启发的合成策略和仿生原理设计构建具有仿生微/纳多级结构的生物材料，通过研究材料表/界面拓扑结构与功能的内在联系，探索仿生结构材料诱导组织再生修复的机制，开发理想的组织再生材料。E-mail：whui@suda.edu.cn
张克勤（1972—），男，教授，博士生导师。研究方向：长期从事软物质与生物物理、生物与多功能复合纤维材料研究，同时进行功能纤维（中空纤维，结构色纤维和纳米复合纤维）的成果转化。E-mail：kqzhang@suda.edu.cn
基金资助:
国家重点研发计划(2017YFA0204600);国家自然科学基金面上项目(51873134);江苏省自然科学基金面上项目(BK20211317);江苏省丝绸工程重点实验室开放课题(KJS1833);南通市科技计划(JC2021043)

Research progress on the construction of three-dimensional porous structure of bone tissue repair scaffolds based on silk fibroin materials

Yunfei SHAO¹, Hui WANG¹, Yiran ZHU¹, Shuchun WANG¹, Yulin JIANG¹, Jianchen HU¹, Jing WANG², Keqin ZHANG¹

^1.Laboratory National Engineering Laboratory for Modern Silk （Suzhou），College of Textile and Clothing Engineering，Soochow University，Suzhou 215123，Jiangsu，China
^2.School of Mechanical Engineering，Xi'an Jiaotong University，Xi'an 710049，Shaanxi，China

Received:2022-04-28 Revised:2022-07-12 Online:2022-08-31 Published:2022-09-08
Contact: Hui WANG, Keqin ZHANG

摘要/Abstract

摘要：

随医学技术和认知水平的提高，骨组织缺损的治疗理念逐渐从组织移植向组织再生模式转变。三维（3D）多孔支架在骨组织工程研究中起着关键性的作用，是种子细胞在形成组织之前赖以生存的生物学载体，能为组织再生提供空间场所。本文针对基于丝素蛋白（SF）生物材料构建3D多孔支架的研究进展进行了总结和讨论。首先，概述了自然骨组织的多层次多孔结构特征；其次，总结了SF材料的组成和结构特征，及其卓越的生物相容性、力学性能和生物可降解性能等特性；随后，着重讨论了SF基3D骨组织修复多孔支架典型的制备技术，包括冷冻干燥法、粒子沥滤法、生物3D打印法、复合制造技术对3D支架多孔结构的控制能力，以及多孔结构对细胞生长行为和骨组织再生的影响；最后，对SF构建的骨组织修复支架所面临的挑战和发展前景进行了展望，强调了合成生物技术为解决SF基多孔支架应用于骨组织工程领域所存在的问题提供了有力的工具。

关键词: 丝素蛋白, 骨组织工程, 三维多孔支架, 结构调控

Abstract:

Bone defects caused by trauma, tumors or congenital diseases seriously affect the physical and mental health of human beings. Autologous bone and allogeneic bone transplantation are the gold standard in clinical treatment, but they have certain limitations due to their limited sources, risks of immune response and infection. In recent years, with the improvement of medical technology and cognitive level, the treatment concept of bone tissue defect has gradually changed from tissue transplantation to tissue regeneration mode. Three-dimensional (3D) porous scaffolds play a key role in bone tissue engineering research, serving as biological carriers for seed cells to survive before forming tissues, providing a space for tissue regeneration. The ideal bone tissue scaffold should have good biocompatibility, a porous structure which is conducive to the growth and differentiation of bone cells, suitable mechanical properties, and matching degradation properties. Successful 3D scaffold material design requires understanding the composition and structure of natural bone tissue, selecting appropriate biomaterials, and controllably constructing 3D porous structures at multi-scales through certain fabrication techniques. Natural bone tissue is a composite material with a hierarchical porous structure, which is composed of dense cortical bone in the outer layer and porous cancellous bone in the inner layer. From the perspective of bionics, the regulation of porous scaffolds at multiple scales is an important link in mimicking the hierarchical structure of bone tissue. Silk fibroin (SF), as a natural protein material with good biocompatibility and biodegradability, excellent mechanical properties and easy processing, has become an excellent candidate for the construction of 3D porous scaffolds. This paper summarizes and discusses the research progress of the construction of 3D porous scaffolds based on SF biomaterials. First of all, the characteristics of the multi-layered porous structure of natural bone tissue are summarized; secondly, the composition and structural characteristics of SF materials, as well as their excellent biocompatibility, mechanical properties and biodegradability are described; subsequently, the typical fabrication techniques of SF-based 3D porous scaffolds for bone tissue repair are introduced, including freeze-drying, particle leaching, 3D bioprinting, and composite manufacturing technology, and their ability to control the porous structure of 3D scaffolds, the effects of porous structure on cell growth behavior and bone tissue regeneration are also discussed; finally, the design and fabrication challenges and development prospects of SF-constructed bone tissue repair scaffolds are prosposed, emphasizing that synthetic biology could provide a powerful tool for solving the problems existing in the application of SF-based porous scaffolds in the field of bone tissue engineering.

Key words: silk fibroin, bone tissue engineering, three-dimensional porous scaffold, structure regulation

中图分类号:

Q819

邵云菲, 王卉, 朱怡然, 王树春, 姜雨淋, 胡建臣, 王晶, 张克勤. 基于丝素蛋白材料构建骨组织修复支架的三维多孔结构体系的研究进展[J]. 合成生物学, 2022, 3(4): 795-809.

Yunfei SHAO, Hui WANG, Yiran ZHU, Shuchun WANG, Yulin JIANG, Jianchen HU, Jing WANG, Keqin ZHANG. Research progress on the construction of three-dimensional porous structure of bone tissue repair scaffolds based on silk fibroin materials[J]. Synthetic Biology Journal, 2022, 3(4): 795-809.

图/表 7

图1 天然骨组织的多尺度结构［23］

Fig. 1 Schematic diagrams for the multi-scale structure of native bone tissue[23]

图2 SF的分层结构和化学结构［31］

Fig. 2 Schematic illustration of hierarchical and chemical structure of SF[31]

图3 Ca2+诱导多级多孔结构Ca/SFS支架形成过程［58］（Ca/SFS支架的SEM照片及其表面生长细胞的增殖和成骨分化情况）

Fig. 3 Schematic diagram of the formation process of Ca2+ induced multi-level porous structure Ca/SFS scaffolds, SEM micrographs of Ca/SFS scaffolds and proliferation and osteogenic differentiation of growing cells on surface [58]

图4 反蛋白石法制备SF支架的示意图及支架结构、孔径分布，盐颗粒（黑色柱）和反蛋白石（灰色柱）支架培养6周后测量的钙含量［68，71］

Fig. 4 Schematic diagram of SF scaffold prepared by inverse opal method, scaffold structure and pore size distribution, calcium content measured after 6 weeks in culture for salt-leached (black columns) and inverse opal (gray columns) scaffolds [68,71]

图5 基于3D打印法可控构建SF支架的3D多孔结构

Fig. 5 Controllable construction of 3D porous structures of SF scaffolds based on 3D print

图6 基于复合制造技术可控构建SF支架的3D多孔结构［93］

Fig. 6 Controllable construction of 3D porous structures of SF scaffolds based on composite manufacturing technology [93]

表1 不同制备方法对SF基三维骨组织修复支架的孔结构调控

Tab. 1 Pore structure regulation of SF-based 3D bone tissue repair scaffolds by different preparation methods

制备方法	调控参数	孔隙特征	可控性	优缺点	参考文献
冷冻干燥	SF浓度、二级结构、混合溶液成分、降温速度和温度	随机（各向同性）、线性（各向异性），通常在50～250 μm	简便，不太可控	有利于生物活性分子结合；孔径较小，互连性差	[47-49]
粒子沥滤	致孔剂的形状和数量	孔隙与致孔剂颗粒形貌一致，通常在200～1000 μm	较简单，一定的可控性	孔隙率高；支架厚度受到限制	[44,54-55]
生物3D打印	打印模型设计	多为十字网格形貌，间距调节范围广，可在200 μm～1 mm	快速成型，精确可控	满足不同形状骨缺损修复；仪器昂贵，墨水难制	[73,76]
复合制造技术	各工艺相关参数	宏观-介观-微观多尺度、多层级结构	多尺度，较高的可控性	获得更多层级支架；各类技术结合较难操作	[81-83]

参考文献 100

1	MÜLLER R. Hierarchical microimaging of bone structure and function[J]. Nature Reviews Rheumatology, 2009, 5(7): 373-381.
2	MA H S, FENG C, CHANG J, et al. 3D-printed bioceramic scaffolds: from bone tissue engineering to tumor therapy[J]. Acta Biomaterialia, 2018, 79: 37-59.
3	MANDAL B B, GRINBERG A, GIL E S, et al. High-strength silk protein scaffolds for bone repair[J]. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(20): 7699-7704.
4	MOHAMMADI H, SEPANTAFAR M, MUHAMAD N, et al. How does scaffold porosity conduct bone tissue regeneration? [J]. Advanced Engineering Materials, 2021, 23(10): 2100463.
5	CHOCHOLATA P, KULDA V, BABUSKA V. Fabrication of scaffolds for bone-tissue regeneration[J]. Materials, 2019, 12(4): 568.
6	NEUBAUER V J, DÖBL A, SCHEIBEL T. Silk-based materials for hard tissue engineering[J]. Materials, 2021, 14(3): 674.
7	SOUNDARYA S P, MENON A H, CHANDRAN S V, et al. Bone tissue engineering: scaffold preparation using chitosan and other biomaterials with different design and fabrication techniques[J]. International Journal of Biological Macromolecules, 2018, 119: 1228-1239.
8	SHAO Y F, QING X C, PENG Y Z, et al. Enhancement of mechanical and biological performance on hydroxyapatite/silk fibroin scaffolds facilitated by microwave-assisted mineralization strategy[J]. Colloids and Surfaces B: Biointerfaces, 2021, 197: 111401.
9	YANG Y, WANG H, ZHU J C, et al. Silk-fibroin-assisted cathodic electrolytic deposition of calcium phosphate for biomedical applications[J]. ACS Biomaterials Science & Engineering, 2019, 5(9): 4302-4310.
10	NIKOLOVA M P, CHAVALI M S. Recent advances in biomaterials for 3D scaffolds: a review[J]. Bioactive Materials, 2019, 4: 271-292.
11	RATHEESH G, VENUGOPAL J R, CHINAPPAN A, et al. 3D fabrication of polymeric scaffolds for regenerative therapy[J]. ACS Biomaterials Science & Engineering, 2017, 3(7): 1175-1194.
12	BURG K J L, PORTER S, KELLAM J F. Biomaterial developments for bone tissue engineering[J]. Biomaterials, 2000, 21(23): 2347-2359.
13	KASHTE S, JAISWAL A K, KADAM S. Artificial bone via bone tissue engineering: current scenario and challenges[J]. Tissue Engineering and Regenerative Medicine, 2017, 14(1): 1-14.
14	LIANG W Q, DONG Y Q, SHEN H L, et al. Materials science and design principles of therapeutic materials in orthopedic and bone tissue engineering[J]. Polymers for Advanced Technologies, 2021, 32(12): 4573-4586.
15	KHOSROPANAH M H, VAGHASLOO M A, SHAKIBAEI M, et al. Biomedical applications of silkworm (Bombyx mori) proteins in regenerative medicine (a narrative review)[J]. Journal of Tissue Engineering and Regenerative Medicine, 2022, 16(2): 91-109.
16	NGUYEN T P, NGUYEN Q V, NGUYEN V H, et al. Silk fibroin-based biomaterials for biomedical applications: a review[J]. Polymers, 2019, 11(12): 1933.
17	BABAIE E, BHADURI S B. Fabrication aspects of porous biomaterials in orthopedic applications: a review[J]. ACS Biomaterials Science & Engineering, 2018, 4(1): 1-39.
18	MBUNDI L, GONZÁLEZ-PÉREZ M, GONZÁLEZ-PÉREZ F, et al. Trends in the development of tailored elastin-like recombinamer-based porous biomaterials for soft and hard tissue applications [J]. Frontiers in Materials, 2021, 7: 601795.
19	SUN W Z, GREGORY D A, TOMEH M A, et al. Silk fibroin as a functional biomaterial for tissue engineering[J]. International Journal of Molecular Sciences, 2021, 22(3): 1499.
20	REZNIKOV N, SHAHAR R, WEINER S. Bone hierarchical structure in three dimensions[J]. Acta Biomaterialia, 2014, 10(9): 3815-3826.
21	DING Z Z, CHENG W N, MIA M S, et al. Silk biomaterials for bone tissue engineering[J]. Macromolecular Bioscience, 2021, 21(8): e2100153.
22	WU S L, LIU X M, YEUNG K W K, et al. Biomimetic porous scaffolds for bone tissue engineering[J]. Materials Science and Engineering: R: Reports, 2014, 80: 1-36.
23	GAO C D, PENG S P, FENG P, et al. Bone biomaterials and interactions with stem cells[J]. Bone Research, 2017, 5: 17059.
24	CHEN H, HAN Q, WANG C Y, et al. Porous scaffold design for additive manufacturing in orthopedics: a review[J]. Frontiers in Bioengineering and Biotechnology, 2020, 8: 609.
25	ZHANG M, LIN R C, WANG X, et al. 3D printing of Haversian bone-mimicking scaffolds for multicellular delivery in bone regeneration[J]. Science Advances, 2020, 6(12): eaaz6725.
26	KARAGEORGIOU V, KAPLAN D. Porosity of 3D biomaterial scaffolds and osteogenesis[J]. Biomaterials, 2005, 26(27): 5474-5491.
27	GÓMEZ S, VLAD M D, LÓPEZ J, et al. Design and properties of 3D scaffolds for bone tissue engineering[J]. Acta Biomaterialia, 2016, 42: 341-350.
28	ZHANG D W, WU X W, CHEN J D, et al. The development of collagen based composite scaffolds for bone regeneration[J]. Bioactive Materials, 2017, 3(1): 129-138.
29	PORTER J R, RUCKH T T, POPAT K C. Bone tissue engineering: a review in bone biomimetics and drug delivery strategies[J]. Biotechnology Progress, 2009, 25(6): 1539-1560.
30	LI J J, EBIED M, XU J, et al. Current approaches to bone tissue engineering: the interface between biology and engineering[J]. Advanced Healthcare Materials, 2018, 7(6): e1701061.
31	WANG C Y, XIA K L, ZHANG Y Y, et al. Silk-based advanced materials for soft electronics[J]. Accounts of Chemical Research, 2019, 52(10): 2916-2927.
32	MELKE J, MIDHA S, GHOSH S, et al. Silk fibroin as biomaterial for bone tissue engineering[J]. Acta Biomaterialia, 2016, 31: 1-16.
33	GUO C C, LI C M, MU X, et al. Engineering silk materials: from natural spinning to artificial processing[J]. Applied Physics Reviews, 2020, 7(1): 011313.
34	HOLLAND C, NUMATA K, RNJAK-KOVACINA J, et al. The biomedical use of silk: past, present, future[J]. Advanced Healthcare Materials, 2019, 8(1): e1800465.
35	ALTMAN G H, DIAZ F, JAKUBA C, et al. Silk-based biomaterials[J]. Biomaterials, 2003, 24(3): 401-416.
36	LU S Z, WANG X Q, LU Q, et al. Insoluble and flexible silk films containing glycerol[J]. Biomacromolecules, 2010, 11(1): 143-150.
37	HU X, SHMELEV K, SUN L, et al. Regulation of silk material structure by temperature-controlled water vapor annealing[J]. Biomacromolecules, 2011, 12(5): 1686-1696.
38	SARTIKA D, WANG C H, WANG D H, et al. Human adipose-derived mesenchymal stem cells-incorporated silk fibroin as a potential bio-scaffold in guiding bone regeneration[J]. Polymers, 2020, 12(4): 853.
39	LI M Z, OGISO M, MINOURA N. Enzymatic degradation behavior of porous silk fibroin sheets[J]. Biomaterials, 2003, 24(2): 357-365.
40	ZHAO C X, WU X F, ZHANG Q, et al. Enzymatic degradation of Antheraea pernyi silk fibroin 3D scaffolds and fibers[J]. International Journal of Biological Macromolecules, 2011, 48(2): 249-255.
41	CAO Y, WANG B C. Biodegradation of silk biomaterials[J]. International Journal of Molecular Sciences, 2009, 10(4): 1514-1524.
42	WANG Y Z, RUDYM D D, WALSH A, et al. In vivo degradation of three-dimensional silk fibroin scaffolds[J]. Biomaterials, 2008, 29(24/25): 3415-3428.
43	WANG Q, CHU Y Y, HE J X, et al. A graded graphene oxide-hydroxyapatite/silk fibroin biomimetic scaffold for bone tissue engineering[J]. Materials Science and Engineering: C, 2017, 80: 232-242.
44	FAROKHI M, MOTTAGHITALAB F, SAMANI S, et al. Silk fibroin/hydroxyapatite composites for bone tissue engineering[J]. Biotechnology Advances, 2018, 36(1): 68-91.
45	WU C T, ZHANG Y F, ZHOU Y H, et al. A comparative study of mesoporous glass/silk and non-mesoporous glass/silk scaffolds: physiochemistry and in vivo osteogenesis[J]. Acta Biomaterialia, 2011, 7(5): 2229-2236.
46	KASOJU N, BORA U. Silk fibroin in tissue engineering[J]. Advanced Healthcare Materials, 2012, 1(4): 393-412.
47	BAI S M, HAN H Y, HUANG X W, et al. Silk scaffolds with tunable mechanical capability for cell differentiation[J]. Acta Biomaterialia, 2015, 20: 22-31.
48	LUJERDEAN C, BACI G M, CUCU A A, et al. The contribution of silk fibroin in biomedical engineering[J]. Insects, 2022, 13(3): 286.
49	MEINEL L, FAJARDO R, HOFMANN S, et al. Silk implants for the healing of critical size bone defects[J]. Bone, 2005, 37(5): 688-698.
50	ROCKWOOD D N, PREDA R C, YÜCEL T, et al. Materials fabrication from Bombyx mori silk fibroin[J]. Nature Protocols, 2011, 6(10): 1612-1631.
51	COLLINS M N, REN G, YOUNG K, et al. Scaffold fabrication technologies and structure/function properties in bone tissue engineering[J]. Advanced Functional Materials, 2021, 31(21): 2010609.
52	CHENG N, DAI J, CHENG X R, et al. Porous CaP/silk composite scaffolds to repair femur defects in an osteoporotic model[J]. Journal of Materials Science Materials in Medicine, 2013, 24(8): 1963-1975.
53	于潇, 马勇, 郭杨, 等. 丝素支架应用于骨组织工程的研究进展[J]. 中国中医骨伤科杂志, 2021, 29(5): 84-88.
	YU X, MA Y, GUO Y, et al. Research progress of silk fibroin scaffolds used in bone tissue engineering[J]. Chinese Journal of Traditional Medical Traumatology & Orthopedics, 2021, 29(5): 84-88.
54	CORREIA C, BHUMIRATANA S, YAN L P, et al. Development of silk-based scaffolds for tissue engineering of bone from human adipose-derived stem cells[J]. Acta Biomaterialia, 2012, 8(7): 2483-2492.
55	TONG S, XU D P, LIU Z M, et al. Construction and in vitro characterization of three-dimensional silk fibroinchitosan scaffolds[J]. Dental Materials Journal, 2015, 34(4): 475-484.
56	YAN L P, SALGADO A J, OLIVEIRA J M, et al. De novo bone formation on macro/microporous silk and silk/nano-sized calcium phosphate scaffolds[J]. Journal of Bioactive and Compatible Polymers, 2013, 28(5): 439-452.
57	MANDAL B B, KUNDU S C. Cell proliferation and migration in silk fibroin 3D scaffolds[J]. Biomaterials, 2009, 30(15): 2956-2965.
58	WANG H, LIU X Y, CHUAH Y J, et al. Design and engineering of silk fibroin scaffolds with biomimetic hierarchical structures[J]. Chemical Communications, 2013, 49(14): 1431-1433.
59	BICHO D, CANADAS R F, GONÇALVES C, et al. Porous aligned ZnSr-doped β-TCP/silk fibroin scaffolds using ice-templating method for bone tissue engineering applications[J]. Journal of Biomaterials Science Polymer Edition, 2021, 32(15): 1966-1982.
60	张伟忠, 李磊, 何贺, 等. 纳米纤维大孔支架制备技术在骨组织工程研究中的应用与意义[J]. 中国组织工程研究, 2020, 24(28): 4437-4444.
	ZHANG W Z, LI L, HE H, et al. Application and significance of nanofibrous macroporous scaffold preparation technology for bone tissue engineering[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(28): 4437-4444.
61	NAZAROV R, JIN H J, KAPLAN D L. Porous 3-D scaffolds from regenerated silk fibroin[J]. Biomacromolecules, 2004, 5(3): 718-726.
62	RAJKHOWA R, GIL E S, KLUGE J, et al. Reinforcing silk scaffolds with silk particles[J]. Macromolecular Bioscience, 2010, 10(6): 599-611.
63	MANIGLIO D, BONANI W, MIGLIARESI C, et al. Silk fibroin porous scaffolds by N₂O foaming[J]. Journal of Biomaterials Science, Polymer Edition, 2018, 29(5): 491-506.
64	ZENG C, YANG Q, ZHU M F, et al. Silk fibroin porous scaffolds for nucleus pulposus tissue engineering[J]. Materials Science and Engineering: C, 2014, 37: 232-240.
65	PARK H J, LEE O J, LEE M C, et al. Fabrication of 3D porous silk scaffolds by particulate (salt/sucrose) leaching for bone tissue reconstruction[J]. International Journal of Biological Macromolecules, 2015, 78: 215-223.
66	廖银琳, 王卉, 张克勤. 医用组织工程多孔丝素支架制备方法的进展[J]. 印染, 2012, 38(10): 48-53.
	LIAO Y L, WANG H, ZHANG K Q. Advances in preparation of porous silk fibroin scaffolds for medical tissue engineering[J]. Dyeing & Finishing, 2012, 38(10): 48-53.
67	宋颖, 邓久鹏, 张炜. 骨组织工程多孔支架制备方法的研究进展[J]. 生物医学工程与临床, 2021, 25(2): 246-250.
	SONG Y, DENG J P, ZHANG W. Progress in preparation methods of porous scaffolds for bone tissue engineering[J]. Biomedical Engineering and Clinical Medicine, 2021, 25(2): 246-250.
68	ZHANG Y S, ZHU C L, XIA Y N. Inverse opal scaffolds and their biomedical applications[J]. Advanced Materials, 2017, 29(33): 1701115.
69	ZHU C, PONGKITWITOON S, QIU J, et al. Design and fabrication of a hierarchically structured scaffold for tendon-to-bone repair[J]. Advanced Materials, 2018, 30(16): e1707306.
70	ZHU C, QIU J, PONGKITWITOON S, et al. Inverse opal scaffolds with gradations in mineral content for spatial control of osteogenesis[J]. Advanced Materials, 2018, 30(29): e1706706.
71	SOMMER M R, VETSCH J R, LEEMANN J, et al. Silk fibroin scaffolds with inverse opal structure for bone tissue engineering[J]. Journal of Biomedical Materials Research Part B, Applied Biomaterials, 2017, 105(7): 2074-2084.
72	DONDERWINKEL I, VAN HEST J C M, CAMERON N R. Bio-inks for 3D bioprinting: recent advances and future prospects[J]. Polymer Chemistry, 2017, 8(31): 4451-4471.
73	RODRIGUEZ M J, DIXON T A, COHEN E, et al. 3D freeform printing of silk fibroin[J]. Acta Biomaterialia, 2018, 71: 379-387.
74	KIM S H, HONG H, AJITERU O, et al. 3D bioprinted silk fibroin hydrogels for tissue engineering[J]. Nature Protocols, 2021, 16(12): 5484-5532.
75	HUANG Y, ZHANG X F, GAO G, et al. 3D bioprinting and the current applications in tissue engineering[J]. Biotechnology Journal, 2017, 12(8): 1600734.
76	DU X Y, WEI D X, HUANG L, et al. 3D printing of mesoporous bioactive glass/silk fibroin composite scaffolds for bone tissue engineering[J]. Materials Science and Engineering: C, 2019, 103: 109731.
77	LEE H, SHIN D, SHIN S, et al. Effect of gelatin on dimensional stability of silk fibroin hydrogel structures fabricated by digital light processing 3D printing[J]. Journal of Industrial and Engineering Chemistry, 2020, 89: 119-127.
78	SCHWAB A, LEVATO R, D'ESTE M, et al. Printability and shape fidelity of bioinks in 3D bioprinting[J]. Chemical Reviews, 2020, 120(19): 11028-11055.
79	ZHENG Z Z, WU J B, LIU M, et al. 3D bioprinting of self-standing silk-based bioink[J]. Advanced Healthcare Materials, 2018, 7(6): e1701026.
80	KIM S H, YEON Y K, LEE J M, et al. Precisely printable and biocompatible silk fibroin bioink for digital light processing 3D printing[J]. Nature Communications, 2018, 9: 1620.
81	WANG Q, HAN G, YAN S, et al. 3D printing of silk fibroin for biomedical applications[J]. Materials, 2019, 12(3): E504.
82	姜雨淋, 王卉, 张克勤. 生物3D打印用丝素蛋白基凝胶墨水的研究进展[J]. 纺织学报, 2021, 42(11): 1-8.
	JIANG Y L, WANG H, ZHANG K Q. Research progress of silk fibroin-based hydrogel bioinks for 3D bio-printing[J]. Journal of Textile Research, 2021, 42(11): 1-8.
83	WEI L, WU S H, KUSS M, et al. 3D printing of silk fibroin-based hybrid scaffold treated with platelet rich plasma for bone tissue engineering[J]. Bioactive Materials, 2019, 4: 256-260.
84	VYAS C, ZHANG J, ØVREBØ Ø, et al. 3D printing of silk microparticle reinforced polycaprolactone scaffolds for tissue engineering applications[J]. Materials Science and Engineering: C, 2021, 118: 111433.
85	APPLEGATE M B, PARTLOW B P, COBURN J, et al. Photocrosslinking of silk fibroin using riboflavin for ocular prostheses[J]. Advanced Materials, 2016, 28(12): 2417-2420.
86	KURLAND N E, DEY T, KUNDU S C, et al. Precise patterning of silk microstructures using photolithography[J]. Advanced Materials, 2013, 25(43): 6207-6212.
87	PEI B Y, WANG Z K, NIE J Y, et al. Highly mineralized chitosan-based material with large size, gradient mineral distribution and hierarchical structure[J]. Carbohydrate Polymers, 2019, 208: 336-344.
88	ROOHANI-ESFAHANI S I, LU Z F, Novel ZREIQAT H., simple and reproducible method for preparation of composite hierarchal porous structure scaffolds[J]. Materials Letters, 2011, 65(17/18): 2578-2581.
89	CHISCA S, MUSTEATA V E, SOUGRAT R, et al. Artificial 3D hierarchical and isotropic porous polymeric materials[J]. Science Advances, 2018, 4(5): eaat0713.
90	DU L L, LI W, JIANG Z Y, et al. Hierarchical macro/micro-porous silk fibroin scaffolds for tissue engineering[J]. Materials Letters, 2019, 236: 1-4.
91	YAN L P, SILVA-CORREIA J, CORREIA C, et al. Bioactive macro/micro porous silk fibroin/nano-sized calcium phosphate scaffolds with potential for bone-tissue-engineering applications[J]. Nanomedicine, 2013, 8(3): 359-378.
92	李东, 张振辉, 郑程程, 等. 低温3D打印联合冷冻干燥技术制备组织工程骨支架的研究[J]. 中国修复重建外科杂志, 2016, 30(3): 292-297.
	LI D, ZHANG Z H, ZHENG C C, et al. Cytocompatibility and preparation of bone tissue engineering scaffold by combining low temperature three dimensional printing and vacuum freeze-drying techniques[J]. Chinese Journal of Reparative and Reconstructive Surgery, 2016, 30(3): 292-297.
93	SOMMER M R, SCHAFFNER M, CARNELLI D, et al. 3D printing of hierarchical silk fibroin structures[J]. ACS Applied Materials & Interfaces, 2016, 8(50): 34677-34685.
94	KARAMAT-ULLAH N, DEMIDOV Y, SCHRAMM M, et al. 3D printing of antibacterial, biocompatible, and biomimetic hybrid aerogel-based scaffolds with hierarchical porosities via integrating antibacterial peptide-modified silk fibroin with silica nanostructure[J]. ACS Biomaterials Science & Engineering, 2021, 7(9): 4545-4556.
95	LIU A P, APPEL E A, ASHBY P D, et al. The living interface between synthetic biology and biomaterial design[J]. Nature Materials, 2022, 21(4): 390-397.
96	KELWICK R J R, WEBB A J, FREEMONT P S. Biological materials: the next frontier for cell-free synthetic biology[J]. Frontiers in Bioengineering and Biotechnology, 2020, 8: 399.
97	TANG T C, AN B L, HUANG Y Y, et al. Materials design by synthetic biology[J]. Nature Reviews Materials, 2021, 6(4): 332-350.
98	KUWANA Y, SEZUTSU H, NAKAJIMA K I, et al. High-toughness silk produced by a transgenic silkworm expressing spider (Araneus ventricosus) dragline silk protein[J]. PLoS One, 2014, 9(8): e105325.
99	XU J, DONG Q L, YU Y, et al. Mass spider silk production through targeted gene replacement in Bombyx mori [J]. Proceedings of the National Academy of Sciences of the United States of America, 2018, 115(35): 8757-8762.
100	YANG Y X, QIAN Z G, ZHONG J J, et al. Hyper-production of large proteins of spider dragline silk MaSp2 by Escherichia coli via synthetic biology approacb[J]. Process Biochemistry, 2016, 51: 484-490.

[1]	刘宽庆, 张以恒. 木质素的生物降解和生物利用[J]. 合成生物学, 2023, (): 1-14.
[2]	赵国淼, 杨鑫, 张媛, 王靖, 谭剑, 魏超, 周娜娜, 李凡, 王小艳. 生物设施平台及其工业应用[J]. 合成生物学, 2023, 4(5): 892-903.
[3]	卢挥, 张芳丽, 黄磊. 合成生物学自动化装置iBioFoundry的构建与应用[J]. 合成生物学, 2023, 4(5): 877-891.
[4]	张志强, 张扬, 邱维宝, 郑海荣. 超声移液及微量移液技术进展和展望[J]. 合成生物学, 2023, 4(5): 916-931.
[5]	张晨悦, 马英群, 王兴, 傅容湛, 黄技伟, 花秀夫, 范代娣, 费强. 全碳素生物转化沼气制备生物航煤制造路线研究进展[J]. 合成生物学, 2023, (): 1-13.
[6]	马孟丹, 尚梦宇, 刘宇辰. CRISPR-Cas9系统在肿瘤生物学中的应用及前景[J]. 合成生物学, 2023, 4(4): 703-719.
[7]	王甜甜, 朱虹, 杨琛. 蓝细菌CRISPRa系统的开发及其代谢工程应用[J]. 合成生物学, 2023, 4(4): 824-839.
[8]	孙美莉, 王凯峰, 陆然, 纪晓俊. 解脂耶氏酵母底盘细胞的工程改造及应用[J]. 合成生物学, 2023, 4(4): 779-807.
[9]	孙翰, 刘进. 真核微藻脂质代谢工程的研究进展和展望[J]. 合成生物学, 2023, (): 1-21.
[10]	孟倩, 尹聪, 黄卫人. 肿瘤类器官及其在合成生物学中的研究进展[J]. 合成生物学, 2023, (): 1-11.
[11]	宋斐, 蔡志明, 黄卫人. 合成生物开启生物医药崭新篇章：预防、诊断与治疗[J]. 合成生物学, 2023, 4(2): 241-243.
[12]	高纤云, 牛灵雪, 见妮, 管宁子. 微生物合成生物学在疾病诊疗上的应用进展[J]. 合成生物学, 2023, 4(2): 263-282.
[13]	刘菱, 郑胜杰, 窦汇溪, 李骁健. 植入式脑机接口在医疗与科研中的作用与应用[J]. 合成生物学, 2023, 4(2): 407-417.
[14]	吕海龙, 王建, 吕浩, 王金, 徐勇, 顾大勇. 合成生物学在下一代基因诊断技术中的应用进展[J]. 合成生物学, 2023, 4(2): 318-332.
[15]	滕小龙, 史硕博. CRISPR/Cas9系统在基因组编辑中的优化与发展[J]. 合成生物学, 2023, 4(1): 67-85.

基于丝素蛋白材料构建骨组织修复支架的三维多孔结构体系的研究进展

Research progress on the construction of three-dimensional porous structure of bone tissue repair scaffolds based on silk fibroin materials

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 7

参考文献 100

相关文章 15

编辑推荐

Metrics

本文评价