药学学报, 2022, 57(4): 1002-1009
引用本文:
程佳玲, 叶军, 王洪亮, 杨艳芳, 陈智洋, 周航, 刘玉玲*. 天然来源丝素蛋白的体内外降解性与生物相容性研究进展[J]. 药学学报, 2022, 57(4): 1002-1009.
CHENG Jia-ling, YE Jun, WANG Hong-liang, YANG Yan-fang, CHEN Zhi-yang, ZHOU Hang, LIU Yu-ling*. Research progress of natural silk fibroin's degradability and biocompatibility in vitro and in vivo[J]. Acta Pharmaceutica Sinica, 2022, 57(4): 1002-1009.

天然来源丝素蛋白的体内外降解性与生物相容性研究进展
程佳玲, 叶军, 王洪亮, 杨艳芳, 陈智洋, 周航, 刘玉玲*
中国医学科学院、北京协和医学院药物研究所, 药物传输技术及新型制剂北京市重点实验室, 北京 100050
摘要:
丝素蛋白是一种天然可降解高分子聚合物,具有稳定无毒、价廉易得及无炎症反应等特点,表现出良好的可降解性和生物相容性,在生物医药领域常作为生物组织工程与药物递送载体的材料广泛应用。本综述介绍了丝素蛋白的结构与组成,以及其体内外生物降解特性与生物相容性研究方法与结果的国内外最新进展,以期为丝素蛋白的进一步深入研究与应用提供参考。
关键词:    丝素蛋白      可降解性      生物相容性      生物组织工程      药物递送系统     
Research progress of natural silk fibroin's degradability and biocompatibility in vitro and in vivo
CHENG Jia-ling, YE Jun, WANG Hong-liang, YANG Yan-fang, CHEN Zhi-yang, ZHOU Hang, LIU Yu-ling*
Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
Silk fibroin is a kind of natural biodegradable polymer, which is stable, non-toxic, cheap and easy to obtain, and has no inflammatory reaction. Silk fibroin shows satisfactory degradability and biocompatibility, widely used as a promising material for biological tissue engineering and drug delivery carrier in the biomedical field. This review introduces the structure and constituent of silk fibroin, summarizes the research progress and methods of evaluating biodegradability and biocompatibility in vivo and in vitro, which provides reference for further research and application of silk fibroin.
Key words:    silk fibroin    degradability    biocompatibility    biological tissue engineering    drug delivery system   
收稿日期: 2021-11-19
DOI: 10.16438/j.0513-4870.2021-1658
基金项目: “十三五”国家科技重大专项(2018ZX09721003,2018ZX09711001);中国医学科学院医学与健康科技创新工程项目(2021-1-I2M-026);国家药典委员会药品标准制修订研究课题(2021Y26).
通讯作者: 刘玉玲,Tel:86-10-83160332,E-mail:ylliu@imm.ac.cn
Email: ylliu@imm.ac.cn
相关功能
PDF(1350KB) Free
打印本文
0
作者相关文章
程佳玲  在本刊中的所有文章
叶军  在本刊中的所有文章
王洪亮  在本刊中的所有文章
杨艳芳  在本刊中的所有文章
陈智洋  在本刊中的所有文章
周航  在本刊中的所有文章
刘玉玲*  在本刊中的所有文章

参考文献:
[1] Zhang X, Liu Y, Zuo Q, et al. 3D bioprinting of biomimetic bilayered scaffold consisting of decellularized extracellular matrix and silk fibroin for osteochondral repair[J]. Int J Bioprint, 2021, 7:85-98.
[2] Parkes M, Myant C, Dini D, et al. Tribology-optimised silk protein hydrogels for articular cartilage repair[J]. Tribol Int, 2015, 89:9-18.
[3] Xu HL, Chen PP, Zhuge DL, et al. Liposomes with silk fibroin hydrogel core to stabilize bFGF and promote the wound healing of mice with deep second-degree scald[J]. Adv Healthc Mater, 2017, 6:1700344.
[4] Suyamud C, Phetdee C, Jaimalai T, et al. Silk fibroin-coated liposomes as biomimetic nanocarrier for long-term release delivery system in cancer therapy[J]. Molecules, 2021, 26:4936-4946.
[5] Rezaei F, Damoogh S, Reis RL, et al. Dual drug delivery system based on pH-sensitive silk fibroin/alginate nanoparticles entrapped in PNIPAM hydrogel for treating severe infected burn wound[J]. Biofabrication, 2020, 13:015005.
[6] Liu YK, Fan JC, Lv MQ, et al. Photocrosslinking silver nanoparticles-aloe vera-silk fibroin composite hydrogel for treatment of full-thickness cutaneous wounds[J]. Regen Biomater, 2021, 8:rbab048.
[7] Huang X, Fu Q, Deng YX, et al. Surface roughness of silk fibroin/alginate microspheres for rapid hemostasis in vitro and in vivo[J]. Carbohyd Polym, 2021, 253:117256.
[8] Han L, Xu NW, Lv SW, et al. Enhanced in vitro and in vivo efficacy of alginate/silk protein/hyaluronic acid with polypeptide microsphere delivery for tissue regeneration of articular cartilage[J]. J Biomed Nanotechnol, 2021, 17:901-909.
[9] Gough CR, Hu X. Air-spun silk-based micro-/nanofibers and thin films for drug delivery[J]. Int J Mol Sci, 2021, 22:9588-9609.
[10] Wu QT, He CH, Wang XC, et al. Sustainable antibacterial surgical suture using a facile scalable silk-fibroin-based berberine loading system[J]. ACS Biomater Sci Eng, 2021, 7:2845-2857.
[11] Hong H, Zhang D, Lin S, et al. Green electrospun silk fibroin nanofibers loaded with cationic ethosomes for transdermal drug delivery[J]. Chem Res Chin Univ, 2021, 37:488-495.
[12] Wu H, Liu S, Xiao L, et al. Injectable and pH-responsive silk nanofiber hydrogels for sustained anticancer drug delivery[J]. ACS Appl Mater Interfaces, 2016, 8:17118-17126.
[13] Numata K, Kaplan DL. Silk-based delivery systems of bioactive molecules[J]. Adv Drug Deliv Rev, 2010, 62:1497-1508.
[14] Liu H, Ge Z, Wang Y, et al. Modification of sericin-free silk fibers for ligament tissue engineering application[J]. J Biomed Mater Res B Appl Biomater, 2007, 82:129-138.
[15] Inoue S, Tanaka K, Arisaka F, et al. Silk fibroin of Bombyx mori is secreted, assembling a high molecular mass elementary unit consisting of H-chain, L-chain, and P25, with a 6:6:1 molar ratio[J]. J Biol Chem, 2000, 275:40517-40528.
[16] Nguyen AT, Huang QL, Yang Z, et al. Crystal networks in silk fibrous materials:from hierarchical structure to ultra performance[J]. Small, 2015, 11:1039-1054.
[17] Lammel AS, Hu X, Park SH, et al. Controlling silk fibroin particle features for drug delivery[J]. Biomaterials, 2010, 31:4583-4591.
[18] Johari N, Moroni L, Samadikuchaksaraei A. Tuning the conformation and mechanical properties of silk fibroin hydrogels[J]. Eur Polym J, 2020, 134:109842-109856.
[19] Dang TT, Chen AZ, Wang SB. Research progress of silk fibroin microsphere as sustained-release carrier of drug[J]. Chem Ind Eng Prog (化工进展), 2012, 31:1587-1591, 1596.
[20] Terry AE, Knight DP, Porter D, et al. pH induced changes in the rheology of silk fibroin solution from the middle division of Bombyx mori silkworm[J]. Biomacromolecules, 2004, 5:768-772.
[21] Cao Y, Wang BC, Chi SP, et al. Silk fibroin used as a drug delivery material[J]. Chin J Tissue Eng Res (中国组织工程研究), 2009, 13:1533-1536.
[22] Tu H. Preparation and Characterization of Wool Keratin/Silk Fibroin Composite Films (基于羊毛角蛋白/丝素蛋白复合膜的制备及其性能表征)[D]. Shanghai:Donghua University, 2017.
[23] Yang LQ, Yang D, Meng S, et al. Research progress of silk fibroin as drug sustained-release carrier[J]. Chin Med Biotecbnol (中国医药生物技术), 2009, 4:449-451.
[24] He ZQ. Drug sustained-release dissolution and decomposition of silk fibroin porous gel[J]. Mod Silk Sci Techno (现代丝绸科学与技术), 1999, 2:24-29.
[25] Min SJ, Hu ZW. Research on drug absorption and releasing function of fibroin and its control[J]. Chin J Biomed Eng (中国生物医学工程学报), 2002, 21:361-366.
[26] Xie X, Zheng Z, Wang X, et al. Low-density silk nanofibrous aerogels:fabrication and applications in air filtration and oil/water purification[J]. ACS Nano, 2021, 15:1048-1058.
[27] Altman GH, Diaz F, Jakuba C, et al. Silk-based biomaterials[J]. Biomaterials, 2003, 24:401-416.
[28] Wang Y, Zheng Z, Cheng Q, et al. Ductility and porosity of silk fibroin films by blending with glycerol/polyethylene glycol and adjusting the drying temperature[J]. ACS Biomater Sci Eng, 2020, 6:1176-1185.
[29] Wendt H, Hillmer A, Reimers K, et al. Artificial skin——culturing of different skin cell lines for generating an artificial skin substitute on cross-weaved spider silk fibres[J]. PLoS One, 2017, 6:e21833.
[30] Xu M, Pradhan S, Agostinacchio F, et al. Easy, scalable, robust, micropatterned silk fibroin cell substrates[J]. Adv Mater Interfaces, 2019, 6:1801822.
[31] Arai T, Freddi G, Innocenti R, et al. Biodegradation of Bombyx mori silk fibroin fibers and films[J]. J Appl Polym Sci, 2004, 91:2383-2390.
[32] Gou S, Chen N, Wu X, et al. Multi-responsive nanotheranostics with enhanced tumor penetration and oxygen self-producing capacities for multimodal synergistic cancer therapy[J]. Acta Pharm Sin B, 2021. DOI:10.1016/j.apsb.2021.07.001.
[33] Gou S, Xie D, Ma Y, et al. Injectable, thixotropic, and multiresponsive silk fibroin hydrogel for localized and synergistic tumor therapy[J]. ACS Biomater Sci Eng, 2020, 6:1052-1063.
[34] Nair LS, Laurencin CT. Biodegradable polymers as biomaterials[J]. Prog Polym Sci, 2007, 32:762-798.
[35] Joung JA, Park MN, You JY, et al. Application of food-grade proteolytic enzyme for the hydrolysis of regenerated silk fibroin from Bombyx mori[J]. J Chem, 2018, 2018:1285823.
[36] Li MZ, Ogiso M, Minoura M. Enzymatic degradation behavior of porous silk fibroin sheets[J]. Biomaterials, 2003, 24:357-365.
[37] Wang F, Zhang YQ. Bioconjugation of silk fibroin nanoparticles with enzyme and peptide and their characterization[J]. Adv Protein Chem Struct Biol, 2015, 98:263-291.
[38] Horan RL, Antle K, Collette AL, et al. In vitro degradation of silk fibroin[J]. Biomaterials, 2005, 26:3385-3393.
[39] Kurioka A, Yamazaki M, Hirano H. Primary structure and possible functions of a trypsin inhibitor of Bombyx mori[J]. Eur J Biochem, 1999, 259:120-126.
[40] Soong HK, Kenyon KR. Adverse reactions to virgin silk sutures in cataract surgery[J]. Ophthalmology, 1984, 91:479-483.
[41] Salthouse TN, Matlaga BF, Wykoff MH. Comparative tissue response to six suture materials in rabbit cornea, sclera, and ocular muscle[J]. Am J Ophthalmol, 1977, 84:224-233.
[42] Rossitch E, Bullard DE, Oakes WJ. Delayed foreign-body reaction to silk sutures in pediatric neurosurgical patients[J]. Child Nerv Syst, 1987, 3:375-378.
[43] Greenwald D, Shumway S, Albear P, et al. Mechanical comparison of 10 suture materials before and after in vivo incubation[J]. J Surg Res, 1994, 56:372-377.
[44] Bucknall TE, Teare L, Ellis H. The choice of a suture to close abdominal incisions[J]. Eur Surg Res, 1983, 15:59-66.
[45] Kojthung A, Meesilpa P, Sudatis B, et al. Effects of gamma radiation on biodegradation of Bombyx mori silk fibroin[J]. Int Biodeterior Biodegrad, 2008, 62:487-490.
[46] Zhao YH. Degradation Behaviors of Nerve Guidance Conduits Made Up of Silk Fibroin In Vitro and In Vivo (丝素蛋白导管体内外降解行为的研究)[D]. Nantong:Nantong University, 2009.
[47] Baran ET, Tuzlakoglu K, Mano JF, et al. Enzymatic degradation behavior and cytocompatibility of silk fibroin-starch-chitosan conjugate membranes[J]. Mater Sci Eng C Mater Biol Appl, 2012, 32:1314-1322.
[48] Maziz A, Leprette O, Boyer L, et al. Tuning the properties of silk fibroin biomaterial via chemical cross-linking[J]. Eur Polym J, 2018, 4:65012-65036.
[49] Panda N, Biswas A, Sukla LB, et al. Degradation mechanism and control of blended eri and tasar silk nanofiber[J]. Appl Biochem Biotechnol, 2014, 174:2403-2412.
[50] Xu Z, Qiu W, Fan X, et al. Stretchable, stable, and degradable silk fibroin enabled by mesoscopic doping for finger motion triggered color/transmittance adjustment[J]. ACS Nano, 2021, 15:12429-12437.
[51] Wen CM, Ye ST, Zhou LX, et al. Silk-induced asthma in children:a report of 64 cases[J]. Ann Allergy, 1990, 65:375-378.
[52] Kurosaki S, Otsuka H, Kunitomo M, et al. Fibroin allergy IgE mediated hypersensitivity to silk suture materials[J]. J Nippon Med Sch, 1999, 66:41-44.
[53] Wang Y, Yao D, Li L, et al. Effect of electrospun silk fibroin-silk sericin films on macrophage polarization and vascularization[J]. ACS Biomater Sci Eng, 2020, 6:3502-3512.
[54] Xiang C, Zhang Y, Guo W, et al. Biomimetic carbon nanotubes for neurological disease therapeutics as inherent medication[J]. Acta Pharm Sin B, 2020, 10:239-248.
[55] Panilaitis B, Altman GH, Chen J, et al. Macrophage responses to silk[J]. Biomaterials, 2003, 24:3079-3085.
[56] Meinel L, Hofmann S, Karageorgiou V, et al. The inflammatory responses to silk films in vitro and in vivo[J]. Biomaterials, 2005, 26:147-155.
[57] Wang Y, Rudym DD, Walsh A, et al. In vivo degradation of three-dimensional silk fibroin scaffolds[J]. Biomaterials, 2008, 29:3415-3428.
[58] Zadegan S, Vahidi B, Nourmohammadi J, et al. Biocompatibility and bioactivity behaviour of coelectrospun silk fibroin-hydroxyapatite nanofibres using formic acid[J]. Micro Nano Lett, 2018, 13:709-713.
[59] Wang D, Wang L, Lou Z, et al. Biomimetic, biocompatible and robust silk Fibroin-MXene film with stable 3D cross-link structure for flexible pressure sensors[J]. Nano Energy, 2020, 78:105252.
[60] Shen L, Guo L, Chen S, et al. Self-assembly of silica spheres on silk fibroin spheres for synthesis of porous hollow silica spheres and their in vitro biocompatibility and drug delivery property[J]. J Non Cryst Solids, 2019, 522:119557.
[61] Guo X, Lin N, Lu S, et al. Preparation and biocompatibility characterization of silk fibroin 3D scaffolds[J]. ACS Appl Bio Mater, 2021, 4:1369-1380.
[62] Heard AJ, Socrate S, Burke KA, et al. Silk-based injectable biomaterial as an alternative to cervical cerclage:an in vitro study[J]. Reprod Sci, 2013, 20:929-936.
[63] Huang L. Preparation, Structures and Properties of Silk Fibroin Based Biomimetic Tissue Engineering Scaffolds (丝素蛋白仿生组织工程支架的成型、结构与性能研究)[D]. Shanghai:Donghua University, 2020.
[64] Gisbert Roca F, Lozano Picazo P, Pérez-Rigueiro J, et al. Conduits based on the combination of hyaluronic acid and silk fibroin:characterization, in vitro studies and in vivo biocompatibility[J]. Int J Biol Macromol, 2020, 148:378-390.
[65] Xie H, Wang J, He Y, et al. Biocompatibility and safety evaluation of a silk fibroin-doped calcium polyphosphate scaffold copolymer in vitro and in vivo[J]. RSC Adv, 2017, 7:46036-46044.
[66] Moraes ML, Lima LR, Vicentini-Oliveira JC, et al. Immunosensor for the diagnostics of autoimmune hemolytic anemia (AIHA) based on immobilization of a monoclonal antibody on a layer of silk fibroin[J]. J Nanosci Nanotechnol, 2019, 19:3772-3776.
[67] Yin GB, Zhang YZ, Wang SD, et al. Study of the electrospun PLA/silk fibroin-gelatin composite nanofibrous scaffold for tissue engineering[J]. J Biomed Mater Res A, 2010, 93:158-163.
[68] Deng AH. Fabrication of the SF/PLLA Compound Tissue Engineering Scaffolds by Supercritical Fluids Technology (超临界流体技术制备丝素/聚乳酸复合组织工程支架的研究)[D]. Quanzhou:Huaqiao University, 2013.
[69] Gou SQ. Application of Silk Fibroin-based Multifunctional Nanomedicine in the Treatment of Ulcerative Colitis (基于丝素蛋白的多功能纳米药物在溃疡性结肠炎治疗中的应用)[D]. Chongqing:Southwest University, 2020.
[70] Gou S, Huang Y, Wan Y, et al. Multi-bioresponsive silk fibroin-based nanoparticles with on-demand cytoplasmic drug release capacity for CD44-targeted alleviation of ulcerative colitis[J]. Biomaterials, 2019, 212:39-54.
[71] Huang Y, Xie D, Gou S, et al. Quadruple-responsive nanoparticle-mediated targeted combination chemotherapy for metastatic breast cancer[J]. Nanoscale, 2021, 13:5765-5779.
[72] Luo Z, Dai Y, Gao H. Development and application of hyaluronic acid in tumor targeting drug delivery[J]. Acta Pharm Sin B, 2019, 9:1099-1112.
[73] Cacciotti I. Multisubstituted hydroxyapatite powders and coatings:the influence of the codoping on the hydroxyapatite performances[J]. Int J Appl Ceram Technol, 2019, 16:1864-1884.