Please wait a minute...

中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2021, Vol. 41 Issue (5): 65-71    DOI: 10.13523/j.cb.2011019
综述     
3D生物打印在软骨修复中的应用*
朱帅,金明杰,杨树林()
南京理工大学环境与生物工程学院 南京 210094
A Review on Applications of 3D Bioprinting in Cartilage Tissue Regeneration Engineering
ZHU Shuai,JIN Ming-jie,YANG Shu-lin()
School of Environmental and Biological Engineering, Nanjing University of Science & Technology, Nanjing 210094, China
 全文: PDF(471 KB)   HTML
摘要:

关节软骨损伤后的自我修复是医学界一直在研究和探讨的难题。3D生物打印技术可以精准的分配载细胞生物材料,构建复杂的三维活体组织,在优化软骨缺损修复组织的内部结构、机械性能以及生物相容性上有很大优势,因此近年来成为软骨修复组织工程领域的研究热点。重点介绍了软骨生物3D生物打印的最新进展,包括软骨生物打印“墨水”材料的选择、种子细胞的来源以及3D生物打印技术的发展。此外,还阐述了3D生物打印技术在组织工程学应用上的部分局限性,并对其在软骨修复领域的发展与应用进行了预测。

关键词: 3D生物打印水凝胶组织工程软骨    
Abstract:

Self-repair is critical but limited on aged and damaged articular cartilages, and therefore, it is necessary to apply a suitable tissue engineering scaffold to promoting the repair and growth of the defective cartilage. 3D bioprinting can accurately distribute cell-bearing biological materials and construct complex three-dimensional living tissues or organs, and such technique becomes a hotspot in cartilage tissue engineering recently. The focus is on the latest progress of cartilage bioprinting in 3D bioprinting, including the selection of “ink” materials for cartilage bioprinting, the source of seed cells, and the development of 3D bioprinting technology. In addition, some limitations of the application of 3D bioprinting technology in tissue engineering are also explained, and its development and application in the field of cartilage repair are predicted.

Key words: 3D printing    Hydrogel    Tissue engineering    Cartilage
收稿日期: 2020-11-09 出版日期: 2021-06-01
ZTFLH:  Q819  
基金资助: * 国家高科技研究发展计划(2014AA022107)
通讯作者: 杨树林     E-mail: yangshulin@njust.edu.cn
服务  
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章  
朱帅
金明杰
杨树林

引用本文:

朱帅,金明杰,杨树林. 3D生物打印在软骨修复中的应用*[J]. 中国生物工程杂志, 2021, 41(5): 65-71.

ZHU Shuai,JIN Ming-jie,YANG Shu-lin. A Review on Applications of 3D Bioprinting in Cartilage Tissue Regeneration Engineering. China Biotechnology, 2021, 41(5): 65-71.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2011019        https://manu60.magtech.com.cn/biotech/CN/Y2021/V41/I5/65

生物材料 软骨修复能力 可打印性
琼脂糖[23] 软骨相容型 可在无支撑情况下打印
海藻酸盐[10] 软骨相容型 需要添加交联剂/增稠剂提高可打印性
硫酸藻酸盐[24] 软骨诱导型 需要利用智能交联的方法提高可打印性
甲基丙烯酸化明胶[17] 软骨相容型 需要添加交联剂/增稠剂提高可打印性
透明质酸[18] 软骨诱导型 需要添加交联剂/增稠剂提高可打印性
纤维蛋白[25] 软骨相容型 需要添加交联剂/增稠剂提高可打印性
胶原蛋白[26] 软骨相容型 胶原蛋白密度越高可打印性越好
聚乙二醇[21] 软骨相容型 需要添加交联剂/增稠剂提高可打印性
聚己内酯[22] 软骨相容型 可热熔融后打印
表1  用于CTE的生物材料
软骨细胞 间充质干细胞 胚胎干细胞
优点 来源广
提取简单
高软骨相容性
高增殖潜能
高分化潜能
免疫原性低、取材方便
增殖快
全能型
多能性
缺点 不具有分化潜能
增殖较慢
成本高
分化条件较复杂
伦理道德问题
分化方向难控制
表2  用于CTE的种子细胞
喷墨式生物打印 挤出式生物打印 激光辅助生物打印
成本 中等
适用黏度 中等 中等-高
成型时间 中等
细胞存活率 85% 40%~95% 95%
优势 低成本
易操作
高效率
可用于低黏度
材料打印
高细胞密度
高细胞存活率
适用黏度范围广
无喷头
高分辨率
高精度
高细胞密度
适用黏度范围广
(1~300 mPa/s)
劣势 适用材料有限
喷头易堵塞
低细胞密度
对细胞有潜在的
热损伤
分辨率有限
剪切力对细胞
的损伤
高成本
成型速度低
三维构建能力差
表3  用于CTE的3D生物打印方法
[1] Murphy L, Helmick C G. The impact of osteoarthritis in the United States. American Journal of Nursing, 2012,112(3):S13-S19.
doi: 10.1097/01.NAJ.0000412646.80054.21
[2] Jadin K D, Wong B L, Bae W C, et al. Depth-varying density and organization of chondrocytes in immature and mature bovine articular cartilage assessed by 3d imaging and analysis. The Journal of Histochemistry and Cytochemistry, 2005,53(9):1109-1119.
doi: 10.1369/jhc.4A6511.2005
[3] Swieszkowski W, Tuan B H S, Kurzydlowski K J, et al. Repair and regeneration of osteochondral defects in the articular joints. Biomolecular Engineering, 2007,24(5):489-495.
pmid: 17931965
[4] Prakash D, Learmonth D. Natural progression of osteo-chondral defect in the femoral condyle. The Knee, 2002,9(1):7-10.
doi: 10.1016/S0968-0160(01)00133-8
[5] Henkel J, Woodruff M A, Epari D R, et al. Bone regeneration based on tissue engineering conceptions-A 21st century perspective. Bone Research, 2013,1(1):216-248.
doi: 10.4248/BR201303002
[6] Ozbolat I T, Yu Y. Bioprinting toward organ fabrication: challenges and future trends. IEEE Transactions on Biomedical Engineering, 2013,60(3):691-699.
doi: 10.1109/TBME.2013.2243912
[7] Chou D T, Wells D, Hong D, et al. Novel processing of iron-manganese alloy-based biomaterials by inkjet 3-D printing. Acta Biomaterialia, 2013,9(10):8593-8603.
doi: 10.1016/j.actbio.2013.04.016
[8] Trachtenberg J E, Placone J K, Smith B T, et al. Extrusion-based 3D printing of poly(propylene fumarate) in a full-factorial design. ACS Biomaterials Science & Engineering, 2016,2(10):1771-1780.
[9] Mandrycky C, Wang Z J, Kim K, et al. 3D bioprinting for engineering complex tissues. Biotechnology Advances, 2016,34(4):422-434.
doi: 10.1016/j.biotechadv.2015.12.011
[10] Kesti M, Eberhardt C, Pagliccia G, et al. Bioprinting complex cartilaginous structures with clinically compliant biomaterials. Advanced Functional Materials, 2015,25(48):7406-7417.
doi: 10.1002/adfm.v25.48
[11] Markstedt K, Mantas A, Tournier I, et al. 3D bioprinting human chondrocytes with nanocellulose-alginate bioink for cartilage tissue engineering applications. Biomacromolecules, 2015,16(5):1489-1496.
doi: 10.1021/acs.biomac.5b00188 pmid: 25806996
[12] Apelgren P, Amoroso M, Lindahl A, et al. Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo. PLoS One, 2017,12(12):e0189428. DOI: 10.1371/journal.pone.0189428.
doi: 10.1371/journal.pone.0189428
[13] You F, Eames B F, Chen X B. Application of extrusion-based hydrogel bioprinting for cartilage tissue engineering. International Journal of Molecular Sciences, 2017,18(7):E1597.
[14] Müller M, Becher J, Schnabelrauch M, et al. Nanostructured Pluronic hydrogels as bioinks for 3D bioprinting. Biofabrication, 2015,7(3):035006.
doi: 10.1088/1758-5090/7/3/035006
[15] Pescosolido L, Schuurman W, Malda J, et al. Hyaluronic acid and dextran-based semi-IPN hydrogels as biomaterials for bioprinting. Biomacromolecules, 2011,12(5):1831-1838.
doi: 10.1021/bm200178w pmid: 21425854
[16] Schuurman W, Levett P A, Pot M W, et al. Gelatin-methacrylamide hydrogels as potential biomaterials for fabrication of tissue-engineered cartilage constructs. Macromolecular Bioscience, 2013,13(5):551-561.
doi: 10.1002/mabi.201200471 pmid: 23420700
[17] Costantini M, Idaszek J, Szöke K, et al. 3D bioprinting of BM-MSCs-loaded ECM biomimetic hydrogels for in vitro neocartilage formation. Biofabrication, 2016,8(3):035002.
doi: 10.1088/1758-5090/8/3/035002
[18] Lam T, Dehne T, Krüger J P, et al. Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue-engineered cartilage. Journal of Biomedical Materials Research Part B, Applied Biomaterials, 2019,107(8):2649-2657.
doi: 10.1002/jbm.v107.8
[19] Cui X F, Breitenkamp K, Finn M G, et al. Direct human cartilage repair using three-dimensional bioprinting technology. Tissue Engineering Part A, 2012,18(11-12):1304-1312.
doi: 10.1089/ten.tea.2011.0543
[20] Gao G F, Schilling A F, Hubbell K, et al. Improved properties of bone and cartilage tissue from 3D inkjet-bioprinted human mesenchymal stem cells by simultaneous deposition and photocrosslinking in PEG-GelMA. Biotechnology Letters, 2015,37(11):2349-2355.
doi: 10.1007/s10529-015-1921-2
[21] Zhu J M, Marchant R E. Design properties of hydrogel tissue-engineering scaffolds. Expert Review of Medical Devices, 2011,8(5):607-626.
doi: 10.1586/erd.11.27
[22] Ruiz-Cantu L, Gleadall A, Faris C, et al. Multi-material 3D bioprinting of porous constructs for cartilage regeneration. Materials Science and Engineering: C, 2020,109:110578.
doi: 10.1016/j.msec.2019.110578
[23] Ahn S, Lee H, Bonassar L J, et al. Cells (MC3T3-E1)-laden alginate scaffolds fabricated by a modified solid-freeform fabrication process supplemented with an aerosol spraying. Biomacromolecules, 2012,13(9):2997-3003.
doi: 10.1021/bm3011352
[24] Ahlfeld T, Cidonio G, Kilian D, et al. Development of a clay based bioink for 3D cell printing for skeletal application. Biofabrication, 2017,9(3):034103.
doi: 10.1088/1758-5090/aa7e96
[25] Levato R, Visser J, Planell J A, et al. Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers. Biofabrication, 2014,6(3):035020.
doi: 10.1088/1758-5082/6/3/035020
[26] Zhang Y S, Yue K, Aleman J, et al. 3D bioprinting for tissue and organ fabrication. Annals of Biomedical Engineering, 2017,45(1):148-163.
doi: 10.1007/s10439-016-1612-8
[27] Brittberg M, Lindahl A, Nilsson A, et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. New England Journal of Medicine, 1994,331(14):889-895.
pmid: 8078550
[28] Peterson L, Minas T, Brittberg M, et al. Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clinical Orthopaedics and Related Research, 2000, (374):212-234.
[29] Qi C, Liu J, Jin Y, et al. Photo-crosslinkable, injectable sericin hydrogel as 3D biomimetic extracellular matrix for minimally invasive repairing cartilage. Biomaterials, 2018,163:89-104.
doi: 10.1016/j.biomaterials.2018.02.016
[30] Koga H, Engebretsen L, Brinchmann J E, et al. Mesenchymal stem cell-based therapy for cartilage repair: a review. Knee Surgery, Sports Traumatology, Arthroscopy, 2009,17(11):1289-1297.
doi: 10.1007/s00167-009-0782-4
[31] 李敏, 孟祥璟, 张祥奎, 等. 水凝胶材料和间充质干细胞在组织工程中的应用进展. 中国生物医学工程学报, 2020,39(3):367-374.
Li M, Meng X J, Zhang X K, et al. Progress in application of hydrogels and mesenchymal stem cells in tissue engineering. Chinese Journal of Biomedical Engineering, 2020,39(3):367-374.
[32] Huang J I, Kazmi N, Durbhakula M M, et al. Chondrogenic potential of progenitor cells derived from human bone marrow and adipose tissue: a patient-matched comparison. Journal of Orthopaedic Research, 2005,23(6):1383-1389.
doi: 10.1016/j.orthres.2005.03.008.1100230621
[33] Sakaguchi Y, Sekiya I, Yagishita K, et al. Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis and Rheumatism, 2005,52(8):2521-2529.
pmid: 16052568
[34] Shim J H, Jang K M, Hahn S K, et al. Three-dimensional bioprinting of multilayered constructs containing human mesenchymal stromal cells for osteochondral tissue regeneration in the rabbit knee joint. Biofabrication, 2016,8(1):014102.
doi: 10.1088/1758-5090/8/1/014102
[35] Yamasaki A, Kunitomi Y, Murata D, et al. Osteochondral regeneration using constructs of mesenchymal stem cells made by bio three-dimensional printing in mini-pigs. Journal of Orthopaedic Research, 2019,37(6):1398-1408.
doi: 10.1002/jor.24206
[36] Hwang N S, Varghese S, Zhang Z J, et al. Chondrogenic differentiation of human embryonic stem cell-derived cells in arginine-Glycine-aspartate-modified hydrogels. Tissue Engineering, 2006,12(9):2695-2706.
doi: 10.1089/ten.2006.12.2695
[37] Hwang N S, Varghese S, Elisseeff J. Derivation of chondrogenically-committed cells from human embryonic cells for cartilage tissue regeneration. PLoS One, 2008,3(6):e2498. DOI: 10.1371/journal.pone.0002498.
doi: 10.1371/journal.pone.0002498
[38] Bigdeli N, Karlsson C, Strehl R, et al. Coculture of human embryonic stem cells and human articular chondrocytes results in significantly altered phenotype and improved chondrogenic differentiation. Stem Cells (Dayton, Ohio), 2009,27(8):1812-1821.
doi: 10.1002/stem.v27:8
[39] Nguyen D, Hägg D A, Forsman A, et al. Cartilage tissue engineering by the 3D bioprinting of iPS cells in a nanocellulose/alginate bioink. Scientific Reports, 2017,7:658.
doi: 10.1038/s41598-017-00690-y pmid: 28386058
[40] Medvedev S P, Grigor’Eva E V, Shevchenko A I, et al. Human induced pluripotent stem cells derived from fetal neural stem cells successfully undergo directed differentiation into cartilage. Stem Cells and Development, 2011,20(6):1099-1112.
doi: 10.1089/scd.2010.0249 pmid: 20846027
[41] Gudapati H, Yan J Y, Huang Y, et al. Alginate gelation-induced cell death during laser-assisted cell printing. Biofabrication, 2014,6(3):035022.
doi: 10.1088/1758-5082/6/3/035022
[42] Xu T, Binder K W, Albanna M Z, et al. Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications. Biofabrication, 2013,5(1):015001.
doi: 10.1088/1758-5082/5/1/015001
[43] Johnson B N, Jia X F. 3D printed nerve guidance channels: computer-aided control of geometry, physical cues, biological supplements and gradients. Neural Regeneration Research, 2016,11(10):1568-1569.
pmid: 27904481
[44] Johnson B N, Lancaster K Z, Zhen G H, et al. 3D printed anatomical nerve regeneration pathways. Advanced Functional Materials, 2015,25(39):6205-6217.
pmid: 26924958
[45] Ozbolat I T, Hospodiuk M. Current advances and future perspectives in extrusion-based bioprinting. Biomaterials, 2016,76:321-343.
doi: 10.1016/j.biomaterials.2015.10.076
[46] Jammalamadaka U, Tappa K. Recent advances in biomaterials for 3D printing and tissue engineering. Journal of Functional Biomaterials, 2018,9(1):E22.
[47] Kang H W, Lee S J, Ko I K, et al. A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nature Biotechnology, 2016,34(3):312-319.
doi: 10.1038/nbt.3413
[1] 袁小晶,尹海梦,樊晓玮,何俊林,郝石磊,季金苟. 角蛋白/海藻酸钠/聚丙烯酰胺水凝胶皮肤敷料的制备及创口修复研究[J]. 中国生物工程杂志, 2021, 41(8): 17-24.
[2] 连将儒,马伟芳. DNA水凝胶应用于环境样品快速检测的研究进展 *[J]. 中国生物工程杂志, 2021, 41(2/3): 107-115.
[3] 宋标标,顾奇. 同轴打印小直径组织工程血管*[J]. 中国生物工程杂志, 2021, 41(10): 42-51.
[4] 余幸鸽,林开利. 基于天然水凝胶的生物材料在骨组织工程中的应用*[J]. 中国生物工程杂志, 2020, 40(5): 69-77.
[5] 王元斗,宿烽,李速明. 光交联水凝胶在组织工程中的研究进展[J]. 中国生物工程杂志, 2020, 40(4): 91-96.
[6] 程平,张洋子,马翾,陈旭,朱保庆,许文涛. 刺激响应型DNA水凝胶的性质及其应用 *[J]. 中国生物工程杂志, 2020, 40(3): 132-143.
[7] 严格,乔韡华,曹红,史嘉玮,董念国. 聚多巴胺的表面修饰功能在组织工程的应用进展*[J]. 中国生物工程杂志, 2020, 40(12): 75-81.
[8] 武慧蓉,温朝辉. 壳聚糖在神经组织工程中的应用 *[J]. 中国生物工程杂志, 2019, 39(6): 73-77.
[9] 康肸,邓爱鹏,杨树林. 壳聚糖基温敏水凝胶的研究进展[J]. 中国生物工程杂志, 2018, 38(5): 79-84.
[10] 段思腾,李光然,马义勇,邱裕佳,李宇,王伟. 负载NGF的可注射壳聚糖透明质酸水凝胶材料理化性能及生物相容性研究[J]. 中国生物工程杂志, 2018, 38(4): 70-77.
[11] 郗来顺,云鹏,王元斗,张冠宏,邢泉生,陈阳生,宿烽. 形状记忆聚合物在组织工程中的应用 *[J]. 中国生物工程杂志, 2018, 38(12): 76-81.
[12] 孙怀远,宋晓康,廖跃华,李晓欧. 压电式微喷技术在细胞打印领域的应用*[J]. 中国生物工程杂志, 2018, 38(12): 82-90.
[13] 李大为, 何进, 何凤利, 刘雅丽, 邓旭东, 叶雅静, 尹大川. 丝素蛋白/壳聚糖复合材料在组织工程中应用的研究进展[J]. 中国生物工程杂志, 2017, 37(10): 111-117.
[14] 张清芳, 刘如明, 肖建辉. 透明质酸在间充质干细胞向软骨细胞分化中的应用[J]. 中国生物工程杂志, 2016, 36(6): 92-99.
[15] 孙泽绪, 赵辰, 廖军义, 王琦, 徐伟, 陈诚, 黄伟. 抑制Runx2的表达增强BMP2诱导的干细胞成软骨分化[J]. 中国生物工程杂志, 2016, 36(4): 57-62.