基于聚己内酯纤维的组织工程支架研究进展
武小童1,2 , 何儿1,2 , 刘来俊1,2 , 李超婧1,2* , 王璐1,2 , 王富军1,2*
1 (东华大学纺织学院,上海 201620)2 (纺织面料技术教育部重点实验室,上海 201620)
Progress in Tissue Engineering Scaffolds Based on Polycaprolactone Fibers
Wu Xiaotong1,2 , He Er1,2 , Liu Laijun1,2 , Li Chaojing1,2* , Wang Lu1,2 , Wang Fujun1,2*
1 (College of Textiles,Donghua University,Shanghai 201620,China)2 (Key Laboratory of Textile Science & Technology,Ministry of Education,Shanghai 201620,China)
摘要 聚己内酯(PCL)是一种生物相容性好、可吸收、易加工改性的聚酯,材料基于PCL纤维的组织工程支架,具有比表面积高、机械性能良好与孔径、孔隙率和纤维取向等结构特征易调控等特点,被广泛应用于组织工程领域。重点综述PCL纤维的组织工程支架的主要应用缺陷(包括细胞亲和力差、降解速度过慢及机械强度低)及改进手段,同时针对基于PCL纤维的组织工程支架在皮肤、血管、神经、肌腱、韧带和软骨等组织再生的最新进展进行归纳总结,发现目前多数研究集中于通过引入生物活性物质或药物以改善细胞-支架相互作用和调控支架降解行为,或通过选取不同的纺丝工艺和参数以改变支架的物理结构,调控支架机械性能与细胞诱导行为。此外,目前多数研究仍停留在实验室阶段,利用基于PCL纤维的组织工程支架低成本、易加工的优势以加快其临床转化是未来重要的发展方向。
关键词 :
聚己内酯 ,
组织工程 ,
纤维 ,
支架
Abstract :Polycaprolactone (PCL) is a kind of biocompatible,absorbable and easily modified polyester. Tissue engineering scaffolds based on PCL fibers are widely used because of their high specific surface area,good mechanical properties,and easy control of pore size,porosity and fiber orientation. In this paper,main application defects of PCL fiber scaffolds,such as poor cell affinity,slow degradation rate and low mechanical strength and the improvement methods were reviewed. At the same time,the latest development of tissue engineering scaffolds based on PCL fiber in the regeneration of skin,blood vessel,nerve,tendon,ligament and cartilage was summarized. It is shown that most of the current studies focused on improving cell-scaffold interaction and regulating the degradation behavior of scaffolds by introducing bioactive substances or drugs,or changing the physical structure of scaffolds by using different spinning processes and parameters to regulate the mechanical properties and cell-behavior induction of scaffolds. In addition,most of the studies are still staying in the laboratory stage. It is an important development direction in the future to promote tissue engineering scaffolds based on PCL fibers with the advantages of low cost and easy processing.
Key words :
polycaprolactone
tissue engineering
fiber
scaffold
收稿日期: 2019-11-18
基金资助: 国家重点研发计划(2018YFC1106202);国家级大学生创新创业训练计划(201910255032);上海市级大学生创新创业训练计划(sh10255056)
通讯作者:
* E-mail:lcj@dhu.edu.cn
引用本文:
武小童, 何儿, 刘来俊, 李超婧, 王璐, 王富军. 基于聚己内酯纤维的组织工程支架研究进展[J]. 中国生物医学工程学报, 2020, 39(5): 611-620.
Wu Xiaotong, He Er, Liu Laijun, Li Chaojing, Wang Lu, Wang Fujun. Progress in Tissue Engineering Scaffolds Based on Polycaprolactone Fibers. Chinese Journal of Biomedical Engineering, 2020, 39(5): 611-620.
链接本文:
http://cjbme.csbme.org/CN/10.3969/j.issn.0258-8021.2020.05.012 或 http://cjbme.csbme.org/CN/Y2020/V39/I5/611
[1] 江文诗,Gomez M P,Paez G,et al.数据之美——聚焦全球器官捐献发展趋势[J].中华移植杂志(电子版),2019,13(1):28-33. [2] Langer R,Vacanti JP.Tissue engineering[J].Science,1993,260(5110):920-926. [3] Guo Baolin,Sun Yang,Finne-Wistrand A,et al.Electroactive porous tubular scaffolds with degradability and non-cytotoxicity for neural tissue regeneration[J].Acta Biomater,2012,8(1):144-153. [4] Khorshidi S,Solouk A,Mirzadeh H,et al.A review of key challenges of electrospun scaffolds for tissue-engineering applications[J].J Tissue Eng Regen Med,2016,10(9):715-738. [5] Seyednejad H,Ghassemi AH,van Nostrum CF,et al.Functional aliphatic polyesters for biomedical and pharmaceutical applications[J].J Control Release,2011,152(1):168-176. [6] Abedalwafa M,Wang Fujun,Wang Lu,et al.Biodegradable poly-epsilon-caprolactone (pcl) for tissue engineering applications:A review[J].Rev Adv Mater Sci,2013,34(2):123-140. [7] Mondal D,Griffith M,Venkatraman SS.Polycaprolactone- based biomaterials for tissue engineering and drug delivery:Current scenario and challenges[J].Int J Polym Mater Po,2016,65(5):255-265. [8] Suwantong O.Biomedical applications of electrospun polycaprolactone fiber mats[J].Polym Adv Technol,2016,27(10):1264-1273. [9] Diaz E,Sandonis I,Blanca Valle M.In vitro degradation of poly(caprolactone)/nha composites[J].J Nanomater,2014,2014:802435. [10] Koleske JV.Chapter 22-blends containing poly(ε-caprolactone) and related polymers[M]//Polymer Blends.New York:Academic Press,1978:369-389. [11] Woodruff MA,Hutmacher DW.The return of a forgotten polymer—polycaprolactone in the 21st century[J].Prog Polym Sci,2010,35(10):1217-1256. [12] Nair LS,Laurencin CT.Biodegradable polymers as biomaterials[J].Prog Polym Sci,2007,32(8):762-798. [13] Malikmammadov E,Tanir TE,Kiziltay A,et al.PCLand PCL-based materials in biomedical applications[J].J Biomat Sci-Polym E,2018,29(7-9):863-893. [14] Li Wanju,Tuli R,Huang Xiaoxue,et al.Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold[J].Biomaterials,2005,26(25):5158-5166. [15] Li Wanju,Tuli R,Okafor C,et al.A three-dimensional nanofibrous scaffold for cartilage tissue engineering using human mesenchymal stem cells[J].Biomaterials,2005,26(6):599-609. [16] Yoshimoto H,Shin YM,Terai H,et al.A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering[J].Biomaterials,2003,24(12):2077-2082. [17] Sharifi F,Patel BB,Dzuilko AK,et al.Polycaprolactone microfibrous scaffolds to navigate neural stem cells[J].Biomacromolecules,2016,17(10):3287-3297. [18] Agrawal A,Lee BH,Irvine SA,et al.Smooth muscle cell alignment and phenotype control by melt spun polycaprolactone fibers for seeding of tissue engineered blood vessels[J].Int J Biomater,2015,2015:434876. [19] Gattazzo F,De Maria C,Whulanza Y,et al.Realisation and characterization of conductive hollow fibers for neuronal tissue engineering[J].J Biomed Mater Res B,2015,103(5):1107-1119. [20] Xue Wen,Chen Peifeng,Wang Fujun,et al.Melt spinning of nano-hydroxyapatite and polycaprolactone composite fibers for bone scaffold application[J].J Mater Sci,2019,54(11):8602-8612. [21] Hsu Shanhui,Huang Sherry,Wang Yachi,et al.Novel nanostructured biodegradable polymer matrices fabricated by phase separation techniques for tissue regeneration[J].Acta Biomater,2013,9(6):6915-6927. [22] Liu Shuqiong,He Zhihang,Xu Guojie,et al.Fabrication of polycaprolactone nanofibrous scaffolds by facile phase separation approach[J].Mat Sci Eng C-Mater,2014,44:201-208. [23] Wang Weizhong,Miao Yingke,Zhou Xiaojun,et al.Local delivery of bmp-2 from poly(lactic-co-glycolic acid) microspheres incorporated into porous nanofibrous scaffold for bone tissue regeneration[J].J Biomed Nanotechnol,2017,13(11):1446-1456. [24] Chen RS,Chen YJ,Chen MH,et al.Cell-surface interactions of rat tooth germ cells on various biomaterials[J].J Biomed Mater Res A,2008,84A(2):567-567. [25] Lee JH,Jung HW,Kang IK,et al.Cell behaviour on polymer surfaces with different functional groups[J].Biomaterials,1994,15(9):705-711. [26] Zhang Qiang,Lv Shun,Lu Jianfeng,et al.Characterization of polycaprolactone/collagen fibrous scaffolds by electrospinning and their bioactivity[J].Int J Biol Macromol,2015,76:94-101. [27] Coimbra P,Santos P,Alves P,et al.Coaxial electrospun PCL/gelatin-ma fibers as scaffolds for vascular tissue engineering[J].Colloid Surface B,2017,159:7-15. [28] Ranjbarvan P,Soleimani M,Samadi Kuchaksaraei A,et al.Skin regeneration stimulation:The role of pcl-platelet gel nanofibrous scaffold[J].Microsc Res Tech,2017,80(5):495-503. [29] Tiyek I,Gunduz A,Yalcinkaya F,et al.Leinfluence of electrospinning parameters on the hydrophilicity of electrospunpolycaprolactone nanofibres[J].J Nanosci Nanotechnol,2019,19(11):7251-7260. [30] Chen Dairui,Bei Jianzhong,Wang Shengguo.Polycaprolactone microparticles and their biodegradation[J].Polym Degrad Stab,2000,67(3):455-459. [31] Dash TK,Konkimalla VB.Poly-ε-caprolactone based formulations for drug delivery and tissue engineering:A review[J].J Control Release,2012,158(1):15-33. [32] Rezwan K,Chen QZ,Blaker JJ,et al.Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering[J].Biomaterials,2006,27(18):3413-3431. [33] Salehi S,Fathi M,Javanmard SH,et al.Generation of PGS/PCL blend nanofibrous scaffolds mimicking corneal stroma structure[J].Macromol Mater Eng,2014,299(4):455-469. [34] Garkhal K,Verma S,Jonnalagadda S,et al.Fast degradable poly(l-lactide-co-ε-caprolactone) microspheres for tissue engineering:Synthesis,characterization,and degradation behavior[J].J Polym Sci Pol Cem,2007,45(13):2755-2764. [35] Wang Siyu,Li Yumei,Zhao Rui,et al.Chitosan surface modified electrospun poly(ε-caprolactone)/carbon nanotube composite fibers with enhanced mechanical,cell proliferation and antibacterial properties[J].Int J Biol Macromol,2017,104:708-715. [36] Li Lingli,Li Guang,Jiang Jianming,et al.Electrospun fibrous scaffold of hydroxyapatite/poly (ε-caprolactone) for bone regeneration[J].J Mater Sci-Mater M,2012,23(2):547-554. [37] Pan Yiwa,Zhou Xin,Wei Yongzhen,et al.Small-diameter hybrid vascular grafts composed of polycaprolactone and polydioxanone fibers[J].Sci Rep,2017,7(1):3615. [38] Wu Huijun,Fan Jintu,Chu CC,et al.Electrospinning of small diameter 3-d nanofibrous tubular scaffolds with controllable nanofiber orientations for vascular grafts[J].J Mater Sci-Mater M,2010,21(12):3207-3215. [39] Baji A,Mai YW,Wong SC,et al.Electrospinning of polymer nanofibers:Effects on oriented morphology,structures and tensile properties[J].Compos Sci Technol,2010,70(5):703-718. [40] Kim BJ,Cheong H,Choi ES,et al.Accelerated skin wound healing using electrospun nanofibrous mats blended with mussel adhesive protein and polycaprolactone[J].J Biomed Mater Res A,2017,105(1):218-225. [41] Sharif S,Ai J,Azami M,et al.Collagen-coated nano-electrospun PCL seeded with human endometrial stem cells for skin tissue engineering applications[J].J Biomed Mater Res B,2018,106(4):1578-1586. [42] Lv Fang,Wang Jie,Xu Peng,et al.A conducive bioceramic/polymer composite biomaterial for diabetic wound healing[J].Acta Biomater,2017,60:128-143. [43] Chutipakdeevong J,Ruktanonchai U,Supaphol P.Hybrid biomimetic electrospun fibrous mats derived from poly(ε-caprolactone) and silk fibroin protein for wound dressing application[J].J Appl Polym Sci,2015,132(11):41653. [44] Ranjbar-Mohammadi M,Rabbani S,Bahrami SH,et al.Antibacterial performance and in vivo diabetic wound healing of curcumin loaded gum tragacanth/poly(ε-caprolactone) electrospun nanofibers[J].Mat Sci Eng C-Mater,2016,69:1183-1191. [45] Liao Nina,Unnithan AR,Joshi MK,et al.Electrospun bioactive poly (ε-caprolactone)–cellulose acetate–dextran antibacterial composite mats for wound dressing applications[J].Colloid Surface A,2015,469:194-201. [46] Zahid S,Khalid H,Ikram F,et al.Bi-layered α-tocopherol acetate loaded membranes for potential wound healing and skin regeneration[J].Mat Sci Eng C-Mater,2019,101:438-447. [47] Gao Jingchen,Chen Siyuan,Tang Di,et al.Mechanical properties and degradability of electrospun PCL/PLGA blended scaffolds as vascular grafts[J].Transactions of Tianjin University,2019,25(2):152-160. [48] Duan NanNan,Geng Xue,Ye Lin,et al.A vascular tissue engineering scaffold with core-shell structured nano-fibers formed by coaxial electrospinning and its biocompatibility evaluation[J].Biomed Mater,2016,11(3):035007. [49] Wang Kai,Chen Xuejiang,Pan Yiwa,et al.Enhanced vascularization in hybrid PCL/gelatin fibrous scaffolds with sustained release of VEGF[J].Biomed Res Int,2015,2015:1-10. [50] Ye Lin,Cao Jie,Chen Lamei,et al.The fabrication of double layer tubular vascular tissue engineering scaffold via coaxial electrospinning and its 3d cell coculture[J].J Biomed Mater Res A,2015,103(12):3863-3871. [51] Gaharwar AK,Nikkhah M,Sant S,et al.Anisotropic poly (glycerol sebacate)-poly (epsilon-caprolactone) electrospun fibers promote endothelial cell guidance[J].Biofabrication,2015,7(1):015001. [52] Agrawal A,Lee BH,Irvine SA,et al.Smooth muscle cell alignment and phenotype control by melt spun polycaprolactone fibers for seeding of tissue engineered blood vessels[J].Int J Biomater,2015,2015:1-8. [53] Entekhabi E,Nazarpak MH,Mortarzadeh F,et al.Design and manufacture of neural tissue engineering scaffolds using hyaluronic acid and polycaprolactone nanofibers with controlled porosity[J].Mat Sci Eng C-Mater,2016,69:380-387. [54] Mohamadi F,Ebrahimi-Barough S,Nourani MR,et al.Electrospun nerve guide scaffold of poly(epsilon-caprolactone)/collagen/nanobioglass:An in vitro study in peripheral nerve tissue engineering[J].J Biomed Mater Res A,2017,105(7):1960-1972. [55] Idini M,Wieringa P,Rocchiccioli S,et al.Glycosaminoglycan functionalization of electrospun scaffolds enhances schwann cell activity[J].Acta Biomater,2019,96:188-202. [56] Mohamadi F,Ebrahimi-Barough S,Nourani MR,et al.Enhanced sciatic nerve regeneration by human endometrial stem cells in an electrospun poly (ε-caprolactone)/collagen/nbg nerve conduit in rat[J].Artif Cell Nanomed B,2018,46(8):1731-1743. [57] Hu Jue,Tian Lingling,Prabhakaran MP,et al.Fabrication of nerve growth factor encapsulated aligned poly(epsilon-caprolactone) nanofibers and their assessment as a potential neural tissue engineering scaffold[J].Polymers (Basel),2016,8(2):54. [58] Low WC,Rujitanaroj PO,Lee DK,et al.Nanofibrous scaffold-mediated rest knockdown to enhance neuronal differentiation of stem cells[J].Biomaterials,2013,34(14):3581-3590. [59] Zamani F,Amani-Tehran M,Zaminy A,et al.Conductive 3D structure nanofibrous scaffolds for spinal cord regeneration[J].Fiber Polym,2017,18(10):1874-1881. [60] Saderi N,Rajabi M,Akbari B,et al.Fabrication and characterization of gold nanoparticle-doped electrospun PCL/chitosan nanofibrous scaffolds for nerve tissue engineering[J].J Mater Sci-Mater M,2018,29(9):134-134. [61] Borah R,Ingavle GC,Sandeman SR,et al.Amine-functionalized electrically conductive core-sheath meh-ppv:PCL electrospun nanofibers for enhanced cell-biomaterial interactions[J].Acs Biomater-Sci Eng,2018,4(9):3327-3346. [62] Barber JG,Handorf AM,Allee TJ,et al.Braided nanofibrous scaffold for tendon and ligament tissue engineering[J].Tissue Engineering Part A,2011,19(11-12):1265-1274. [63] Gomoll AH,Minas T.The quality of healing:Articular cartilage[J].Wound Repair Regen,2014,22(S1):30-38. [64] Arabi A,Boggs E,Patel MR,et al.Surface modification of electrospun polycaprolactone fibers and effect on cell proliferation[J].Surf Innov,2014,2(1):47-59. [65] Munir N,Callanan A.Novel phase separated polycaprolactone/collagen scaffolds for cartilage tissue engineering[J].Biomed Mater,2018,13(5):051001. [66] Cai Yanli,Li Jinlan,Poh CK,et al.Collagen grafted 3D polycaprolactone scaffolds for enhanced cartilage regeneration[J].J Mater Chem B,2013,1(43):5971-5976. [67] Deepthi S,Jeevitha K,Nivedhitha Sundaram M,et al.Chitosan-hyaluronic acid hydrogel coated poly(caprolactone) multiscale bilayer scaffold for ligament regeneration[J].Chem Eng J,2015,260:478-485. [68] Chen CH,Chen SH,Kuo CY,et al.Response of dermal fibroblasts to biochemical and physical cues in aligned polycaprolactone/silk fibroin nanofiber scaffolds for application in tendon tissue engineering[J].Nanomaterials-Basel,2017,7(8):219. [69] Jiang Wenlu,Li Long,Zhang Ding,et al.Incorporation of aligned pcl-peg nanofibers into porous chitosan scaffolds improved the orientation of collagen fibers in regenerated periodontium[J].Acta Biomater,2015,25:240-252. [70] Calejo I,Costa-Almeida R,Reis RL,et al.A textile platform using continuous aligned and textured composite microfibers to engineer tendon-to-bone interface gradient scaffolds[J].Adv Healthc Mater,2019,8(15):1900200. [71] Han F,Zhang P,Sun Y,et al.Hydroxyapatite-doped polycaprolactone nanofiber membrane improves tendon-bone interface healing for anterior cruciate ligament reconstruction[J].Int J Nanomedicine,2015,10(1):7333-7343. [72] Wu Geng,Deng Xuefeng,Song Jinqi,et al.Enhanced biological properties of biomimetic apatite fabricated polycaprolactone/chitosan nanofibrous bio-composite for tendon and ligament regeneration[J].J Photoch Photobio B,2018,178:27-32. [73] Mahoney C,Conklin D,Waterman J,et al.Electrospun nanofibers of poly(epsilon-caprolactone)/depolymerized chitosan for respiratory tissue engineering applications[J].J Biomat Sci-Polym E,2016,27(7):611-625. [74] Semnani D,Naghashzargar E,Hadjianfar M,et al.Evaluation of pcl/chitosan electrospun nanofibers for liver tissue engineering[J].Int J Polym Mater Po,2017,66(3):149-157. [75] Jansen K,Castilho M,Aarts S,et al.Fabrication of kidney proximal tubule grafts using biofunctionalized electrospun polymer scaffolds[J].Macromol Biosci,2019,19(2):1800412. [76] Sharif F,Tabassum S,Mustafa W,et al.Bioresorbable antibacterial pcl-pla-nha composite membranes for oral and maxillofacial defects[J].Polym Composite,2019,40(4):1564-1575.
[1]
金儿, 冯远静, 曾庆润, 陈余凯, 黄胜威, 阮林辉. 数据驱动的三叉神经纤维束自动分割算法 [J]. 中国生物医学工程学报, 2020, 39(4): 385-393.
[2]
李敏, 孟祥璟, 张祥奎, 刘波, 段崇刚, 张兰英, 张岱州, 凌沛学. 水凝胶材料和间充质干细胞在组织工程中的应用进展 [J]. 中国生物医学工程学报, 2020, 39(3): 367-374.
[3]
张一帆, 徐铭恩, 王玲, 张翮. 利用同轴3D打印技术构建促内皮细胞生长类血管组织工程支架 [J]. 中国生物医学工程学报, 2020, 39(2): 206-214.
[4]
钱力, 王建飞, 金炼, 宋彪, 黄彦淇, 朱红蕾, 鄢盛杰, 邬小玫. 从CT数据到带纤维走向的全心脏有限元模型的建立 [J]. 中国生物医学工程学报, 2020, 39(2): 180-189.
[5]
李相成, 索海瑞, 王玲, 徐铭恩. 基于3D打印羟基磷灰石支架的填充结构与力学性能研究 [J]. 中国生物医学工程学报, 2020, 39(1): 91-96.
[6]
刘语菲, 张智玲, 王艳颖, 董云生, 张琳, 王淑芳. 外泌体及其在组织工程中的应用 [J]. 中国生物医学工程学报, 2020, 39(1): 109-113.
[7]
唐靓, 罗涛, 杨亚冬, 杨耿, 徐怡朦, 张文元. 3D生物打印的肝结构体植入兔纤维化肝的研究 [J]. 中国生物医学工程学报, 2019, 38(6): 726-732.
[8]
陈思敏, 谢国平, 高亚男, 战海鹤, 吴琳华. 组织工程材料在修复心肌损伤中的应用研究进展 [J]. 中国生物医学工程学报, 2019, 38(6): 753-758.
[9]
许克惠, 李娇娇, 李香玉, 陈佳龙. 光固化3D打印软组织材料的性能研究进展 [J]. 中国生物医学工程学报, 2019, 38(5): 628-635.
[10]
朱文仙, 袁明, 唐华东. 聚乙烯胺及其衍生物在生物医学工程中的应用进展 [J]. 中国生物医学工程学报, 2019, 38(4): 490-497.
[11]
徐学盖, 吴凤新, 高爱军, 孟洁, 温涛, 刘健, 徐樑华, 许海燕. 三维多孔电磁复合支架构建与理化表征 [J]. 中国生物医学工程学报, 2019, 38(4): 447-454.
[12]
谭艳林, 罗春媛, 陈凯瑞, 张强, 熊博凯, 刘秀飘, 杨佩佩, 杨羽晨. 磷酸钙支架材料促血管生成影响的研究 [J]. 中国生物医学工程学报, 2019, 38(4): 498-502.
[13]
彭坤, 李婧, 王斯睿, 夏骏, 乔爱科. 可降解血管支架结构设计及优化的研究进展 [J]. 中国生物医学工程学报, 2019, 38(3): 367-374.
[14]
赵亮, 李霞飞, 李成成, 闫欢欢, 张其清. 应用Triton-x100加丹参酚酸B制备脱细胞血管支架及其血液相容性研究 [J]. 中国生物医学工程学报, 2019, 38(2): 201-207.
[15]
杨雪, 邵华英, 张琼月, 吴小红. 聚乙二醇-b-聚己内酯/聚己内酯单分散电喷微球的制备与亲水性研究 [J]. 中国生物医学工程学报, 2019, 38(1): 77-83.