聚氨酯在生物医学领域的研究进展

doi:10.16085/j.issn.1000-6613.2019-1914

摘要/Abstract

摘要：

传统的金属材料和陶瓷材料由于刚性过强而缺乏适当的挠性和弹性，对于人体组织某些部位的代用和修补出现不同程度的副作用。鉴于此，兼具刚性与柔性、良好的生物相容性和血液适应性等特点的聚氨酯材料引起了众多研究者的关注。一系列医用聚氨酯材料被研发并广泛应用，在医药领域占据着重要地位。本文首先简要介绍了医用聚氨酯的发展背景，总结了其主要的组成结构和性能特点。主要综述了聚氨酯在人造心脏及辅器、人造血管及支架、人造皮肤、伤口敷料和记忆矫形等领域的研究进展。然后重点概述了目前医用可降解聚氨酯材料的研究现状，并对医用聚氨酯材料现存问题进行了探讨，指出聚氨酯在该领域进一步发展的关键技术是实现准确把控聚氨酯材料在生物体内的降解性。

关键词: 聚氨酯, 生物医药, 生物降解, 组织工程, 生物稳定性

Abstract:

Traditional metal materials and ceramic materials are not suitable for replacement and repair of some parts of human tissues because of their excessive rigidity and inferior flexibility. In this case, polyurethane materials with preferable rigidity and flexibility, better biocompatibility and blood adaptability have attracted more attention of many researchers. A series of medical polyurethane materials have been developed and widely used, which plays an important role in the field of medicine. In this paper, the development background, main composition and properties of medical polyurethane was briefly introduced. The research and application progress of polyurethane in artificial heart accessories, artificial blood vessels and scaffolds, artificial skin, dressings and memory orthotics are intensively summarized. Furthermore, an overview of research on medical degradable polyurethane materials is presented, and the current problems on the study of medical polyurethane materials are discussed. The key technology for the further development of polyurethane in medical field is to accurately control the biodegradability of polyurethane materials.

Key words: polyurethane, biological medicine, biodegradable, tissue engineering, biological stability

中图分类号:

TQ322.9

林晓琪, 陈维胜, 张芹芹. 聚氨酯在生物医学领域的研究进展[J]. 化工进展, 2020, 39(S1): 212-218.

Xiaoqi LIN, Weisheng CHEN, Qinqin ZHANG. Research progress of polyurethanes in the biomedical field[J]. Chemical Industry and Engineering Progress, 2020, 39(S1): 212-218.

图/表 4

图1 细胞在聚氨酯/水凝胶层的生长状态[28]

图2 纳米SiO2增强的聚氨酯弹性体作为人造皮肤的物化性能表现[40]

图3 用纱布、聚氨酯/硅氧烷和聚氨酯/硅氧烷/氧化石墨烯治疗小鼠创面的照片[49]

图4 用正畸形状记忆聚氨酯制作腕关节矫形器的图像[54]

参考文献 77

1	王强，李瑞欣，封严，等. 医用聚氨酯的改性及其在生物医学中的应用进展[J]. 塑料科技, 2010, 38(9): 91-96.
	WANG Qiang, LI Ruixin, FENG Yan，et al. Research progress on modification and its application of medical polyurethane in biomedicine[J]. Plastics Science and Technology, 2010, 38(9): 91-96.
2	AKUTSU T, DREYER B, KOLFF W J. Polyurethane artificial heart valves in animals[J]. Journal of Applied Physiology, 1959, 14: 1045-1048.
3	BERNACCA G M, MACKAY T G, WILKINSON R, et al. Calcification and fatigue failure in a polyurethane heart valve[J]. Biomaterials, 1995, 16(4): 279-285.
4	BORETOS J W, PIERCE W S. Segmented polyurethane: a new elastomer for biomedical applications[J]. Science, 1967, 158(3807): 1481-1482.
5	BERNACCA G M, O′CONNOR B, WILLIAMS D F, et al. Hydrodynamic function of polyurethane prosthetic heart valves: influences of Young's modulus and leaflet thickness[J]. Biomaterials, 2002, 23(1): 45-50.
6	GALLOCHER S L, AGUIRRE A F, KASYANOV V, et al. A novel polymer for potential use in a trileaflet heart valve[J]. Journal of Biomedical Materials Research B: Applied Biomaterials, 2006, 79(2): 325-334.
7	WHEATLEY D. Polyurethane: material for the next generation of heart valve prostheses?[J]. European Journal of Cardio-Thoracic Surgery, 2000, 17(4): 440-448.
8	PROKOPOVICH P, PERNI S, PICCIRILLO C, et al. Frictional properties of light-activated antimicrobial polymers in blood vessels[J]. Journal of Materials Science: Materials in Medicine, 2010, 21(2): 815-821.
9	BELANGER M C, MAROIS Y, ROY R, et al. Selection of a polyurethane membrane for the manufacture of ventricles for a totally implantable artificial heart: blood compatibility and biocompatibility studies[J]. Artificial Organs, 2000, 24(11): 879-888.
10	WANG X, WU P, HU X, et al. Polyurethane membrane/knitted mesh-reinforced collagen-chitosan bilayer dermal substitute for the repair of full-thickness skin defects via a two-step procedure[J]. Journal of the Mechanical Behavior of Biomedical Materials, 2016, 56: 120-133.
11	WANG X, LI Q, HU X, et al. Fabrication and characterization of poly(L-lactide-co-glycolide) knitted mesh-reinforced collagen-chitosan hybrid scaffolds for dermal tissue engineering[J]. Journal of the Mechanical Behavior of Biomedical Materials, 2012, 8: 204-215.
12	SINGH A K, MEHRA D S, NIYOGI U K, et al. Breathability studies of electron beam curable polyurethane pressure sensitive adhesive for bio-medical application[J]. Radiation Physics and Chemistry, 2014, 103: 75-83.
13	SAMPATH KUMAR N, SANTHOSH C, VATHALURU SUDAKARAN S, et al. Electrospun polyurethane and soy protein nanofibres for wound dressing applications[J]. IET Nanobiotechnology, 2018, 12(2): 94-98.
14	UNNITHAN A R, GNANASEKARAN G, SATHISHKUMAR Y, et al. Electrospun antibacterial polyurethane-cellulose acetate-zein composite mats for wound dressing[J]. Carbohydr. Polym., 2014, 102: 884-892.
15	JUNG Y C, CHO J W. Application of shape memory polyurethane in orthodontic[J]. Journal of Materials Science: Materials in Medicine, 2010, 21(10): 2881-2886.
16	KIM S Y, LEE S H, CHO S K, et al. Comparison of the accuracy of digitally fabricated polyurethane model and conventional gypsum model[J]. Journal of Advanced Prosthodontics, 2014, 6(1): 1-7.
17	DUNNILL M S. Fibrinoid necrosis in the branches of the pulmonary artery in chronic non-specific lung disease[J]. British Journal of Diseases of the Chest, 1960, 54(4): 355-358.
18	SACHWEH J S, DAEBRITZ S H. Novel "biomechanical" polymeric valve prostheses with special design for aortic and mitral position: a future option for pediatric patients?[J]. ASAIO Journal, 2006, 52(5): 575-580.
19	THOMAS V, JAYABALAN M. A new generation of high flex life polyurethane urea for polymer heart valve: studies on in vivo biocompatibility and biodurability[J]. Journal of Biomedical Materials Research, Part A, 2009, 89(1): 192-205.
20	ANDERHEIDEN D, KLEE D, HCKER H, et al. Surface modification of a biocompatible polymer based on polyurethane for artificial blood vessels[J]. Journal of Materials Science: Materials in Medicine, 1992, 3(1): 1-4.
21	GUELCHER S A. Biodegradable polyurethanes: synthesis and applications in regenerative medicine[J]. Tissue Engineering B: Reviews, 2008, 14(1): 3-17.
22	FREED L E, VUNJAK-NOVAKOVIC G. Culture of organized cell communities[J]. Advanced Drug Delivery Reviews, 1998, 33(1/2): 15-30.
23	LI M, MONDRINOS M J, GANDHI M R, et al. Electrospun protein fibers as matrices for tissue engineering[J]. Biomaterials, 2005, 26(30): 5999-6008.
24	MATSUDA T, IHARA M, INOGUCHI H, et al. Mechano-active scaffold design of small-diameter artificial graft made of electrospun segmented polyurethane fabrics[J]. Journal of Biomedical Materials Research Part A, 2005, 73A(1): 125-131.
25	STANKUS J J, SOLETTI L, FUJIMOTO K, et al. Fabrication of cell microintegrated blood vessel constructs through electrohydrodynamic atomization[J]. Biomaterials, 2007, 28(17): 2738-2746.
26	SHIN J W, LEE Y J, HEO S J, et al. Manufacturing of multi-layered nanofibrous structures composed of polyurethane and poly(ethylene oxide) as potential blood vessel scaffolds[J]. Journal of Biomaterials Science Polymer Edition, 2009, 20(5/6): 757-771.
27	DETTA N, ERRICO C, DINUCCI D, et al. Novel electrospun polyurethane/gelatin composite meshes for vascular grafts[J]. Journal of Materials Science: Materials in Medicine, 2010, 21(5): 1761-1769.
28	HUANG Y, HE K, WANG X. Rapid prototyping of a hybrid hierarchical polyurethane-cell/hydrogel construct for regenerative medicine[J]. Materials Science & Engineering C: Materials for Biological Applications, 2013, 33(6): 3220-3229.
29	HEINLIN J, SCHREML S, BABILAS P, et al. Cutaneous wound healing therapeutic interventions[J]. Der Hautarzt, 2010, 61(7): 611-626.
30	BALASUBRAMANI M, KUMAR T R, BABU M. Skin substitutes: a review[J]. Burns, 2001, 27(5): 534-544.
31	BUCHANAN P J, KUNG T A, CEDERNA P S. Evidence-based medicine[J]. Plastic and Reconstructive Surgery, 2014, 134(6): 1391-1404.
32	BÖTTCHER-HABERZETH S, BIEDERMANN T, REICHMANN E. Tissue engineering of skin[J]. Burns, 2010, 36(4): 450-460.
33	BANYARD D A, BOURGEOIS J M, WIDGEROW A D, et al. Regenerative biomaterials[J]. Plastic and Reconstructive Surgery, 2015, 135(6): 1740-1748.
34	PHILANDRIANOS C, ANDRAC-MEYER L, MORDON S, et al. Comparison of five dermal substitutes in full-thickness skin wound healing in a porcine model[J]. Burns, 2012, 38(6): 820-829.
35	O’BRIEN F J, HARLEY B A, YANNAS I V, et al. The effect of pore size on cell adhesion in collagen—GAG scaffolds[J]. Biomaterials, 2005, 26(4): 433-441.
36	ZHONG S P, ZHANG Y Z, LIM C T. Tissue scaffolds for skin wound healing and dermal reconstruction[J]. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2010, 2(5): 510-525.
37	MA L. Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering[J]. Biomaterials, 2003, 24(26): 4833-4841.
38	HARLEY B, LEUNG J, SILVA E, et al. Mechanical characterization of collagen-glycosaminoglycan scaffolds[J]. Acta Biomaterialia, 2007, 3(4): 463-474.
39	FIROOZI N, REZAYAN A H, TABATABAEI REZAEI S J, et al. Synthesis of poly(ε-caprolactone)-based polyurethane semi-interpenetrating polymer networks as scaffolds for skin tissue regeneration[J]. International Journal of Polymeric Materials and Polymeric Biomaterials, 2017, 66(16): 805-811.
40	NIKJE M M A, GARMARUDI A B. Application of SiO₂ nanoparticles for thermophysical improvement of integral skin polyurethane elastomers[J]. Advanced Composite Materials, 2011, 20(1): 79-89.
41	YOO H J, KIM H D. Characteristics of waterborne polyurethane/poly(N-vinylpyrrolidone) composite films for wound-healing dressings[J]. Journal of Applied Polymer Science, 2008, 107(1): 331-338.
42	YOO H J, KIM H D. Synthesis and properties of waterborne polyurethane hydrogels for wound healing dressings[J]. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2008, 85B(2): 326-333.
43	HERGENROTHER R W, XUE-HAI Y, COOPER S L. Blood-contacting properties of polydimethylsiloxane polyureaurethanes[J]. Biomaterials, 1994, 15(8): 635-640.
44	CHUN Y C, KIM K S, SHIN J S, et al. Synthesis and characterization of poly(siloxane-urethane)s[J]. Polymer International, 1992, 27(2): 177-185.
45	KAJIYAMA M, KAKIMOTO M, IMAI Y. Synthesis and properties of new multiblock copolymers based on dimethyl siloxane and N-phenylated polyureas[J]. Macromolecules, 1990, 23(5): 1244-1248.
46	YILGÖR E, BURGAZ E, YURTSEVER E, et al. Comparison of hydrogen bonding in polydimethylsiloxane and polyether based urethane and urea copolymers[J]. Polymer, 2000, 41(3): 849-857.
47	KHIL M S, CHA D I, KIM H Y, et al. Electrospun nanofibrous polyurethane membrane as wound dressing[J]. Journal of Biomedical Materials Research, 2003, 67B(2): 675-679.
48	YARI A, YEGANEH H, BAKHSHI H. Synthesis and evaluation of novel absorptive and antibacterial polyurethane membranes as wound dressing[J]. Journal of Materials Science: Materials in Medicine, 2012, 23(9): 2187-2202.
49	SHAMS E, YEGANEH H, NADERI-MANESH H, et al. Polyurethane/siloxane membranes containing graphene oxide nanoplatelets as antimicrobial wound dressings: in vitro and in vivo evaluations[J]. Journal of Materials Science: Materials in Medicine, 2017, 28(5).
50	CHOI S J, LEE J H, LEE Y H, et al. Synthesis and properties of polyurethane-urea-based liquid bandage materials[J]. Journal of Applied Polymer Science, 2011, 121(6): 3516-3524.
51	LENDLEIN A, LANGER R. Biodegradable, elastic shape-memory polymers for potential biomedical applications[J]. Science, 2002, 296(5573): 1673-1676.
52	PRISACARIU C. Polyurethane elastomers[M]. Berlin: Springer-Verlag Wien, 2011: 61-66.
53	FARZANEH S, FITOUSSI J, LUCAS A, et al. Shape memory effect and properties memory effect of polyurethane[J]. Journal of Applied Polymer Science, 2013, 128(5): 3240-3249.
54	MENG Q, HU J, ZHU Y. Properties of shape memory polyurethane used as a low-temperature thermoplastic biomedical orthotic material: influence of hard segment content[J]. Journal of Biomaterials Science, Polymer Edition, 2008, 19(11): 1437-1454.
55	AHMAD M, LUO J, MIRAFTAB M. Feasibility study of polyurethane shape-memory polymer actuators for pressure bandage application[J]. Science and Technology of Advanced Materials, 2012, 13(1): 015006.
56	ROBERTS A P, HUGHES A W. Complications with antibiotics used prophylactically in joint replacement surgery: a case report of cephradine-induced pseudomembranous colitis[J]. International orthopaedics, 1985, 8(4): 299-302.
57	SPRINGER B D, SCOTT R D, SAH A P, et al. McKeever hemiarthroplasty of the knee in patients less than sixty years old[J]. Journal of Bone and Joint Surgery, American Volume, 2006, 88(2): 366-371.
58	HALLOCK R H, FELL B M. Unicompartmental tibial hemiarthroplasty: early results of the UniSpacer knee[J]. Clinical Orthopaedics and Related Research, 2003, 416: 154-163.
59	SISTO D J, MITCHELL I L. UniSpacer arthroplasty of the knee[J]. Journal of Bone and Joint Surgery, 2005, 87(8): 1706-1711.
60	MEDLEY J B, PILLIAR R M, WONG E W, et al. Hydrophilic polyurethane elastomers for hemiarthroplasty: a preliminary invitro wear study[J]. Engineering in Medicine, 2016, 9(2): 59-65.
61	DOWSON D, FISHER J, JIN Z M, et al. Design considerations for cushion form bearings in artificial hip joints[J]. Proceedings of the Institution of Mechanical Engineers Part H: Journal of Engineering in Medicine, 1991, 205(2): 59-68.
62	AUGER D D, DOWSON D, FISHER J, et al. Friction and lubrication in cushion form bearings for artificial hip joints[J]. Proceedings of the Institution of Mechanical Engineers Part H: Journal of Engineering in Medicine, 1993, 207(1): 25-33.
63	LUO Y, MCCANN L, INGHAM E, et al. Polyurethane as a potential knee hemiarthroplasty biomaterial: an in-vitro simulation of its tribological performance[J]. Proceedings of the Institution of Mechanical Engineers H: Journal of Engineering in Medicine, 2010, 224(3): 415-425.
64	DHOLLANDER A, VERDONK P, VERDONK R. Treatment of painful, irreparable partial meniscal defects with a polyurethane scaffold: midterm clinical outcomes and survival analysis[J]. The American Journal of Sports Medicine, 2016, 44(10): 2615-2621.
65	OKADA M. Chemical syntheses of biodegradable polymers[J]. Progress in Polymer Science, 2002, 27(1): 87-133.
66	GUAN J, SACKS M S, BECKMAN E J, et al. Biodegradable poly(ether ester urethane)urea elastomers based on poly(ether ester) triblock copolymers and putrescine: synthesis, characterization and cytocompatibility[J]. Biomaterials, 2004, 25(1): 85-96.
67	COHN D, HOTOVELY-SALOMON A. Biodegradable multiblock PEO/PLA thermoplastic elastomers: molecular design and properties[J]. Polymer, 2005, 46(7): 2068-2075.
68	ZHANG J, WU M, YANG J, et al. Anionic poly(lactic acid)-polyurethane micelles as potential biodegradable drug delivery carriers[J]. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2009, 337(1/2/3): 200-204.
69	STOREY R F, WIGGINS J S, PUCKETT A D. Hydrolyzable poly(ester-urethane) networks from L-lysine diisocyanate and D,L-lactide/ε-caprolactone homo- and copolyester triols[J]. Journal of Polymer Science A: Polymer Chemistry, 1994, 32(12): 2345-2363.
70	MARCOS-FERNáNDEZ A, ABRAHAM G A, VALENTíN J L, et al. Synthesis and characterization of biodegradable non-toxic poly(ester-urethane-urea)s based on poly( ε-caprolactone) and amino acid derivatives[J]. Polymer, 2006, 47(3): 785-798.
71	PARAMONOV S E, BACHELDER E M, BEAUDETTE T T, et al. Fully acid-degradable biocompatible polyacetal microparticles for drug delivery[J]. Bioconjugate Chemistry, 2008, 19(4): 911-919.
72	DUARAH R, SINGH Y P, GUPTA P, et al. Smart self-tightening surgical suture from a tough bio-based hyperbranched polyurethane/reduced carbon dot nanocomposite[J]. Biomedical Materials, 2018, 13(4): 045004.
73	SUN P, ZHOU D, GAN Z. Novel reduction-sensitive micelles for triggered intracellular drug release[J]. Journal of Controlled Release, 2011, 155(1): 96-103.
74	MATHESON L A, SANTERRE J P, LABOW R S. Changes in macrophage function and morphology due to biomedical polyurethane surfaces undergoing biodegradation[J]. Journal of Cellular Physiology, 2004, 199(1): 8-19.
75	WAGNER H, BELLER F K, PFAUTSCH M. Electron and light microscopy examination of capsules around breast implants[J]. Plastic and Reconstructive Surgery, 1977, 60(1): 49-55.
76	BUCKY L P, EHRLICH H P, SOHONI S, et al. The capsule quality of saline-filled smooth silicone, textured silicone, and polyurethane implants in rabbits: a long-term study[J] Plastic and Reconstructive Surgery, 1994, 93(6): 1123-1131.
77	SZYCHER M, SICILIANO A A. An assessment of 2,4-TDA formation from Surgitek polyurethane foam under simulated physiological conditions[J]. Journal of Biomaterials Applications, 1991, 5(4): 323-336.

[1]	李光文, 华渠成, 黄作鑫, 达志坚. 聚甲基丙烯酸酯类黏度指数改进剂的研究进展[J]. 化工进展, 2023, 42(3): 1562-1571.
[2]	席慧敏, 钱坤, 俞科静, 李杰, 张中威, 熊自明, 张耀良. 基于二硫键和氢键的自修复聚氨酯弹性体的制备、改性及其应用[J]. 化工进展, 2023, 42(2): 934-943.
[3]	胡锦健, 李龙, 董子靖. 碳纳米材料在PU纱线基柔性应变传感器中的应用[J]. 化工进展, 2023, 42(2): 872-883.
[4]	辛华, 彭琪, 李阳帆, 张岩, 陈悦, 李新琦. 含氟聚氨酯二甲基丙烯酸酯为芯材的微胶囊制备及自修复性能[J]. 化工进展, 2023, 42(10): 5406-5413.
[5]	刘雅娟. 浸没式PAC-AMBRs系统中PAC缓解膜污染的研究进展[J]. 化工进展, 2023, 42(1): 457-468.
[6]	付佳, 谌伦建, 徐冰, 华绍烽, 李从强, 杨明坤, 邢宝林, 仪桂云. 模拟煤炭气化废水中苯酚的微生物降解[J]. 化工进展, 2023, 42(1): 526-537.
[7]	岳瑶, 蒲梦凡, 王文瑞, 赵俭波, 曹辉. 聚天冬氨酸凝胶的制备及生物降解性[J]. 化工进展, 2022, 41(8): 4491-4497.
[8]	胡瑶瑶, 魏铭, 李博申, 董月林, 董群峰, 刘传奇. 硅/巯基复合改性光固化WPUA涂料制备及其性能[J]. 化工进展, 2022, 41(6): 3186-3193.
[9]	李博申, 魏铭, 胡瑶瑶, 董月林, 董群锋, 杨立峰. 改性h-BN/聚氨酯丙烯酸酯涂料的制备与性能[J]. 化工进展, 2022, 41(6): 3194-3202.
[10]	陆少锋, 崔杉杉, 师文钊, 李苏松, 谢艳, 杨乾诚. 交联水性聚氨酯固-固相变材料的制备及性能[J]. 化工进展, 2022, 41(5): 2574-2581.
[11]	史慕杨, 芦博慧, 王锦康, 晋阳, 葛明桥. 染料掺杂发光聚氨酯复合材料的制备及性能[J]. 化工进展, 2022, 41(4): 2029-2037.
[12]	严成飞, 余彩莉, 张发爱. 松香基荧光水性聚氨酯的制备及性能[J]. 化工进展, 2022, 41(11): 6061-6067.
[13]	汪润民, 张晓东, 徐成华, 于丹丹, 余冉. 高效重质石油降解菌群构建及降解性能评价[J]. 化工进展, 2022, 41(10): 5653-5660.
[14]	李婷, 杜少辉, 崔锦峰, 王仰辉, 李虎林, 郭润兰, 王蓬, 王振军, 郭军红, 杨保平. 磷-硼杂化预聚物嵌段水性聚氨酯纸张施胶剂的制备和性能[J]. 化工进展, 2022, 41(10): 5549-5557.
[15]	陈露蕊, 曹利锋. 温度对厌氧耗氢产甲烷的影响研究进展[J]. 化工进展, 2021, 40(S1): 326-333.