纳米羟基磷灰石增强聚己内酯/明胶纤维膜的制备及其性能

doi:10.16085/j.issn.1000-6613.2019-1212

摘要/Abstract

摘要：

引导组织再生膜在引导组织再生术中发挥着关键作用，高性能的引导组织再生膜能更好地促进组织再生修复。本文以纳米羟基磷灰石（n-HA）、聚己内酯（PCL）、明胶（Gel）为原料，通过静电纺丝法制备了不同含量n-HA增强的PCL/Gel/n-HA纤维膜，并对其形貌、组成、力学性能及降解性能进行了研究。SEM结果表明，纤维膜中的纤维形态良好，纤维直径大致分布于200～400nm之间，交联后纤维直径明显增加；TEM结果表明，n-HA较均匀分散在纤维中，随着n-HA含量的增加，n-HA在纤维膜表面发生聚集。力学测试结果表明，随着n-HA含量的增加显著提高了纤维膜的拉伸强度和断裂伸长率，当n-HA含量约为15%时，其拉伸强度和伸长率分别达到9.18MPa和180%。n-HA加入后，纤维膜的降解速率明显降低，n-HA含量约为15%的复合纤维膜体外降解12周以后约降解25%。本文制备的PCL/Gel/n-HA纤维膜的力学性能和降解速率能满足临床对引导组织再生膜的性能要求。

关键词: 静电纺丝, 聚己内酯, 明胶, 纳米羟基磷灰石

Abstract:

Guided tissue regeneration (GTR) membrane plays pivotal roles in GTR treatment. In current study, polycaprolactone (PCL), gelatin (Gel) and nano-hydroxyapatite (n-HA) were selected as raw materials to prepare PCL/Gel/n-HA fibrous GTR membranes reinforced with different n-HA content by electrospinning technique. The effects of n-HA content on the morphology, mechanical strength, hydrophilicity and in vitro degradation rate of the three fibrous membranes were investigated. The results showed that the fibrous membranes owned good fibrous structure, and the fiber diameter was mainly distributed between 200～400nm. The diameter of the fibers increased significantly after crosslinking. With the increase of n-HA content, the aggregation of n-HA particles in the fibers and on the surface of fibers could be observed. The mechanical test showed that the tensile strength and elongation at break of the fibrous membranes increased with the n-HA content. The highest tensile strength and elongation of the PCL/Gel/n-HA membrane were 9.18MPa and 180%, respectively, when the weight percentage of n-HA was 15%. In addition, the incorporation of n-HA reduced the degradation rates of the fabricated fibrous membranes. The excellent mechanical properties and proper degradation rate of the prepared PCL/Gel/n-HA fibrous GTR membrane can meet the needs of clinical requirements.

Key words: electrospinning, polycaprolactone, gelatin, nano-hydroxyapatite

中图分类号:

TQ34

任欣,金蜀鄂,李玉宝,李吉东. 纳米羟基磷灰石增强聚己内酯/明胶纤维膜的制备及其性能[J]. 化工进展, 2020, 39(4): 1439-1446.

Xin REN,Shu’e JIN,Yubao LI,Jidong LI. Preparation and performance of nano-hydroxyapatite reinforced polycaprolactone/gelatin fibrous membrane for guided tissue regeneration[J]. Chemical Industry and Engineering Progress, 2020, 39(4): 1439-1446.

图/表 7

图1 不同n-HA含量纤维膜交联前的扫描电镜图、纤维直径分布图和透射电镜图

图2 不同n-HA含量纤维膜交联后扫描电镜图和纤维直径分布图

图3 不同n-HA含量的纤维膜红外谱图

图4 n-HA和不同n-HA含量纤维膜的XRD谱图

图5 纤维膜的热重曲线

图6 纤维膜应力-应变曲线及力学强度统计直方图

图7 纤维膜体外降解图

参考文献 45

1	LI W, DING Y, YU S, et al. Multifunctional chitosan-45S5 bioactive glass-poly(3-hydroxybutyrate-co-3-hydroxyvalerate) microsphere composite membranes for guided tissue/bone regeneration[J]. ACS Applied Materials & Interfaces, 2015, 7(37): 20845-20854.
2	BOTTINO M C, THOMAS V, SCHMIDT G, et al. Recent advances in the development of GTR/GBR membranes for periodontal regeneration-a materials perspective[J]. Dent. Mater., 2012, 28(7): 703-721.
3	NASAJPOUR A, ANSARI S, RINOLDI C, et al. A multifunctional polymeric periodontal membrane with osteogenic and antibacterial characteristics[J]. Adv. Funct. Mater, 2018, 28(3): 1703437.
4	JIN S E, SUN F H, ZOU Q, et al. Fish collagen and hydroxyapatite reinforced poly(lactide-co-glycolide) fibrous membrane for guided bone regeneration[J]. Biomacromolecules, 2019, 20(5): 2058-2067.
5	CHEN H B, QIAN Y Z, XIA Y, et al. Enhanced osteogenesis of ADSCs by the synergistic effect of aligned fibers containing collagen I[J]. ACS Appl. Mater. Interfaces, 2016, 8(43): 29289-29297.
6	KARFELD-Sulzer L S, GHAYOR C, SIEGENTHALER B, et al. Comparative study of NMP-preloaded and dip-loaded membranes for guided bone regeneration of rabbit cranial defects[J]. J. Tissue Eng. Regen. Med., 2017, 11(2): 425-433.
7	ZHOU T, LIU X, SUI B Y, et al. Development of fish collagen/bioactive glass/chitosan composite nanofibers as a GTR/GBR membrane for inducing periodontal tissue regeneration[J]. Biomed. Mater., 2017, 12(5): 055004.
8	ZHANG E S, ZHU C S, YANG J, et al. Electrospun PDLLA/PLGA composite membranes for potential application in guided tissue regeneration[J]. Mater. Sci. Eng. C (Mater. Biol. Appl., 2016, 58: 278-285.
9	QASIM S B, NAJEEB S, DELAINE-SMITH R M, et al. Potential of electrospun chitosan fibers as a surface layer in functionally graded GTR membrane for periodontal regeneration[J]. Dent. Mater., 2017, 33(1): 71-83.
10	MEHTA D S, GOWDA T M, WADHAWAN A. Gore-tex® versus resolut adapt® GTR membranes with perioglas® in periodontal regeneration[J]. Contemporary Clinical Dentistry, 2012, 3(4):406-411.
11	SCHLEGEL A K, MOHLER H, BUSCH F, et al. Preclinical and clinical studies of a collagen membrane (Bio-Gide®)[J]. Biomaterials, 1997, 18(7): 535-538.
12	薛利军, 武峰, 赵彬. 引导骨组织再生术在口腔种植中的应用[J]. 现代口腔医学杂志, 2017(5): 303-306.
	XUE Lijun, WU Feng, ZHAO Bin. Application of guided bone tissue regeneration in oral implants[J]. Modern Journal of Stomatology, 2017(5): 303-306.
13	FERREIRA A M, GENTILE P, ChIONO V, et al. Collagen for bone tissue regeneration[J]. Acta Biomater., 2012, 8(9): 3191-3200.
14	BUNYARATAVEJ P. Collagen membranes: a review[J]. Journal of Periodontology, 2001, 72(2): 215.
15	ZHANG S G. Fabrication of novel biomaterials through molecular self-assembly[J]. Nat. Biotechnol., 2003, 21(10): 1171-1178.
16	ZHAO J H, HAN W Q, CHEN H D, et al. Preparation, structure and crystallinity of chitosan nano-fibers by a solid–liquid phase separation technique[J]. Carbohydrate Polymers, 2011, 83(4): 1541-1546.
17	MUNCHOW E A, ALBUQUERQUE M T, ZERO B, et al. Development and characterization of novel ZnO-loaded electrospun membranes for periodontal regeneration[J]. Dent. Mater., 2015, 31(9): 1038-1051.
18	XUE J, SHI R, NIU Y, et al. Fabrication of drug-loaded anti-infective guided tissue regeneration membrane with adjustable biodegradation property[J]. Colloids and Surfaces B (Biointerfaces), 2015, 135: 846-854.
19	REN K, WANG Y, SUN T, et al. Electrospun PCL/gelatin composite nanofiber structures for effective guided bone regeneration membranes[J]. Mater. Sci. Eng. C (Mater. Biol. Appl., 2017, 78: 324-332.
20	KHAKESTANI M, JAFARI S H, ZAHEDI P, et al. Physical, morphological, and biological studies on PLA/nHA composite nanofibrous webs containing Equisetum arvense, herbal extract for bone tissue engineering[J]. J. Appl. Polym. Sci., 2017, 134: 45343.
21	张华林, 冯佳, 李咏梅. PLGA牙周引导组织再生膜的仿生矿化研究[J]. 哈尔滨医药, 2011, 31(4): 241-242.
	ZHANG Hualin, FENG Jia, LI Yongmei. Biomimetic mineralization of PLGA guided tissue regeneration membrane[J]. Harbin Pharmaceutical, 2011, 31(4): 241-242.
22	YU L, FENG Y, LI Q, et al. PLGA/SF blend scaffolds modified with plasmid complexes for enhancing proliferation of endothelial cells[J]. Reactive and Functional Polymers, 2015, 91/92: 19-27.
23	CHEN Z G, WEI B, MO X M, et al. Mechanical properties of electrospun collagen-chitosan complex single fibers and membrane[J]. Materials Science and Engineering C, 2009, 29(8): 2428-2435.
24	GAUTAM S, CHOU C F, DINDA A K, et al. Fabrication and characterization of PCL/gelatin/chitosan ternary nanofibrous composite scaffold for tissue engineering applications[J]. J. Mater. Sci., 2013, 49(3): 1076-1089.
25	SANT S, HWANG C M, LEE S H, et al. Hybrid PGS-PCL microfibrous scaffolds with improved mechanical and biological properties[J]. J. Tissue. Eng. Regen. Med., 2011, 5(4): 283-291.
26	ALVAREZ P M A, GUARINO V, CIRILLO V, et al. In vitro mineralization and bone osteogenesis in poly(epsilon-caprolactone)/gelatin nanofibers[J]. J. Biomed. Mater. Res. A, 2012, 100(11): 3008-3019.
27	吴晓楠, 苗雷英, 刘玉, 等. 电纺聚己内酯/Ⅰ型胶原蛋白/纳米羟基磷灰石复合材料的制备及其生物相容性研究[J]. 口腔医学, 2015, 35(4): 245-249.
	WU Xiaonan, MIAO Leiying, LIU Yu, et al. Preparation and biocompatibility of electrospun polycaprolactone/type-Ⅰ collagen/nanophase hydroxyapatite composite fibrous scaffold[J]. Stomatology, 2015, 35(4): 245-249.
28	LINH B N T, MIN Y K, LEE B T. Hybrid hydroxyapatite nanoparticles-loaded PCL/GE blend fibers for bone tissue engineering[J]. J. Biomater. Sci. Polym. Ed., 2013, 24(5): 520-538.
29	ITO Y, HASUDA H, KAMITAKAHARA M, et al. A composite of hydroxyapatite with electrospun biodegradable nanofibers as a tissue engineering material[J]. J. Biosci. Bioeng., 2005, 100(1): 43-49.
30	KHAN A S, HUSSAIN A N, SIDRA L, et al. Fabrication and in vivo evaluation of hydroxyapatite/carbon nanotube electrospun fibers for biomedical/dental application[J]. Mater. Sci. Eng. C (Mater. Biol. Appl., 2017, 80, 387-396.
31	FU L, WANG Z F, DONG S J, et al. Bilayer poly(lactic-co-glycolic acid)/nano-hydroxyapatite membrane with barrier function and osteogenesis promotion for guided bone regeneration[J]. Materials, 2017, 10(3): 257.
32	RAJZER I, MENASZEK E, KWIATKOWSKI R, et al. Bioactive nanocomposite PLDL/nano-hydroxyapatite electrospun membranes for bone tissue engineering[J]. J. Mater. Sci. Mater. Med., 2014, 25(5): 1239-1247.
33	ZHANG L, LI Y B, ZUO Y, et al. In vitro and in vivo evaluation on the bioactivity of ZnO containing nano-hydroxyapatite/chitosan cement[J]. Journal of Biomedical Materials Research Part A, 2010, 93(1): 269-279.
34	LI L M, ZUO Y, ZOU Q, et al. Hierarchical structure and mechanical improvement of an n-HA/GCO-PU composite scaffold for bone regeneration[J]. ACS Applied Materials & Interfaces, 2015, 7(40): 22618-22629.
35	FARIDI-MAJIDI R, NEZAFATI N, PAZOUKI M, et al. Evaluation of morphology and cell behaviour of a novel synthesized electrospun poly(vinyl pyrrolidone)/poly(vinyl alcohol)/hydroxyapatite nanofibers[J]. Nanomedicine Journal, 2017, 4(2): 107-114.
36	ZHANG S, HUANG Y Q, YANG X P, et al. Gelatin nanofibrous membrane fabricated by electrospinning of aqueous gelatin solution for guided tissue regeneration[J]. Journal of Biomedical Materials Research Part A, 2009, 90(3): 671-679.
37	REN X, CHEN C, HOU Y, et al. Biodegradable chitosan-based composites with dual functions acting as the bone scaffold and the inflammation inhibitor in the treatment of bone defects[J]. International Journal of Polymeric Materials and Polymeric Biomaterials, 2018, 67(12): 703-710.
38	GUO Z Z, XU J M, DING S, et al. In vitro evaluation of random and aligned polycaprolactone/gelatin fibers via electrospinning for bone tissue engineering[J]. Journal of Biomaterials Science: Polymer Edition, 2015, 26(15): 989-1001.
39	LI D W, CHEN W M, SUN B B, et al. A comparison of nanoscale and multiscale PCL/gelatin scaffolds prepared by disc-electrospinning[J]. Colloids Surf. B (Biointerfaces), 2016, 146: 632-641.
40	GOMES S R, RODRIGUES G, MARTINS G G, et al. In vitro and in vivo evaluation of electrospun nanofibers of PCL, chitosan and gelatin: a comparative study[J]. Materials Science & Engineering C (Materials for Biological Applications), 2015, 46: 348-358.
41	徐子颉, 马超, 汪飞, 等. 原位制备聚己内酯和羟基磷灰石复合材料[J]. 同济大学学报, 2011, 39(10): 1524-1527.
	XU Zijie, MA Chao, WANG Fei, et al. Synthesis of HAP composites by oranic sol-gel process[J]. Journal of Tongji University, 2011, 39(10): 1524-1527.
42	陈佳佳, 陈广美, 邹铁梅, 等. 纳米羟基磷灰石与聚己内酯复合电纺纤维膜[J]. 功能高分子学报, 2012, 1: 40-46.
	CHEN Jiajia, CHEN Guangmei, ZOU Tiemei, et al. Composites of nano-hydroxyapatite and polycaprolactone composite fibers by electrospinning[J]. Journal of Functional Polymers, 2012, 1: 40-46.
43	LIU H H, ZHANG L, LI J D, et al. Physicochemical and biological properties of nano-hydroxyapatite-reinforced aliphatic polyurethanes membranes[J]. Journal of Biomaterials Science: Polymer Edition, 2010, 21(12): 1619-1636.
44	范利丹, 胡潇依, 秦刚, 等. PPC/HA复合纤维膜结晶性能和力学性能表征[J]. 塑料, 2017, 5: 94-98.
	FAN Lidan, HU Xiaoyi, QIN Gang, et al. Crystallization and mechanical properties of PPC/HA composite fibers membrane[J]. Plastic, 2017, 5: 94-98.
45	MASOUDI R M, NOURI K S, GHASEMI-Mobarakeh L, et al. Fabrication and characterization of two-layered nanofibrous membrane for guided bone and tissue regeneration application[J]. Materials Science & Engineering C (Materials for Biological Applications), 2017, 80: 75-87.

[1]	王慧, 刘新懿, 王伟, 万同, 厉宗洁, 王劭妤, 程博闻. 静电纺特殊形貌纳米纤维的应用研究进展[J]. 化工进展, 2022, 41(8): 4341-4356.
[2]	王喜倩, 尹国强, 郭清兵, 何明. 多巴胺表面修饰角蛋白/聚乳酸纳米纤维膜的制备及性能[J]. 化工进展, 2022, 41(1): 373-381.
[3]	金浩, 刘杏, 林咏梅. 植酸改性的明胶复合膜制备及其结构与性能分析[J]. 化工进展, 2021, 40(7): 3847-3853.
[4]	李祥业, 白天娇, 翁昕, 张冰, 王珍珍, 何铁石. 电纺聚丙烯腈基碳纳米纤维在超级电容器中的应用[J]. 化工进展, 2021, 40(6): 3314-3329.
[5]	崔卓安, 綦戎辉. 应用静电纺丝技术的电催化剂及载体材料制备研究进展[J]. 化工进展, 2021, 40(3): 1395-1412.
[6]	李根, 李吉东. 可注射nHA/PU复合多孔骨修复支架制备及表征[J]. 化工进展, 2021, 40(12): 6800-6806.
[7]	饶瑞晔, 毛竹简, 林晓榆, 郭绍英, 胡家朋. 脱乙酰基改性乙酸纤维薄膜对乳化油分离及积垢机理的探究[J]. 化工进展, 2021, 40(10): 5415-5423.
[8]	邓建辉, 杨晓青, 方称辉, 曹栋清, 李梁君, 张国庆, 郭建维. 静电纺丝/静电喷雾技术在电池领域的应用进展[J]. 化工进展, 2021, 40(10): 5600-5614.
[9]	李纯, 孙丽霞, 孙建华, 周利琴, 徐大鹏, 张友全, 廖丹葵. 静电纺丝法制备ZnO构建酪氨酸酶生物传感器检测邻苯二酚[J]. 化工进展, 2020, 39(7): 2795-2801.
[10]	丁姣, 赖锐豪, 陈文杰, 黄素青, 尹国强. 化学助剂优化静电纺角蛋白纳米纤维性能进展[J]. 化工进展, 2020, 39(10): 4155-4163.
[11]	王梓,林凤采,熊明诚,张松华,卢贝丽,黄彪. 纤维素基有机-无机杂化复合膜的制备及其吸附性能[J]. 化工进展, 2019, 38(9): 4204-4211.
[12]	吕婷婷,安瑛,刘宇健,李好义,谭晶,杨卫民. 静电纺丝制备蛋清蛋白/聚氧化乙烯纳米纤维[J]. 化工进展, 2019, 38(12): 5487-5491.
[13]	孙墨杰,林东尧,王钊,王世杰,王久生,王冬. 静电纺丝制备镍铁纳米纤维及其析氧性能[J]. 化工进展, 2019, 38(10): 4645-4650.
[14]	姚子琪,马东明,雷文龙,焦志伟,李好义,徐小东,张有忱. 熔体静电纺丝直写技术在组织工程中的应用进展[J]. 化工进展, 2019, 38(08): 3756-3762.
[15]	张帅, 王斯瑶, 姜召, 方涛. 静电纺丝技术在氨硼烷水解脱氢催化剂制备中的应用[J]. 化工进展, 2019, 38(07): 3194-3206.