Alginate fiber: Development and biomedical application

doi:10.3969/j.issn.2095-4344.2013.12.019

Abstract

Abstract:

BACKGROUND: At present, alginate fiber possesses various forms and functions, which is increasingly used in biomedicine and clinical medicine.
OBJECTIVE: To comprehensively review the structure and feature of alginate fiber and to introduce the biomedical application of its blend fiber with chitosan or gelation.
METHODS: PubMed database and Wanfang database were retrieved by the first author for literature about alginate fiber production process, the alginate fiber structure and properties, biomedical application of alginate fiber, and related blended fiber characteristics and applications, published from 1990 to 2012.
RESULTS AND CONCLUSION: Alginate has been widely applied in agriculture and chemical industry, biological control, tissue engineering, drug delivery system, wound repair, and environmental purification. New hybrid fibers obtained through blending modification cannot only improve the shortcomings of alginate fiber applications, but also be endued with more performances, as biomaterials which have become a research hotspot nowadays and in the future. At present, development of biomedical materials is going towards environmental protection, high functionality, and intellectualized directions. Seaweed fibers, chitosan fibers, gelatin fibers and their blend fibers, which are present with a rich storage in natural, low cost, excellent biocompatibility and degradation, have great potential and have been expected to have further development in biomedicine and bionic medicine.

Key words: biomaterials, biomaterial academic discussion, alginic acid, alginate fiber, chitosan, gelatine, blend fiber, tissue engineering, review

CLC Number:

R318

Lin Xiao-hua, Huang Zong-hai, Yu Jin-long. Alginate fiber: Development and biomedical application[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(12): 2218-2224.

Figures/Tables 4

2.1.1 海藻的生物相容性及无毒性海藻酸盐含有多种氨基酸，具有良好的生物相容性，在二价阳离子(大多数为钙离子)存在条件下可交联形成网状开放晶格的水凝胶，该水凝胶具有很好的亲水性，包埋在水凝胶中的细胞可进行以渗透扩散为主的营养和代谢物质交换，其酶解产物对人体无毒害作用[9-10]。同时有研究证实，成纤维细胞、软骨细胞和成骨细胞可在藻酸钙水凝胶中成活并形成细胞外基质[11-12]，血管内皮生长因子、血小板衍生因子等多种生长因子也可整合在海藻酸盐水凝胶中，通过注射进入体内稳定地释放到组织中[13]，这些为藻酸钙水凝胶作为组织工程基质材料的研究提供了依据。海藻酸盐微粒适合作为双向传输系统的载体，因为两种蛋白质的大小会表现出截然不同的释放动力学，海藻酸相对温和的凝胶过程使蛋白质和细胞整入粒子后能保存所有的生物活性[14]。另外，de Vos等[15]用海藻酸盐-聚赖氨酸-海藻酸盐包埋胰岛细胞植入大鼠体内的研究发现：只有当海藻酸盐非常纯(古罗糖醛酸组分在40%-45%)时才能有效提高其生物相容性。 2.1.2 海藻的高吸湿性海藻酸纤维大分子结构中含有大量的羟基和羧基，而且海藻纤维内无定形区较大，膨润性好，所以海藻纤维具有很强的吸湿性，最多可以吸收近20倍的液体。测试发现，海藻酸医用敷料的吸湿性能主要是通过渗出液中的Ca2+与海藻酸纤维的Na+交换，最重要的影响因素之一就是纤维的内部结构：高M和G单元的海藻酸钠/钙纤维的吸湿性能大于高G单元的海藻酸钙纤维，从而具有优良的凝胶性能[16]。 2.1.3 海藻纤维的生物凝胶性和高透氧性海藻纤维凝胶化性能与“盒子”的特定大小，“盒子”包装的层数，协同作用的强弱程度以及分子稳定程度有关[17]。海藻纤维吸湿后形成亲水性凝胶，与亲水基团结合的“自由水”成为氧气传递的通道，氧气经吸附、扩散、解吸过程，从外界环境进入伤口组织内；另外，海藻纤维大分子骨架连接点(纤维的高G 段)也是氧气可通过的微孔。藻酸钙膜为表面光滑柔韧和顺应性较好的半透明状生物薄膜，其水气透过性能和对中小分子质量物质通透性良好，有阻止细胞和细菌通过的屏障效能[18]。海藻纤维的生物成胶性和高透氧性为包埋移植胰岛细胞簇治疗糖尿病提供了有利条件[19]。 2.1.4 海藻纤维的生物降解性海藻纤维能被微生物降解成二氧化碳和水，是一种良好的环境友好材料。目前研究提示γ射线照射可以降低海藻酸纤维的分子量，或高碘酸盐氧化治疗可以导致海藻酸主干水解作用增强，从而增加其从体内清除出去的速度[20]。目前组织工程医学已将各种海洋生物来源的多糖类应用于骨关节等疾病的治疗上，其中以海藻酸复合材料研究应用最广[21]。 2.1.5 海藻纤维的抗菌性目前已鉴定出的海藻中含有脂类、酚类、萜类、多糖类、卤化物、含硫化合物等多种多样抗菌活性物质。从绿藻石中发现的3-O-β-D glucopyranosyl clerosterol类固醇，见图2，在抑链球菌、假单胞菌、枯草芽孢杆方面与 200 μg/disc 的氨卡青霉素比较，均显示了相当甚至更好的抗菌效果， Sandsdalen 等[22]从墨角藻中分离鉴定出的一种多羟基化岩藻多酚具有很强的杀菌能力，表现出抗5 种革兰阳性菌和2 种阴性菌的作用；从圈扇藻分离得到的一种带20碳骨架的间苯三酚，见图3，具有抗革兰阴性菌和阳性菌活性，因而该间苯三酚具有作为金黄色葡萄球菌和枯草芽孢杆菌抗生素的潜在应用前景[23]。总之，海藻类中含有多种抗菌活性物质，已成为寻找新型更具活性抗菌新药的研究热点。"

2.1.6 海藻纤维的生物学性能特点海藻酸钠不单能通过增强巨噬细胞和人浆细胞的溶解活性和刺激这些细胞分泌大量白细胞介素1和白细胞介素6 等而促进人体免疫功能，而且海藻酸钠还表现出抑制肿瘤生长等功能，经实验表明，海藻酸钠能抑制小鼠的S-180、欧利希腹水癌和同种肠化生癌。甚至有研究发现，MM块含量水平高的海藻酸钠抗肿瘤活性增高，并发现甘露糖醛酸残基是海藻酸钠中活性细胞动素的诱导者[24]。还有研究表明藻酸盐有预防高血脂和脂肪肝的作用，并能使血小板聚集性下降，对预防血栓性疾病有益[25]。 2.2 海藻酸共混纤维的特性及目前在医学上研究应用情况近年有较多学者研究发现藻酸钙膜是一种理想的膜引导组织再生材料，它具有可降解性且膜降解时间与组织再生时间同步而且其中所含钙锌离子有止血效能，能在膜下迅速形成凝血块，保证了作为骨再生基础的血肿完整性，因此藻酸钙膜相对于其他生物膜材料更具优势，前景广阔[26]。但海藻纤维存在的主要问题是机械性能如强力低等缺点。运用高分子之间的共混技术是改善高聚物材料性能的有效方法，可改善纤维的各种性能。下面分别讲述了目前研究比较多的海藻酸/壳聚糖共混纤维、海藻酸/明胶共混纤维。 2.2.1 海藻酸与壳聚糖共混纤维壳聚糖于甲壳类动物的壳中提取，降解产物是氨基葡萄糖，生物相容性好，可抑制修复过程中有细胞毒性的NO生成[27]，同时具有抗炎、镇痛、成膜性，促进转化生长因子和血小板衍生生长因子的产生，从而促进凝血和创伤愈合[28]，能被生物体内的溶菌酶降解并完全吸收的特点[29]。有动物实验表明在生理温度下向心肌缺血的胚胎干细胞周围注射壳聚糖有利于保存细胞的存活能力，壳聚糖可以原位凝胶，表现出改善细胞功能和促进新生血管形成的优势[30]。 Knill 等[31]研究表明，用水解后的壳聚糖溶液处理海藻酸钠纤维能够加固纤维的结构，提高纤维的拉伸性能，同时发现水解壳聚糖/海藻酸钠纤维具有一定的抗菌性能，能够缓慢地释放抗菌物质。其复合物因具有良好的生物相容性、生物可降解性、有效免疫隔离作用，在生物材料、药物控释等领域显示出广阔的应用前景。近年来的研究多为利用壳聚糖-海藻酸盐复合物制备新型膜材料、纤维敷料[32]、可注射的制剂[33]，制备微纳米粒子来包裹细胞、蛋白和药物等[34-38]。国内外以壳聚糖和海藻酸钠为基质体系研究胃内漂浮制剂的报道也比较常见[39-40]。有研究采用共沉淀法制备合成纳米羟基磷灰石/壳聚糖-海藻酸钠三元复合材料，与人体骨相似，有较高生物活性和一定的柔韧性及强度，该复合材料弥补了纳米羟基磷灰石/壳聚糖脆性大、力学性能差等不足，有望成为一种理想的骨修复替代材料[41]。 2.2.2 海藻酸与明胶共混纤维明胶是动物皮、骨等结缔组织中的胶原经部分水解和热变性而得到的大分子蛋白质，具有良好透水透气性，可活化巨噬细胞，良好的生物相容性，体内完全吸收性，对人体无毒以及容易成型等特性；作为生物蛋白，还可促进生长因子的释放，刺激细胞增殖，有利于保持细胞活力[42]，因此明胶被看作为具有很大潜力的环境友好生物材料。海藻酸/明胶共混纤维生物相容性好，黏附性强，具有促进伤口愈合的活性功能及止血功能，用作医用纱布、创面敷料时可以为创面提供密闭环境，有效隔绝了外界细菌的侵入，同时该环境储留的创面渗液中含有巨噬细胞、淋巴细胞、单核细胞等，这有利于白细胞介导的宿主吞噬细胞发挥作用，增强局部杀菌能力。该共混纤维也具有较好的药物缓释作用，可与局部抗菌药物组合制成基因工程敷料用于感染创面；也可与活性生长因子或活性细胞组合制成基因工程敷料用于顽固性溃疡及烧伤创面。海藻酸/明胶共混纤维因具有高吸湿性而常被用作面部创伤敷料、鼻内镜手术后黏膜创面敷料及儿科填充物以吸收渗出液、减少黏膜水肿、抑制细菌生长等[43]。目前海藻酸/明胶共混微粒也被用于研究制造人造心脏组织进行移植[44]。"

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