CN113969435A - 含纳米活性炭的海藻酸钠复合纤维的制备方法及其应用 - Google Patents
含纳米活性炭的海藻酸钠复合纤维的制备方法及其应用 Download PDFInfo
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- CN113969435A CN113969435A CN202111295683.4A CN202111295683A CN113969435A CN 113969435 A CN113969435 A CN 113969435A CN 202111295683 A CN202111295683 A CN 202111295683A CN 113969435 A CN113969435 A CN 113969435A
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- sodium alginate
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Abstract
本发明公开了含纳米活性炭的海藻酸钠复合纤维的制备方法及其应用,涉及海藻酸钠纤维技术领域。所得海藻酸盐纤维具有良好的力学性能和生物相容性,同时稳定性和安全性高。其技术方案为:采用注射式湿法纺丝工艺制备ACNP/SA复合纤维,采用纳米活性炭对海藻酸钠复合纤维力学性能进行增强,制得的含纳米活性炭的海藻酸盐纤维,表面较纯海藻酸盐纤维光滑、紧密,解决了海藻酸盐纤维沟槽缺陷问题,有助于纤维力学性能提升;纳米活性炭对海藻酸盐纤维起到了一定的支撑作用,且有利于增加纤维孔隙率降低扩散阻力,增强纤维的通透性。ACNP/SA复合纤维在体外对细胞无毒性,具有良好的细胞相容性和生物安全性,在医学材料领域具有开发和应用价值。
Description
技术领域
本发明涉及海藻酸钠纤维技术领域,特别是涉及含纳米活性炭的海藻酸钠复合纤维的制备方法及其应用。
背景技术
海藻酸钠(Sodium alginate,SA)是一种水溶性阴离子天然多糖,具有良好的生物相容性、生物降解性、无毒性以及能够提供细胞识别位点等功能特性,常被作为生物医用材料应用于医疗领域中。SA可与多价金属阳离子螯合交联形成凝胶状、膜状、微胶囊或纤维状等各种材料。其中,海藻酸钠纤维由于其独特的结构性能,可被加工成织物、非织造布和各种医用复合材料,如止血材料、促愈合材料、组织工程支架和药物释放材料等。然而,由于SA为线性分子链,链间不能有效缠结,使得海藻酸盐纤维材料结构疏松、溶胀易破裂而缺乏强度和弹性,难以实现复杂的三维结构和较高的机械强度,在很大程度上影响其加工性能和更广泛的应用。
近年来研究发现,加入纳米材料后获得的SA纳米复合材料具有许多独特的物理化学性能。碳材料作为地球上应用最广泛的材料一直是科学研究的重点。截至目前,已有大量的碳纳米材料改性海藻酸盐纤维的报道,如碳纳米纤维、碳纳米管、纤维素纳米晶体或氧化石墨烯纳米片等,可以增强海藻酸盐纤维材料的力学性能。活性炭作为碳材料复合SA的研究也有报道,但都聚焦在活性炭的吸附能力上,而纳米级活性炭改性海藻酸盐纤维性能应用于医学材料的研究鲜有报道。
纳米活性炭(Active carbon nanoparticles,ACNP),是一种低毒、生物相容性高的碳材料,具有很强的药物吸附性能,药物缓释性能。临床上,常被用作淋巴引流的指示剂和药物缓释剂,也是目前唯一用于临床的碳材料。因此,从医学材料的角度考虑,纳米活性炭改性海藻酸盐纤维材料的性能值得探究。然而随着纳米材料的深入研究,碳纳米材料对人类健康的潜在危害引起人们的关注。有研究报道短碳纳米纤维对成纤维细胞有毒性,能降低细胞的活力,其毒性的长度阈值大约189±17nm。
综上,将纳米活性炭应用于海藻酸盐纤维尚未有实质性进展,其产品性能如何未可知。
细胞封装技术是指将细胞包裹在半透明的封装基质中,该技术在细胞治疗、细胞移植、细胞存储/运输、细胞分析、组织工程以及再生医学等诸多领域具有重要应用价值。
1980年,Anthony M Sum等人利用液滴形成技术结合海藻酸钠和氯化钙、聚赖氨酸(PLL)、以及聚乙烯亚胺(PED)之间的交联反应,首次制备了胰岛微胶囊,并将其植入到链脲佐菌素诱导的糖尿病大鼠腹腔内,结果发现,植入的胰岛微胶囊在2~3周内可有效降低糖尿病大鼠的血糖水平;此外,细胞长期培养实验发现,该胰岛微胶囊可以保持形态和功能完整长达15周以上。为了提高微胶囊的生物相容性,Anthony M Sun等人随后建立了海藻酸钠-聚赖氨酸海藻酸钠(APA)微胶囊制备。与此同时,研究者们陆续实现了对肝细胞、杂交瘤细胞、肾细胞、基因修饰细胞的封装,以及多种细胞的共封装。
理想的封装材料特点之一是完全惰性、不引起异体转移受者免疫反应或囊周过度纤维化(PFO),虽然现有技术中,对海藻酸钠和其他封装材料进行的改进减少了PFO,提高了移植细胞的存活率,但Kamperman T等人在《Trends Biotechnol》发表的“Single-cellmicrogels:Technology,challenges,and applications”中指出,海藻酸钠材料不具有对动物细胞任何特异性的生物信号和响应反应,难以维持封装细胞的正常活性和生长。
可见,海藻酸钠材料用于细胞封装在细胞存活性、生物相容性等方面仍存在缺陷。
发明内容
本发明的目的在于提供一种含纳米活性炭的海藻酸钠复合纤维的制备方法,所得海藻酸盐纤维具有良好的力学性能和生物相容性,同时稳定性和安全性高。
本发明的设计思路是:采用注射式湿法纺丝工艺制备纳米活性炭与海藻酸钠的复合纤维,采用纳米活性炭对海藻酸钠复合纤维力学性能进行增强,同时制得力学性能、稳定性、通透性和生物相容性更优的产品。
为实现本发明的上述目的,本发明提供了如下所述的技术方案:
作为本发明的第一个方面,在于提供了含纳米活性炭的海藻酸钠复合纤维的制备方法,包括如下步骤:
步骤1、取海藻酸钠粉末溶于水中,过滤除菌,备用,为海藻酸钠溶液;
步骤2、取纳米活性炭灭菌,备用;
步骤3、称取步骤2所得的灭菌后的纳米活性炭溶解在步骤1所得的海藻酸钠溶液中,制得混合溶液;
步骤4、采用湿法纺丝工艺,将步骤3所得的混合溶液流入到氯化钙溶液中钙化,钙化完成后洗涤,即得。
优选的,步骤1中海藻酸钠溶液含量为1.5%~3.0%(w/v),更优选2.5%(w/v)。
优选的,步骤2中纳米活性炭在121℃灭菌20min。
优选的,步骤3中纳米活性炭与海藻酸钠溶液的重量比为(2~8):100,更优选为2:100。
优选的,步骤4中氯化钙溶液含量为1%~3%(w/v),更优选为1.5%(w/v)。
优选的,所述纳米活性炭粒径为50~300nm,更优选200nm。
优选的,称取海藻酸钠粉末,溶于蒸馏水中,制成2.5%(w/v)的海藻酸钠溶液,0.45μm滤器过滤除菌,备用;同时,取纳米活性炭在121℃灭菌20min,备用;称取灭菌后的纳米活性炭溶解在海藻酸钠溶液中,制得混合溶液,纳米活性炭与海藻酸钠溶液的重量比为2:100,采用湿法纺丝工艺,调节注射泵流量将混合溶液流入到1.5%(w/v)氯化钙溶液中钙化15min,蒸馏水洗涤2次,制得海藻酸盐纤维。
更进一步的,所述注射泵流量为1000μl/min。
制备生物医学材料需要较高的稳定性、通透性和生物相容性。为了满足以上要求,分别对海藻酸钠溶液的浓度、钙离子浓度对产品的影响进行了对比研究。
研究发现,海藻酸钠水凝胶受浓度影响明显,浓度小,通透性大、力学性能低,不利于加工利用;浓度高,溶液黏度高,力学性能增加但不利于物质的通过;根据研究和对比,本发明采用海藻酸钠溶液浓度为1.5%~3.0%(w/v),鉴于本研究的最终目标是制备生物医学材料,需要较高的稳定性、通透性和生物相容性,更优选2.5%(w/v)。
另外,Ca2+浓度对凝胶的力学性能影响较大。Ca2+浓度低时,凝胶网状孔径较大,凝胶机械稳定性差,容易破裂,不利于使用;Ca2+浓度较高时,凝胶结构致密,传质性能差,不利于内外物质交换。根据实验研究和对比,本发明选择氯化钙浓度1.5%,此时对细胞毒性小,又利于成胶。
现有技术研究发现,单纯海藻酸钠分子制备凝胶纤维力学性能不佳,虽然通过不断调整纺丝工艺参数,提高了海藻酸盐纤维的力学性能,但仍不能满足其后加工和使用性能;本发明选取纳米活性炭为增强体,在实施例中研究了不同添加浓度对海藻酸盐纤维性能的影响,发现,随着ACNP浓度的增加,海藻酸盐纤维的透光性变差,同时结果表明,添加适量的纳米活性炭可显著增强海藻酸盐纤维力学性能,尤其是在纳米活性炭与海藻酸钠溶液比例为2:100~4:100时,纤维断裂伸长率远高于其他比例、断裂应力较高,溶胀率高,同时,具有更好的生物稳定性和生物安全性,能作为封装细胞的医用材料。同时,本发明中提供了复合状态的纳米活性炭,复合活性炭材料粒径较小,在体内具有更好生物相容性。
作为本发明的第二个方面,在于提供所述制备方法制得的含纳米活性炭的海藻酸钠复合纤维用于细胞封装应用。所述细胞包括但不限于胰岛细胞、甲状腺细胞和甲状旁腺细胞。
与现有技术相比,本发明的有益效果是:
1、本发明提供了含纳米活性炭的海藻酸钠复合纤维的制备方法,制得了力学性能和生物相容性最佳的ACNP/SA复合纤维;
2、本发明提供了新的海藻酸盐复合纤维材料,所制得的含纳米活性炭的海藻酸盐纤维表面较纯海藻酸盐纤维光滑、紧密,解决了海藻酸盐纤维沟槽缺陷问题,有助于纤维力学性能提升;纳米活性炭对海藻酸盐纤维起到了一定的支撑作用,且有利于增加纤维孔隙率降低扩散阻力,增强纤维的通透性;
3、本发明研究发现纳米活性炭在添加量0%-2%之间时,海藻酸盐纤维伸长性能、断裂应力和溶胀率同时增加;当ACNP添加量为2%时所制备的海藻酸盐纤维的断裂伸长率比未添加的海藻酸盐纤维提高了80.2%,断裂应力增加了42.5%;
4、对比海藻酸盐纤维,本发明添加2%和4%浓度的ACNP复合到海藻酸盐纤维后,浸出液表现出更好的支持MIN6细胞生长的特性;这说明ACNP/SA复合纤维在体外对细胞无毒性,具有良好的细胞相容性和生物安全性,在医学材料领域具有开发和应用价值。
附图说明
构成本发明的一部分的说明书附图用来提供对本发明的进一步理解,本发明的示意性实施例及其说明用于解释本发明,并不构成对本发明的不当限定。
图1为倒置显微镜观察图像,
其中,图a.0%ACNP/SA、b.2%ACNP/SA、c.4%ACNP/SA、d.8%ACNP/SA是在放大倍率为100时图像;e.8%ACNP/SA是在放大倍率为200时图像;
图2为海藻酸钠复合纤维表面形貌图,
其中,a.0%ACNP/SA在倒置显微镜下10×观察;b.0%ACNP/SA在扫描电镜下观察;c.2%ACNP/SA在倒置显微镜下10×观察;d.2%ACNP/SA在扫描电镜下观察;
图3为不同ACNP浓度的海藻酸钠复合纤维在生理盐水中的溶胀曲线;
图4为不同海藻酸钠复合纤维浸出液对MIN6细胞生长的影响对照图,
其中,每个时间点中由左向右依次为对照组、0%ACNP/SA、2%ACNP/SA、4%ACNP/SA。
具体实施方式
应该指出,以下详细说明都是示例性的,旨在对本发明提供进一步的说明。除非另有指明,本文使用的所有技术和科学术语具有与本发明所属技术领域的普通技术人员通常理解的相同含义。
需要注意的是,这里所使用的术语仅是为了描述具体实施方式,而非意图限制根据本发明的示例性实施方式。
实施例1,ACNP/SA复合纤维的制备:
1、实验材料及方法
1.1试剂与仪器
海藻酸钠(MW:100,000-200,000g/mol,G Content:65%-70%),Sigma Aldrich;
ACNP,200nm,上海海诺碳业有限公司;
CaCl2,AR,天津市大茂化学试剂厂;
蒸馏水为二次蒸馏水,自制。
MIN6细胞系是从表达类人猿病毒40大T抗原(受胰岛素启动子控制)的转基因非肥胖糖尿病小鼠胰岛瘤中建立的,其内分泌功能与胰腺组织非常接近,是研究胰岛细胞功能的理想模型。本实验MIN6细胞由齐鲁医院内分泌科提供。
Regulus8200型扫描电子显微镜,日立;
PHG-9140A干燥箱,上海慧泰仪器有限公司;
LongerPump注射泵,河北保定兰格恒流泵有限公司;
CSS-88100型微机控制电子万能试验机,长春试验机研究所有限公司。
1.2ACNP改性海藻酸盐纤维的制备
称取SA粉末,溶于蒸馏水中,制成2.5%(w/v)的海藻酸钠溶液,0.45μm滤器过滤除菌,备用。同时,ACNP在121℃灭菌20min,备用。用20mL注射器(5#针头)吸取2.5%的SA溶液10mL,称取一定量的ACNP溶解在SA溶液中,制得混合溶液。采用湿法纺丝工艺,调节注射泵流量(1000μl/min)将混合溶液流入到1.5%(w/v)氯化钙溶液中钙化15min,蒸馏水洗涤2次,制得海藻酸盐纤维。
按ACNP:SA溶液质量比,分别制备ACNP/SA比例为0%、2%、4%、8%的海藻酸盐纤维,如表1所示。
表1 ACNP/SA复合纤维的配方
样品 | 重量比(ACNP:SA溶液) | SA含量 |
0%ACNP/SA | 0:100 | 2.5% |
2%ACNP/SA | 2:100 | 2.5% |
4%ACNP/SA | 4:100 | 2.5% |
8%ACNP/SA | 8:100 | 2.5% |
1.3 ACNP/SA复合纤维的物理表征
1.3.1扫描电子显微镜观察(SEM):将纤维冷冻干燥24h后用,采用扫描电镜观察样品结构形貌,加速电压2kV。
倒置显微镜下观察不同ACNP质量比的海藻酸盐纤维,如图1,其中,图a、b、c和d分别对应0%ACNP/SA、2%ACNP/SA、4%ACNP/SA、8%ACNP/SA,可见,随着ACNP浓度的增加海藻酸盐纤维的透光性变差,添加8%的海藻酸盐纤维100×光学显微镜下观察时无光线透过,图e对应8%ACNP/SA在放大倍率为200时图像,在200×下观察,仍有少量光线透过,但同时也观察到ACNP的聚集现象(图e)。因此,海藻酸盐纤维作为封装细胞的医学材料时,ACNP的添加量不应超过8%。
倒置显微镜下观察制备的ACNP/SA复合纤维的表面形貌,如图2,其中,图a、b、c和d分别对应0%ACNP/SA倒置显微镜下10×观察、0%ACNP/SA扫描电镜下观察、2%ACNP/SA倒置显微镜下10×观察、2%ACNP/SA扫描电镜下观察,可见,不添加ACNP的ACNP/SA复合纤维表面存在纵向沟槽,而添加ACNP的ACNP/SA复合纤维未观察到沟槽,且光滑度好。传统湿法纺丝的特点是纺丝液通过喷嘴直接进入凝固浴凝固成型,该成型过程往往会导致纤维的表面沟槽缺陷,成为制约纤维力学性能的主要因素之一。本研究添加少量ACNP后未观察到纤维沟槽缺陷,这可能是后续研究中测得力学性能提升的原因之一。
将0%ACNP/SA、2%ACNP/SA复合纤维冻干,表面进行喷金处理后,用扫描电镜观察纤维表面。图2中,在相同放大率下,0%ACNP/SA纤维表面结构比较均匀致密,表面均匀分布着小孔(图b)。2%ACNP/SA纤维表面孔径更大,且ACNP错落有致的镶嵌于纤维膜表面(图d),在囊孔有支撑作用,这种结构有利于提高纤维的吸附性和通透性。
1.3.2ACNP/SA复合纤维直径的测试:随机选取制备的海藻酸盐纤维,倒置显微镜下测试每条海藻酸盐纤维3个距离的横截面直径取平均值D(mm)。结果见表2。
1.3.3ACNP/SA复合纤维拉伸性能的测试:参照国标GB/T7689.5-2001,通过万能实验机对复合纤维进行断裂伸长率和断裂应力测试。实验条件设定为室温下进行测试,拉伸速度为20mm/min。断裂伸长率(Stretch),定义为:Stretch=(L-L0)/L0×100%。其中,L0为初始长度,L为拉伸断裂时长度(单位:mm)。断裂应力(Fracture Stress),定义为:σ=P/A。其中,P为断裂强力(单位N);A为截面面积(单位m2)。
1.3.3.1断裂伸长率:
单纯的海藻酸钠形成的纤维质地硬脆,断裂伸长率较低,在加工和使用过程中易发生断裂。本研究对制备的复合纤维的断裂伸长率进行测试,每根复合纤维取样测5次进行数据分析,结果如表2所示,可见,当ACNP添加量为2%时所制备的ACNP/SA复合纤维的断裂伸长率比未添加的海藻酸盐纤维提高了80.2%。这表明适量ACNP的加入对改善海藻酸盐纤维的力学性能起到了重要作用。
表2纳米活性炭对海藻酸纤维断裂伸长率的影响
**P<0.01,与相同条件下不含ACNP相比。
1.3.3.2断裂应力:
断裂应力表示纤维截面积上能承受的最大拉伸力,是各种材料通用的表示材料相对强度的指标,是衡量纤维抵抗拉伸强度的指标之一。本研究通过万能试验机对样本施加轴向拉力进行拉伸试验,测量样本断裂强力计算出纤维的断裂应力。从表3可以看出,添加ACNP后海藻酸盐复合纤维的断裂应力得到了提高,添加量2%的ACNP/SA复合纤维提高了42.5%,再增加ACNP的含量,断裂应力并没有持续增加,实验测得添加4%时,断裂应力仅提高了16.2%。
表3纳米活性炭对海藻酸纤维断裂应力的影响
综上所知,适量的添加ACNP(0-2%)可以提高海藻酸盐纤维断裂伸长率、断裂应力等力学性能。然而,持续增加ACNP(4%)力学性能并未随之增加(见表2、表3)。可能的原因是,ACNP表面存在羟基、羧基等亲水基团与SA分子结构的羟基可共价结合,当纺丝原液中ACNP的含量较低时,ACNP与SA凝胶形成均匀的网格,能有效的传递SA所受的作用力,从而提高复合纤维的韧性。但ACNP占比增加后,ACNP在SA基质中发生团聚,使得SA分子自身的交联密度也下降,破坏了有序的网格结构,削弱ACNP和SA基质之间的传递作用,脆性增加,最终导致ACNP/SA复合纤维的力学性能不再增加反而逐渐降低。因此,少量ACNP的加入既有利于纤维的亲水性能,又能增加延伸性能,可避免溶胀对力学性能的不利影响。
1.3.4ACNP/SA复合纤维溶胀率的测试:采用溶胀率(Swelling Rate,SR)来描述凝胶的吸水能力。将一定量的纤维在50℃真空烘箱中干燥24h后称量(Wd),然后将干燥的样品浸泡在37℃恒温的50ml生理盐水中,每20min取出1次,吸干表面水分后取出称量(Ws,至到质量不再增加达平衡溶胀状态。溶胀率(SR)按公式:SR=(Ws-Wd)/Wd计算增重率。每个样品测量三个平行样后,进行数据分析。
溶胀率是生物材料亲水性的重要评价指标之一。溶胀率越高,材料的亲水性越好,利于物质扩散,利于材料内细胞所需营养物质进入和代谢产物的排出。但较高的溶胀率会降低材料的力学性能,体内使用时容易脱落,回收不完全而存留体内导致潜在的安全风险。因此,有必要对ACNP/SA复合纤维溶胀性能进行探讨。从图3中可以看出,在ACNP添加量2%时,ACNP/SA复合纤维的溶胀率最大。可能的原因是,少量添加的ACNP能起到支撑骨架的作用,降低SA分子自身的交联度,SA游离的氢键与水分子结合,提高了吸水性能。另外,活性炭高度发达的孔隙构造可能为纤维提供了丰富的内表面积,其表面含有亲水性功能基团和离子型灰分,亲水性基团改善凝胶的亲水性,而离子型灰分提高了内外渗透压差,使得海藻酸盐纤维在生理盐水中溶胀度比单纯的SA更高。但随着活性炭用量的进一步增加,如增至4%,刚性的活性炭颗粒产生聚集挤压作用,破坏了基本的网格结构,导致其吸液能力降低,溶胀率减小。另外,添加ACNP后,复合纤维到达平衡溶胀率的时间变短(图3),表明ACNP/SA复合纤维后期的抗溶胀性能得到了提高。前期快速溶胀的可能原因是ACNP的骨架作用,使得纤维孔隙变大利于液体的进入快速达到平衡所致。
综上分析,少量ACNP(0-2%)的加入既有利于纤维的亲水性能,又能增加延伸性能,可避免溶胀对力学性能的不利影响。
1.4ACNP/SA复合纤维的生物相容性研究
1.4.1生物稳定性测试:量取2cm制备好的海藻酸盐纤维,加入1mL的10%FBS的DMEM培养基,37℃的二氧化碳培养基中放置21天。分别于第0天、第7天、第14天和第21天观察纤维的形态变化,并测试纤维浸提液在490nm处的吸光度值。以1mL的10%FBS的DMEM培养基作为空白对照。结果如表4所示。
表4不同ACNP/AS纤维于第0天、第7天、第14天和第21天吸光度值
浓度 | 0d | 7d | 14d | 21d |
Blank | 0.131±0.00259 | — | — | — |
0% | 0.131±0.00224 | 0.188±0.00308 | 0.258±0.0354 | 0.322±0.00567 |
2% | 0.132±0.00205 | 0.176±0.00893 | 0.220±0.0378* | 0.239±0.00904** |
4% | 0.130±0.0328 | 0.187±0.00687 | 0.338±0.0709** | 0.416±0.0209** |
**P<0.01,与相同条件下无ACNP比较。
如表4所示,随着时间的延长,各组浸出液的吸光度值逐渐升高,说明海藻酸盐纤维会不断浸出更多不明物质到培养液中。对比三组浸出液组,第7天时,吸光值差异不显著,但第14天、第21天时,4%组明显高于其他两组,而2%组最小,差异显著。以上结果表明,2%的ACNP添加促进海藻酸盐纤维具有更好的生物稳定性。
1.4.2细胞毒性测试:ACNP/SA复合纤维的细胞毒性测试采用浸提液法。ACNP/SA复合纤维干燥箱内50℃干燥24h,加入完全培养基浸泡24h,去除纤维得浸提液培养液。同时,将MIN6细胞悬液密度调整到5×103/ml,接种于96孔板上,每孔100μL,置于37℃、5%的CO2的培养箱中培养24h后。吸出旧的培养液,换入新的浸提液培养液,不含浸提液的为对照组,37℃、5%的CO2的培养箱中培养24-96h,每个样品做5个重复孔。分别在24h、48h和96h时取出细胞培养板,在各孔中加含10%的CCK8培养基100μL,在细胞培养箱中放置1h,取上清液用酶标仪在450nm下测试吸光值。
理论上,海藻酸钠是一种具有良好生物相容性的天然多糖,纳米活性炭是一种生物相容性好的惰性碳材料,且两者都是CFDA批准的医用材料,复合后制备的纤维安全性高,而且细胞相容性较好。为了评估所制备的ACNP/SA复合纤维的生物相容性和应用潜力,实验中使用CCK-8法检测复合材料对MIN6细胞毒性。以OD值表征细胞存活率,OD值越高,细胞存活率越高。在细胞培养过程中,细胞适应后会随着时间的推移细胞数量增加,活率增加。如图4所示,随着时间的推移,0%ACNP/SA浸出液培养影响MIN6细胞的增殖,其可能的原因是2.5%的海藻酸盐纤维的浸出液对MIN6有生长抑制作用。本实验中,对比海藻酸盐纤维,添加2%和4%浓度的ACNP复合到海藻酸盐纤维后,浸出液表现出友好的支持MIN6细胞生长的特性,消除了海藻酸凝胶材料对细胞的不利影响。接种后第1d、第2d和第4d,对照组和ACNP添加组的细胞活力差异不显著,这说明ACNP/SA复合纤维复合纤维在体外对细胞无毒性。因此,可认为ACNP/SA复合纤维具有良好的细胞相容性和生物安全性,能作为封装细胞的医用材料。
实施例2,ACNP/SA复合纤维的制备:
采用与实施例1相同的原料、设备和制备方法制备和检测不同含量配比的产品,并观察ACNP/SA复合纤维的物理表征、测定纤维直径、拉伸性能、生物相容性和细胞毒性。结果汇总如表5所示:
表5复合纤维中纳米活性炭对ACNP/SA复合纤维断裂伸长率的影响
综合以上实验结果表明,浓度2.5%的SA中添加质量比(ACNP:SA)2%的ACNP,1.5%CaCl2凝固浴中湿法纺丝可制备力学性能和生物相容性能最佳的ACNP/SA复合纤维。添加ACNP可改善海藻酸钠纤维沟槽缺陷问题,有助于纤维力学性能提升。少量(0%-2%)ACNP的加入既有利于纤维的亲水性能,又增加力学性能,断裂伸长率最高提高了80.2%,断裂应力提高了42.5%,避免了纤维溶胀对力学性能的不利影响。2%的ACNP添加量促进海藻酸钠纤维具有更好的生物稳定性和更低的细胞毒性。ACNP/SA复合纤维具有良好的力学性能和生物相容性,在医学材料领域具有开发和应用价值。
本发明提供的含纳米活性炭的海藻酸钠复合纤维可用于封装胰岛细胞,已进行糖尿病的治疗,或封装甲状(旁)腺细胞,以治疗甲状腺切除的患者,为胰岛细胞或甲状(旁)腺细胞提供支撑结构,模拟天然胰岛或甲状(旁)腺的微观和宏观环境,使植入的细胞与机体形成免疫隔离屏障。本发明为封装细胞提供了新的具有良好的力学性能、生物相容性、更好的生物稳定性和更低的细胞毒性的复合纤维材料。
以上所述仅为本发明的优选实施例而已,并不用于限制本发明,对于本领域的技术人员来说,本发明可以有各种更改和变化。凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (10)
1.含纳米活性炭的海藻酸钠复合纤维的制备方法,其特征在于,包括如下步骤:
步骤1、取海藻酸钠粉末溶于水中,过滤除菌,备用,为海藻酸钠溶液;
步骤2、取纳米活性炭灭菌,备用;
步骤3、称取步骤2所得的灭菌后的纳米活性炭溶解在步骤1所得的海藻酸钠溶液中,制得混合溶液;
步骤4、采用湿法纺丝工艺,将步骤3所得的混合溶液流入到氯化钙溶液中钙化,钙化完成后洗涤,即得。
2.根据权利要求1所述的含纳米活性炭的海藻酸钠复合纤维的制备方法,其特征在于,步骤1中海藻酸钠溶液含量为1.5%~3.0%(w/v)。
3.根据权利要求1所述的含纳米活性炭的海藻酸钠复合纤维的制备方法,其特征在于,步骤1中海藻酸钠溶液含量为2.5%(w/v)。
4.根据权利要求1所述的含纳米活性炭的海藻酸钠复合纤维的制备方法,其特征在于,步骤2中纳米活性炭在121℃灭菌20min。
5.根据权利要求1所述的含纳米活性炭的海藻酸钠复合纤维的制备方法,其特征在于,步骤3中纳米活性炭与海藻酸钠溶液的重量比为(2~8):100。
6.根据权利要求1所述的含纳米活性炭的海藻酸钠复合纤维的制备方法,其特征在于,步骤3中纳米活性炭与海藻酸钠溶液的重量比为2:100。
7.根据权利要求1所述的含纳米活性炭的海藻酸钠复合纤维的制备方法,其特征在于,步骤4中氯化钙溶液含量为1%~10%(w/v),更优选为1.5%(w/v)。
8.根据权利要求1所述的含纳米活性炭的海藻酸钠复合纤维的制备方法,其特征在于,所述纳米活性炭粒径为50~300nm,更优选200nm。
9.根据权利要求1所述的含纳米活性炭的海藻酸钠复合纤维的制备方法,其特征在于,称取海藻酸钠粉末,溶于蒸馏水中,制成2.5%(w/v)的海藻酸钠溶液,0.45μm滤器过滤除菌,备用;同时,取纳米活性炭在121℃灭菌20min,备用;称取灭菌后的纳米活性炭溶解在海藻酸钠溶液中,制得混合溶液,纳米活性炭与海藻酸钠溶液的重量比为2:100,采用湿法纺丝工艺,调节注射泵流量1000μl/min将混合溶液流入到1.5%(w/v)氯化钙溶液中钙化15min,蒸馏水洗涤2次,制得海藻酸盐纤维。
10.根据权利要求1~9任一项制得的所述含纳米活性炭的海藻酸钠复合纤维的应用,其特征在于,用于细胞封装,所述细胞包括但不限于胰岛细胞、甲状腺细胞和甲状旁腺细胞。
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103820880A (zh) * | 2014-01-21 | 2014-05-28 | 东南大学 | 一种海藻酸钙纤维及其制备方法 |
KR20150019486A (ko) * | 2013-08-14 | 2015-02-25 | 연세대학교 원주산학협력단 | 분말활성탄이 담지된 다공성 알긴산 겔 복합체의 제조방법 및 이를 이용한 오염물질 제거용 흡착제 |
CN104963031A (zh) * | 2015-07-09 | 2015-10-07 | 厦门百美特生物材料科技有限公司 | 一种改性生物质纤维及其制备方法 |
CN106521706A (zh) * | 2016-11-15 | 2017-03-22 | 青岛大学 | 一种纤维素纳米纤丝/海藻酸盐复合纤维的制备方法 |
CN108588901A (zh) * | 2018-05-18 | 2018-09-28 | 青岛明月生物医用材料有限公司 | 一种负载活性炭的海藻酸盐纤维的制备方法 |
-
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- 2021-11-03 CN CN202111295683.4A patent/CN113969435A/zh active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20150019486A (ko) * | 2013-08-14 | 2015-02-25 | 연세대학교 원주산학협력단 | 분말활성탄이 담지된 다공성 알긴산 겔 복합체의 제조방법 및 이를 이용한 오염물질 제거용 흡착제 |
CN103820880A (zh) * | 2014-01-21 | 2014-05-28 | 东南大学 | 一种海藻酸钙纤维及其制备方法 |
CN104963031A (zh) * | 2015-07-09 | 2015-10-07 | 厦门百美特生物材料科技有限公司 | 一种改性生物质纤维及其制备方法 |
CN106521706A (zh) * | 2016-11-15 | 2017-03-22 | 青岛大学 | 一种纤维素纳米纤丝/海藻酸盐复合纤维的制备方法 |
CN108588901A (zh) * | 2018-05-18 | 2018-09-28 | 青岛明月生物医用材料有限公司 | 一种负载活性炭的海藻酸盐纤维的制备方法 |
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