CN117323457A - 一种3d打印创可贴及其制备方法 - Google Patents
一种3d打印创可贴及其制备方法 Download PDFInfo
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- CN117323457A CN117323457A CN202311502172.4A CN202311502172A CN117323457A CN 117323457 A CN117323457 A CN 117323457A CN 202311502172 A CN202311502172 A CN 202311502172A CN 117323457 A CN117323457 A CN 117323457A
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- hydrogel
- aid
- safflower polysaccharide
- gelatin
- band
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Abstract
本发明公开了一种3D打印创可贴及其制备方法。本发明将明胶(GelMA)和重组胶原蛋白(rColMA)进行改性，并与罗氏菌素和GelMA/红花多糖微球混合，利用三维打印技术构建3D水凝胶结构，并将其固定在粘性自愈合水凝胶ACG上，获得具有抗菌、促血管化和调免疫功能的水凝胶创可贴。
Description
技术领域
本发明属于组织工程材料领域，具体地涉及一种3D打印创可贴及其制备方法。
背景技术
由细菌引起的传染病已成为日益严重的健康问题，每年导致数百万人患病和死亡。细菌感染引起的慢性皮肤缺损难以修复，因为炎症反应最终导致细胞死亡和组织坏死，并减缓伤口修复过程。有效预防创面感染，提高患者愈合效率对于创面感染的治疗至关重要。因此，预防术后感染是外科临床工作的重要组成部分。除了确保无菌操作外，常见的伤口抗菌方法在术后护理中尤为重要。然而，传统的清洗、消毒、清洁纱布覆盖等方法已不能完全满足当今多重耐药菌数量迅速增加的环境下的抗感染要求。因此，探索克服多药耐药菌的新治疗策略是临床创面手术抗感染治疗需要解决的重要问题。
近年来，许多利用细菌素来抗菌，但大多数细菌素为多肽或蛋白质类物质，它们的抗菌特性通常受到蛋白酶的破坏，而罗伊氏菌素是由小分子水溶性中性物质组成的混合物，因而它的抑菌活性不会被蛋白酶破坏，具有更强的稳定性。罗氏菌素可以抑制核糖核酸还原酶活性，而这种酶DNA合成所必需的，因此罗氏菌素可以通过干扰细菌DNA复制来抑制细菌增殖。由于罗伊氏素既具广谱抗菌特性，又对人和动物无害，可用于调节肠道菌群分布；杀死口腔病原菌以预防龋齿；作为抗感染治疗剂，其用途正逐步被广泛开发。
伤口愈合是一个复杂的生物学过程，涉及一系列动态事件，包括止血、炎症、细胞增殖和分化、新血管和肉芽组织形成、胶原合成、皮肤上皮化和伤口收缩。由于潮湿的环境和频繁的运动，动态全层皮肤创面愈合仍然是一个复杂的问题。近年来，多功能水凝胶在伤口修复方面有很大的应用前景。
水凝胶具有优异的保湿、吸水、透明可视化和生物相容性等特性，已作为组织工程概念引入创面修复领域。这些优点是医用敷料不可缺少的，它保证了伤口湿润，吸收了伤口渗出物，便于伤口监测。III型重组胶原蛋白作为一种新型医用材料，具有与人胶原蛋白相应片段100％相似、结构正确、生物活性高、安全性高等优点，已广泛应用于创面修复领域。有研究报道，单一的胶原蛋白水凝胶在实际应用中存在抗菌活性差、易受外界刺激损伤、机械强度不足、降解性不可控等局限性，限制了其在生物医学中的应用。为了解决这些问题，通过添加甲基丙烯酰明胶形成互穿聚合物网络，提高水凝胶的力学性能，降低水凝胶的降解率。然而，传统的水凝胶只能保持伤口湿润，但湿性环境可能有助于细菌生长。
水凝胶敷料作为感染伤口愈合治疗的新探索极具应用价值和前景。相对于水凝胶敷料直接作用于伤口，传统的水凝胶敷料越来越显示出其局限性，不能愈合，形状匹配差，伤口滞留能力弱以及存在伤口易感染等问题。
因此，需要研发出一种抗菌、促血管化和调免疫功能的水凝胶创可贴。
发明内容
针对现有技术的上述缺陷，本发明提供了一种抗菌、促血管化和调免疫功能的水凝胶创可贴及其制备方法。
本发明的技术目的是通过以下技术方案来实现的：
本发明提供一种3D打印创可贴，其配方包括有改性Ⅲ型胶原蛋白、甲基丙烯酸化明胶、红花多糖微球及罗伊氏菌素，其重量比为(2-4)：(1-2)：(0.002-0.01)：(0.01-0.03)。
优选地，本发明所述改性Ⅲ型胶原蛋白、甲基丙烯酸化明胶、红花多糖微球及罗伊氏菌素的重量比为2：1：0.002：0.01。红花多糖是红花中主要有效成分之一，为均一的杂多糖，主要由两种组分构成，其中SPS-1由甘露糖、葡萄糖、半乳糖组成，SPS-2由葡萄糖、甘露糖、木糖、鼠李糖组成，具有三螺旋结构，葡萄糖是其主要组成部分。红花多糖具有抗肿瘤、免疫调节、抗氧化等活性，其中抗氧化作用的同时无细胞毒性，具有良好的应用前景。然而，红花多糖分子量大，细胞膜通透性差，不易穿透皮肤表皮，局部药物治疗效果难以发挥。为了克服这一问题，明胶微球(GelMA)被用作用来封装红花多糖系统的载体。
进一步地，本发明所述改性Ⅲ型胶原蛋白通过以下方法制得：称取0.5～1.5g的Ⅲ型胶原蛋白充分溶解后，调节pH值至6.8～7.2,加入0.5mL～1.5mL甲基丙烯酸酐反应，除去未反应的物质，离心、过滤、冻干后即得。
进一步地，本发明所述甲基丙烯酸化明胶通过以下方法制得：称取10～30g明胶溶解，加入5～20mL甲基丙烯酸酐反应，除去未反应的物质，离心、过滤、冻干后即得。
进一步地，本发明所述红花多糖微球通过以下方法制得：称取0.1g～0.3g甲基丙烯酸化明胶和0.1mg～0.3mg红花多糖溶解，加入2～6mg光引发剂(优选为苯基(2,4,6-三甲基苯甲酰基)磷酸锂盐)，混匀后用微流控装置制备红花多糖微球，将微球光交联，除去微球表面的氟化油，离心即得。
进一步地，本发明制备红花多糖微球中氟化油：红花多糖-GelMA溶液流速比为2：1～3：1。
进一步地，本发明3D打印水凝胶基底采用ACG改性甘氨酸，所述ACG改性甘氨酸通过以下方法制得：将5g～10g甘氨酸、50～100mL去离子水、10～20mg碳酸钾、20～40mL二乙醚低温溶解，将5mL～13mL丙烯酰氯与10mL～30mL乙醚的溶液缓慢滴入，反应完成后调节pH值至12±0.1，除去有机相，收集水层，合并酸化至pH值至2.0±0.1，除去有机相，收集有机层并干燥，溶液过滤、浓缩、沉淀、纯化、干燥即得。
本发明的另一技术目的是提供一种上述的3D打印创可贴的制备方法，包括以下步骤：用ACG改性甘氨酸作为3D打印水凝胶基底，将红花多糖微球、罗伊氏菌素、改性Ⅲ型胶原蛋白、甲基丙烯酸化明胶混匀后倒入打印机中，将水凝胶打印成型，用缓冲液冲洗干净，即得。
进一步地，本发明3D打印机的条件为光强度：14～16mW/cm2、曝光时间：12～16s、基层层数：1～3层、基层曝光时间：10～20s。
本发明相对于现有技术具有如下有益效果：
本发明将甲基丙烯酸化明胶(GelMA)和Ⅲ型胶原蛋白(rColMA)进行改性，并与罗伊氏菌素和GelMA/红花多糖微球混合，利用三维打印技术构建3D水凝胶结构，并将其固定在粘性自愈合水凝胶ACG上，以期获得具有抗菌、促血管化和调免疫功能的水凝胶创可贴。
1、利用水凝胶构建物理屏障，隔绝外部细菌感染，同时负载的罗氏菌素(罗氏菌素具有稳定的抗菌性)，与其他的细菌素，具有稳定的抗菌特性，且更加安全。
2、本发明所制得的释放红花多糖的GelMA水凝胶，能够抑制细菌生长、促进血管化和巨噬细胞表型极化作用，增强感染创面愈合的治疗效果。ACG水凝胶基底具有很强的粘附性，能够将水凝胶贴在创面部位，隔绝外源细菌的感染，避免创面的二次感染。
附图说明
图1是本发明的实施例1的水凝胶降解曲线。
图2是本发明实施例1的红花多糖的释放曲线。
图3是本发明实施例1的水凝胶体外抗菌。
图4是本发明对比例1-3及实施例1的不同实验组促血管生成。
图5是本发明对比例1-3及实施例1的不同实验组诱导巨噬细胞极化流式散点图。
具体实施方式
为了更好地说明本发明的技术目的、技术方案和优点，现结合附图与具体实施例对本发明做进一步说明。
本发明实施例所用到的Ⅲ型胶原蛋白购买自创健生物科技(江苏)有限公司，所用罗伊氏菌素购买自上海麦克林生化科技有限公司；本发明所用苯基(2,4,6-三甲基苯甲酰基)磷酸锂盐购自上海引昌新材料有限公司。
一、3D打印水凝胶创可贴的配方
表1 1mL水凝胶制备各组分质量分数表
二、3D打印水凝胶创可贴的制备
一)、前处理
1、改性Ⅲ型胶原蛋白(Col3MA)制备
称取1g的Ⅲ型胶原蛋白(rCol3)溶解在50mL的蒸馏水中，充分溶解后，调节pH＝7,加入1mL的甲基丙烯酸酐，常温下反应24h，蒸馏水透析3-5日(截留分子量：3500)，离心10000rpm 5min，中性滤纸过滤，-80℃冻干，即得改性的Ⅲ型胶原蛋白。
2、甲基丙烯酸化明胶蛋白(GelMA)制备
称取20g的明胶溶解在250mL的蒸馏水中，60℃溶解后，加入12mL的甲基丙烯酸酐，常温下反应8h，蒸馏水透析3-5日(截留分子量：3500)，离心(8000rpm)5min，中性滤纸过滤，-80℃冻干，即得甲基丙烯酸化明胶蛋白(GelMA)。
3、负载红花多糖的微球的制备
称取0.2g GelMA和0.2mg红花多糖溶于2mL去离子水中，加入0.004g LAP，充分混合后，利用微流控装置制备红花多糖微球。流速比为氟化油：红花多糖-GelMA溶液为2.5：1，收集得到微球后，光交联30s，得到稳定的微球，加入破乳剂除去微球表面的氟化油，离心收集即得。
4、ACG改性甘氨酸的制备
将甘氨酸(7.50g，0.0999摩尔)、去离子水80mL、碳酸钾15mg、二乙醚30mL加入三颈玻璃瓶中，置于冰浴中，猛烈搅拌。将9mL丙烯酰氯与20mL乙醚的溶液滴加0.5小时后，在室温下搅拌4小时。反应混合物用2mol的氢氧化钠碱化至pH值＝12，然后用乙酸乙酯萃取除去有机相。收集清澈的水层，合并，加入6mol HCl酸化至pH 2.0，然后用乙酸乙酯再次萃取。收集有机层，用无水硫酸钠干燥，然后将溶液过滤、浓缩并在石油醚中沉淀。采用反复沉淀法进行进一步纯化，最终产物在真空中干燥。
二)、3D打印水凝胶创可贴的制备方法
将制备好的GelMA/Col3MA溶液和红花多糖微球，罗伊氏菌素倒入打印机中将水凝胶打印成型(光强：14mW/cm2、曝光时间：14s、基层层数：1层、基层曝光时间：15s)，用PBS溶液将打印好的水凝胶支架冲洗3-6次，得到GelMA/Col3MA水凝胶支架。3D打印水凝胶基底采用ACG改性甘氨酸。
三、性能测试
1、降解性能(降解率)
将实施例1所制得水凝胶冷冻干燥后称取质量，记为W0，再将初始的样品浸泡分别在PBS含1000U/ml溶菌酶的PBS溶液中，置于恒温摇床(37℃，70rpm)。在测量的时间点，取出水凝胶，用超纯水洗涤后冻干，将其冷冻干燥，干燥后准确称取质量，记(Wt)。采用公式计算出支架的体外降解率：
降解率(％)＝(W0-Wt)/W0×100％
如图1所示，为水凝胶在有酶和无酶的PBS溶液中的降解性能，分别对应的是这两种条件下水凝胶降解21天不同时间点的降解结果，从水凝胶失重曲线可知水凝胶在初始的降解7天时间内，表现出较高的降解速率，随后的降解有所减慢，降解至21天时，有酶条件下的水凝胶已经完全降解，而无酶的水凝胶降解至90％以上。说明该水凝胶材料有着良好的生物可降解性。
2、药物释放
将实施例1所制得水凝胶置于5mL PBS溶液中，在37℃下孵育，在同时间点(1、3、6、12、24、48、72、96、120、144h)收集上清液，并补回相同体积的溶液。将收集到的上清液用紫外分光光度计检测红花多糖的含量，计算累积释放速率。累积释放公式：累积释放率(％)＝药物释放量/药物总含量×100％。
如图2为水凝胶的体外药物释放曲线，这说明在脂质体与水凝胶的双重负载下，药物的缓控释得到增强，有利于药物的长期停留。
3、体外抗菌实验
采用琼脂盘扩散试验和表面接触试验对实施例1所制备的水凝胶(罗伊氏菌素不同浓度下)对大肠杆菌(E.coli)和金黄色葡萄球菌(S.aureus)的抑菌活性进行了评价。大肠杆菌和金黄色葡萄球菌在37℃的Luria-Bertani(LB)肉汤中复活过夜。所有水凝胶样品在检测前均经紫外线照射灭菌。结果如图3所示，随着罗伊氏菌素浓度增加，水凝胶能够很明显的抑制大肠杆菌和金黄色葡萄球菌的生长，具有很好的抗菌性。
4、体外成血管实验
将基质胶置于冰上，在4℃中解冻过夜；孔板和移液枪头置于-20℃预冷过夜；溶解后的基质胶在冰上与DMEM基础培养基以体积比1:1混合，每孔100μL加入至24孔板，铺匀后置于37℃二氧化碳培养箱中静置30分钟以上，待完全成胶。HUVEC用0.05％的胰酶消化，重悬于DMEM基础培养基中，以每孔10万的细胞密度接种于基质胶上，随后用水凝胶浸提液培养4小时和8小时，在光学显微镜下观察并拍摄成管情况。如图4所示，空白组(control)不促进血管的形成，对比例1因含有改性Ⅲ型胶原蛋白稍微有些促进血管的形成；对比例2添加了罗伊氏菌素(抗菌作用)，不影响促进血管形成；对比例3及实施例1因含有红花多糖的水凝胶组能明显的促进血管的形成。
5、体外诱导巨噬细胞极化
小鼠单核巨噬细胞白血病细胞RAW264.7用DMEM完全培养基培养，冷PBS吹打，离心，用DMED完全培养基重悬，接种于6孔板；每孔加入20ng/mL脂多糖(LPS)诱导培养24小时使其极化为M1型巨噬细胞，随后将培养基吸弃，替换为水凝胶浸提液，继续培养24小时。如图5所示，空白组(Conrtrol、LPS即添加了诱导液)、对比例1没有促进诱导巨噬细胞由M1型转为M2型；对比例2、对比例3促进诱导巨噬细胞由M1型转为M2型效果不明显；实施例1的水凝胶很明显能够诱导巨噬细胞由M1型转为M2型。
1-5项的性能测试表明：该水凝胶体系具有良好的细胞相容性，促进细胞迁移、血管生成和M2巨噬细胞极化功能，能够明显促进感染伤口的愈合。具体地：水凝胶对大肠杆菌(E.coli)和金黄色葡萄球菌(S.aureus)具有良好的抗菌活性，在全层皮肤缺损模型中进行的体内伤口愈合评估显示，水凝胶具有明显的再生伤口愈合性能，显示了其作为新型伤口处理敷料的巨大潜力。
通过以上性能测试可知，本发明所涉及的的水凝胶创可贴用于感染创面愈合，具有良好生物功能的水凝胶敷料的制备方法，该水凝胶体系具有稳定的抗菌性，能够促进血管生成，调节免疫功能、促进细胞增殖迁移，及促进伤口愈合的作用。克服现有用于治疗感染创面愈合水凝胶敷料所欠缺的一些问题，多种物质复合，保持了原物质的优点，解决了单一原有材料性能的不足。本发明制备操作简单，所需的原材料易得，有望在生物医学工程材料领域得到广泛的应用。
以上实施例仅用以说明本发明的技术方案而非对本发明保护范围的限制，除此之外，本发明还可以其它方式实现，尽管参照上述实施例对本发明进行了详细的说明，所属领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，但这些修改或替换均在本发明的保护范围之内。
Claims (10)
1.一种3D打印创可贴，其特征在于，其配方包括有改性Ⅲ型胶原蛋白、甲基丙烯酸化明胶、红花多糖微球及罗伊氏菌素，其重量比为(2-4)：(1-2)：(0.002-0.01)：(0.01-0.03)。
2.根据权利要求1所述的3D打印创可贴，其特征在于，所述改性Ⅲ型胶原蛋白、甲基丙烯酸化明胶、红花多糖微球及罗伊氏菌素的重量比为2：1：0.002：0.01。
3.根据权利要求1或2所述的3D打印创可贴，其特征在于，所述改性Ⅲ型胶原蛋白通过以下方法制得：称取0.5～1.5g的Ⅲ型胶原蛋白充分溶解后，调节pH值至6.8～7.2,加入0.5mL～1.5mL甲基丙烯酸酐反应，除去未反应的物质，离心、过滤、冻干后即得。
4.根据权利要求1或2所述的3D打印创可贴，其特征在于，所述甲基丙烯酸化明胶通过以下方法制得：称取10～30g明胶溶解，加入5～20mL甲基丙烯酸酐反应，除去未反应的物质，离心、过滤、冻干后即得。
5.根据权利要求1或2所述的3D打印创可贴，其特征在于，所述红花多糖微球通过以下方法制得：称取0.1g～0.3g甲基丙烯酸化明胶和0.1mg～0.3mg红花多糖溶解，加入2～6mg光引发剂，混匀后用微流控装置制备红花多糖微球，将微球光交联，除去微球表面的氟化油，离心即得。
6.根据权利要求5所述的3D打印创可贴，其特征在于，所述光引发剂为苯基(2,4,6-三甲基苯甲酰基)磷酸锂盐。
7.根据权利要求5所述的3D打印创可贴，其特征在于，制备红花多糖微球中氟化油：红花多糖-GelMA溶液流速比为2：1～3：1。
8.根据权利要求1或2所述的3D打印创可贴，其特征在于，3D打印水凝胶基底采用ACG改性甘氨酸，所述ACG改性甘氨酸通过以下方法制得：将5g～10g甘氨酸、50～100mL去离子水、10～20mg碳酸钾、20～40mL二乙醚低温溶解，将5mL～13mL丙烯酰氯与10mL～30mL乙醚的溶液缓慢滴入，反应完成后调节pH值至12±0.1，除去有机相，收集水层，合并酸化至pH值至2.0±0.1，除去有机相，收集有机层并干燥，溶液过滤、浓缩、沉淀、纯化、干燥即得。
9.一种如权利要求1～8中任意一项所述的3D打印创可贴的制备方法，其特征在于，包括以下步骤：用ACG改性甘氨酸作为3D打印水凝胶基底，将红花多糖微球、罗伊氏菌素、改性Ⅲ型胶原蛋白、甲基丙烯酸化明胶混匀后倒入打印机中，将水凝胶打印成型，用缓冲液冲洗干净，即得。
10.根据权利要求9所述得3D打印创可贴的制备方法，其特征在于，3D打印机的条件为光强度：14～16mW/cm2、曝光时间：12～16s、基层层数：1～3层、基层曝光时间：10～20s。
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Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0986408A1 (en) * | 1997-06-03 | 2000-03-22 | Innogenetics N.V. | New medicaments based on polymers composed of methacrylamide-modified gelatin |
| CN107744601A (zh) * | 2017-09-06 | 2018-03-02 | 盐城工业职业技术学院 | 一种基于蚕丝微球生物墨水的三维打印伤口包覆材料及其制备方法 |
| CN110755678A (zh) * | 2019-11-13 | 2020-02-07 | 中国矿业大学 | 一种基于绿色原位还原的3d打印抗菌水凝胶伤口敷料 |
| CN110790950A (zh) * | 2019-10-21 | 2020-02-14 | 南京理工大学 | 光交联重组胶原蛋白水凝胶、制备方法及其在3d生物打印中的应用 |
| CN113559328A (zh) * | 2021-08-10 | 2021-10-29 | 南京工业大学 | 一种生物墨水及其制备方法 |
| CN113621149A (zh) * | 2021-08-20 | 2021-11-09 | 江南大学 | 一种3d打印抗菌水凝胶敷料及其制备方法 |
| CN113876741A (zh) * | 2021-09-28 | 2022-01-04 | 四川大学 | 湿态可粘附的口腔凝胶贴片的制备与应用 |
| WO2022045967A1 (en) * | 2020-08-31 | 2022-03-03 | National University Of Singapore | Hydrogels and methods of fabrication thereof |
| CN115887737A (zh) * | 2022-11-11 | 2023-04-04 | 诺一迈尔(苏州)生命科技有限公司 | 一种生物体内可降解组织贴片及其制备方法 |
| CN116589861A (zh) * | 2022-12-14 | 2023-08-15 | 广东省中医院（广州中医药大学第二附属医院、广州中医药大学第二临床医学院、广东省中医药科学院） | 水凝胶及其制备方法和应用 |
| CN116870243A (zh) * | 2023-08-10 | 2023-10-13 | 广州创赛生物医用材料有限公司 | 一种具有止血抗炎作用的水凝胶及其制备方法和应用 |
-
2023
- 2023-11-10 CN CN202311502172.4A patent/CN117323457B/zh active Active
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0986408A1 (en) * | 1997-06-03 | 2000-03-22 | Innogenetics N.V. | New medicaments based on polymers composed of methacrylamide-modified gelatin |
| CN107744601A (zh) * | 2017-09-06 | 2018-03-02 | 盐城工业职业技术学院 | 一种基于蚕丝微球生物墨水的三维打印伤口包覆材料及其制备方法 |
| CN110790950A (zh) * | 2019-10-21 | 2020-02-14 | 南京理工大学 | 光交联重组胶原蛋白水凝胶、制备方法及其在3d生物打印中的应用 |
| CN110755678A (zh) * | 2019-11-13 | 2020-02-07 | 中国矿业大学 | 一种基于绿色原位还原的3d打印抗菌水凝胶伤口敷料 |
| WO2022045967A1 (en) * | 2020-08-31 | 2022-03-03 | National University Of Singapore | Hydrogels and methods of fabrication thereof |
| CN113559328A (zh) * | 2021-08-10 | 2021-10-29 | 南京工业大学 | 一种生物墨水及其制备方法 |
| CN113621149A (zh) * | 2021-08-20 | 2021-11-09 | 江南大学 | 一种3d打印抗菌水凝胶敷料及其制备方法 |
| CN113876741A (zh) * | 2021-09-28 | 2022-01-04 | 四川大学 | 湿态可粘附的口腔凝胶贴片的制备与应用 |
| CN115887737A (zh) * | 2022-11-11 | 2023-04-04 | 诺一迈尔(苏州)生命科技有限公司 | 一种生物体内可降解组织贴片及其制备方法 |
| CN116589861A (zh) * | 2022-12-14 | 2023-08-15 | 广东省中医院（广州中医药大学第二附属医院、广州中医药大学第二临床医学院、广东省中医药科学院） | 水凝胶及其制备方法和应用 |
| CN116870243A (zh) * | 2023-08-10 | 2023-10-13 | 广州创赛生物医用材料有限公司 | 一种具有止血抗炎作用的水凝胶及其制备方法和应用 |
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