CN114177368A - 掺硒羟基磷灰石纳米增强的胶原gbr膜及其制备方法 - Google Patents
掺硒羟基磷灰石纳米增强的胶原gbr膜及其制备方法 Download PDFInfo
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Abstract
本专利公开了掺硒羟基磷灰石纳米增强的胶原GBR膜及其制备方法,制备方法包括步骤:(1)制备掺硒羟基磷灰石(Se‑HAP),将Se/(Se+P)通过溶剂热法合成Se‑HAP纳米结构;(2)将动物皮胶原加到醋酸溶液中搅拌配制胶原溶液,机械搅拌至完全溶解,利用间隔低温超声方式使得胶原分散均匀;加入Se‑HAP纳米线粉末于水溶液中,充分搅拌制成Se‑HAP浆体,将所述胶原溶液与所述Se‑HAP浆体混合均匀得到胶原/Se‑HAP混合溶液超声处理后,再将浓缩成胶原蛋白溶液离心处理后放在冷冻装置上冷却至0℃以下,冷冻干燥即可得到所述掺硒羟基磷灰石纳米线增强的胶原GBR膜,可应用在引导骨再生的医疗康复,具有抗菌性、促成骨分化再生优良性能。
Description
技术领域
本专利涉及医药技术领域,特别涉及一种掺硒羟基磷灰石纳米增强的胶原GBR膜及其制备方法。
背景技术
颅、颌面骨缺损的修复在整形外科和口腔颌面外科的治疗中仍是挑战,通常需要使用骨粉和引导组织再生膜进行修复,但较大的缺损修复仍然是临床中的难点。引导骨再生(guided bone regeneration,GBR)技术:基于覆盖骨缺损区域的屏障膜特性,阻止来自周围软组织的成纤维细胞侵袭,让骨面处的成骨细胞有足够的时间黏附、增殖、成骨分化,最终实现骨组织再生和修复的目的。在复杂骨缺损区如牙槽骨萎缩区,抗菌性也是GBR膜必不可少的性能,生物材料植入骨缺损区域后,免疫反应和细菌感染影响骨再生的成功。
GBR技术若要完成骨缺损区域的修复,GBR膜除了应该具有良好的生物相容性和双层结构,理想的GBR膜需要具备以下条件:1、屏障膜。这是最重要的一点,GBR膜应具有足够的强度,能够保证骨再生的空间环境,并具有良好的固位和稳定。同时具有骨再生周期匹配的降解速率,保证有足够的时间和良好的空间等待骨再生组织成长。2、良好的成骨微环境环境。进行骨再生的骨缺损区域,必须是健康的,并保证没有潜在的感染源。在骨愈合过程中,病原菌在创面处定植引起的感染被认为是引导骨再生失败的主要原因之一。在复杂骨缺损区,抑菌性也是GBR膜必不可少的性能,生物材料植入骨缺损区域后,免疫反应和细菌感染影响骨再生的成功,抗菌GBR膜引导骨再生是一种很有前途的预防感染和引导骨再生的治疗方法。3、促骨再生。被新骨置换前,可以为新骨生长提供支架,帮助新骨生长。因此,GBR要同时实现所有的理想功能即如何实现结构与功能的统一仍是一个难以解决的问题,有待研发具有促骨能力以及软组织相容性和抗菌性的屏障膜。
胶原Bio-Gide膜(Geistlich Pharma,Wolhusen,瑞士)是使用最广泛的生物可降解膜,具有许多优点:具有良好的生物相容性和降解性,能够促进细胞的粘附和增殖,作为GBR膜在临床上已取得一定的疗效。然而临床应用中,Bio-Gide生物膜存在降解率高、机械性能差、抗菌性能差等不足,不利于骨缺损的远期再生修复。
发明内容
针对现有技术的不足,本发明的首要目的是提供掺硒羟基磷灰石纳米增强的胶原GBR膜的制备方法。
本发明的另一目的在于公开了上述方法制备得到的掺硒羟基磷灰石纳米增强的胶原GBR膜,应用在引导骨再生康复,具有抗菌性、促成骨分化再生性能。
发明人在实验发现,可通过SeO3 2-或者SeO4 2-离子取代HAP中OH-或PO4 3-可制备掺硒羟基磷灰石(Se-HAP),Se-HAP由于硒元素的掺入而具有具有抗骨肿瘤和抗菌作用,同时低掺杂量的Se-HAP能够促进骨髓间充质干细胞向成骨细胞的分化。人们通过硒的生物学作用研究发现硒能显著地影响免疫系统,增强细胞免疫、体液免疫及非特异性免疫功能。研究表明,Se-HAP具有纳米针、纳米线、纳米片等纳米结构,Se-HAP纳米针、纳米线或纳米片能够很好地增强胶原支架的强度,改善其力学性能。故采用Se-HAP纳米线增强胶原双层GBR,能够很好地增强胶原GBR膜的强度,改善其力学性能,同时期待赋予GBR膜良好的抗菌性、促成骨分化再生性能。相对于临床应用的Bio-Gide生物膜,掺硒羟基磷灰石纳米增强的胶原GBR膜具有更加优异的骨再生修复性能,在引导骨再生及其相关疾病方面显示出良好的前景。
本发明提供掺硒羟基磷灰石纳米增强的胶原GBR膜制备方法,包括步骤:
(1)制备掺硒羟基磷灰石(Se-HAP),将Se/(Se+P)通过溶剂热法合成Se-HAP纳米结构体;
(2)将动物I型胶原加到醋酸溶液中搅拌配制胶原溶液,机械搅拌至完全溶解,利用间隔低温超声方式使得胶原分散均匀;加入Se-HAP纳米粉末于水溶液中,充分搅拌制成Se-HAP浆体,将所述胶原溶液与所述Se-HAP浆体混合均匀得到胶原/Se-HAP混合溶液超声处理后,再将浓缩成胶原蛋白溶液离心处理后放在冷冻装置上,所述胶原蛋白溶液从室温冷却至0℃以下,直到完全冻结一段时间,冷冻干燥即可得到所述掺硒羟基磷灰石纳米增强的胶原GBR膜(即Col@Se-HAP GBR膜)。
进一步,步骤(1)中:是将摩尔分数为0.05%-0.4%的Se/(Se+P)通过溶剂热法合成掺硒的Se-HAP纳米线、或纳米针、或纳米片结构体。
所述Se/(Se+P)的摩尔分数分别取0.05%、0.1%、0.2%和0.3%,分别对应命名为0.5Se-HAP、1Se-HAP、2Se-HAP和3Se-HAP,通过溶剂热法合成掺硒的Se-HAP纳米结构体。
进一步,步骤(1)具体包括,将NaOH溶于去离子水中,冰水浴中机械搅拌并加入去离子水、甲醇和油酸,将CaCl2水溶液逐滴一起加入混合得到混合液,搅拌后,再将NaH2PO4·2H2O和Na2SeO3逐滴加入所述混合液中,将得到的混合物转移到高压釜中,密封并在170℃-200℃下加热,然后得到的浆体加入大量的无水乙醇搅拌,并过滤收集;再用乙醇和去离子水洗多次,最后得到Se-HAP纳米结构体。
进一步,步骤(2)中,具体是在定向冷冻装置上,所述胶原蛋白溶液从室温冷却到负50℃-负60℃冷却,直到完全冻结,然后将冻结的所述胶原蛋白溶液保存在负70℃以下温度的冰箱中直到进一步冷冻一段时间后,冷冻干燥即可得到所述掺硒羟基磷灰石纳米增强的胶原GBR膜。
更进一步,步骤(2)中,是将动物I型胶原加到0.5%(v/v)醋酸溶液中搅拌配制40mg/mL的胶原溶液,冰水浴机械搅拌至完全溶解;利用间隔低温超声法使得胶原分散均匀;加入Se-HAP纳米线粉末于水溶液中,充分搅拌制成Se-HAP浆体,将所述胶原溶液与所述Se-HAP浆体,在冰水浴中机械搅拌混合均匀,得到胶原/Se-HAP混合溶液超声处理后,将浓缩成胶原蛋白溶液倒入圆柱形的铜模具中,风干后离心后,将铜模具放在定向冷冻装置上,所述胶原蛋白溶液从室温冷却至负60℃,直到完全冻结一段时间,冷冻干燥即可得到所述掺硒羟基磷灰石纳米增强的胶原GBR膜。
本发明还提供一种掺硒羟基磷灰石纳米增强的胶原GBR膜,是根据上述制备方法得到。是表面多孔有序、底面致密光滑的胶原/Se-HAP双层GBR膜。
本发明还提供掺硒羟基磷灰石纳米增强的胶原GBR膜在骨再生修复的应用,所述掺硒羟基磷灰石纳米增强的胶原GBR膜是根据上述制备方法得到,应用在引导骨再生康复,具有抗菌性、促成骨分化再生性能。
本发明相对于现有技术具有如下的优点及效果:
(1)本发明基于化学组成和结构的材料改造,发明的掺硒羟基磷灰石纳米增强的胶原GBR膜,它具有双层结构,一侧设计紧凑光滑,防止非成骨细胞干扰骨缺损部位成骨相关细胞的聚集与骨修复,而另一侧则多孔且粗糙,便于骨缺损附近成骨细胞黏附与募集。大大提高胶原双层GBR膜的力学性能、抗菌性能、成骨性能。多功能的致密光滑/多孔有序双层结构的胶原/Se-HAP GBR膜的构建,为GBR膜诱导修复骨缺损研究提供了利于成骨的微环境。
(2)本发明基于化学组成对骨髓间充质干细胞的成骨分化性能探究,不同高分子稳定硒纳米粒子(Col I-SeNPs,CS-SeNPs,LET-SeNPs,PVP-SeNPs),<10uM浓度的硒纳米粒子中,胶原与硒的Col I-SeNPs具有最优的生物相容性和促成骨性能。而Se-HAP能缓释钙离子、磷酸根与亚硒酸根离子,<10uM硒浓度的3Se-HAP具有良好的生物相容性,在促进骨髓间充质成骨分化性能方面:3SeHAP>Col I-SeNPs>LET-SeNPs>CS-SeNPs>PVP-SeNPs。
(3)本发明通过选取掺硒羟基磷灰石纳米线增强胶原GBR膜,致密光滑/多孔有序双层结构的胶原/Se-HAP的GBR膜具有抗菌和促进成骨等多效性能,揭示GBR膜骨修复的生理过程,开创了一个新的骨再生修复应用领域,为合成更好的骨修复材料提供新的技术指导。
(4)本发明提供掺硒羟基磷灰石纳米增强的胶原GBR膜制备方法原料廉价易得,合成和生产步骤可操作性强,容易扩大合成规模,实现新生物材料的商业化和应用。
独特的制备步骤,比如将Se/(Se+P)通过溶剂热法合成Se-HAP纳米结构,是将NaH2PO4·2H2O和Na2SeO3逐滴加入所述混合液中,将得到的混合物转移到高压釜中,密封并在170℃-200℃下加热,然后得到的浆体加入大量的无水乙醇搅拌,这样高温密闭高压下可以更好的将纳米硒融入到GBR膜微孔中,大大增强抗菌能力和胶原支架的强度,改善其力学性能。
步骤(2)中,将所述胶原溶液与所述Se-HAP浆体,在冰水浴中机械搅拌混合均匀,得到胶原/Se-HAP混合溶液超声处理后,将浓缩成胶原蛋白溶液倒入圆柱形的铜模具中,风干后离心后,将铜模具放在定向冷冻装置上,所述胶原蛋白溶液从室温冷却至负60℃,直到完全冻结再在负80℃的冰箱中直到进一步冷冻一段时间,这样方式形成独特的双层结构,一层紧凑光滑,防止非成骨细胞干扰骨缺损部位成骨相关细胞的聚集与骨修复,而另一侧则多孔且粗糙,便于骨缺损附近成骨细胞黏附与募集。
(5)通过对比动物实验和商用的Bio-Gide生物膜进行骨再生修复证明,掺硒羟基磷灰石纳米线增强的胶原GBR膜具有更加优异的骨再生修复性能,在引导骨再生及其相关疾病方面显示出良好的前景。
(6)通过探究不同质量分数(wt%,10、20、30、40、50、60、70、80%Se-HAP)胶原/Se-HAP复合膜中,30-50%Se-HAP的复合膜的综合性能最优,具有良好的力学性能、抗菌性能和促成骨性能。
附图说明
图1:羟基磷灰石(HAP)和掺硒羟基磷灰石(3Se-HAP)透射电镜图与元素分析图,其中(A)照片对应HAP,(B)照片对应3Se-HAP。
图2:不同掺硒量(Se/(Se+P))的Se-HAP对骨髓间充质干细胞(mBMSCs)的细胞相容性(A:MTT实验和B:死活荧光染色),以及促成骨分化的影响(14天)试验结果。
图3:Col@Se-HAP GBR膜的扫描电镜图(A)、红外图谱(B)、促mBMSCs细胞成骨分化性能(C:碱性磷酸酶染色)和抗菌性能研究(D:金黄色葡萄球菌抑菌圈)。
图4:本发明Col@Se-HAP双层GBR膜的屏蔽作用(2weeks):细胞免疫荧光染色后的激光共聚焦图:Col I(I型胶原)、nucleus(细胞核)、F-actin(F肌动蛋白)、NIH3T3(成纤维细胞)、mBMSCs(小鼠骨髓间充质干细胞)。
图5:本发明Col@Se-HAP双层GBR膜在大鼠颅骨缺损修复4weeks后的Micro-CT。对照组:商用Bio-gide胶原膜。
具体实施方式
下面结合实施例及附图对本发明作进一步详细的描述,但本发明的实施方式不限于此。
本发明提供掺硒羟基磷灰石纳米增强的胶原GBR膜应用在引导骨再生康复,具有抗菌性、促成骨分化再生性能。
实施例一,本发明提供掺硒羟基磷灰石纳米增强的胶原GBR膜制备方法,包括步骤:
(1)制备掺硒羟基磷灰石(Se-HAP),将Se/(Se+P)通过溶剂热法合成Se-HAP纳米结构体;是将摩尔分数为0.05%-0.4%的Se/(Se+P)通过溶剂热法合成掺硒的Se-HAP纳米线、或纳米针、或纳米片结构体。
进一步,步骤(1)具体包括,将9-10g NaOH溶于140-150mL去离子水中,冰水浴中机械搅拌并加入去120-140mL离子水、50-60mL甲醇和100-110mL油酸,将2.5-3.5g的CaCl2水溶液逐滴一起加入混合得到混合液,搅拌后,再将180-190mL的NaH2PO4·2H2O(8-9.5g)和Na2SeO3(0.02-0.035g)一起逐滴加入所述混合液中,将得到的混合物转移到高压釜中,密封并在170℃-200℃下加热,然后得到的浆体加入大量的无水乙醇搅拌,并过滤收集;再用乙醇和去离子水洗多次,最后得到Se-HAP纳米结构体。
(2)将动物I型胶原加到醋酸溶液中搅拌配制胶原溶液,机械搅拌至完全溶解,利用间隔低温超声方式使得胶原分散均匀;加入Se-HAP纳米线粉末于水溶液中,充分搅拌制成Se-HAP浆体,将所述胶原溶液与所述Se-HAP浆体混合均匀得到胶原/Se-HAP混合溶液超声处理后,再将浓缩成胶原蛋白溶液离心处理后放在冷冻装置上,所述胶原蛋白溶液从室温冷却至0℃以下,直到完全冻结一段时间,冷冻干燥即可得到所述掺硒羟基磷灰石纳米增强的胶原GBR膜(即Col@Se-HAP GBR膜)。
实施例二,本发明提供掺硒羟基磷灰石纳米增强的胶原GBR膜制备方法,包括,
步骤(1)、制备掺硒羟基磷灰石(Se-HAP),将Se/(Se+P)通过溶剂热法合成Se-HAP纳米结构体。
所述Se/(Se+P)的摩尔分数分别取0%、0.05%、0.1%、0.2%和0.3%,分别对应命名为HAP、0.5Se-HAP、1Se-HAP、2Se-HAP和3Se-HAP,分别通过溶剂热法合成HAP纳米线和不同掺硒量的Se-HAP纳米结构。这样可以做对比试验,筛选出最佳硒含量的Se-HAP纳米线。
比如摩尔分数0.3%的Se-HAP纳米线合成过程如下。将10.05g NaOH溶于150mL去离子水中,冰水浴中机械搅拌加入135mL去离子水,60mL甲醇和105mL油酸混合,120mLCaCl2(3.33g)水溶液逐滴加入上述溶液,搅拌30min,取180mL NaH2PO4·2H2O(9.33g)和Na2SeO3(0.031g)逐滴加入混合液中,将得到的混合物转移到特氟龙内衬不锈钢高压釜中,密封并在180℃下加热24h。然后得到的浆体加入大量的无水乙醇搅拌,并用200目筛过滤收集。再用乙醇和去离子水洗多次,再分散在去离子水(15mg/g)中,得到Se/(Se+P)摩尔分数0.3%的Se-HAP纳米线(即3Se-HAP)。
参见图1-2,可以参照上述步骤制备HAP纳米线和不同掺硒量的Se-HAP纳米线,并按照不同的Se/(Se+P)摩尔分数制备Se-HAP纳米线探究不同掺硒量,观察对骨髓间充质干细胞成骨性能的影响。
步骤(2)、制备表面多孔有序、底面致密光滑的胶原/SeHAP双层GBR膜。
通过HAP/Se-HAP对mBMSCs(小鼠骨髓间充质干细胞)成骨分化的影响(见图2),筛选出3Se-HAP作为复合支架的最优Se-HAP纳米线增强胶原支架。首先,将动物I型胶原加到0.5%(v/v)醋酸溶液中搅拌配制40mg/mL的胶原溶液,冰水浴机械搅拌至完全溶解。利用间隔低温超声法(每超声10min,停留10min)使得胶原分散均匀。按照不同浓度加入Se-HAP纳米线粉末于水溶液中,充分搅拌制成浆体,将胶原溶液与Se-HAP浆体混合,使得HAP/SeHAP的质量为3%,冰水浴中机械搅拌使得胶原和Se-HAP混合均匀。将混合溶液超声处理后,将高浓度胶原/Se-HAP混合溶液浓缩成胶原蛋白溶液(0.5mL,40mg/mL)被倒入圆柱形的铜模具中,风干后再加入0.5mL所述混合溶液。离心后,将铜模具放在定向冷冻装置上,溶液以-5℃/min速率从20℃至-60℃冷却。最终温度保持在-60℃,直到样品完全冻结。然后将样品保存在-80℃的冰箱中直到进一步冷冻12h后,冷冻干燥即可得到所述掺硒羟基磷灰石纳米增强的胶原GBR膜(即Col@Se-HAP GBR膜)。
作为实验对比,采用不同高分子:鼠尾I型胶原(Col I)、壳聚糖(CS),香菇多糖(LET)、聚乙烯吡咯烷酮(PVP)制备得到的硒纳米粒子,实验结果发现通过采用鼠尾I型胶原(Col I)与硒结合制备的复合材料,其促干细胞成骨分化效果最优。
通过上述方法制备的掺硒羟基磷灰石纳米增强的胶原GBR膜试验结果如下。
图2是不同掺硒量(Se/(Se+P))的Se-HAP对骨髓间充质干细胞(mBMSCs)的细胞相容性结果(A:MTT实验和B:死活荧光染色),以及促成骨分化的影响(14天):HAP/SeHAP的作用浓度为50μg/mL。50μg/mL掺硒羟基磷灰石对mBMSCs细胞没有毒性,同时促进mBMSCs细胞的成骨分化。
图3是Col@Se-HAP GBR膜的扫描电镜图(A)、红外图谱(B)、促mBMSCs细胞成骨分化性能(C:碱性磷酸酶染色)和抗菌性能研究(D:金黄色葡萄球菌抑菌圈)。通过实验证明,与HAP纳米线对比,3Se-HAP具有更加优异的成骨性能和抗菌性能;同时与纯胶原支架相比,复合支架Col@Se_HAP具有更加优异的成骨性能和抗菌性能。
图4是本发明Col@Se-HAP双层GBR膜的屏蔽作用(2weeks):细胞免疫荧光染色后的激光共聚焦图:Col I(I型胶原)、nucleus(细胞核)、F-actin(F肌动蛋白)、NIH3T3(成纤维细胞)、mBMSCs(小鼠骨髓间充质干细胞)。
可见,本发明Col@Se-HAP双层GBR膜能很好阻止NIH3T3细胞的侵袭。结果说明一侧致密光滑面可以防止非成骨细胞干扰骨缺损部位成骨相关细胞的聚集与骨修复,而另一侧多孔且粗糙,便于骨缺损附近成骨细胞黏附与募集。
图5:本发明Col@Se-HAP双层GBR膜在大鼠颅骨缺损修复4weeks后的Micro-CT。对照组:商用Bio-gide胶原膜。可见Col@Se-HAP双层引导骨再生GBR膜,基于覆盖骨缺损区域的屏障膜特性,阻止来自周围软组织的成纤维细胞侵袭,让骨面处的成骨细胞有足够的时间黏附、增殖、成骨分化,最终实现骨组织再生和修复的目的。骨再生修复性能优于现有产品商用Bio-gide胶原膜。
本发明通过合成的掺硒羟基磷灰石纳米增强的胶原GBR膜,经发现相对于商用的Bio-Gide胶原膜具有更好促进成骨再生的治疗效果,为临床骨再生手术提供新的策略及选择。
发明人经过透射电镜和元素分析显示我们成功制备了掺硒羟基磷灰石纳米线。同时我们使用小鼠骨髓间充质干细胞验证Se-HAP和Col@Se-HAP GBR膜促进成骨分化的能力和屏蔽成纤维细胞侵袭的能力,同时通过金黄色葡萄球菌的抑菌圈实验验证Se-HAP和Col@Se-HAP的良好的抗菌性能。最终,发明人在大鼠颅骨缺损模型中验证Col@Se-HAP GBR膜促骨再生的性能,并发现Col@Se-HAP GBR膜相对商用的Bio-gide膜具有优异的骨缺损修复能力,能够快速地促进颅骨缺损的骨再生修复。
综上所述,本发明不仅展示了掺硒羟基磷灰石纳米线和Col@Se-HAP双层GBR膜制备方法,而且为GBR膜的促骨再生机制及今后在骨缺损再生治疗中的临床应用提供了更多的证据。
上述实施例为本发明较佳的实施方式,但本发明的实施方式并不受上述实施例的限制,其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化,均应为等效的置换方式,都包含在本发明的保护范围之内。
Claims (10)
1.掺硒羟基磷灰石纳米增强的胶原GBR膜制备方法,其特征在于,包括步骤:
(1)制备掺硒羟基磷灰石(Se-HAP),将Se/(Se+P)通过溶剂热法合成Se-HAP纳米结构体;
(2)将动物I型胶原加到醋酸溶液中搅拌配制胶原溶液,机械搅拌至完全溶解,利用间隔低温超声方式使得胶原分散均匀;加入Se-HAP纳米粉末于水溶液中,充分搅拌制成Se-HAP浆体,将所述胶原溶液与所述Se-HAP浆体混合均匀得到胶原/Se-HAP混合溶液超声处理后,再将浓缩成胶原蛋白溶液离心处理后放在冷冻装置上,所述胶原蛋白溶液从室温冷却至0℃以下,直到完全冻结一段时间,冷冻干燥即可得到所述掺硒羟基磷灰石纳米增强的胶原GBR膜。
2.根据权利要求1所述掺硒羟基磷灰石纳米增强的胶原GBR膜制备方法,其特征在于,步骤(1)中:是将摩尔分数为0.05%-0.4%的Se/(Se+P)通过溶剂热法合成掺硒的Se-HAP纳米线、或纳米针、或纳米片结构体。
3.根据权利要求2所述掺硒羟基磷灰石纳米增强的胶原GBR膜制备方法,其特征在于,步骤(1)中:所述Se/(Se+P)的摩尔分数分别取0.05%、0.1%、0.2%和0.3%,分别对应命名为0.5Se-HAP、1Se-HAP、2Se-HAP和3Se-HAP,通过溶剂热法合成掺硒的Se-HAP纳米结构体。
4.根据权利要求1所述掺硒羟基磷灰石纳米增强的胶原GBR膜制备方法,其特征在于,步骤(1)具体包括,
将NaOH溶于去离子水中,冰水浴中机械搅拌并加入去离子水、甲醇和油酸,将CaCl2水溶液逐滴一起加入混合得到混合液,搅拌后,再将NaH2PO4·2H2O和Na2SeO3逐滴加入所述混合液中,将得到的混合物转移到高压釜中,密封并在170℃-200℃下加热,然后得到的浆体加入大量的无水乙醇搅拌,并过滤收集;再用乙醇和去离子水洗多次,最后得到Se-HAP纳米结构体。
5.根据权利要求1所述掺硒羟基磷灰石纳米增强的胶原GBR膜制备方法,其特征在于,步骤(2)中,具体是在定向冷冻装置上,所述胶原蛋白溶液从室温冷却到负50℃-负60℃冷却,直到完全冻结,然后将冻结的所述胶原蛋白溶液保存在负70℃以下温度的冰箱中直到进一步冷冻一段时间后,冷冻干燥即可得到所述掺硒羟基磷灰石纳米增强的胶原GBR膜。
6.根据权利要求1所述掺硒羟基磷灰石纳米增强的胶原GBR膜制备方法,其特征在于,步骤(2)中,
是将动物I型胶原加到0.5%(v/v)醋酸溶液中搅拌配制40mg/mL的胶原溶液,冰水浴机械搅拌至完全溶解;利用间隔低温超声法使得胶原分散均匀;加入Se-HAP纳米线粉末于水溶液中,充分搅拌制成Se-HAP浆体,将所述胶原溶液与所述Se-HAP浆体,在冰水浴中机械搅拌混合均匀,得到胶原/Se-HAP混合溶液超声处理后,将浓缩成胶原蛋白溶液倒入圆柱形的铜模具中,风干后离心后,将铜模具放在定向冷冻装置上,所述胶原蛋白溶液从室温冷却至负60℃,直到完全冻结一段时间,冷冻干燥即可得到所述掺硒羟基磷灰石纳米增强的胶原GBR膜。
7.一种掺硒羟基磷灰石纳米增强的胶原GBR膜,其特征在于,是根据权利要求1-6任意一项的所述制备方法得到。
8.根据权利要求7所述一种掺硒羟基磷灰石纳米增强的胶原GBR膜,其特征在于,是表面多孔有序、底面致密光滑的胶原/Se-HAP双层GBR膜。
9.一种掺硒羟基磷灰石纳米增强的胶原GBR膜在骨再生修复的应用,其特征在于,所述掺硒羟基磷灰石纳米增强的胶原GBR膜是根据权利要求1-6任意一项的所述制备方法得到。
10.根据权利要求9所述一种掺硒羟基磷灰石纳米增强的胶原GBR膜在骨再生修复的应用,其特征在于,具体是应用在引导骨再生康复,具有抗菌性、促成骨分化再生性能。
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