CN115120775B - 一种骨修复支架材料及其制备方法 - Google Patents
一种骨修复支架材料及其制备方法 Download PDFInfo
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Abstract
本发明公开一种骨修复支架材料及其制备方法、应用,该制备方法首先制备包含磷酸钙寡聚体和胶原蛋白的核纺丝液,再制备包含丝素蛋白和VEGF的壳纺丝液,最后利用同轴静电纺丝得到具备壳‑核结构的复合同轴静电纺丝纳米纤维。VEGF为骨修复过程中的血管化提供有效供给,丝素蛋白与VEGF一起形成支架结构的壳,为缓释VEGF,达到长效血管化提供了保障,可实现核缓慢降解,达到长效促进骨修复的目的;同轴静电纺丝得到的纳米纤维结构,模拟了骨基质的纤维状结构,为骨修复提供了支架结构。本发明制备的骨修复支架材料不仅可以从促进骨修复营养供给的血管化上对骨修复过程进行加强,而且可发挥磷酸钙寡聚体促进成骨过程的作用,促进骨缺损修复。
Description
技术领域
本发明涉及生物医学工程技术领域,尤其是一种骨修复支架材料及其制备方法。
背景技术
磷酸钙材料可与细胞产生相互作用,参与多种生物矿化的性质奠定了其在骨组织工程研究中不可撼动的地位。因此在众多生物活性材料中,归属于陶瓷类别的磷酸钙材料因与天然骨组织无机组分的高度相似以及参与生物矿化的优秀生物活性受到了学界广泛的关注。磷酸钙材料作为骨组织材料的优势在于:(1)天然骨骼的主要无机成分是生物磷灰石,人体内存在大量的钙和磷离子。(2)许多磷酸钙材料通过宿主细胞介导的途径降解,这样既保证了材料降解速率与自然骨组织再生速率的相协调,还避免了可能出现的材料过快降解引发的生物兼容性问题。(3)钙离子和磷酸根离子被证实与骨细胞存在相互作用,特别是磷酸根离子被发现具有一定的骨诱导性。(4)磷酸钙材料大多价格低廉,制备出的生物支架成本也会相应降低。显而易见,磷酸钙材料天然具有的性质与理想材料的需求相呼应。但是磷酸钙材料的最大缺点就是其机械强度较低,无法作为与天然骨成分相似的无机成分进入骨修复材料中,这是磷酸钙材料迈向临床应用的最大阻碍之一。
骨创伤初期形成的血肿及伴随的炎症反应激活了骨修复的过程,血管内皮生长因子(VEGF)在这一过程中发挥重要作用。骨愈合早期阶段主要是软骨组织的形成,VEGF能调节骨髓、骨膜和周围肌肉的骨骼干细胞向软骨细胞或成骨细胞分化。另外对于膜内骨成骨,膜内骨骨修复发生被证实在很大程度上依赖于血管生成和成骨的共同作用,VEGF对两者的偶联起着至关重要的作用。在骨修复的过程中,VEGF可以激活内皮细胞,调节血管的通透性并促进新生血管的形成并募集成骨细胞,这些都为成骨相关细胞的增殖及矿化提供了充足的营养物质及原料保障。由于新血管生成以及成骨细胞募集对于骨缺损修复的重要作用,VEGF受到了研究界广泛的关注,但是其半衰期不到1个小时。
发明内容
本发明提供一种骨修复支架材料及其制备方法,用于克服现有技术中磷酸钙无法作为与天然骨成分相似的无机成分进入骨修复材料中等缺陷,也实现了延长VEGF的作用时间,使血管化与成骨化同时进行,最终促进骨修复过程的问题。
为实现上述目的,本发明提出一种骨修复支架材料的制备方法,包括以下步骤:
S1:配制CaCl2·2H2O乙醇溶液和磷酸乙醇溶液;
S2:取所述CaCl2·2H2O乙醇溶液置于烧杯中,加入三乙胺(TEA),静置3~5min,再加入所述磷酸乙醇溶液,封口后搅拌30~60min,得到寡聚体悬浊液;
S3:将所述寡聚体悬浊液离心、弃上清、乙醇重悬,重复离心-弃上清-乙醇重悬过程若干次,然后将重悬液定容至设定体积,得到磷酸钙寡聚体溶液;
S4:将所述磷酸钙寡聚体溶液和胶原蛋白加入到聚己内酯电纺液中,搅拌1~3h,得到核纺丝液;
S5:将丝素蛋白和VEGF混合均匀后4℃抚育过夜或者37℃抚育4小时,再加入到聚己内酯电纺液中,搅拌1~3h,得到壳纺丝液;
S6:利用所述核纺丝液和壳纺丝液,通过同轴静电纺丝,得到骨修复支架材料。
为实现上述目的,本发明还提出一种骨修复支架材料,由上述所述制备方法制备得到;所述骨修复支架材料为具备壳-核结构的复合同轴静电纺丝纳米纤维,内核为磷酸钙寡聚体和胶原蛋白,外壳为丝素蛋白和VEGF。
为实现上述目的,本发明还提出一种骨修复支架材料的应用,将上述所述制备方法制备得到的骨修复支架材料或者上述所述骨修复支架材料应用于骨组织工程领域。
与现有技术相比,本发明的有益效果有:
本发明提供的骨修复支架材料的制备方法首先制备包含透明胶状的磷酸钙寡聚体和胶原蛋白的核纺丝液,再制备包含丝素蛋白和VEGF的壳纺丝液,最后利用同轴静电纺丝得到具备壳-核结构的复合同轴静电纺丝纳米纤维,内核为磷酸钙寡聚体和胶原蛋白,外壳为丝素蛋白和VEGF。VEGF为骨修复过程中的血管化提供有效供给,丝素蛋白与VEGF一起形成支架结构的壳,为缓释VEGF,达到长效血管化提供了保障,可实现核缓慢降解,达到长效促进骨修复的目的;同时同轴静电纺丝得到的纳米纤维结构,模拟了骨基质的纤维状结构,为骨修复提供了支架结构。本发明制备的骨修复支架材料不仅可以从促进骨修复营养供给的血管化上对骨修复过程进行加强,而且可发挥在聚合物中分散性更好的磷酸钙寡聚体促进成骨过程的作用,促进骨缺损修复。本发明制得的骨修复支架材料在骨组织工程领域具有很大的应用前景。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案,下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图仅仅是本发明的一些实施例,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图示出的结构获得其他的附图。
图1为本发明实施例1制得的CaPO的透射电镜图;
图2为本发明实施例1制得的CaPO,C/COL和骨修复支架材料的FTIR谱图;
图3为本发明实施例1制得的CaPO,C/COL和骨修复支架材料的扫描电子显微镜图片;
图4为本发明实施例1中的支架材料在模拟体液浸泡14天后CaPO,C/COL和骨修复支架材料的扫描电子显微镜图片;
图5为本发明实施例1中的支架材料上培养成骨细胞矿化诱导培养21天后对矿化结节进行茜素红染色的图片;
图6为本发明实施例1中的支架材料上培养HUVEC 5天后免疫荧光染色的图片。
本发明目的的实现、功能特点及优点将结合实施例,参照附图做进一步说明。
具体实施方式
下面将结合本发明实施例中的附图,对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明的一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
另外,本发明各个实施例之间的技术方案可以相互结合,但是必须是以本领域普通技术人员能够实现为基础,当技术方案的结合出现相互矛盾或无法实现时应当认为这种技术方案的结合不存在,也不在本发明要求的保护范围之内。
无特殊说明,所使用的药品/试剂均为市售。
本发明提出一种骨修复支架材料的制备方法,包括以下步骤:
S1:配制CaCl2·2H2O乙醇溶液和磷酸乙醇溶液。
S2:取所述CaCl2·2H2O乙醇溶液置于烧杯中,加入三乙胺(TEA)静置3~5min,再加入所述磷酸乙醇溶液,封口后搅拌30~60min,得到寡聚体悬浊液。
S3:将所述寡聚体悬浊液离心、弃上清、乙醇重悬,重复离心-弃上清-乙醇重悬过程若干次,然后将重悬液定容至设定体积,得到磷酸钙寡聚体(CaPO)溶液。
S4:将所述磷酸钙寡聚体溶液(CaPO)和胶原蛋白(COL)加入到聚己内酯(PCL)电纺液中,搅拌1~3h,得到核纺丝液。
S5:将丝素蛋白(SF)和VEGF(V)混合均匀后4℃抚育过夜或者37℃抚育4小时,再加入到聚己内酯(PCL)电纺液中,搅拌1~3h,得到壳纺丝液。
S6:利用所述核纺丝液和壳纺丝液,通过同轴静电纺丝,得到骨修复支架材料。
静电纺丝规避了以往苛刻的加工条件,使得生物成分在纺丝和后处理过程中保持构象稳定,可将一些性质较为不稳定的生物成分纳入组织工程。通过静电纺丝制备的生物支架具有较高的孔隙率与合适的孔洞尺寸,可以有效地促进成骨相关细胞的黏附、增殖和分化等生命活动。
同轴静电纺丝技术通过两条进液线路同时输出不同的电纺溶液。该技术可以制备具有核壳结构的纳米纤维,大大拓宽了纤维理化性质、成分的多样性。同时由于核壳两层物质具有不同的降解速率,使得具有核壳结构的静电纺丝纤维具有更优越的细胞因子及药物负载性质。
CaPS颗粒自身很难均匀地混入含有聚合物的电纺液中,而磷酸钙寡聚体呈现出透明胶状的外观,大大增强了其在聚合物溶液中的分散性。
优选地,在步骤S1中,所述CaCl2·2H2O乙醇溶液中CaCl2·2H2O浓度为20~30mmol/L;所述磷酸乙醇溶液中磷酸浓度为20~30mmol/L,为后续控制钙离子与磷酸根离子的浓度提供基础。
优选地,在步骤S2中,所述CaCl2·2H2O中的钙离子与磷酸中的磷酸根离子的摩尔比为0.66~1.50:1,以便更充分的形成磷酸钙寡聚体。
优选地,在步骤S2中,所述TEA的用量控制在4~5mL。为了阻止磷酸根离子和钙离子大量接合形成磷酸钙沉淀,TEA与钙离子的摩尔比例越高,形成的寡聚体分子量越小,将其用量控制在4-5mL。
优选地,在步骤S3中,所述离心的离心力为8000~10000g,时间为30min。
优选地,在步骤S4中,所述磷酸钙寡聚体溶液的加入量为5~20mg;所述胶原蛋白的加入量为2~3mg,通过模拟骨基质中的钙离子与胶原蛋白的比例,使磷酸钙寡聚体与胶原蛋白能够充分接触,通过分子间相互作用力吸附在一起。
优选地,在步骤S5中,所述丝素蛋白的加入量为5~20mg;所述VEGF的加入量为2~4μg,通过控制VEGF的量,可以控制诱导血管的形成,给予血管生长的最适微环境;通过控制丝素蛋白的量,可以为成骨细胞提供最适生长的微环境。
优选地,在步骤S4和S5中,所述聚己内酯电纺液中聚己内酯浓度为10%;所述聚己内酯电纺液的溶剂为六氟异丙醇。六氟异丙醇是一种静电纺丝中常用的电纺液溶剂,极性强,能与多种有机物和水互溶。另外六氟异丙醇易挥发,在静电纺丝的过程中即可自动从体系中去除,避免产生额外的干扰因素。若电纺液过稀或过粘稠,则在喷口处难以形成稳定的泰勒锥,电纺液可能会以微小液滴的形式喷洒在阴极承接容器上。而数控注射泵的推进速度和电压大小会影响产物纤维尺寸的大小,并且过快的推进速度往往会使同轴静电纺丝喷嘴发生堵塞,影响产物纤维均一性。
优选地,在步骤S6中,所述同轴静电纺丝的电压为15~25kV,进样速度为0.50~0.75ml/h。
本发明还提出一种骨修复支架材料,由上述所述制备方法制备得到;所述骨修复支架材料为具备壳-核结构的复合同轴静电纺丝纳米纤维,内核为磷酸钙寡聚体和胶原蛋白(C/COL),外壳为丝素蛋白和VEGF(SF/V)。
本发明还提出一种骨修复支架材料的应用,将上述所述制备方法制备得到的骨修复支架材料或者上述所述骨修复支架材料应用于骨组织工程领域。
实施例1
本实施例提供一种骨修复支架材料的制备方法,包括以下步骤:
配制25mM(mmol/L)CaCl2·2H2O的乙醇溶液及25mM磷酸的乙醇溶液,取60ml25mMCaCl2·2H2O的乙醇溶液转入干净烧杯中,加入4.16mlTEA,加入磁力搅拌子,静置3min,再向该混合液中加入25mM磷酸的乙醇溶液,锡纸封口后磁力搅拌30min。至此可以得到半透明的灰白色寡聚体悬浊液。将悬浊液8000g离心30min,弃上清,乙醇重悬后再离心重复前一步骤两次,弃上清。乙醇重悬分散并定容至10ml。得到磷酸钙寡聚体(CaPO)溶液。
将15mg CaPO及2.5mg胶原蛋白(COL)加入1ml的聚己内酯(PCL)电纺液(PCL溶解于六氟异丙醇)中,搅拌1h,作为核(CaPO/COL,C/COL)。将15mg丝素蛋白(SF)和2.66ug的VEGF(V)混合均匀后4℃抚育过夜,再加入1ml的PCL电纺液中,搅拌1h,作为壳(SF/V)。
通过同轴静电纺丝技术制备促进血管化的磷酸钙寡聚体纳米纤维骨修复支架材料,具备内芯为C/COL,外壳为SF/V,通过调节电压为19kV,调节进样速度为0.50ml/h,得到具备“壳-核”结构的复合同轴静电纺丝纳米纤维(C/COL+SF/V),即促进血管化的磷酸钙寡聚体纳米纤维骨修复支架材料。
实施例1中促进血管化的磷酸钙寡聚体纳米纤维骨修复支架材料的表征测量及结果:
图1所示的磷酸钙寡聚体(CaPO)的平均粒径约为1nm。则该结果可以证明通过TEA介导的磷酸钙寡聚体制备是有效的,通过该方法可以制备出一种具有创新性的CaPS材料。
图2为CaPO,C/COL和骨修复支架材料的FTIR谱图,谱图中三种支架在581.3cm-1和1110.7cm-1处均出现了磷酸根的吸收峰。其中骨修复支架材料在1520cm-1与1630cm-1处均可观察到CaPO与C/COL中未出现的吸收峰,这两个峰对应丝素蛋白中的β折叠中的酰胺键(分别为II型与I型),从微观结构上证实了通过同轴静电纺丝的方式,丝素蛋白可以与磷酸钙寡聚体、胶原蛋白形成具有“壳-核”结构的复合生物活性材料。CaPO,C/COL和骨修复支架材料三者谱图总体上没有明显的变化,说明Col、SF、VEGF的掺杂并未对生物活性材料的化学结构造成大的破坏。上述结果表明各组分基团之间广泛存在分子间作用力,从而相互作用,形成了不同的复合生物活性材料。
图3为CaPO,C/COL和骨修复支架材料的扫描电子显微镜图片。对于同一区域采用了1微米和500纳米两个尺度去观察三种生物活性材料支架的表面形貌。从图3的六张子图中可以观察到三种生物活性材料支架均形成了基本的相互联通的孔洞结构,这也初步呼应了骨组织工程生物活性材料支架中机械性能、生物相容性的需求。通过传统静电纺丝与同轴静电纺丝两种方法制备的生物活性材料纤维均未出现团聚、褶皱和断裂等现象。
图4为在模拟体液浸泡14天后CaPO,C/COL和骨修复支架材料的SEM图片。从图4可以看到,经过14天模拟体液的浸泡,CaPO支架在纤维的小部分部位形成了表面光滑的球形结节,C/COL支架在纤维的小部分部位形成了表面粗糙,形似立方体的沉积结节。而在骨修复支架材料中可以观察到典型的矿化结节,在支架纤维表面产生了大量的片状结晶,这是局部钙离子大量聚集的结果,这些片状结晶最终相互交错团聚,形成椭球形的结节位点。从图4中可以基本推断出骨修复支架材料自身具备优异的促生物矿化能力,表现出显著的生物活性。
图5为在矿化诱导培养21天后,对6孔板中种植在三种生物活性材料支架上的BMSC细胞外基质中的矿化结节进行了茜素红染色,并在两种比例尺和两种显微镜(7倍,体式镜;100倍,荧光显微镜)下对其进行了观察。C/COL、骨修复支架材料两组支架材料与CaPO支架材料相比,经过茜素红染色出现了数量明显更多的深红色矿化结节。而骨修复支架材料与C/COL两组,从该放大尺度观察,矿化结节数量大致相同,无明显区别。另外,在CaPO、C/COL和骨修复支架材料三组中,大部分染色后的矿化结节大小类似,仅有CaPO组有零星几个较大的深红色矿化结节。从荧光显微镜的观察结果可以看出,CaPO支架上,经过21天的矿化诱导培养,出现了少量略大,呈红紫色的矿化结节,表明这些位点矿化程度较高。而在C/COL支架中,出现了较多的红紫色结节,且每个结节外围出现了呈红色,辐射状向外扩散的较低矿化水平的区域。相似的结果也能在骨修复支架材料组中观察得到,不同的是与C/COL组相比,红紫色高度矿化结节的数量更多,面积更大,且可以观察到更广泛的红色,辐射状向外扩散并部分相交汇的较低矿化水平的区域。这些结果表明在三种支架材料中,骨诱导性由强自弱的排序为骨修复支架材料、C/COL、CaPO。
图6为对种植于三种支架材料中培养五天后的人脐静脉内皮细胞(HUVEC)进行的免疫荧光实验。CD31是一个分子量为130kDa的免疫球蛋白超家族成员。通常位于血管内皮细胞之间的紧密连接处,与血管生成有直接的关系,常被用作血管生成的标志物。用绿色荧光表示HUVEC中普遍存在的肌动蛋白(Actin),红色表示HUVEC的CD31分子,蓝色表示被二脒基苯基吲哚(DAPI)染色的细胞核。观察CaPO支架组的图片,仅能在支架表面发现少量HUVEC,并且种植在该种生物活性材料支架表面的HUVEC的CD31表达量相对较少,荧光信号较弱。C/COL支架组中,可以观察到略多于CaPO支架组的HUVEC。并且种植在该组支架的HUVEC的图下部可以看到两个紧密连接的细胞,另外,C/COL组HUVEC的CD31荧光信号也要强于CaPO组的HUVEC,表明在该生物活性材料表面黏附的HUVEC表达了更多的CD31。观察种植在骨修复支架材料的HUVEC,我们可以观察到其表达了大量了CD31,细胞形态均呈伸展状,细胞与细胞之间存在相互连接的细丝状CD31,细胞在该支架上表现出了最活跃的与成血管相似的生命活动。该实验的总体结果表明,相较于CaPO支架,骨修复支架材料和C/COL支架可以更好地促进HUVEC之间的相互作用与CD31的表达,且骨修复支架材料的促进作用要明显强于C/COL。因此,骨修复支架材料在血管化上由于其它两种支架材料。
实施例2
本实施例提供一种骨修复支架材料的制备方法,包括以下步骤:
配制20mM(mmol/L)CaCl2·2H2O的乙醇溶液及20mM磷酸的乙醇溶液,取80mlCaCl2·2H2O乙醇溶液转入干净烧杯中,加入4mlTEA,加入磁力搅拌子,静置4min,再向该混合液中加入磷酸乙醇溶液,锡纸封口后磁力搅拌40min。至此可以得到半透明的灰白色寡聚体悬浊液。将悬浊液9000g离心30min,弃上清,乙醇重悬后再离心重复前一步骤两次,弃上清。乙醇重悬分散并定容至10ml。得到磷酸钙寡聚体(CaPO)溶液。
将5mg CaPO及2mg胶原蛋白(COL)加入1ml的聚己内酯(PCL)电纺液(PCL溶解于六氟异丙醇)中,搅拌2h,作为核(CaPO/COL,C/COL)。将5mg丝素蛋白(SF)和2ug的VEGF(V)混合均匀后4℃抚育过夜,再加入1ml的PCL电纺液中,搅拌2h,作为壳(SF/V)。
通过同轴静电纺丝技术制备促进血管化的磷酸钙寡聚体纳米纤维骨修复支架材料,具备内芯为C/COL,外壳为SF/V,通过调节电压为15kV,调节进样速度为0.60ml/h,得到具备“壳-核”结构的复合同轴静电纺丝纳米纤维(C/COL+SF/V),即促进血管化的磷酸钙寡聚体纳米纤维骨修复支架材料。
实施例3
本实施例提供一种骨修复支架材料的制备方法,包括以下步骤:
配制30mM(mmol/L)CaCl2·2H2O的乙醇溶液及30mM磷酸的乙醇溶液,取40mlCaCl2·2H2O乙醇溶液转入干净烧杯中,加入5mlTEA,加入磁力搅拌子,静置5min,再向该混合液中加入磷酸乙醇溶液,锡纸封口后磁力搅拌60min。至此可以得到半透明的灰白色寡聚体悬浊液。将悬浊液10000g离心30min,弃上清,乙醇重悬后再离心重复前一步骤两次,弃上清。乙醇重悬分散并定容至10ml。得到磷酸钙寡聚体(CaPO)溶液。
将20mg CaPO及3mg胶原蛋白(COL)加入1ml的聚己内酯(PCL)电纺液(PCL溶解于六氟异丙醇)中,搅拌3h,作为核(CaPO/COL,C/COL)。将20mg丝素蛋白(SF)和4ug的VEGF(V)混合均匀后37℃抚育4小时,再加入1ml的PCL电纺液中,搅拌3h,作为壳(SF/V)。
通过同轴静电纺丝技术制备促进血管化的磷酸钙寡聚体纳米纤维骨修复支架材料,具备内芯为C/COL,外壳为SF/V,通过调节电压为25kV,调节进样速度为0.75ml/h,得到具备“壳-核”结构的复合同轴静电纺丝纳米纤维(C/COL+SF/V),即促进血管化的磷酸钙寡聚体纳米纤维骨修复支架材料。
以上所述仅为本发明的优选实施例,并非因此限制本发明的专利范围,凡是在本发明的发明构思下,利用本发明说明书及附图内容所作的等效结构变换,或直接/间接运用在其他相关的技术领域均包括在本发明的专利保护范围内。
Claims (7)
1.一种骨修复支架材料的制备方法,其特征在于,包括以下步骤:
S1:配制CaCl2·2H2O乙醇溶液和磷酸乙醇溶液;所述CaCl2·2H2O乙醇溶液中CaCl2·2H2O浓度为20~30 mmol/L;所述磷酸乙醇溶液中磷酸浓度为20~30 mmol/L;
S2:取所述CaCl2·2H2O乙醇溶液置于烧杯中,加入三乙胺,静置3~5 min,再加入所述磷酸乙醇溶液,封口后搅拌30~60 min,得到寡聚体悬浊液;所述CaCl2·2H2O中的钙离子与磷酸中的磷酸根离子的摩尔比为0.66~1.50:1;
S3:将所述寡聚体悬浊液离心、弃上清、乙醇重悬,重复离心-弃上清-乙醇重悬过程若干次,然后将重悬液定容至设定体积,得到磷酸钙寡聚体溶液;
S4:将所述磷酸钙寡聚体溶液和胶原蛋白加入到聚己内酯电纺液中,搅拌1~3 h,得到核纺丝液;
S5:将丝素蛋白和VEGF混合均匀后4℃孵育过夜或者37℃孵育4小时,再加入到聚己内酯电纺液中,搅拌1~3 h,得到壳纺丝液;
S6:利用所述核纺丝液和壳纺丝液,通过同轴静电纺丝,得到骨修复支架材料。
2.如权利要求1所述的制备方法,其特征在于,在步骤S2中,所述三乙胺的用量控制在4~5mL。
3.如权利要求1所述的制备方法,其特征在于,在步骤S3中,所述离心的离心力为8000~10000g,时间为30min。
4.如权利要求1所述的制备方法,其特征在于,在步骤S4中,所述磷酸钙寡聚体溶液的加入量为5~20 mg;所述胶原蛋白的加入量为2~3 mg。
5.如权利要求1所述的制备方法,其特征在于,在步骤S5中,所述丝素蛋白的加入量为5~20 mg;所述VEGF的加入量为2~4μg。
6.如权利要求1所述的制备方法,其特征在于,在步骤S4和S5中,所述聚己内酯电纺液中聚己内酯浓度为10%;所述聚己内酯电纺液的溶剂为六氟异丙醇。
7.一种骨修复支架材料,其特征在于,由权利要求1~6任一项所述制备方法制备得到;所述骨修复支架材料为具备壳-核结构的复合同轴静电纺丝纳米纤维,内核为磷酸钙寡聚体和胶原蛋白,外壳为丝素蛋白和VEGF。
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---|
Three-Dimensional Hierarchical Composite Scaffolds Consisting of Polycaprolactone, β-Tricalcium Phosphate, and Collagen Nanofibers: Fabrication, Physical Properties, and In Vitro Cell Activity for Bone Tissue Regeneration;Yeo, M, 等;BIOMACROMOLECULES;第12卷(第2期);第 502-510页 * |
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