CN106390193A - 一种应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片制备方法 - Google Patents
一种应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片制备方法 Download PDFInfo
- Publication number
- CN106390193A CN106390193A CN201611087329.1A CN201611087329A CN106390193A CN 106390193 A CN106390193 A CN 106390193A CN 201611087329 A CN201611087329 A CN 201611087329A CN 106390193 A CN106390193 A CN 106390193A
- Authority
- CN
- China
- Prior art keywords
- diaphragm
- neurosurgery
- biodegradable
- polyelectrolyte
- growth factor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L89/00—Compositions of proteins; Compositions of derivatives thereof
-
- D—TEXTILES; PAPER
- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
- D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
- D06M15/00—Treating fibres, threads, yarns, fabrics, or fibrous goods made from such materials, with macromolecular compounds; Such treatment combined with mechanical treatment
- D06M15/01—Treating fibres, threads, yarns, fabrics, or fibrous goods made from such materials, with macromolecular compounds; Such treatment combined with mechanical treatment with natural macromolecular compounds or derivatives thereof
- D06M15/03—Polysaccharides or derivatives thereof
-
- D—TEXTILES; PAPER
- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
- D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
- D06M15/00—Treating fibres, threads, yarns, fabrics, or fibrous goods made from such materials, with macromolecular compounds; Such treatment combined with mechanical treatment
- D06M15/01—Treating fibres, threads, yarns, fabrics, or fibrous goods made from such materials, with macromolecular compounds; Such treatment combined with mechanical treatment with natural macromolecular compounds or derivatives thereof
- D06M15/15—Proteins or derivatives thereof
-
- D—TEXTILES; PAPER
- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
- D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
- D06M15/00—Treating fibres, threads, yarns, fabrics, or fibrous goods made from such materials, with macromolecular compounds; Such treatment combined with mechanical treatment
- D06M15/19—Treating fibres, threads, yarns, fabrics, or fibrous goods made from such materials, with macromolecular compounds; Such treatment combined with mechanical treatment with synthetic macromolecular compounds
- D06M15/21—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds
- D06M15/356—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds of other unsaturated compounds containing nitrogen, sulfur, silicon or phosphorus atoms
- D06M15/3562—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds of other unsaturated compounds containing nitrogen, sulfur, silicon or phosphorus atoms containing nitrogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/32—Materials or treatment for tissue regeneration for nerve reconstruction
-
- D—TEXTILES; PAPER
- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
- D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
- D06M2101/00—Chemical constitution of the fibres, threads, yarns, fabrics or fibrous goods made from such materials, to be treated
- D06M2101/02—Natural fibres, other than mineral fibres
- D06M2101/10—Animal fibres
- D06M2101/12—Keratin fibres or silk
-
- D—TEXTILES; PAPER
- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
- D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
- D06M2101/00—Chemical constitution of the fibres, threads, yarns, fabrics or fibrous goods made from such materials, to be treated
- D06M2101/16—Synthetic fibres, other than mineral fibres
- D06M2101/30—Synthetic polymers consisting of macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- D06M2101/32—Polyesters
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Textile Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Vascular Medicine (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明涉及一种应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片,通过以下方法制得:将生物可降解聚合物材料,溶于极性、易挥发有机溶剂中,通过静电纺丝方法,制得由直径为纳米尺度的超细纤维组成的膜片;通过层层自组装技术将促进脑组织血管再生和/或促进神经再生的生长因子负载至膜片上,经干燥制得产品。其优点表现在:无毒性,在体内降解后不会产生有害物质,具有良好的生物相容性。可以避免有机溶剂、强酸强碱、高温等因素造成生长因子失活,组装的聚电解质可以保证膜片上负载的生长因子保持良好的活性。在脑部血管梗阻部位长期控制释放VEGF、NGF等生长因子,由此可以诱导调控脑组织血管梗阻部位的血管再生以及神经再生。
Description
技术领域
本发明涉及纳米生物医学技术领域,具体地说,是一种应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片及制备方法。
背景技术
缺血性脑血管疾病是直接威胁人类健康的重大疾病,常见于颅内外血管狭窄或闭塞、脑动脉硬化性小血管病变、烟雾病等【Qiu L,Ng G,Tan EK,et al.Chronic cerebralhypoperfusion enhances Tau hyperphosphorylation and reduces autophagy inAlzheimer's disease mice.Sci Rep,2016;6:23964.Araki Y,Takagi Y,Ueda K,etal.Cognitive function of patients with adult moyamoya disease.J StrokeCerebrovasc Dis,2014;23:1789-1794.Su SH,Hai J,Zhang L,et al.Assessment ofcognitive function in adult patients with hemorrhagic moyamoya disease whoreceived no surgical revascularization.Eur J Neurol,2013;20:1081-1087.】,长期的脑供血不足可导致神经细胞变性、凋亡、患者认知功能障碍以及社会行为能力低下等【Wang Z,Fan J,Wang J,et al.Chronic cerebral hypoperfusion induces long-lasting cognitive deficits accompanied by long-term hippocampal silentsynapses increase in rats.Behav Brain Res,2016;301:243-252.】,严重影响了患者的生存质量,临床上尚缺乏有效的治疗措施。
颅内外血管重建通过直接或间接方法将颅外血管与颅内血管沟通,重建缺血区脑循环,临床用于治疗缺血性脑血管病【Reynolds MR,Derdeyn CP,Grubb RL Jr,etal.Extracranial-intracranial bypass for ischemia cerebrovascular diease:whathave we learned from the carotid occlusion surgery study.Neurosurg Focus,2014;36:E9.】。直接颅内外血管搭桥术有助于迅速改善脑血流,但在手术过程中需临时阻断受血血管,有可能加重脑缺血;血管重建后脑血流动力学急剧变化诱发再灌注损伤、脑出血、过度灌注;迟发性吻合血管闭塞导致搭桥手术失败等风险【Jinlu Yu,Lei Shi,YunbaoGuo et al.,Progress on Complications of Direct Bypass for MoyamoyaDisease.Int J Med Sci.2016;13(8):578–587.】。直接颅内外血管搭桥手术主要用于巨大颅底肿瘤切除或复杂颅内动脉瘤孤立时,需临时牺牲颅内主要受累供血动脉,其临床应用范围极为有限。
临床和相关基础研究显示颅内外间接搭桥是一种安全的血管重建方法,将颞肌、硬膜或血管贴敷于缺血区脑组织,颅外血管以“按需生长”的方式向颅内生长,避免直接搭桥仅限于受血血管分布范围的局限性,并且不受急性脑缺血时间窗的限制,可在围缺血期的任何时间进行手术;同时也可规避直接血管搭桥所引起的缺血再灌注损伤【Starke RM,Komotar RJ,Hickman ZL,et al.Clinical features,surgical treatment,and long-term outcome in adult patients with moyamoya disease.J Neurosurg.2009;111:936-942.】。但间接颅内外血管搭桥术后血管再生程度存在明显的个体化差异,临床效果报道不一,如何实时调控缺血区脑组织中的血管再生已成为临床上亟待解决的关键问题。
血管内皮生长因子(vascular endothelial growth factor,VEGF)是促进血管生成的关键因子,可实时调节血管内皮细胞的分裂与增殖,参与多种生理病理过程,如组织损伤修复、脑外伤、脑卒中等【Carmeliet P,Jain RK.Molecular mechanisms and clinicalapplications of angiogenesis.Nature.2011;473:298-307.】;通过直接激活神经祖细胞分化和成熟、轴突生长,具有神经保护作用【Dumpich M,Mannherz HG,Theiss C.VEGFsignaling regulates cofilin and the Arp2/3-complex within the axonal growthcone.Curr Neurovasc Res.2015;12:293-307.】。有研究在颅内外间接血管重建过程中,局部移植表达VEGF-A的成肌细胞,结果发现皮层血管生成有所增加,但局部脑血流改善并不明显,可能与移植细胞粘附、迁移和VEGF-A表达有关【Hecht N,Marushima A,Nieminen M,Kremenetskaia I,von Degenfeld G,Woitzik J,et al.Myoblast-mediated genetherapy improves functional collateralization in chronic cerebralhypoperfusion.Stroke.2015;46:203-211.】。由此可见,VEGF局部释放有助于提高间接颅内外血管搭桥术后的血管再生,但如何实时有效控释VEGF,促进缺血区脑组织中血管“按需生长”,目前仍缺乏有效的方法。而且采用局部注射无法直接作用于间接血管搭桥的组织界面,对脑皮层的血管再生缺乏持续的刺激作用。
综上所述,现有文献的报导中,尚未有关于本发明中所述的生物可降解纳米纤维膜片,并以生长因子控释的方式促进缺血脑组织中的血管和(或)神经再生的相关研究报道。
发明内容
本发明的目的是针对现有技术中的不足,提供一种应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片。
本发明的再一的目的是,提供该生物可降解纳米纤维膜片的制备方法。
为实现上述目的,本发明采取的技术方案是:一种应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片,通过以下方法制得:将生物可降解聚合物材料,溶于极性、易挥发有机溶剂中,通过静电纺丝方法,制得由直径为纳米尺度的超细纤维组成的膜片;通过层层自组装技术将促进脑组织血管再生和/或促进神经再生的生长因子或多肽序列负载至膜片上,经干燥制得产品。
所述的生物可降解聚合物材料为:聚己内酯、聚乳酸、聚乳酸-羟基乙酸共聚物、丝素蛋白、胶原蛋白中的一或几种。
所述的极性、易挥发有机溶剂为:三氯甲烷、二氯甲烷、N,N-二甲基甲酰胺、甲醇、乙醇、六氟异丙醇、三氟乙酸、甲酸、乙酸或丙酮中的一种或几种溶剂的混合物。
静电纺丝方法所施加直流高压范围为:10-30KV,流量为0.1-1ml/h,时间为3-5h,喷丝头距离收集装置的距离为:20-100cm。
促进脑组织血管再生的生长因子为血管内皮生长因子。
促进脑组织神经再生的生长因子为神经生长因子。
所述的层层自组装技术为聚电解质的静电层层自组装技术。
所述的聚电解质包括带正电的聚电解质和带负电的聚电解质,所述的带正电的聚电解质为聚乙烯亚胺、聚丙烯胺盐酸盐、胶原蛋白、壳聚糖中的一种或几种;所述的带负电的聚电解质为聚苯乙烯磺酸钠、海藻酸钠、透明质酸、硫酸软骨素中的一种或几种。
层层自组装技术的实现方法为:将膜片用水洗涤后真空干燥后待用,将干燥后的膜片浸入聚烯丙胺溶液中浸泡,然后用水浸泡;再将促进脑组织血管再生和/或促进神经再生的生长因子制成生长因子溶液,把膜片置于所述的生长因子溶液中浸泡吸附,然后用水洗涤;然后依次浸入带负电的聚电解质溶液、生长因子溶液和带正电的聚电解质溶液中,循环5-10次,每次浸泡后均用水洗脱;完成后用氮气气流干燥,即得到产品。
为实现上述第二个目的,本发明采取的技术方案是:所述的制备方法包括以下步骤:将生物可降解聚合物材料,溶于极性、易挥发有机溶剂中,通过静电纺丝方法,制得由直径为纳米尺度的超细纤维组成的膜片,将膜片用水洗涤后真空干燥后待用;将干燥后的膜片浸入聚烯丙胺溶液中浸泡,然后用水浸泡;再将血管内皮生长因子和/或神经生长因子制成生长因子溶液,把膜片置于所述的生长因子溶液中浸泡吸附,然后用水洗涤;然后将膜片依次浸入带负电的聚电解质溶液、生长因子溶液和带正电的聚电解质溶液中,循环5-10次,每次浸泡后均用水洗脱;完成后用氮气气流干燥,即得到产品;
所述的生物可降解聚合物材料为:聚己内酯、聚乳酸、聚乳酸-羟基乙酸共聚物、丝素蛋白、胶原蛋白中的一或几种;
所述的极性、易挥发有机溶剂为:三氯甲烷、二氯甲烷、N,N-二甲基甲酰胺、甲醇、乙醇、六氟异丙醇、三氟乙酸、甲酸、乙酸或丙酮中的一种或几种溶剂的混合物;
静电纺丝方法所施加直流高压范围为:10-30KV,流量为0.1-1ml/h,时间为3-5h,喷丝头距离收集装置的距离为:20-100cm;
所述的带正电的聚电解质为聚乙烯亚胺、聚丙烯胺盐酸盐、胶原蛋白、壳聚糖中的一种或几种;
所述的带负电的聚电解质为聚苯乙烯磺酸钠、海藻酸钠、透明质酸、硫酸软骨素中的一种或几种。
本发明优点在于:
本发明的应用于脑神经外科间接搭桥术的生物可降解纳米纤维膜片无毒性,在体内降解后不会产生有害物质,具有良好的生物相容性。通过层层自组装技术在纳米纤维膜片上负载生长因子,可以避免有机溶剂、强酸强碱、高温等因素造成生长因子失活,组装的聚电解质可以保证膜片上负载的生长因子保持良好的活性。该纳米纤维膜片可以在脑部血管梗阻部位长期控制释放VEGF、NGF等生长因子,由此可以诱导调控脑组织血管梗阻部位的血管再生以及神经再生。
附图说明
附图1:负载生长因子的纳米纤维膜片电镜图。
附图2:生长因子释放曲线。本发明能够在30天以上控释生长因子,药物释放图充分说明了按本发明所得到的产品能保证在神经外科间接搭桥术后的药物控释功能,促进缺血脑组织中血管生成以及神经再生。
具体实施方式
下面结合实施例对本发明提供的具体实施方式作详细说明。
实施例1
采用PCL为原料,溶解于三氯甲烷/N,N-二甲基甲酰胺混合溶液中(体积比9:1),制成浓度为6%(wt)的溶液。将此混合物溶液加入到通过注射泵控制的静电纺丝注射器中,设定高压发生器的电压为15KV,收集距离为15cm,可以获得由直径为纳米尺度的超细纤维组成的膜片,然后将此膜片用去离子水多次洗涤后真空干燥后待用。将干燥后的膜片浸入聚烯丙胺(PAH,0.1-1mg/ml)溶液中,浸泡30-60分钟,然后用去离子水浸泡10分钟。再将VEGF和NGF制成0.1-10μg/ml浓度的混合生长因子溶液,把膜片置于此生长因子溶液中浸泡10-20分钟进行吸附,然后用去离子水洗涤。然后依次浸入聚苯乙烯磺酸钠(PSS,0.1-1mg/ml)溶液、生长因子溶液和聚烯丙胺(PAH,0.1-1mg/ml)溶液中,循环5-10次,每次浸泡10-20分钟,每次浸泡后均用去离子水洗脱。完成后用氮气气流干燥。即得到应用于脑神经外科间接搭桥术的生物可降解纳米纤维膜片。
实施例2
采用PLGA为原料,溶解于六氟异丙醇中,制成浓度为7%(wt)的溶液。将此混合物溶液加入到通过注射泵控制的静电纺丝注射器中,设定高压发生器的电压为14KV,收集距离为15cm,可以获得由直径为纳米尺度的超细纤维组成的膜片,然后将此膜片用去离子水多次洗涤后真空干燥后待用。将干燥后的膜片浸入聚烯丙胺(PAH,0.1-1mg/ml)溶液中,浸泡30-60分钟,然后用去离子水浸泡10分钟。再将VEGF和NGF制成0.1-10μg/ml浓度的混合生长因子溶液,把膜片置于此生长因子溶液中浸泡10-20分钟进行吸附,然后用去离子水洗涤。然后依次浸入聚苯乙烯磺酸钠(PSS,0.1-1mg/ml)溶液、生长因子溶液和壳聚糖(Chitosan,0.1-1mg/ml)溶液中,循环5-10次,每次浸泡10-20分钟,每次浸泡后均用去离子水洗脱。完成后用随后用氮气气流干燥。即得到应用于脑神经外科间接搭桥术的生物可降解纳米纤维膜片。
实施例3
采用PCL和胶原蛋白(collagen)为原料(比例为2:1),溶解于六氟异丙醇中,制成浓度为7%(wt)的溶液。将此混合物溶液加入到通过注射泵控制的静电纺丝注射器中,设定高压发生器的电压为15KV,收集距离为15cm,可以获得由直径为纳米尺度的超细纤维组成的膜片,然后将此膜片用去离子水多次洗涤后真空干燥后待用。将干燥后的膜片浸入聚烯丙胺(PAH,0.1-1mg/ml)溶液中,浸泡30-60分钟,然后用去离子水浸泡10分钟。再将VEGF和NGF制成0.1-10μg/ml浓度的混合生长因子溶液,把膜片置于此生长因子溶液中浸泡10-20分钟进行吸附,然后用去离子水洗涤。然后依次浸入海藻酸钠/PSS混合溶液(海藻酸钠,0.1-1mg/ml;PSS,0.1-1mg/ml)、生长因子溶液和胶原蛋白/聚烯丙胺混合溶液(Collagen,0.1-1mg/ml;PAH,0.1-1mg/ml)溶液中,循环5-10次,每次浸泡10-20分钟,每次浸泡后均用去离子水洗脱。完成后用随后用氮气气流干燥。即得到应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片。
采用静电纺丝技术制备生物可降解聚合物如聚已内酯、聚乳糖、聚乳酸-羟基乙酸共聚物、胶原蛋白、丝素蛋白的纳米纤维薄膜,该纳米纤维薄薄膜是一种非免疫源性纳米级材料,可完全降解吸收,具有优良的细胞粘附性和生物相容性。通过层层自组装技术,可将带有相反电荷的聚电解质逐层吸附到纳米纤维膜的纤维上,由于VEGF本身带有负电荷,可被带正电荷的聚电解质吸附,从而在组装过程中,VEGF可逐层被吸附到聚电解质层中。通过这种方法可有效调控VEGF的缓释,促进缺血区血管网络化生成,有望克服间接颅内外血管重建过程中血管再生不足的缺陷,根本改善患者预后。
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员,在不脱离本发明方法的前提下,还可以做出若干改进和补充,这些改进和补充也应视为本发明的保护范围。
Claims (10)
1.一种应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片,其特征在于,所述的应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片通过以下方法制得:将生物可降解聚合物材料,溶于极性、易挥发有机溶剂中,通过静电纺丝方法,制得由直径为纳米尺度的超细纤维组成的膜片;通过层层自组装技术将促进脑组织血管再生和/或促进神经再生的生长因子或多肽序列负载至膜片上,经干燥制得产品。
2.根据权利要求1所述的应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片,其特征在于,所述的生物可降解聚合物材料为:聚己内酯、聚乳酸、聚乳酸-羟基乙酸共聚物、丝素蛋白、胶原蛋白中的一或几种。
3.根据权利要求1所述的应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片,其特征在于,所述的极性、易挥发有机溶剂为:三氯甲烷、二氯甲烷、N,N-二甲基甲酰胺、甲醇、乙醇、六氟异丙醇、三氟乙酸、甲酸、乙酸或丙酮中的一种或几种溶剂的混合物。
4.根据权利要求1所述的应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片,其特征在于,静电纺丝方法所施加直流高压范围为:10-30KV,流量为0.1-1ml/h,时间为3-5h,喷丝头距离收集装置的距离为:20-100cm。
5.根据权利要求1所述的应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片,其特征在于,促进脑组织血管再生的生长因子为血管内皮生长因子。
6.根据权利要求1所述的应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片,其特征在于,促进脑组织神经再生的生长因子为神经生长因子。
7.根据权利要求1所述的应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片,其特征在于,所述的层层自组装技术为聚电解质的静电层层自组装技术。
8.根据权利要求7所述的应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片,其特征在于,所述的聚电解质包括带正电的聚电解质和带负电的聚电解质,所述的带正电的聚电解质为聚乙烯亚胺、聚丙烯胺盐酸盐、胶原蛋白、壳聚糖中的一种或几种;所述的带负电的聚电解质为聚苯乙烯磺酸钠、海藻酸钠、透明质酸、硫酸软骨素中的一种或几种。
9.根据权利要求7所述的应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片,其特征在于,层层自组装技术的实现方法为:将膜片用水洗涤后真空干燥后待用,将干燥后的膜片浸入聚烯丙胺溶液中浸泡,然后用水浸泡;再将促进脑组织血管再生和/或促进神经再生的生长因子制成生长因子溶液,把膜片置于所述的生长因子溶液中浸泡吸附,然后用水洗涤;然后依次浸入带负电的聚电解质溶液、生长因子溶液和带正电的聚电解质溶液中,循环5-10次,每次浸泡后均用水洗脱;完成后用氮气气流干燥,即得到产品。
10.根据权利要求1所述的应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片的制备方法,其特征在于,所述的制备方法包括以下步骤:将生物可降解聚合物材料,溶于极性、易挥发有机溶剂中,通过静电纺丝方法,制得由直径为纳米尺度的超细纤维组成的膜片,将膜片用水洗涤后真空干燥后待用;将干燥后的膜片浸入聚烯丙胺溶液中浸泡,然后用水浸泡;再将血管内皮生长因子和/或神经生长因子制成生长因子溶液,把膜片置于所述的生长因子溶液中浸泡吸附,然后用水洗涤;然后将膜片依次浸入带负电的聚电解质溶液、生长因子溶液和带正电的聚电解质溶液中,循环5-10次,每次浸泡后均用水洗脱;完成后用氮气气流干燥,即得到产品;
所述的生物可降解聚合物材料为:聚己内酯、聚乳酸、聚乳酸-羟基乙酸共聚物、丝素蛋白、胶原蛋白中的一或几种;
所述的极性、易挥发有机溶剂为:三氯甲烷、二氯甲烷、N,N-二甲基甲酰胺、甲醇、乙醇、六氟异丙醇、三氟乙酸、甲酸、乙酸或丙酮中的一种或几种溶剂的混合物;
静电纺丝方法所施加直流高压范围为:10-30KV,流量为0.1-1ml/h,时间为3-5h,喷丝头距离收集装置的距离为:20-100cm;
所述的带正电的聚电解质为聚乙烯亚胺、聚丙烯胺盐酸盐、胶原蛋白、壳聚糖中的一种或几种;
所述的带负电的聚电解质为聚苯乙烯磺酸钠、海藻酸钠、透明质酸、硫酸软骨素中的一种或几种。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201611087329.1A CN106390193B (zh) | 2016-12-01 | 2016-12-01 | 一种应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201611087329.1A CN106390193B (zh) | 2016-12-01 | 2016-12-01 | 一种应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN106390193A true CN106390193A (zh) | 2017-02-15 |
CN106390193B CN106390193B (zh) | 2019-04-23 |
Family
ID=58083114
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201611087329.1A Active CN106390193B (zh) | 2016-12-01 | 2016-12-01 | 一种应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN106390193B (zh) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106963982A (zh) * | 2017-04-24 | 2017-07-21 | 广东医科大学附属医院 | 一种具有抗菌保湿适宜组织粘附的修复材料及其制备方法和应用 |
CN107096065A (zh) * | 2017-04-05 | 2017-08-29 | 浙江大学 | 含多聚唾液酸复合纳米纤维膜及制备方法和应用 |
CN107929817A (zh) * | 2017-12-01 | 2018-04-20 | 蒋文明 | 一种可降解血管支架材料的制备方法 |
CN109602953A (zh) * | 2019-01-31 | 2019-04-12 | 上海市同济医院 | 一种新型长效缓释VEGF和bFGF可降解生物纳米膜片及其制备方法 |
CN113183594A (zh) * | 2021-04-07 | 2021-07-30 | 广东工业大学 | 用于表皮修复的静电纺丝功能性纳米纤维薄膜的制备方法 |
CN113293626A (zh) * | 2021-04-08 | 2021-08-24 | 南雄阳普医疗科技有限公司 | 一种创面敷料及其制备方法和应用 |
CN113750294A (zh) * | 2021-08-31 | 2021-12-07 | 四川大学 | 负载多种基因载体微球的神经修复支架及制备方法 |
CN113818244A (zh) * | 2021-08-03 | 2021-12-21 | 广东医科大学附属医院 | 一种分子内交联自组装膜修饰纺丝纳米纤维材料及其制备方法与应用 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR3099361A1 (fr) * | 2019-07-30 | 2021-02-05 | Les Laboratoires Osteal Medical | Membrane barrière textile |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010021971A1 (en) * | 2008-08-18 | 2010-02-25 | Massachusetts Institute Of Technology | Highly reactive multilayer assembled coating of metal oxides on organic and inorganic substrates |
CN101791431A (zh) * | 2010-02-04 | 2010-08-04 | 同济大学 | 一种生物可降解促牙周组织再生膜片的制备方法 |
CN103751847A (zh) * | 2013-11-25 | 2014-04-30 | 同济大学 | 促组织再生控释多重生长因子自组装涂层的制备方法 |
-
2016
- 2016-12-01 CN CN201611087329.1A patent/CN106390193B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010021971A1 (en) * | 2008-08-18 | 2010-02-25 | Massachusetts Institute Of Technology | Highly reactive multilayer assembled coating of metal oxides on organic and inorganic substrates |
CN101791431A (zh) * | 2010-02-04 | 2010-08-04 | 同济大学 | 一种生物可降解促牙周组织再生膜片的制备方法 |
CN103751847A (zh) * | 2013-11-25 | 2014-04-30 | 同济大学 | 促组织再生控释多重生长因子自组装涂层的制备方法 |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107096065A (zh) * | 2017-04-05 | 2017-08-29 | 浙江大学 | 含多聚唾液酸复合纳米纤维膜及制备方法和应用 |
CN106963982A (zh) * | 2017-04-24 | 2017-07-21 | 广东医科大学附属医院 | 一种具有抗菌保湿适宜组织粘附的修复材料及其制备方法和应用 |
CN107929817A (zh) * | 2017-12-01 | 2018-04-20 | 蒋文明 | 一种可降解血管支架材料的制备方法 |
CN109602953A (zh) * | 2019-01-31 | 2019-04-12 | 上海市同济医院 | 一种新型长效缓释VEGF和bFGF可降解生物纳米膜片及其制备方法 |
CN113183594A (zh) * | 2021-04-07 | 2021-07-30 | 广东工业大学 | 用于表皮修复的静电纺丝功能性纳米纤维薄膜的制备方法 |
CN113293626A (zh) * | 2021-04-08 | 2021-08-24 | 南雄阳普医疗科技有限公司 | 一种创面敷料及其制备方法和应用 |
CN113818244A (zh) * | 2021-08-03 | 2021-12-21 | 广东医科大学附属医院 | 一种分子内交联自组装膜修饰纺丝纳米纤维材料及其制备方法与应用 |
CN113818244B (zh) * | 2021-08-03 | 2023-07-18 | 广东医科大学附属医院 | 一种分子内交联自组装膜修饰纺丝纳米纤维材料及其制备方法与应用 |
CN113750294A (zh) * | 2021-08-31 | 2021-12-07 | 四川大学 | 负载多种基因载体微球的神经修复支架及制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN106390193B (zh) | 2019-04-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN106390193A (zh) | 一种应用于神经外科间接血管搭桥术的生物可降解纳米纤维膜片制备方法 | |
Nemati et al. | Current progress in application of polymeric nanofibers to tissue engineering | |
Avsar et al. | Levan based fibrous scaffolds electrospun via co-axial and single-needle techniques for tissue engineering applications | |
Yang et al. | Neural tissue engineering: The influence of scaffold surface topography and extracellular matrix microenvironment | |
Farokhi et al. | Prospects of peripheral nerve tissue engineering using nerve guide conduits based on silk fibroin protein and other biopolymers | |
Annabi et al. | 25th anniversary article: Rational design and applications of hydrogels in regenerative medicine | |
JP5638554B2 (ja) | 治療薬デリバリー用ドラッグ放出生分解性繊維 | |
He et al. | Engineering of biomimetic nanofibrous matrices for drug delivery and tissue engineering | |
Wang et al. | Bioengineered scaffolds for spinal cord repair | |
Yao et al. | Bioinspired silk fibroin materials: From silk building blocks extraction and reconstruction to advanced biomedical applications | |
Chiono et al. | Artificial scaffolds for peripheral nerve reconstruction | |
Kalani et al. | Electrospun core-sheath poly (vinyl alcohol)/silk fibroin nanofibers with Rosuvastatin release functionality for enhancing osteogenesis of human adipose-derived stem cells | |
CN105536055B (zh) | 一种形状记忆型高弹性活性纳米纤维支架及其应用 | |
Liu et al. | Nano-fibrous and ladder-like multi-channel nerve conduits: Degradation and modification by gelatin | |
RU2496526C1 (ru) | Тканеинженерный сосудистый графт малого диаметра и способ его изготовления | |
CN105582576B (zh) | 提高内皮祖细胞外泌体释放并促进骨缺损修复的生物材料、制备方法及用途 | |
AU2018248085A1 (en) | Nanofibers comprising fibroin as well as system comprising hydrogel and said nanofibers | |
CN102525697A (zh) | 载药覆膜支架及其制备方法 | |
JP2019510753A (ja) | マイクロrna遺伝子を介した新規な組織工学的な神経構築及びその神経欠陥修復における使用 | |
Yu et al. | Fabrication and characterization of electrospun thermoplastic polyurethane/fibroin small-diameter vascular grafts for vascular tissue engineering | |
CN110975008B (zh) | 一种具有电刺激和促血管生成作用的神经修复载药系统的制备方法 | |
Song et al. | Additive manufacturing of nerve guidance conduits for regeneration of injured peripheral nerves | |
Jabbari et al. | Bacterial cellulose-based composites for nerve tissue engineering | |
Zhang et al. | Electrospun nanofibers for manipulating soft tissue regeneration | |
Gelain | Novel opportunities and challenges offered by nanobiomaterials in tissue engineering |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |