CN111249533B - 去铁敏缓释微泡修饰的复合孔径静电纺丝支架及其制备方法 - Google Patents
去铁敏缓释微泡修饰的复合孔径静电纺丝支架及其制备方法 Download PDFInfo
- Publication number
- CN111249533B CN111249533B CN202010020156.1A CN202010020156A CN111249533B CN 111249533 B CN111249533 B CN 111249533B CN 202010020156 A CN202010020156 A CN 202010020156A CN 111249533 B CN111249533 B CN 111249533B
- Authority
- CN
- China
- Prior art keywords
- release
- desferrioxamine
- sustained
- electrostatic spinning
- composite
- 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.)
- Expired - Fee Related
Links
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 title claims abstract description 71
- 229960000958 deferoxamine Drugs 0.000 title claims abstract description 71
- 238000013268 sustained release Methods 0.000 title claims abstract description 67
- 239000012730 sustained-release form Substances 0.000 title claims abstract description 67
- 238000010041 electrostatic spinning Methods 0.000 title claims abstract description 66
- 239000002131 composite material Substances 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 29
- 239000011257 shell material Substances 0.000 claims abstract description 26
- 239000011148 porous material Substances 0.000 claims abstract description 23
- 229920000642 polymer Polymers 0.000 claims abstract description 20
- 239000007788 liquid Substances 0.000 claims abstract description 17
- 239000011162 core material Substances 0.000 claims abstract description 12
- 238000001523 electrospinning Methods 0.000 claims abstract description 12
- 239000011258 core-shell material Substances 0.000 claims abstract description 7
- 239000000178 monomer Substances 0.000 claims abstract description 7
- 238000006116 polymerization reaction Methods 0.000 claims abstract description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 6
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 claims abstract description 5
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000004945 emulsification Methods 0.000 claims abstract description 3
- 229910052742 iron Inorganic materials 0.000 claims abstract description 3
- 102000012422 Collagen Type I Human genes 0.000 claims description 23
- 108010022452 Collagen Type I Proteins 0.000 claims description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 14
- 239000002202 Polyethylene glycol Substances 0.000 claims description 13
- 229920001223 polyethylene glycol Polymers 0.000 claims description 13
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 11
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 11
- 239000002245 particle Substances 0.000 claims description 11
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 239000000839 emulsion Substances 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 230000009471 action Effects 0.000 claims description 6
- 238000011068 loading method Methods 0.000 claims description 6
- 239000012528 membrane Substances 0.000 claims description 5
- 238000012360 testing method Methods 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 238000009826 distribution Methods 0.000 claims description 3
- 238000004108 freeze drying Methods 0.000 claims description 3
- 230000004048 modification Effects 0.000 claims description 3
- 238000012986 modification Methods 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 239000003381 stabilizer Substances 0.000 claims description 2
- 239000012530 fluid Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 28
- 210000000988 bone and bone Anatomy 0.000 abstract description 27
- 239000011664 nicotinic acid Substances 0.000 abstract description 7
- 230000001678 irradiating effect Effects 0.000 abstract description 4
- 210000004204 blood vessel Anatomy 0.000 abstract description 2
- 230000012010 growth Effects 0.000 abstract description 2
- 230000003068 static effect Effects 0.000 abstract 1
- 230000003213 activating effect Effects 0.000 description 28
- 238000005516 engineering process Methods 0.000 description 19
- 239000000835 fiber Substances 0.000 description 19
- 239000010410 layer Substances 0.000 description 19
- 239000012792 core layer Substances 0.000 description 11
- 239000002775 capsule Substances 0.000 description 10
- 230000004913 activation Effects 0.000 description 8
- 230000007547 defect Effects 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 7
- 230000001976 improved effect Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000008439 repair process Effects 0.000 description 5
- 239000012190 activator Substances 0.000 description 4
- 230000033115 angiogenesis Effects 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 238000007306 functionalization reaction Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- TZJALUIVHRYQQB-XFDQAQKOSA-N Icariin Natural products O(C)c1ccc(C2=C(O[C@H]3[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O3)C(=O)c3c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O4)c(C/C=C(\C)/C)c3O2)cc1 TZJALUIVHRYQQB-XFDQAQKOSA-N 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- TZJALUIVHRYQQB-XLRXWWTNSA-N icariin Chemical compound C1=CC(OC)=CC=C1C1=C(O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)C(=O)C2=C(O)C=C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-XLRXWWTNSA-N 0.000 description 2
- TZJALUIVHRYQQB-UHFFFAOYSA-N icariine Natural products C1=CC(OC)=CC=C1C1=C(OC2C(C(O)C(O)C(C)O2)O)C(=O)C2=C(O)C=C(OC3C(C(O)C(O)C(CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000011164 ossification Effects 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 229920001690 polydopamine Polymers 0.000 description 2
- 239000004626 polylactic acid Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000009987 spinning Methods 0.000 description 2
- 230000008467 tissue growth Effects 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- 239000002407 tissue scaffold Substances 0.000 description 2
- 230000006444 vascular growth Effects 0.000 description 2
- 206010065687 Bone loss Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 description 1
- 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 210000001188 articular cartilage Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000010478 bone regeneration Effects 0.000 description 1
- 230000003848 cartilage regeneration Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229910001448 ferrous ion Inorganic materials 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000007641 inkjet printing Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002062 molecular scaffold Substances 0.000 description 1
- 239000002121 nanofiber Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000002071 nanotube Substances 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 238000000059 patterning Methods 0.000 description 1
- 230000003239 periodontal effect Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 230000002760 pro-activator Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KSBAEPSJVUENNK-UHFFFAOYSA-L tin(ii) 2-ethylhexanoate Chemical compound [Sn+2].CCCCC(CC)C([O-])=O.CCCCC(CC)C([O-])=O KSBAEPSJVUENNK-UHFFFAOYSA-L 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
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
- A61L27/50—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
- A61L27/14—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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01D5/00—Formation of filaments, threads, or the like
- D01D5/0007—Electro-spinning
- D01D5/0015—Electro-spinning characterised by the initial state of the material
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01D5/00—Formation of filaments, threads, or the like
- D01D5/28—Formation of filaments, threads, or the like while mixing different spinning solutions or melts during the spinning operation; Spinnerette packs therefor
- D01D5/30—Conjugate filaments; Spinnerette packs therefor
- D01D5/34—Core-skin structure; Spinnerette packs therefor
-
- 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
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
-
- 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
-
- 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
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
-
- 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
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
- A61L2300/622—Microcapsules
-
- 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
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Mechanical Engineering (AREA)
- Textile Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Materials For Medical Uses (AREA)
Abstract
本申请涉及一种去铁敏缓释微泡修饰的复合孔径静电纺丝支架及其制备方法,采用乙交酯和/或丙交酯作为单体进行聚合反应制备聚合物,以上述聚合物作为壳材料,以去铁敏为核材料,采用快速乳化法制备核壳结构的去铁敏缓释微泡;采用含有铁敏缓释微泡的芯液和壳液进行同轴静电纺丝,得到去铁敏静缓释微泡修饰静电纺丝支架;采用激光照射上述静电纺丝支架进行扩孔,得到去铁敏缓释微泡修饰的复合孔径静电纺丝支架。本申请不仅得到了10‑500微米的复合孔径的仿生支架,为新骨、血管的生长提供了良好的条件,而且实现去铁敏的释放能够在初期具有足够浓度,并且能够保持长时间的缓释效果。
Description
技术领域
本申请涉及一种用于骨修复的组织支架及其制备方法,具体涉及一种去铁敏缓释微泡修饰的复合孔径静电纺丝支架及其制备方法。
背景技术
临界骨缺损修复是一种棘手的临床难题,目前临界尺寸骨缺损治疗的金标准是自体骨移植。然而,供区骨组织数量有限,术后供区骨缺损、疼痛、感染等多种并发症严重限制了自体骨移植的推广应用。而在临界尺寸骨缺损的修复中,移植物血管化不足易导致死骨形成、肢体功能难以恢复,因此,研发具有良好血管化及功能化的移植物成为国内外研究的热点。骨组织工程技术不断发展为改善移植物血管化及功能化性能、提高临界尺寸骨缺损治疗效果提供了新策略。骨缺损修复过程中,血管生成对成骨及功能化具有重要的启动和促进作用。然而,目前的骨组织工程支架植入体内后,血管化能力不足,难以满足临床需要,研究表明,成分、结构仿生及良好的激活因子缓释性能是提高骨组织工程支架血管化和功能化的有效方法。因此,研发具有成分结构仿生、缓释促血管生成激活因子的骨组织工程支架具有非常重要的意义。
中国专利2009100401133公开了一种基于自体细胞的人工关节软骨及其制备方法,其将含有细胞因子的水溶胶溶液通过喷墨打印的方式引入静电纺丝获得的含交联剂的纤维上获得仿生支架。中国专利2018100827366公开了一种载淫羊藿苷和去铁胺的聚乳酸基骨组织支架及制备方法和应用,其在聚多巴胺层修饰的聚乳酸微米纤维支架在表面固定淫羊藿苷和去铁胺,聚多巴胺层提高了材料的亲水性能和成血管能力。但上述方案中激活因子都设置在支架表面,在前期基本全部释放导致无法发挥缓释效果。中国专利201210180611X公开了一种微纳米纤维骨修复支架及其制备方法,其在静电纺丝液中添加具有含有激活因子的核壳结构的颗粒制备了包埋核壳颗粒的支架。中国专利2017110984759公开了一种载药型静电纺丝引导组织再生膜的制备方法,其在静电纺丝液中添加天然纳米管负载激活因子制备了包埋核壳颗粒的纤维膜。上述方案将在于激活因子的物质包埋于纤维中能够显著改善激活因子的缓释功能,但负责激活因子的载体物质包埋在纤维中,对纤维的形貌、力学性能有影响,而且存在初期激活因子释放不足的情况。中国专利2017110518241公开了一种促进软骨再生的纳米纤维支架的制备方法,其采用Nell-1负载的壳聚糖纳米颗粒溶液作为芯层纺丝液,胶原/PLLA-CL混合液作为壳层纺丝液,然后通过同轴静电纺丝制备具有芯-壳层间结构。中国专利2014102896080公开了一种用于牙周组织的生物支架材料及其制备方法,其由壳层溶液和芯层荣鳄鱼通过同轴静电纺丝制成,壳层溶液和芯层溶液是将各含有一种基因质粒的载体复合物纳米微球分别溶液与可降解的有机高分子溶剂中混匀后制得。上述方案将含有激活因子的载体通过同轴静电纺丝设置在纤维芯层,其能够更好的实现激活因子的缓释效果,但由于纤维壳层的阻隔,初期激活因子释放不足的情况加剧。因此,激活因子如何在初期能够保持一定浓度而又能够实现长时间的缓释需要进一步研究。
骨的超微结构极其复杂,兼具宏观孔隙(孔径>100微米)和微观孔隙(孔径<20微米),互相连通开放的孔隙有利于骨组织生长。骨组织再生情况与支架的孔隙率和孔径密切相关。其中,新骨形成的最佳孔径为100-350微米,大于400微米的孔隙更有利于血管生成,进而促进骨组织再生。常规静电纺丝支架的孔径较小,阻碍细胞进入与组织生长。因此,只有增大材料孔径及孔隙率才能促进细胞在支架上的迁移与增殖,并有利于血管化及骨修复。目前增加静电纺丝支架孔径的方法主要由图案化接收装置、盐析法、超声法、激光致孔等多种方法。但扩孔方法通常仅实现扩孔的目的,对激活因子的释放很少有相关研究报道。
发明内容
本申请采用同轴静电纺丝法将含有激活因子去铁敏的缓释微泡设置于纤维的芯层,再通过激光致孔法实现对静电纺丝支架的扩孔,不仅得到了10-500微米的复合孔径的仿生支架,为新骨、血管的生长提供了良好的条件,而且部分纤维被激光快速加热、融化及蒸发,使得部分包封在芯层的缓释微泡被打开,部分缓释微泡能够直接暴露于支架表面,部分缓释微泡仍然被封装在纤维芯层,从而实现去铁敏的释放不仅能够在初期具有足够浓度,而且能够保持长时间的缓释效果。本申请具体技术方案如下:
一种去铁敏缓释微泡修饰的复合孔径静电纺丝支架,其通过如下步骤制备:
1)去铁敏缓释微泡的制备
采用乙交酯和/或丙交酯作为单体进行聚合反应制备聚合物,以上述聚合物作为壳材料,以去铁敏为核材料,采用快速乳化法制备核壳结构的去铁敏缓释微泡;
2)去铁敏缓释微泡修饰静电纺丝支架的制备
采用含有铁敏缓释微泡的芯液和壳液进行同轴静电纺丝,得到去铁敏缓释微泡修饰静电纺丝支架;
3)激光扩孔制备复合孔径静电纺丝支架
采用激光照射步骤2)获得的静电纺丝支架进行扩孔,得到去铁敏缓释微泡修饰的复合孔径静电纺丝支架。
优选的,在步骤1)中,在单体聚合反应中添加聚乙二醇进行嵌段改性得到聚合物,其中聚乙二醇的分子量为400-4000,聚乙二醇与单体的质量比为0.5-2:10。
优选的,在步骤1)中,以去铁敏水溶液为内水相,聚合物的乙酸乙酯溶液为油相,含稳定剂的盐水溶液为外水相,制备W/O/W型复合乳化液,反复通过孔径为1-5微米的膜,萃取乙酸乙酯后,洗涤、冷冻干燥,得到粒径均匀的去铁敏缓释微泡。
优选的,在步骤1)中,制备的聚合物亲水性测试接触角<45°,粘度<1.5,断裂伸长率<5%。
优选的,在步骤1)中,去铁敏缓释微泡粒径为0.5-8微米,粒径分布DPI<0.1,载药率>50%,载药量为3-50%。
优选的,在步骤2)中,静电纺丝的芯液由去铁敏缓释微泡、I型胶原、六氟异丙醇组成,铁敏缓释微泡质量含量为1-10%,I型胶原质量含量为5-15%。
优选的,在步骤2)中,静电纺丝的壳液由羟基磷灰石、I型胶原、六氟异丙醇组成,羟基磷灰石质量含量为5-15%,I型胶原质量含量为5-15%。
优选的,在步骤2)中,静电高压为1-50千伏,接收距离为50-300mm,电纺丝速率为0.05-0.2ml/min。
优选的,在步骤3)中,激光输出功率为2-6W,作用时间为25-45s,波长为800nm。
优选的,在步骤3)中,制备的去铁敏缓释微泡修饰的复合孔径静电纺丝支架的孔隙率为65-85%,孔径范围为10-500微米。
本申请的有益效果:
(1)本申请将缓释微泡、静电纺丝、激光扩孔三种技术有机结合,在对静电纺丝支架实现扩孔的同时,也改善了激活因子的释放特性。现有技术中的激活因子的释放要么几乎在前期完成大部分释放,而无法实现长效作用;要么能够实现较好的缓释作用,但在前期难以提供足够量的初始浓度的激活因子。而实现前期具有充足的激活因子且又能实现后期仍然具有良好的缓释作用,似乎在一种技术上具有矛盾的性质,虽然通过多种激活因子释放技术复合(例如在采用包埋技术的同时再采用表面固定技术)能够实现兼顾前期和后期激活因子的释放,但多种技术的采用本身制备步骤繁多较为复杂,而且多种技术之间并无相互关联,仅仅属于技术上的简单叠加。本申请通过将负载激活因子的缓释微泡设置在静电纺丝的芯层,再巧妙地结合激光扩孔技术,不仅实现了缓释微泡和激光扩孔两种技术本身的作用,而且还使得上述两种技术之间产生功能上的彼此支持,意外地获得了初期足够浓度激活因子,而缓释作用仍然存在。将缓释微泡设置在静电纺丝纤维的芯层主要作用是使得激活因子被微泡和纤维壳层多重包封以具备优良的缓释效果,激光扩孔的作用是将有机物融化蒸发从而实现扩孔作用,在本技术方案中,部分纤维的芯壳层会被激光烧失,从而将纤维打开使得部分缓释微泡暴露于支架表面,而部分缓释微泡由于激光作用导致壳层被打开,从而能够快速释放出激活因子,而仍有大部分缓释微泡被包封在纤维壳层中,因此,激光扩孔导致产生了不同形态的缓释微泡,而不同形态的缓释微泡即能够实现初期的激活因子的快速释放,又能够实现激活因子的长效缓释。该技术相比多种技术叠加的方案制备工艺简单,能够通过调节缓释微泡含量、激光作用功率等参数简单调控激活因子的释放过程。本申请采用缓释微泡设置在静电纺丝芯层结合激光扩孔是解决激活因子释放问题的关键,其他缓释技术或扩孔技术无法实现本申请激活因子同时满足前期和后期释放的效果。
(2)本申请采用聚乙二醇对乙交酯和/或丙交酯的聚合物进行改性,主要是改善聚合物的亲水性,从而使得缓释微泡的壳层具有良好的亲水性,其不仅增加了良好的生物相容性,还进一步改进了激活因子的释放效果,实验表明,采用聚乙二醇改性的聚合物作为缓释微泡的壳层,能够进一步延长缓释效果。
(3)本申请采用I型胶原和羟基磷灰石原作为静电纺丝的壳液,具有良好的生物相容性和良好的成骨性能,更符合仿生需求;采用缓释微泡的壳层具有良好的生物降解性能,去铁敏作为激活因子成本低廉,且其能够在生理和病理条件下通过螯合亚铁离子抑制HIF-1α降解,进而促进新血管生成和骨再生,抑制骨丢失。因此,本申请所制备的支架具有结构仿生、成本可控的效果,能够作为治疗临界骨缺损的优质材料。
具体实施方式
下面结合具体实施例对本发明作进一步说明,以使本领域的技术人员可以更好的理解本发明并能予以实施,但所举实施例不作为对本发明的限定。
实施例1
1)去铁敏缓释微泡的制备
在聚合管中加入8g丙交酯、2g乙交酯,1g聚乙二醇2000,再加入0.5g的0.3%辛酸亚锡的二氯甲烷溶液作为催化剂,将聚合管真空加热至150℃使混合物质熔融混合均匀,并保温8h。自然降温后用丙酮溶解并用水沉淀、洗涤得到作为壳层材料的聚合物。上述制备的聚合物亲水性测试接触角为30°,粘度为1.2,断裂伸长率为4.5%。
将0.5g去铁敏溶解在10mL水中作为内水相,然后5g聚合物溶于100mL乙酸乙酯中作为油相,将内水相通过充分搅拌分散于油相中得到W/O型乳液;将10gPVA和25gNaCl溶于500mL水中作为外水相,将W/O型乳液通过充分搅拌分散于外水相中得到W/O/W型乳液,在1000KPa条件下反复通过孔径为1.2微米的膜8次得到粒径均一的W/O/W型乳液,按照体积比为1:8的比例分批将乳液导入0.8%NaCl水溶液充分搅拌萃取乙酸乙酯,得打固化缓释胶囊,洗涤后经冷冻干燥得到去铁敏缓释微泡。上述制备的去铁敏缓释微泡粒径为1.18微米,粒径分布DPI<0.1,载药率为80%,载药量为38%。
2)去铁敏缓释微泡修饰静电纺丝支架的制备
静电纺丝的芯液由去铁敏缓释微泡、I型胶原、六氟异丙醇组成,去铁敏缓释微泡质量含量为5%,I型胶原质量含量为10%;静电纺丝的壳液由羟基磷灰石、I型胶原、六氟异丙醇组成,羟基磷灰石质量含量为10%,I型胶原质量含量为10%;采用同轴静电纺丝法制备,其中,静电高压为15千伏,接收距离为100mm,电纺丝速率为0.1ml/min,制备得到去铁敏静缓释微泡修饰静电纺丝支架。
3)激光扩孔制备复合孔径静电纺丝支架
采用激光照射上述获得的静电纺丝支架进行扩孔,其中,激光输出功率为4W,作用时间为35s,波长为800nm,得到去铁敏缓释微泡修饰的复合孔径静电纺丝支架。该支架的孔隙率为72%,孔径范围为10-500微米。
实施例2
1)去铁敏缓释微泡的制备:该步骤与实施例1相同。
2)去铁敏缓释微泡修饰静电纺丝支架的制备
静电纺丝的芯液由去铁敏缓释微泡、I型胶原、六氟异丙醇组成,去铁敏缓释微泡质量含量为10%,I型胶原质量含量为5%;静电纺丝的壳液由羟基磷灰石、I型胶原、六氟异丙醇组成,羟基磷灰石质量含量为15%,I型胶原质量含量为15%;采用同轴静电纺丝法制备,其中,静电高压为50千伏,接收距离为200mm,电纺丝速率为0.05ml/min,制备得到去铁敏静缓释微泡修饰静电纺丝支架。
3)激光扩孔制备复合孔径静电纺丝支架
采用激光照射上述获得的静电纺丝支架进行扩孔,其中,激光输出功率为2W,作用时间为45s,波长为800nm,得到去铁敏缓释微泡修饰的复合孔径静电纺丝支架。
实施例3
1)去铁敏缓释微泡的制备:该步骤与实施例1相同。
2)去铁敏缓释微泡修饰静电纺丝支架的制备
静电纺丝的芯液由去铁敏缓释微泡、I型胶原、六氟异丙醇组成,去铁敏缓释微泡质量含量为1%,I型胶原质量含量为15%;静电纺丝的壳液由羟基磷灰石、I型胶原、六氟异丙醇组成,羟基磷灰石质量含量为5%,I型胶原质量含量为5%;采用同轴静电纺丝法制备,其中,静电高压为1千伏,接收距离为50mm,电纺丝速率为0.2ml/min,制备得到去铁敏静缓释微泡修饰静电纺丝支架。
3)激光扩孔制备复合孔径静电纺丝支架
采用激光照射上述获得的静电纺丝支架进行扩孔,其中,激光输出功率为6W,作用时间为25s,波长为800nm,得到去铁敏缓释微泡修饰的复合孔径静电纺丝支架。
实施例4
与实施例1相同,但在步骤1)中未加入聚乙二醇。
对比例1
与实施例1相同,但不采用步骤3)。
对比例2
与实施例1相同,但芯层不添加缓释微泡,而在壳层添加在缓释微泡。
对比例3
与实施例1相同,但静电纺丝的芯液组成为去铁敏、I型胶原、六氟异丙醇组成,去铁敏缓释微泡质量含量为0.5%,I型胶原质量含量为10%。
采用第5天检测的去铁敏累计释放量表示激活因子的初期浓度,采用去铁敏累计释放量80%所需天数表示激活因子的缓释能力。各样品测试结果如表1所示。
表1
通过实施例1-3可以看出,本申请的去铁敏缓释微泡修饰的复合孔径静电纺丝支架在初期去铁敏的释放量具有足够的浓度,基本能达到10%左右,而持续缓释能力也非常显著,基本能够到60天左右。其说明本申请的支架在对静电纺丝支架实现扩孔的同时,也改善了激活因子的释放特性,实现了去铁敏的释放不仅能够在初期具有足够浓度,而且能够保持长时间的缓释效果。通过对比实施例1和对比例1可以发现,由于没有采用激光扩孔技术,其前期激活因子释放量较低,而且由于没有进行扩孔,其孔径将难以适合血管生长。而本申请通过激光进行扩孔不仅能够具有适宜血管生成的孔径,而且由于激光的烧失作用使得包封的部分缓释胶囊被打开或出现于支架表面,其促进了前期激活因子的释放量。其说明本申请的激光扩孔作用不仅起到了扩孔作用,还与设置在纤维芯层的缓释胶囊技术实现有机结合,调整了激活因子的释放特性。通过对比实施例1和对比例2可以发现,将缓释胶囊设置在纤维壳层相对于设置在纤维芯层能够获得更高的激活因子释放量,这与更多的缓释胶囊在支架表面有关,但该设置对于缓释作用的效果有明显影响,而且前期释放的激活因子过多也可能造成激活效率下降。其说明将缓释胶囊设置在纤维芯层能够起到更好的效果。通过对比实施例1和对比例3可以发现,设置缓释胶囊能够相对于未设置缓释胶囊能够进一步阻碍激活因子的释放,在结合激光扩孔的技术上,如果不采用缓释胶囊技术,其缓释效果将大大降低。通过对比实施例1与对比例1-3可以看出,本申请将缓释微泡、静电纺丝、激光扩孔三种技术有机结合是获得优异效果的关键。通过对比实施例1和实施例4可以发现,如果缓释胶囊的壳层材料采用聚乙二醇进行亲水性修饰,其能够降低初期激活因子的释放量,但同时增加了缓释能力,其说明聚乙二醇的亲水性改性阻碍了去铁敏的释放或聚乙二醇的引入减缓了聚合物的降解从而减缓了去铁敏的释放。
本申请将缓释微泡、静电纺丝、激光扩孔三种技术巧妙结合,通过将缓释胶囊设置在静电纺丝纤维的芯层结合激光扩孔,获得了适合新骨、血管生长的孔径与缓释效果的同时,还意外获得了足够的前期激活因子释放浓度,实现了良好的激活因子释放效果。本申请制备方法简单,全部采用仿生、可降解材料,具有良好的生物相容性,为治疗临界骨缺损提供了可供选择的解决方案。
以上所述实施例仅是为充分说明本发明而所举的较佳的实施例,本发明的保护范围不限于此。本技术领域的技术人员在本发明基础上所作的等同替代或变换,均在本发明的保护范围之内。本发明的保护范围以权利要求书为准。
Claims (8)
1.一种去铁敏缓释微泡修饰的复合孔径静电纺丝支架,其特征在于,通过如下步骤制备:
1)去铁敏缓释微泡的制备
采用乙交酯和/或丙交酯作为单体进行聚合反应制备聚合物,以上述聚合物作为壳材料,以去铁敏为核材料,采用快速乳化法制备核壳结构的去铁敏缓释微泡;
2)去铁敏缓释微泡修饰静电纺丝支架的制备
采用含有铁敏缓释微泡的芯液和壳液进行同轴静电纺丝,得到去铁敏缓释微泡修饰静电纺丝支架;
3)激光扩孔制备复合孔径静电纺丝支架
采用激光照射步骤2)获得的静电纺丝支架进行扩孔,得到去铁敏缓释微泡修饰的复合孔径静电纺丝支架;
在步骤1)中,在单体聚合反应中添加聚乙二醇进行嵌段改性得到聚合物,其中聚乙二醇的分子量为400-4000,聚乙二醇与单体的质量比为0.5-2:10;
在步骤1)中,以去铁敏水溶液为内水相,聚合物的乙酸乙酯溶液为油相,含稳定剂的盐水溶液为外水相,制备W/O/W型复合乳化液,反复通过孔径为1-5微米的膜,萃取乙酸乙酯后,洗涤、冷冻干燥,得到粒径均匀的去铁敏缓释微泡。
2.根据权利要求1所述的复合孔径静电纺丝支架,其特征在于,在步骤1)中,制备的聚合物亲水性测试接触角<45°,粘度<1.5,断裂伸长率<5%。
3.根据权利要求1所述的复合孔径静电纺丝支架,其特征在于,在步骤1)中,去铁敏缓释微泡粒径为0.5-8微米,粒径分布DPI<0.1,载药率>50%,载药量为3-50%。
4.根据权利要求1所述的复合孔径静电纺丝支架,其特征在于,在步骤2)中,静电纺丝的芯液由去铁敏缓释微泡、I型胶原、六氟异丙醇组成,铁敏缓释微泡质量含量为1-10%,I型胶原质量含量为5-15%。
5.根据权利要求1所述的复合孔径静电纺丝支架,其特征在于,在步骤2)中,静电纺丝的壳液由羟基磷灰石、I型胶原、六氟异丙醇组成,羟基磷灰石质量含量为5-15%,I型胶原质量含量为5-15%。
6.根据权利要求1所述的复合孔径静电纺丝支架,其特征在于,在步骤2)中,静电高压为1-50千伏,接收距离为50-300mm,电纺丝速率为0.05-0.2ml/min。
7.根据权利要求1所述的复合孔径静电纺丝支架,在步骤3)中,激光输出功率为2-6W,作用时间为25-45s,波长为800nm。
8.根据权利要求1所述的复合孔径静电纺丝支架,在步骤3)中,制备的去铁敏缓释微泡修饰的复合孔径静电纺丝支架的孔隙率为65-85%,孔径范围为10-500微米。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010020156.1A CN111249533B (zh) | 2020-01-09 | 2020-01-09 | 去铁敏缓释微泡修饰的复合孔径静电纺丝支架及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010020156.1A CN111249533B (zh) | 2020-01-09 | 2020-01-09 | 去铁敏缓释微泡修饰的复合孔径静电纺丝支架及其制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN111249533A CN111249533A (zh) | 2020-06-09 |
CN111249533B true CN111249533B (zh) | 2021-01-08 |
Family
ID=70946741
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010020156.1A Expired - Fee Related CN111249533B (zh) | 2020-01-09 | 2020-01-09 | 去铁敏缓释微泡修饰的复合孔径静电纺丝支架及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111249533B (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111973795B (zh) * | 2020-07-10 | 2022-08-02 | 中国人民解放军总医院 | 一种肝癌切除术后止血及防癌复发敷料 |
CN115957374B (zh) * | 2022-12-16 | 2024-06-25 | 吉林大学 | 一种具备核壳结构的金属人工骨植入物及其制备方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103154339A (zh) * | 2010-08-06 | 2013-06-12 | 科学技术设备委员会 | 电纺纤维的方法 |
CN105624830A (zh) * | 2016-01-06 | 2016-06-01 | 东华大学 | 一种抗紫外pan/go同轴纳米纤维及其制备方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1807707B (zh) * | 2006-01-13 | 2010-04-14 | 清华大学 | 一种微纳米尺度下核壳结构复合纤维的制备方法及其应用 |
GB0711007D0 (en) * | 2007-06-07 | 2007-07-18 | Isis Innovation | Polymeric microparticles |
PT2214646T (pt) * | 2007-10-05 | 2021-09-29 | Univ Wayne State | Dendrímeros para libertação sustentada de compostos |
CN102188756A (zh) * | 2011-05-12 | 2011-09-21 | 天津市海河医院 | 一种含药缓释降解骨支架的制备方法 |
CN102228695A (zh) * | 2011-07-04 | 2011-11-02 | 广州舒泰生物技术有限公司 | 一种碱性成纤维细胞生长因子缓释载体的制备方法 |
-
2020
- 2020-01-09 CN CN202010020156.1A patent/CN111249533B/zh not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103154339A (zh) * | 2010-08-06 | 2013-06-12 | 科学技术设备委员会 | 电纺纤维的方法 |
CN105624830A (zh) * | 2016-01-06 | 2016-06-01 | 东华大学 | 一种抗紫外pan/go同轴纳米纤维及其制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN111249533A (zh) | 2020-06-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5638554B2 (ja) | 治療薬デリバリー用ドラッグ放出生分解性繊維 | |
Rahmati et al. | Electrospinning for tissue engineering applications | |
JP6774528B2 (ja) | 材料に基づく細胞治療のための注射可能孔形成性ハイドロゲル | |
Piao et al. | Biomedical applications of gelatin methacryloyl hydrogels | |
Yao et al. | Bioinspired silk fibroin materials: From silk building blocks extraction and reconstruction to advanced biomedical applications | |
CN111184909B (zh) | 一种透明质酸缓释填充物及制备方法 | |
CN105536055B (zh) | 一种形状记忆型高弹性活性纳米纤维支架及其应用 | |
CN111249533B (zh) | 去铁敏缓释微泡修饰的复合孔径静电纺丝支架及其制备方法 | |
Qian et al. | The state-of-the-art application of functional bacterial cellulose-based materials in biomedical fields | |
WO2001010421A1 (en) | Drug releasing biodegradable fiber implant | |
CN107865979A (zh) | 一种基于微流控技术和静电纺丝技术的三维纳米纤维支架及其制备方法 | |
Saremi et al. | Tissue‐engineered nerve graft using silk‐fibroin/polycaprolactone fibrous mats decorated with bioactive cerium oxide nanoparticles | |
US7056332B2 (en) | Nucleic acid biomaterials and methods of formation and use | |
Ghasemkhah et al. | Potential core–shell designed scaffolds with a gelatin‐based shell in achieving controllable release rates of proteins for tissue engineering approaches | |
US7931918B2 (en) | Collagen-based microspheres and methods of preparation and uses thereof | |
Rahimzadegan et al. | Influence of reducing agents on in situ synthesis of gold nanoparticles and scaffold conductivity with emphasis on neural differentiation | |
Keaswejjareansuk et al. | Degradable alginate hydrogel microfiber for cell-encapsulation based on alginate lyase loaded nanoparticles | |
CN115487358B (zh) | 一种用于软骨组织修复的凝胶复合支架及制备方法 | |
CN108939133B (zh) | 一种抗菌促愈合的蚕丝蛋白护创材料及其制备方法 | |
CN114522256B (zh) | 一种聚羟基脂肪酸酯载药放疗微球及其制备方法和应用 | |
WO2009006792A1 (en) | Collagen-based microspheres and methods of preparation and use thereof | |
Norouzi et al. | Adipose-derived stem cells growth and proliferation enhancement using poly (lactic-co-glycolic acid)(PLGA)/fibrin nanofiber mats | |
Xu et al. | Electrospun three-dimensional nanofibrous scaffolds based on polycaprolactone for stem cells differentiation and bone regeneration | |
WO2004075939A1 (ja) | 生分解性樹脂及びリン酸カルシウムを含む再生医療用材料及びその製造方法 | |
EP1265952A1 (en) | Microporous polymer matrices |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20210108 |