骨修复用电纺纤维支架的制备与性能研究
|
摘要
随着组织工程和再生医学的发展,组织工程材料为临床上骨缺损或衰竭的修复和治疗提供了希望。近年来,对骨组织工程支架的研究受到了广泛关注。针对骨组织的特点,将生物活性陶瓷材料引入聚合物基体形成复合结构,能有效地模拟骨的化学成分,以提高其生物活性;同时,结构高度仿生化的纳米纤维支架有望对骨细胞的生长产生刺激,从而诱导骨的形成。所以,设计和制备聚合物/生物活性陶瓷纳米复合纤维,有望为骨组织工程提供必需的支架材料。
在本课题组以前的工作基础上,本文制备并研究了聚(乳酸-羟基乙酸)/羟基磷灰石(PLGA/HA)复合纤维支架的生物相容性。将自制的颗粒状纳米羟基磷灰石(HAp)与市售的针状羟基磷灰石(aHA)分别与PLGA溶液混合,通过静电纺丝技术制备了多孔网状且孔间连通的PLGA/HAp和PLGA/aHA复合纳米纤维膜支架。HAp和aHA能均匀地分散在PLGA中,且HAp的复合更有效地提高了PLGA纤维在模拟体液中的生物矿化性能。将新生小鼠颅骨源性的成骨样细胞系(MC3T3-E1细胞)培养在纤维支架上,支架能有效地维持细胞的活性并促进其增殖,但细胞在PLGA/HAp纤维膜上的形态更为铺展,分泌了更多的碱性磷酸酶(ALP),表明该类PLGA/HAp复合纤维膜具有更强的成骨活性。
通过模拟天然骨中胶原和羟基磷灰石的矿化自组装过程,制备了PLGA/胶原/HA复合纤维膜支架。利用等离子体处理提高了PLGA纤维的亲水性,使得胶原有效地涂层修饰在表面。修饰后的PLGA/胶原纤维能在模拟体液中生物矿化,矿物颗粒先在纤维表面成核再逐渐长大至绒球状的晶体,随着时间的延长甚至覆盖了纤维膜表面。通过X-射线能谱(EDS)、红外光谱(FTIR)对其化学成分的分析及X-射线衍射能谱(XRD)和透射电镜(TEM)的晶型判断,证实了矿物颗粒是由HA晶体构成的聚集体。矿化制备的复合纤维膜的力学性能得到了改善。MC3T3-E1成骨细胞的体外培养表明,胶原改性纤维膜和沉积HA的复合纤维膜均能维持细胞的活性,且有利于细胞的铺展生长;尤其是矿化复合纤维膜上的细胞在培养14d后表达了更高的ALP活性,说明其具有较强的维持成骨细胞表型的能力。这种高度仿生化的复合纤维有望成为骨组织工程和再生医学中理想的活性支架。
针对纤维支架因纤维致密堆积而孔径偏小的问题,用不同方法探索了制备双孔型纤维膜的可行性。发现将PLGA纤维与氯化钠(NaCl)颗粒在电纺过程中共混掺杂再将NaCl沥滤的方法,可以制备具有大孔结构的纳米纤维膜。再进一步通过胶原改性和矿化技术,可获得双孔型PLGA/胶原/HA复合纤维膜,且HA在纤维表面及大孔内均有沉积。我们认为,该类双孔型复合纤维有望在保持细胞活性的同时解决细胞渗透的难题,具有在骨组织工程中最终实质性应用的潜力。
With the development of tissue engineering and regenerative medicine, biomaterial scaffolds play more and more important role in the clinical repair and therapy of bone loss or damage.Recently,the study of bone tissue engineering scaffolds has been attracted much attention.In particular,incorporation of bioactive ceramics into polymer matrix is assumed to mimic the composition of natural bone extracellular matrix(ECM),thus can enhance cell growth and response.Meanwhile, highly porous biomimetic nanofibrous structure may bring additional stimulus to the cultured cells and finally induce bone formation.Therefore,the design and preparation of nanofibrous polymer/bioactive ceramics composite scaffold is one of the supreme methods for obtaining ideal bone tissue engineering scaffolds.
Based on the previous research work in our laboratory, poly(lactide-co-glycolide)/nano-hydroxyapatite(PLGA/HA) composite scaffold was firstly studied.The composites were prepared by electrospinning of PLGA solution having both synthesized hydroxyapatite particles(HAp) or commercially acicular hydroapatite(aHA).The electrospun composite scaffold showed a randomly interconnected and highly porous structure composed of continuous bead-free nonwoven nanofibers.Both HAp and aHA concentration of 5wt%could disperse well in the PLGA fiber matrix.In vitro mineralization in a 5×simulated body fluid(SBF) revealed that the PLGA/HAp nanofibrous scaffold had a stronger biomineralization ability than the PLGA/aHA and control PLGA scaffolds.In vitro culture of neonatal mouse calvaria-derived MC3T3-E1 osteoblasts reveals that all the samples could support cell proliferation and showed increase of viability,but the cells cultured on the PLGA/HAp nanofibers showed more spreading morphology.Despite the similar level of the cell viability and cell number at each time interval,the alkaline phosphatase(ALP) secretion was significantly enhanced on the PLGA/HAp scaffolds, indicating the higher bioactivity of the as-prepared nano-HAp and the success of the present method for preparing biomimetic scaffold for bone tissue engineering.
By simulating the self-assembly process of collagen nanofibers and hydroxyapatite particles in the formation of natural bone,PLGA/collagen/HA ternary nanofibrous composite scaffolds were further fabricated.Using plasma treatment to initially improve the hydrophilicity of PLGA electrospun fibers, collagen molecules could be easily coated on the surface.The modified fibers were successively immersed into 5×SBF to induce mineral deposition.The mineral particles were firstly nucleated on the surface of single fibers and gradually grown up to velvetball-like microparticles,even covering the whole surface of the nanofibrous scaffolds.Both chemical analysis by energy-dispersive X-ray spectrum(EDS) and fourier transform infrared spectroscopy(FTIR),and crystal determination by X-ray diffractometer(XRD) and transmission electron microscopy(TEM) showed that the minerals were aggregation composited of tiny HA nanoparticles.The mechanical properties of the nanofibers were enhanced after collagen coating and HA deposition. All the control PLGA,PLGA/collagen and PLGA/collagen/HA nanofibrous scaffolds could maintain the viability of MC3T3-E1 osteoblasts.However,the latter two showed better ability to induce cell spreading.Particularly,cells on the PLGA/collagen/HA composite scaffolds secreted more ALP after 14d culture, indicating the higher bioactivity for the growth and phenotype expression of the cultured osteoblasts.The high biomimetic PLGA/collagen/HA nanofibrous composite scaffold are expected to be an ideal bioactive candidate for bone regeneration.
To overcome the problem of small pore size of the dense nanofibrous scaffolds, different methods were tried to explore the feasibility of preparing dual-porous nanofibers.Studies found that compounding sodium chloride(NaCl) particles with PLGA fibers during the electrospinning process could be a useful way.After particle leaching,nanofibrous scaffolds with certain larger pores were prepared.Still,by collagen modification and HA deposition,dual-porous PLGA/collagen/HA composite scaffolds were finally obtained.HA could be mineralized on both the surface of the fibers and inside the large holes.It is expected that such nanofibrous composite scaffolds with dual-porosity could not only enhance the cell growth but also improve the cell infiltration into the scaffolds,thus have the potential to be ultimate applied as ideal scaffolds for bone tissue engineering and regenerative medicine.
在本课题组以前的工作基础上,本文制备并研究了聚(乳酸-羟基乙酸)/羟基磷灰石(PLGA/HA)复合纤维支架的生物相容性。将自制的颗粒状纳米羟基磷灰石(HAp)与市售的针状羟基磷灰石(aHA)分别与PLGA溶液混合,通过静电纺丝技术制备了多孔网状且孔间连通的PLGA/HAp和PLGA/aHA复合纳米纤维膜支架。HAp和aHA能均匀地分散在PLGA中,且HAp的复合更有效地提高了PLGA纤维在模拟体液中的生物矿化性能。将新生小鼠颅骨源性的成骨样细胞系(MC3T3-E1细胞)培养在纤维支架上,支架能有效地维持细胞的活性并促进其增殖,但细胞在PLGA/HAp纤维膜上的形态更为铺展,分泌了更多的碱性磷酸酶(ALP),表明该类PLGA/HAp复合纤维膜具有更强的成骨活性。
通过模拟天然骨中胶原和羟基磷灰石的矿化自组装过程,制备了PLGA/胶原/HA复合纤维膜支架。利用等离子体处理提高了PLGA纤维的亲水性,使得胶原有效地涂层修饰在表面。修饰后的PLGA/胶原纤维能在模拟体液中生物矿化,矿物颗粒先在纤维表面成核再逐渐长大至绒球状的晶体,随着时间的延长甚至覆盖了纤维膜表面。通过X-射线能谱(EDS)、红外光谱(FTIR)对其化学成分的分析及X-射线衍射能谱(XRD)和透射电镜(TEM)的晶型判断,证实了矿物颗粒是由HA晶体构成的聚集体。矿化制备的复合纤维膜的力学性能得到了改善。MC3T3-E1成骨细胞的体外培养表明,胶原改性纤维膜和沉积HA的复合纤维膜均能维持细胞的活性,且有利于细胞的铺展生长;尤其是矿化复合纤维膜上的细胞在培养14d后表达了更高的ALP活性,说明其具有较强的维持成骨细胞表型的能力。这种高度仿生化的复合纤维有望成为骨组织工程和再生医学中理想的活性支架。
针对纤维支架因纤维致密堆积而孔径偏小的问题,用不同方法探索了制备双孔型纤维膜的可行性。发现将PLGA纤维与氯化钠(NaCl)颗粒在电纺过程中共混掺杂再将NaCl沥滤的方法,可以制备具有大孔结构的纳米纤维膜。再进一步通过胶原改性和矿化技术,可获得双孔型PLGA/胶原/HA复合纤维膜,且HA在纤维表面及大孔内均有沉积。我们认为,该类双孔型复合纤维有望在保持细胞活性的同时解决细胞渗透的难题,具有在骨组织工程中最终实质性应用的潜力。
With the development of tissue engineering and regenerative medicine, biomaterial scaffolds play more and more important role in the clinical repair and therapy of bone loss or damage.Recently,the study of bone tissue engineering scaffolds has been attracted much attention.In particular,incorporation of bioactive ceramics into polymer matrix is assumed to mimic the composition of natural bone extracellular matrix(ECM),thus can enhance cell growth and response.Meanwhile, highly porous biomimetic nanofibrous structure may bring additional stimulus to the cultured cells and finally induce bone formation.Therefore,the design and preparation of nanofibrous polymer/bioactive ceramics composite scaffold is one of the supreme methods for obtaining ideal bone tissue engineering scaffolds.
Based on the previous research work in our laboratory, poly(lactide-co-glycolide)/nano-hydroxyapatite(PLGA/HA) composite scaffold was firstly studied.The composites were prepared by electrospinning of PLGA solution having both synthesized hydroxyapatite particles(HAp) or commercially acicular hydroapatite(aHA).The electrospun composite scaffold showed a randomly interconnected and highly porous structure composed of continuous bead-free nonwoven nanofibers.Both HAp and aHA concentration of 5wt%could disperse well in the PLGA fiber matrix.In vitro mineralization in a 5×simulated body fluid(SBF) revealed that the PLGA/HAp nanofibrous scaffold had a stronger biomineralization ability than the PLGA/aHA and control PLGA scaffolds.In vitro culture of neonatal mouse calvaria-derived MC3T3-E1 osteoblasts reveals that all the samples could support cell proliferation and showed increase of viability,but the cells cultured on the PLGA/HAp nanofibers showed more spreading morphology.Despite the similar level of the cell viability and cell number at each time interval,the alkaline phosphatase(ALP) secretion was significantly enhanced on the PLGA/HAp scaffolds, indicating the higher bioactivity of the as-prepared nano-HAp and the success of the present method for preparing biomimetic scaffold for bone tissue engineering.
By simulating the self-assembly process of collagen nanofibers and hydroxyapatite particles in the formation of natural bone,PLGA/collagen/HA ternary nanofibrous composite scaffolds were further fabricated.Using plasma treatment to initially improve the hydrophilicity of PLGA electrospun fibers, collagen molecules could be easily coated on the surface.The modified fibers were successively immersed into 5×SBF to induce mineral deposition.The mineral particles were firstly nucleated on the surface of single fibers and gradually grown up to velvetball-like microparticles,even covering the whole surface of the nanofibrous scaffolds.Both chemical analysis by energy-dispersive X-ray spectrum(EDS) and fourier transform infrared spectroscopy(FTIR),and crystal determination by X-ray diffractometer(XRD) and transmission electron microscopy(TEM) showed that the minerals were aggregation composited of tiny HA nanoparticles.The mechanical properties of the nanofibers were enhanced after collagen coating and HA deposition. All the control PLGA,PLGA/collagen and PLGA/collagen/HA nanofibrous scaffolds could maintain the viability of MC3T3-E1 osteoblasts.However,the latter two showed better ability to induce cell spreading.Particularly,cells on the PLGA/collagen/HA composite scaffolds secreted more ALP after 14d culture, indicating the higher bioactivity for the growth and phenotype expression of the cultured osteoblasts.The high biomimetic PLGA/collagen/HA nanofibrous composite scaffold are expected to be an ideal bioactive candidate for bone regeneration.
To overcome the problem of small pore size of the dense nanofibrous scaffolds, different methods were tried to explore the feasibility of preparing dual-porous nanofibers.Studies found that compounding sodium chloride(NaCl) particles with PLGA fibers during the electrospinning process could be a useful way.After particle leaching,nanofibrous scaffolds with certain larger pores were prepared.Still,by collagen modification and HA deposition,dual-porous PLGA/collagen/HA composite scaffolds were finally obtained.HA could be mineralized on both the surface of the fibers and inside the large holes.It is expected that such nanofibrous composite scaffolds with dual-porosity could not only enhance the cell growth but also improve the cell infiltration into the scaffolds,thus have the potential to be ultimate applied as ideal scaffolds for bone tissue engineering and regenerative medicine.
引文
1.Langer R,Vacanti JP.Tissue Engineering.Science 1993;260(5110):920-926.
2.Yannas Ⅳ,Burke JF,Orgill DP,Skrabut EM.Wound Tissue Can Utilize a Polymeric Template to Synthesize a Functional Extension of Skin.Science 1982;215(4529):174-176.
3.Yannas Ⅳ,Lee E,Orgill DP,Skrabut EM,Murphy GF.Synthesis and Characterization of a Model Extracellular-Matrix That Induces Partial Regeneration of Adult Mammalian Skin.Proceedings of the National Academy of Sciences of the United States of America 1989;86(3):933-937.
4.Wolter JR,Meyer RE Sessile macrophages forming clear endothelium-like membrane on inside of successful keratoprosthesis.Trans Am Ophthalmol Soc 1984;82:187-202.
5.龚逸鸿.聚乳酸多孔支架的制备、改性及组织工程化软骨的构建.浙江大学博士学位论文2006.
6.商庆新,曹谊林,张涤生.生物工程领域的崭新前沿-组织工程.引进国外医药技术与设备1999;5(11):11-15.
7.Bonassar LJ,Vacanti CA.Tissue engineering:the first decade and beyond.J Cell Biochem Suppl 1998;30-31:297-303.
8.Saltzman WM,Parkhurst MR,Parsons-Wingerter P,Zhu WH.Three-dimensional cell cultures mimic tissues.Ann N Y Acad Sci 1992;665:259-273.
9.Vacanti JP,Langer R,Upton J,Marler JJ.Transplantation of cells in matrices for tissue regeneration.Adv Drug Deliv Rev 1998;33(1-2):165-182.
10.劳为德.修复医学与组织工程.北京.化学工业出版社.2003;35-37.
11.杨志明.组织工程.北京.化学工业出版社.2001:123-124,166-167.
12.Heath CA.Cells for tissue engineering.Trends Biotechnol 2000;18(1):17-19.
13.Vandenburgh H,Del Tatto M,Shansky J,Lemaire J,Chang A,Payumo F,et al.Tissue-engineered skeletal muscle organoids for reversible gene therapy.Hum Gene Ther 1996;7(17):2195-2200.
14.Fontaine M,Hansen LK,Thompson S,Uyama S,Ingber DE,Langer R,et al. Transplantation of genetically altered hepatocytes using cell-polymer constructs.Transplant Proc 1993;25(1 Pt 2):1002-1004.
15.邓明安,周燕,华平,谭文松.人皮肤成纤维细胞在不同培养系统中的生长代谢特性.生物工程学报2001;7(3):336-338.
16.Kim BS,Mooney DJ.Development of biocompatible synthetic extracellular matrices for tissue engineering.Trends Biotechnol 1998;16(5):224-230.
17.Gilbert JC,Takada T,Stein JE,Langer R,Vacanti JP.Cell transplantation of genetically altered cells on biodegradable polymer scaffolds in syngeneic rats.Transplantation 1993;56(2):423-427.
18.姚康德,尹玉姬.组织工程相关生物材料.北京.化学工业出版社.2003:16-17.
19.Saltzman WM.Weaving cartilage at zero g:the reality of tissue engineering in space.Proc Natl Acad Sci U S A 1997;94(25):13380-13382.
20.胡江,陶祖莱.组织工程研究进展.生物医学工程学杂志2000;17(1):75-79.
21.Hutmacher DW.Scaffolds in tissue engineering bone and cartilage.Biomaterials 2000;21(24):2529-2543.
22.Hynes RO.Integrins:versatility,modulation,and signaling in cell adhesion.Cell 1992;69(1):11-25.
23.Cook AD,Hrkach JS,Gao NN,Johnson IM,Pajvani UB,Cannizzaro SM,et al.Characterization and development of RGD-peptide-modified poly(lactic acid-co-lysine) as an interactive,resorbable biomaterial.J Biomed Mater Res 1997;35(4):513-523.
24.Pollok JM,Kluth D,Cusick RA,Lee H,Utsunomiya H,Ma PX,et al.Formation of spheroidal aggregates of hepatocytes on biodegradable polymers under continuous-flow bioreactor conditions.Eur J Pediatr Surg 1998;8(4):195-199.
25.Lee CH,Singla A,Lee Y.Biomedical applications of collagen.Int J Pharm 2001;221(1-2):1-22.
26.Furthmayr H,Timpl R.Immunochemistry of collagens and procollagens.Int Rev Connect Tissue Res 1976;7:61-99.
27.Maeda M,Tani S,Sano A,Fujioka K.Microstructure and release characteristics of the minipellet,a collagen-based drug delivery system for controlled release of protein drugs.J Control Release 1999;62(3):313-324.
28.Kuzuya M,Kinsella JL.Induction of endothelial cell differentiation in vitro by fibroblast-derived soluble factors.Exp Cell Res 1994;215(2):310-318.
29.Sams AE,Minor RR,Wootton JA,Mohammed H,Nixon AJ.Local and remote matrix responses to chondrocyte-laden collagen scaffold implantation in extensive articular cartilage defects.Osteoarthritis Cartilage 1995;3(1):61-70.
30.Liao SS,Cui FZ,Zhu Y.Osteoblasts adherence and migration through three-dimensional porous mineralized collagen based composite:nHAC/PLA.J Bioact Comp Poly 2004;19:117-130.
31.吴慧玲,谷志远.透明质酸对关节软骨的影响及作用机制.国外医学口腔医学分册1999;26(1):30-33.
32.Godbey WT,Atala A.In vitro systems for tissue engineering.Ann N Y Acad Sci 2002;961:10-26.
33.周庆亮.聚乳酸软骨组织工程支架的制备、降解及细胞相容性研究.浙江大学硕士学位论文 2005.
34.Chu CR,Monosov AZ,Amiel D.In situ assessment of cell viability within biodegradable polylactic acid polymer matrices.Biomaterials 1995;16(18):1381-I384.
35.蔡晴,石桂欣,贝建中,王身国.聚(丙交酯-乙交酯)共聚物细胞支架降解行为的研究.第三届全国组织工程学术会议论文集 433-436.
36.俞耀庭,张兴栋.生物医用材料.天津.天津大学出版社.2003;50-51.
37.Xue JM,Tan CH,Lukito D.Biodegradable polymer-silica xerogel composite microspheres for controlled release of gentamicin.J Biomed Mater Res B Appl Biomater 2006;78(2):417-422.
38.高长有,马列.医用高分子材料.北京.化学工业出版社.2006:227-228.
39.Zhao F,Yin Y,Lu WW,Leong JC,Zhang W,Zhang J,et al.Preparation and histological evaluation of biomimetic three-dimensional hydroxyapatite/chitosan-gelatin network composite scaffolds.Biomaterials 2002;23(15):3227-3234.
40.Kim K,Yu M,Zong X,Chiu J,Fang D,Seo YS,et al.Control of degradation rate
and hydrophilicity in electrospun non-woven poly(D,L-lactide) nanofiber scaffolds
for biomedical applications.Biomaterials 2003;24(27):4977-4985.
41.Hoffrnan AS.Hydrogels for biomedical applications.Adv Drug Deliv Rev
2002;54(1):3-12.
42.Balakrishnan B,Jayakrishnan A.Self-cross-linking biopolymers as injectable in
situ forming biodegradable scaffolds.Biomaterials 2005;26(18):3941-3951.
43.Ma Z,Gao C,Gong Y,Shen J.Cartilage tissue engineering PLLA scaffold with
surface immobilized collagen and basic fibroblast growth factor.Biomaterials
2005;26(11 ):1253-1259.
44.Ma PX,Choi JW.Biodegradable polymer scaffolds with well-defined
interconnected spherical pore network.Tissue Eng 2001;7(1 ):23-33.
45.Chen G;Ushida T,Tateishi T.Preparation of poly(L-lactic acid) and
poly(DL-lactic-co-glycolic acid) foams by use of ice microparticulates.Biomaterials
2001;22(18):2563-2567.
46.Madihally SV,Matthew HW.Porous chitosan scaffolds for tissue engineering.Biomaterials 1999;20(12):1133-1142.
47.Rocha LB,Goissis G,Rossi MA.Biocompatibility of anionic collagen matrix as scaffold for bone healing.Biomaterials 2002;23(2):449-456.
48.Chen YL,Lee HP,Chan HY,Sung LY,Chen HC,Hu YC.Composite chondroitin-6-sulfate/dermatan sulfate/chitosan scaffolds for cartilage tissue engineering.Biomaterials 2007;28(14):2294-2305.
49.马列,胶原基组织工程真皮支架的构建.浙江大学博士学位论文 2004.
50.Nam YS,Park TG.Porous biodegradable polymeric scaffolds prepared by thermally induced phase separation.J Biomed Mater Res 1999;47(1):8-17.
51.Liu X,Ma PX.Polymeric scaffolds for bone tissue engineering.Ann Biomed Eng 2004;32(3):477-486.
52.高长有,胡小红,管建均,李安,沈家骢.热致相分离技术制备聚氨酯多孔膜的条件控制.高分子学报2001;19(3):351-356.
53.Li WJ,Laurencin CT,Caterson EJ,Tuan RS,Ko FK.Electrospun nanofibrous structure:a novel scaffold for tissue engineering.J Biomed Mater Res 2002;60(4):613-621.
54.Yoshimoto H,Shin YM,Terai H,Vacanti JP.A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering.Biomaterials 2003;24(12):2077-2082.
55.Zhang Y,Ouyang H,Lim CT,Ramakrishna S,Huang ZM.Electrospinning of gelatin fibers and gelatin/PCL composite fibrous scaffolds.J Biomed Mater Res B Appl Biomater 2005;72(1):156-165.
56.Mooney DJ,Mazzoni CL,Breuer C,McNamara K,Hem D,Vacanti JP,et al.Stabilized polyglycolic acid fibre-based tubes for tissue engineering.Biomaterials 1996:17(2):115-124.
57.罗丙红,卢泽俭.组织工程用高度多孔生物可降解支架的制备.国外医学生物医学工程分册 2001;24(4):154-158.
58.Hile DD,Amirpour ML,Akgerman A,Pishko MV.Active growth factor delivery from poly(D,L-lactide-co-glycolide) foams prepared in supercritical CO(2).J Control Release 2000;66(2-3):177-185.
59.Sheridan MH,Shea LD,Peters MC,Mooney DJ.Bioabsorbable polymer scaffolds for tissue engineering capable of sustained growth factor delivery.J Control Release 2000;64(1-3):91-102.
60.Khil MS,Bhattarai SR,Kim HY,Kim SZ,Lee KH.Novel fabricated matrix via electrospinning for tissue engineering.J Biomed Mater Res B Appl Biomater 2005;72(1):117-124.
61.Borden M,Attawia M,Khan Y,Laurencin CT.Tissue engineered microsphere-based matrices for bone repair:design and evaluation.Biomaterials 2002;23(2):551-559.
62.Borden M,Attawia M,Laurencin CT.The sintered microsphere matrix for bone tissue engineering:in vitro osteoconductivity studies.J Biomed Mater Res 2002;61(3):421-429.
63.Borden M,El-Amin SF,Attawia M,Laurencin CT.Structural and human cellular assessment of a novel microsphere-based tissue engineered scaffold for bone repair. Biomaterials 2003;24(4):597-609.
64.Woodfield TB,Malda J,de Wijn J,Peters F,Riesle J,van Blitterswijk CA.Design of porous scaffolds for cartilage tissue engineering using a three-dimensional fiber-deposition technique.Biomaterials 2004;25(18):4149-4161.
65.Hutmacher DW,Sittinger M,Risbud MV.Scaffold-based tissue engineering:rationale for computer-aided design and solid free-form fabrication systems.Trends Biotechnol 2004;22(7):354-362.
66.Temenoff JS,Mikos AG.Injectable biodegradable materials for orthopedic tissue engineering.Biomaterials 2000;21(23):2405-2412.
67.Xu HH,Weir MD,Simon CG.Injectable and strong nano-apatite scaffolds for cell/growth factor delivery and bone regeneration.Dent Mater 2008;24(9):1212-1222.
68.洪奕.可注射性聚乳酸细胞微载体/壳聚糖水凝胶复合支架的构建.浙江大学博士学位论文 2005.
69.Lao L,Tan H,Wang Y,Gao C.Chitosan modified poly(L-lactide) microspheres as cell microcarriers for cartilage tissue engineering.Colloids Surf B Biointerfaces 2008;66(2):218-225.
70.Hu X,Zhou J,Zhang N,Tan H,Gao C.Preparation and properties of an injectable scaffold of poly(lactic-co-glycolic acid) microparticles/chitosan hydrogel.J Mech Behav Biomed Mater 2008;1(4):352-359.
71.Elam JH,Elam M.Surface modification of intravenous catheters to reduce local tissue reactions.Biomaterials 1993;14(11):861-864.
72.Sawhney AS,Pathak CP,Hubbell JA.Interfacial photopolymerization of poly(ethylene glycol)-based hydrogels upon alginate-poly(1-lysine) microcapsules for enhanced biocompatibility.Biomaterials 1993;14(13):1008-1016.
73.Tan JS,Butterfield DE,Voycheck CL,Caldwell KD,Li JT.Surface modification of nanoparticles by PEO/PPO block copolymers to minimize interactions with blood components and prolong blood circulation in rats.Biomaterials 1993;14(11):823-833.
74.Zhu H,Ji J,Lin R,Gao C,Feng L,Shen J.Surface engineering of poly(DL-lactic acid) by entrapment of alginate-amino acid derivatives for promotion of chondrogenesis.Biomaterials 2002;23(15):3141-3148.
75. Wang DA, Ji J, Gao CY, Yu GH, Feng LX. Surface coating of stearyl poly(ethylene oxide) coupling-polymer on polyurethane guiding catheters with poly(ether urethane) film-building additive for biomedical applications. Biomaterials 2001;22(12):1549-1562.
76. Yang J, Bei J, Wang S. Enhanced cell affinity of poly (D,L-lactide) by combining plasma treatment with collagen anchorage. Biomaterials 2002;23(12):2607-2614.
77. Khang G, Jeon JH, Lee JW, Cho SC, Lee HB. Cell and platelet adhesions on plasma glow discharge-treated poly(lactide-co-glycolide). Biomed Mater Eng 1997;7(6):357-368.
78. Lee JH, Khang G, Lee JW, Lee HB. Interaction of Different Types of Cells on Polymer Surfaces with Wettability Gradient. J Colloid Interface Sci 1998;205(2):323-330.
79. Khang G, Lee SJ, Lee JH, Kim YS, Lee HB. Interaction of fibroblast cells on poly(lactide-co-glycolide) surface with wettability chemogradient. Biomed Mater Eng 1999;9(3):179-187.
80. Zhu Y, Gao C, Liu X, Shen J. Surface modification of polycaprolactone membrane via aminolysis and biomacromolecule immobilization for promoting cytocompatibility of human endothelial cells. Biomacromolecules 2002;3(6):1312-1319.
81. Durrani AA, Hayward JA, Chapman D. Biomembranes as models for polymer surfaces. II. The syntheses of reactive species for covalent coupling of phosphorylcholine to polymer surfaces. Biomaterials 1986;7(2): 121-125.
82. Hayward JA, Durrani AA, Lu Y, Clayton CR, Chapman D. Biomembranes as models for polymer surfaces. IV. ESCA analyses of a phosphorylcholine surface covalently bound to hydroxylated substrates. Biomaterials 1986;7(4):252-258.
83. Ma Z, Gao C, Gong Y, Ji J, Shen J. Immobilization of natural macromolecules on poly-L-lactic acid membrane surface in order to improve its cytocompatibility. J Biomed Mater Res 2002;63(6):838-847.
84. Ma Z, Gao C, Shen J. Surface modification of poly-L-lactic acid (PLLA) membrane by grafting acrylamide: an effective way to improve cytocompatibility for chondrocytes. J Biomater Sci Polym Ed 2003;14(1):13-25.
85. Lahann J, Klee D, Thelen H, Bienert H, Vorwerk D, Hocker.H. Improvement of haemocompatibility of metallic stents by polymer coating. J Mater Sci Mater Med 1999;10(7):443-448.
86. Alanazi A, Nojiri C, Kido T, Noguchi T, Ohgoe Y, Matsuda T, et al. Engineering analysis of diamond-like carbon coated polymeric materials for biomedical applications. Artif Organs 2000;24(8):624-627.
87. Jones MI, McColl IR, Grant DM, Parker KG, Parker TL. Protein adsorption and platelet attachment and activation, on TiN, TiC, and DLC coatings on titanium for cardiovascular applications. J Biomed Mater Res 2000;52(2):413-421.
88. Dion I, Rouais F, Trut L, Baquey C, Monties JR, Havlik P. TiN coating: surface characterization and haemocompatibility. Biomaterials 1993;14(3):169-176.
89. Sato H, Tsuji H, Ikeda S, Ikemoto N, Ishikawa J, Nishimoto S. Enhanced growth of human vascular endothelial cells on negative ion (Ag-)-implanted hydrophobic surfaces. J Biomed Mater Res 1999;44(1):22-30.
90. Svorcik V, Rybka V, Hnatowicz V, Smetana K, Jr. Structure and biocompatibility of ion beam modified polyethylene. J Mater Sci Mater Med 1997;8(7):435-440.
91. Chen G, Ushida T, Tatsuya T. Hybrid Biomaterials for Tissue Engineering: A Preparative Method for PLA or PLGA-Collagen Hybrid Sponges. Adv Mater 2000; 12:455-457.
92. Wan Y, Qu X, Lu J, Zhu C, Wan L, Yang J, et al. Characterization of surface property of poly(lactide-co-glycolide) after oxygen plasma treatment. Biomaterials 2004;25(19):4777-4783.
93. He W, Ma Z, Yong T, Teo WE, Ramakrishna S. Fabrication of collagen-coated biodegradable polymer nanofiber mesh and its potential for endothelial cells growth. Biomaterials 2005;26(36):7606-7615.
94. Griesser HJ, Chatelier RC, Gengenbach TR, Johnson G, Steele JG. Growth of human cells on plasma polymers: putative role of amine and amide groups. J Biomater Sci Polym Ed 1994;5(6):531-554.
95.李晓明,冯庆玲.骨组织工程材料发展现状及未来发展方向.生物骨科材料与临床研究2004;1(4):44-47.
96.Murugan R,Ramakrishna S.Development of nanocomposites for bone grafting.Composites Science and Technology 2005;65:2385-2406.
97.王颖俊.电纺PLGA及PLGA/羟基磷灰石纳米纤维材料研究.浙江大学硕士学位论文 2007.
98.刘舒佳,王东.骨组织工程的研究现状.实用骨科杂志 2006;12(3):232-235.
99.Rezwan K,Chen QZ,Blaker JJ,Boccaccini AR.Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering.Biomaterials 2006;27(18):3413-3431.
100.Ber S,Torun Kose G,Hasirci V.Bone tissue engineering on patterned collagen films:an in vitro study.Biomaterials 2005;26(14):1977-1986.
101.Engstrom PE,Shi XQ,Tronje G,Larsson A,Welander U,Frithiof L,et al.The effect of hyaluronan on bone and soft tissue and immune response in wound healing.J Periodontol 2001;72(9):1192-1200.
102.Karp JM,Sarraf F,Shoichet MS,Davies JE.Fibrin-filled scaffolds for bone-tissue engineering:An in vivo study.J Biomed Mater Res A 2004;71(1):162-171.
103.Seol YJ,Lee JY,Park YJ,Lee YM,Young K,Rhyu IC,et al.Chitosan sponges as tissue engineering scaffolds for bone formation.Biotechnol Lett 2004;26(13):1037-1041.
104.Wang L,Shelton RM,Cooper PR,Lawson M,Triffitt JT,Barralet JE.Evaluation of sodium alginate for bone marrow cell tissue engineering.Biomaterials 2003;24(20):3475-3481.
105.Montjovent MO,Mark S,Mathieu L,Scaletta C,Scherberich A,Delabarde C,et al.Human fetal bone cells associated with ceramic reinforced PLA scaffolds for tissue engineering.Bone 2008;42(3):554-564.
106.Kim SS,Sun Park M,Jeon O,Yong Choi C,Kim BS.Poly(lactide-co-glycolide)/hydroxyapatite composite scaffolds for bone tissue engineering.Biomaterials 2006;27(8):1399-1409.
107. Ngiam M, Liao S, Patil AJ, Cheng Z, Chan CK, Ramakrishna S. The fabrication of nano-hydroxyapatite on PLGA and PLGA/collagen nanofibrous composite scaffolds and their effects in osteoblastic behavior for bone tissue engineering. Bone 2009;45(1):4-16.
108. Wutticharoenmongkol P, Pavasant P, Supaphol P. Osteoblastic phenotype expression of MC3T3-E1 cultured on electrospun polycaprolactone fiber mats filled with hydroxyapatite nanoparticles. Biomacromolecules 2007;8(8):2602-2610.
109. Wang YW, Wu Q, Chen GQ. Attachment, proliferation and differentiation of osteoblasts on random biopolyester poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds. Biomaterials 2004;25(4):669-675.
110. Brook IM, Hatton PV. Glass-ionomers: bioactive implant materials. Biomaterials 1998;19(6):565-571.
111. Xu F, Li Y, Deng Y, Xiong J. Porous nano-hydroxyapatite/poly(vinyl alcohol) composite hydrogel as artificial cornea fringe: characterization and evaluation in vitro. J Biomater Sci Polym Ed 2008; 19(4):431-439.
112. TenHuisen KS, Brown PW. The formation of hydroxyapatite-gelatin composites at 38 degrees C. J Biomed Mater Res 1994;28(1):27-33.
113. TenHuisen KS, Martin RI, Klimkiewicz M, Brown PW. Formation and properties of a synthetic bone composite: hydroxyapatite-collagen. J Biomed Mater Res 1995;29(7):803-810.
114. Rodrigues CV, Serricella P, Linhares AB, Guerdes RM, Borojevic R, Rossi MA, et al. Characterization of a bovine collagen-hydroxyapatite composite scaffold for bone tissue engineering. Biomaterials 2003;24(27):4987-4997.
115. Marra KG, Szem JW, Kumta PN, DiMilla PA, Weiss LE. In vitro analysis of biodegradable polymer blend/hydroxyapatite composites for bone tissue engineering. J Biomed Mater Res 1999;47(3):324-335.
116. Navarro M, Ginebra MP, Planell JA, Zeppetelli S, Ambrosio L. Development and cell response of a new biodegradable composite scaffold for guided bone regeneration. J Mater Sci Mater Med 2004;15(4):419-422.
117. Liao SS, Cui FZ, Zhang W, Feng QL. Hierarchically biomimetic bone scaffold materials: nano-HA/collagen/PLA composite. J Biomed Mater Res B Appl Biomater 2004;69(2):158-165.
118. Hohling HJ. Collagen mineralization in bone, dentine, cementum and cartilage. Naturwissenschaften 1969;56(9):466.
119. Cui FZ, Li Y, Ge J. Self-assembly of mineralized collagen composites. Materials Science and Engineering R 2007;57(2)1-27.
120. Lickorish D, Guan L, Davies JE. A three-phase, fully resorbable, polyester/calcium phosphate scaffold for bone tissue engineering: Evolution of scaffold design. Biomaterials 2007;28(8):1495-1502.
121. Liu X, Smith LA, Hu J, Ma PX. Biomimetic nanofibrous gelatin/apatite composite scaffolds for bone tissue engineering. Biomaterials 2009;30(12):2252-2258.
122. Maniatopoulos C, Sodek J, Melcher AH. Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats. Cell Tissue Res 1988;254(2):317-330.
123. Lieberman JR, Daluiski A, Einhorn TA. The role of growth factors in the repair of bone. Biology and clinical applications. J Bone Joint Surg Am 2002;84-A(6): 1032-1044.
124. Gori F, Thomas T, Hicok KC, Spelsberg TC, Riggs BL. Differentiation of human marrow stromal precursor cells: bone morphogenetic protein-2 increases OSF2/CBFA1, enhances osteoblast commitment, and inhibits late adipocyte maturation. J Bone Miner Res 1999;14(9):1522-1535.
125. Chen B, Lin H, Wang J, Zhao Y, Wang B, Zhao W, et al. Homogeneous osteogenesis and bone regeneration by demineralized bone matrix loading with collagen-targeting bone morphogenetic protein-2. Biomaterials 2007;28(6):1027-1035.
126. Xie J, Li X, Xia Y. Putting Electrospun Nanofibers to Work for Biomedical Research. Macromol Rapid Commun 2008;29(22):1775-1792.
127. Liang D, Hsiao BS, Chu B. Functional electrospun nanofibrous scaffolds for biomedical applications. Adv Drug Deliv Rev 2007;59(14):1392-1412.
128.Deitzel JM,Kleinmeyer J,Harris D,Tan NCB.The effect of processing variables on the morphology of electrospun nanofibers and textiles.Polymer 2001;42:261-272.
129.Buchko JC,Chen CL,Shen Y,Martin CD.Processing and microstructural characterization of porous biocompatible protein polymer thin films.Polymer 1999;40:7397-7407.
130.Zong XH,Kim K,Fang DF,Ran SF,Hsiao SB,Chu B.Structure and process relationship of electrospun bioabsorbable nanofiber membranes.Polymer 2002;43:4403-4412.
131.Megelski S,Stephens JS,Chase DB,Rabolt JF.Micro- and nanostructured surface morphology on electrospun polymer fibers.Macromolecule 2002;35(22):8456-8466.
132.王颖俊,高长有.溶剂挥发性对PLGA电纺纤维直径及其膜动态力学性能的影响.组织工程与重建外科杂志2007:3:7-10.
133.Jaeger R,Bergshoef MM,Batlle CMI,Schonherr H,Vancso GJ.Electrospinning of ultra-thin polymer fibers.Macromol Symp 1998;127:141-150.
134.Yang F,Murugan R,Wang S,Ramakrishna S.Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissue engineering.Biomaterials 2005;26(15):2603-2610.
135.Zhong S,Teo WE,Zhu X,Beuerman RW,Ramakrishna S,Yung LY.An aligned nanofibrous collagen scaffold by electrospinning and its effects on in vitro fibroblast culture.J Biomed Mater Res A 2006;79(3):456-463.
136.Xu CY,Inai R,Kotaki M,Rarnakrishna S.Aligned biodegradable nanofibrous structure:a potential scaffold for blood vessel engineering.Biomaterials 2004;25(5):877-886.
137.Lee CH,Shin HJ,Cho IH,Kang YM,Kim IA,Park KD,et al.Nanofiber alignment and direction of mechanical strain affect the ECM production of human ACL fibroblast.Biomaterials 2005;26(11):1261-1270.
138.Yang D,Lu B,Zhao Y,Jiang X.Fabrication of aligned fibirous arrays by magnetic electrospinning.Adv Mater 2007;19:3702-3706.
139. Agarwal S, Greiner A, Wendorff JH. Electrospinning of Manmade and Biopolymer Nanofibers-Progress in Techniques, Materials, and Applications. Adv Funct Mater 2009; 19:1-17
140. Kidoaki S, Kwon IK, Matsuda T. Mesoscopic spatial designs of nano- and microfiber meshes for tissue-engineering matrix and scaffold based on newly devised multilayering and mixing electrospinning techniques. Biomaterials 2005;26(1):37-46.
141. Kim HW, Ju-Ha Song JH; Kim HE. Nanofiber generation of gelatin-hydroxyapatite biomimetics for guided tissue regeneration. Adv Funct Mater 2005;15(12):1988-1994.
142. Sun ZC, Zussman E, Yarin AL, Wendorff JH, Greiner A. Compound core-shell polymer nanofibers by co-electrospinning. Adv Mater 2003; 15:1929-1932.
143. Yu JH, Fridrikh SV, Rutledge GC. Production of submicrometer diameter fibers by two-fluid electrospinning. Adv Mater (Weinheim, Germany) 2004; 16:1562-1566.
144. Jiang H, Hu Y, Zhao P, Li Y, Zhu K. Modulation of protein release from biodegradable core-shell structured fibers prepared by coaxial electrospinning. J Biomed Mater Res B Appl Biomater 2006;79(1):50-57.
145. Townsend-Nicholson A, Jayasinghe SN. Cell electrospinning: a unique biotechnique for encapsulating living organisms for generating active biological microthreads/scaffolds. Biomacromolecules 2006;7(12):3364-3369.
146. Sanders EH, Kloefkorn R, Bowlin GL, Simpson DG, Wnek GE. Two-phase electrospinning from a single electrified jet: microencapsulation of aqueous reservoirs in poly(ethylene-co-vinyl acetate) fibers. Macromolecules 2003;36:3803-3805.
147. Baker BM, Mauck RL. The effect of nanofiber alignment on the maturation of engineered meniscus constructs. Biomaterials 2007;28(11): 1967-1977.
148. Lee YH, Lee JH, An IG, Kim C, Lee DS, Lee YK, et al. Electrospun dual-porosity structure and biodegradation morphology of Montmorillonite reinforced PLLA nanocomposite scaffolds. Biomaterials 2005;26(16):3165-3172.
149. Nam J, Huang Y, Agarwal S, Lannutti J. Improved cellular infiltration in electrospun fiber via engineered porosity. Tissue Eng 2007;13(9):2249-2257.
150. Kim TG, Chung HJ, Park TG Macroporous and nanofibrous hyaluronic acid/collagen hybrid scaffold fabricated by concurrent electrospinning and deposition/leaching of salt particles. Acta Biomater 2008;4(6): 1611-1619.
151. Baker BM, Gee AO, Metter RB, Nathan AS, Marklein RA, Burdick JA, et al. The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers. Biomaterials 2008;29(15):2348-2358.
152. Martinez E, Engel E, Planell JA, Samitier J. Effects of artificial micro- and nano-structured surfaces on cell behaviour. Ann Anat 2009; 191(1): 126-135.
153. Tian F, Hosseinkhani H, Hosseinkhani M, Khademhosseini A, Yokoyama Y, Estrada GG, et al. Quantitative analysis of cell adhesion on aligned micro- and nanofibers. J Biomed Mater Res A 2008;84(2):291-299.
154. Takahashi Y, Tabata Y. Effect of the fiber diameter and porosity of non-woven PET fabrics on the osteogenic differentiation of mesenchymal stem cells. J Biomater Sci Polym Ed 2004; 15(1):41-57.
155. Li M, Guo Y, Wei Y, MacDiarmid AG, Lelkes PI. Electrospinning polyaniline-contained gelatin nanofibers for tissue engineering applications. Biomaterials 2006;27(13):2705-2715.
156. Zong X, Bien H, Chung CY, Yin L, Fang D, Hsiao BS, et al. Electrospun fine-textured scaffolds for heart tissue constructs. Biomaterials 2005;26(26):5330-5338.
157. Venugopal J, Ramakrishna S. Biocompatible nanofiber matrices for the engineering of a dermal substitute for skin regeneration. Tissue Eng 2005;11(5-6):847-854.
158. Chong EJ, Phan TT, Lim IJ, Zhang YZ, Bay BH, Ramakrishna S, et al. Evaluation of electrospun PCL/gelatin nanofibrous scaffold for wound healing and layered dermal reconstitution. Acta Biomater 2007;3(3):321-330.
159. Kenawy el R, Layman JM, Watkins JR, Bowlin GL, Matthews JA, Simpson DG, et al. Electrospinning of poly(ethylene-co-vinyl alcohol) fibers. Biomaterials 2003;24(6):907-913.
160. Kumbar SG, James R, Nukavarapu SP, Laurencin CT. Electrospun nanofiber scaffolds: engineering soft tissues. Biomed Mater 2008;3(3):034002.
161. Liao S, Li B, Ma Z, Wei H, Chan C, Ramakrishna S. Biomimetic electrospun nanofibers for tissue regeneration. Biomed Mater 2006;1(3):R45-53.
162. Ma Z, Kotaki M, Yong T, He W, Ramakrishna S. Surface engineering of electrospun polyethylene terephthalate (PET) nanofibers towards development of a new material for blood vessel engineering. Biomaterials 2005;26(15):2527-2536.
163. Schnell E, Klinkhammer K, Balzer S, Brook G, Klee D, Dalton P, et al. Guidance of glial cell migration and axonal growth on electrospun nanofibers of poly-epsilon-caprolactone and a collagen/poly-epsilon-caprolactone blend. Biomaterials 2007;28(19):3012-3025.
164. Ahmed I, Liu HY, Mamiya PC, Ponery AS, Babu AN, Weik T, et al. Three-dimensional nanofibrillar surfaces covalently modified with tenascin-C-derived peptides enhance neuronal growth in vitro. J Biomed Mater Res A 2006;76(4):851-860.
165. Patel S, Kurpinski K, Quigley R, Gao H, Hsiao BS, Poo MM, et al. Bioactive nanofibers: synergistic effects of nanotopography and chemical signaling on cell guidance. Nano Lett 2007;7(7):2122-2128.
166. Chew SY, Mi R, Hoke A, Leong KW. Aligned Protein-Polymer Composite Fibers Enhance Nerve Regeneration: A Potential Tissue-Engineering Platform. Adv Funct Mater 2007; 17(8): 1288-1296.
167. Li WJ, Danielson KG, Alexander PG, Tuan RS. Biological response of chondrocytes cultured in three-dimensional nanofibrous poly(epsilon-caprolactone) scaffolds. J Biomed Mater Res A2003;67(4):1105-1114.
168. Subramanian A, Vu D, Larsen GF, Lin HY. Preparation and evaluation of the electrospun chitosan/PEO fibers for potential applications in cartilage tissue engineering. J Biomater Sci Polym Ed 2005;16(7):861-873.
169. Meng W, Kim SY, Yuan J, Kim JC, Kwon OH, Kawazoe N, et al. Electrospun PHBV/collagen composite nanofibrous scaffolds for tissue engineering. J Biomater Sci Polym Ed 2007;18(1):81-94.
170. Shields KJ, Beckman MJ, Bowlin GL, Wayne JS. Mechanical properties and cellular proliferation of electrospun collagen type II. Tissue Eng 2004;10(9-10):1510-1517.
171. Griffith LG, Naughton G. Tissue engineering—current challenges and expanding opportunities. Science 2002;295(5557): 1009-1014.
172. Fujihara K, Kotaki M, Ramakrishna S. Guided bone regeneration membrane made of polycaprolactone/calcium carbonate composite nano-fibers. Biomaterials 2005;26(19):4139-4147.
173. Kim HW, Lee HH, Knowles JC. Electrospinning biomedical nanocomposite fibers of hydroxyapatite/poly(lactic acid) for bone regeneration. J Biomed Mater Res A 2006;79(3):643-649.
174. Chen J, Chu B, Hsiao BS. Mineralization of hydroxyapatite in electrospun nanofibrous poly(L-lactic acid) scaffolds. J Biomed Mater Res A 2006;79(2):307-317.
175. Yu HS, Hong SJ, Kim HW. Surface-mineralized polymeric nanofiber for the population and osteogenic stimulation of rat bone-marrow stromal cell. Mater Chem Phys 2009; 113:873-877.
176. Agarwal S, Wendorff JH, Gre A. Progress in the Field of Electrospinning for Tissue Engineering Applications. Adv Mater 2009;21:3343-3351.
177. Zhao HG, Ma L, Gao CY, Wang JF, Shen JC. Fabrication and properties of injectable β-tricalcium phosphate particles/fibrin gel composite scaffolds for bone tissue engineering. Mater Sci Eng C 2009;29:836-842.
178. Li Y, Kong F, Weng W. Preparation and characterization of novel biphasic calcium phosphate powders (alpha-TCP/HA) derived from carbonated amorphous calcium phosphates. J Biomed Mater Res B Appl Biomater 2009;89B(2):508-517.
179. Jayasuriya AC, Shah C, Ebraheim NA, Jayatissa AH. Acceleration of biomimetic mineralization to apply in bone regeneration. Biomed Mater 2008;3(1):15003.
180. Kim YJ, Sah RL, Doong JY, Grodzinsky AJ. Fluorometric assay of DNA in cartilage explants using Hoechst 33258. Anal Biochem 1988;174(1):168-176.
181. Thomas V, Dean DR, Jose MV, Mathew B, Chowdhury S, Vohra YK. Nanostructured biocomposite scaffolds based on collagen coelectrospun with nanohydroxyapatite.Biomacromolecules 2007;8(2):631-637.
182.Zhang HL,Liu JS,Yao ZW,Yang J,Pan LZ,Chen ZQ.Biomimetic mineralization of electrospun poly(lactic-co-glycolic acid)/multi-walled carbon nanotubes composite scaffolds in vitro.Mater Lett 2009;63(27):2313-2316.
183.Zhang P,Hong Z,Yu T,Chen X,Jing X.In vivo mineralization and osteogenesis of nanocomposite scaffold of poly(lactide-co-glycolide) and hydroxvapatite surface-grafted with ooly(L-lactide).Biomaterials 2009;30(1):58-70.
184.胡小红.软骨修复用水凝胶的制备和性能研究.浙江大学博士学位论文2009.
185.Lee J,Tae G,Kim YH,Park IS,Kim SH.The effect of gelatin incorporation into electrospun poly(L-lactide-co-epsilon-caprolactone) fibers on mechanical properties and cytocompatibility.Biomaterials 2008;29(12):1872-1879.
186.Tan H,Wu J,Lao L,Gao C.Gelatin/chitosan/hyaluronan scaffold integrated with PLGA microspheres for cartilage tissue engineering.Acta Biomater 2009;5(1):328-337.
187.Zhang Y,Venugopal JR,El-Turki A,Ramakrishna S,Su B,Lim CT.Electrospun biomimetic nanocomposite nanofibers of hydroxyapatite/chitosan for bone tissue engineering.Biomaterials 2008;29(32):4314-4322.
188.Dulgar-Tulloch AJ,Bizios R,Siegel RW.Human mesenchymal stem cell adhesion and proliferation in response to ceramic chemistry and nanoscale topography.J Biomed Mater Res A 2009;90(2):586-594.
189.Cui Y,Liu Y,Jing X,Zhang P,Chen X.The nanocomposite scaffold of poly(lactide-co-glycolide) and hydroxyapatite surface-grafted with L-lactic acid oligomer for bone repair.Acta Biomater 2009;5(7):2680-2692.
190.Tsukamoto Y,Fukutani S,Moil M.Hydroxyapatite-induced alkaline phosphatase activity of human pulp fibroblasts.J Mater Sci-Mater Med 1992;3:180-183.
191.Ruoslahti E,Pierschbacher MD.New perspectives in cell adhesion:RGD and integrins.Science 1987;238(4826):491-497.
192.谈华平.生物活性软骨组织工程支架的制备与性能研究.浙江大学博士学位论文2007.
193.王淡兮,孙秀兰.蛋白质定量检测方法的探讨.粮食与食品工业2009;16(4):49-51&62.
194.Rhee SH,Lee JD,Tanaka J.Nucleation of hydroxyapatite crystal through chemical interaction with collagen.J Am Ceram Soc 2000;83:2890-2892.
195.Liu C,Han Z,Czernuszka JT.Gradient collagen/nanohydroxyapatite composite scaffold:development and characterization.Acta Biomater 2009;5(2):661-669.
196.Ekaputra AK,Prestwich GD,Cool SM,Hutmacher DW.Combining electrospun scaffolds with electrosprayed hydrogels leads to three-dimensional cellularization of hybrid constructs.Biomacromolecules 2008;9(8):2097-2103.
197.Pham QP,Sharma U,Mikos AG.Electrospun poly(epsilon-caprolactone)microfiber and multilayer nanofiber/microfiber scaffolds:characterization of scaffolds and measurement of cellular infiltration.Biomacromolecules 2006;7(10):2796-2805.
2.Yannas Ⅳ,Burke JF,Orgill DP,Skrabut EM.Wound Tissue Can Utilize a Polymeric Template to Synthesize a Functional Extension of Skin.Science 1982;215(4529):174-176.
3.Yannas Ⅳ,Lee E,Orgill DP,Skrabut EM,Murphy GF.Synthesis and Characterization of a Model Extracellular-Matrix That Induces Partial Regeneration of Adult Mammalian Skin.Proceedings of the National Academy of Sciences of the United States of America 1989;86(3):933-937.
4.Wolter JR,Meyer RE Sessile macrophages forming clear endothelium-like membrane on inside of successful keratoprosthesis.Trans Am Ophthalmol Soc 1984;82:187-202.
5.龚逸鸿.聚乳酸多孔支架的制备、改性及组织工程化软骨的构建.浙江大学博士学位论文2006.
6.商庆新,曹谊林,张涤生.生物工程领域的崭新前沿-组织工程.引进国外医药技术与设备1999;5(11):11-15.
7.Bonassar LJ,Vacanti CA.Tissue engineering:the first decade and beyond.J Cell Biochem Suppl 1998;30-31:297-303.
8.Saltzman WM,Parkhurst MR,Parsons-Wingerter P,Zhu WH.Three-dimensional cell cultures mimic tissues.Ann N Y Acad Sci 1992;665:259-273.
9.Vacanti JP,Langer R,Upton J,Marler JJ.Transplantation of cells in matrices for tissue regeneration.Adv Drug Deliv Rev 1998;33(1-2):165-182.
10.劳为德.修复医学与组织工程.北京.化学工业出版社.2003;35-37.
11.杨志明.组织工程.北京.化学工业出版社.2001:123-124,166-167.
12.Heath CA.Cells for tissue engineering.Trends Biotechnol 2000;18(1):17-19.
13.Vandenburgh H,Del Tatto M,Shansky J,Lemaire J,Chang A,Payumo F,et al.Tissue-engineered skeletal muscle organoids for reversible gene therapy.Hum Gene Ther 1996;7(17):2195-2200.
14.Fontaine M,Hansen LK,Thompson S,Uyama S,Ingber DE,Langer R,et al. Transplantation of genetically altered hepatocytes using cell-polymer constructs.Transplant Proc 1993;25(1 Pt 2):1002-1004.
15.邓明安,周燕,华平,谭文松.人皮肤成纤维细胞在不同培养系统中的生长代谢特性.生物工程学报2001;7(3):336-338.
16.Kim BS,Mooney DJ.Development of biocompatible synthetic extracellular matrices for tissue engineering.Trends Biotechnol 1998;16(5):224-230.
17.Gilbert JC,Takada T,Stein JE,Langer R,Vacanti JP.Cell transplantation of genetically altered cells on biodegradable polymer scaffolds in syngeneic rats.Transplantation 1993;56(2):423-427.
18.姚康德,尹玉姬.组织工程相关生物材料.北京.化学工业出版社.2003:16-17.
19.Saltzman WM.Weaving cartilage at zero g:the reality of tissue engineering in space.Proc Natl Acad Sci U S A 1997;94(25):13380-13382.
20.胡江,陶祖莱.组织工程研究进展.生物医学工程学杂志2000;17(1):75-79.
21.Hutmacher DW.Scaffolds in tissue engineering bone and cartilage.Biomaterials 2000;21(24):2529-2543.
22.Hynes RO.Integrins:versatility,modulation,and signaling in cell adhesion.Cell 1992;69(1):11-25.
23.Cook AD,Hrkach JS,Gao NN,Johnson IM,Pajvani UB,Cannizzaro SM,et al.Characterization and development of RGD-peptide-modified poly(lactic acid-co-lysine) as an interactive,resorbable biomaterial.J Biomed Mater Res 1997;35(4):513-523.
24.Pollok JM,Kluth D,Cusick RA,Lee H,Utsunomiya H,Ma PX,et al.Formation of spheroidal aggregates of hepatocytes on biodegradable polymers under continuous-flow bioreactor conditions.Eur J Pediatr Surg 1998;8(4):195-199.
25.Lee CH,Singla A,Lee Y.Biomedical applications of collagen.Int J Pharm 2001;221(1-2):1-22.
26.Furthmayr H,Timpl R.Immunochemistry of collagens and procollagens.Int Rev Connect Tissue Res 1976;7:61-99.
27.Maeda M,Tani S,Sano A,Fujioka K.Microstructure and release characteristics of the minipellet,a collagen-based drug delivery system for controlled release of protein drugs.J Control Release 1999;62(3):313-324.
28.Kuzuya M,Kinsella JL.Induction of endothelial cell differentiation in vitro by fibroblast-derived soluble factors.Exp Cell Res 1994;215(2):310-318.
29.Sams AE,Minor RR,Wootton JA,Mohammed H,Nixon AJ.Local and remote matrix responses to chondrocyte-laden collagen scaffold implantation in extensive articular cartilage defects.Osteoarthritis Cartilage 1995;3(1):61-70.
30.Liao SS,Cui FZ,Zhu Y.Osteoblasts adherence and migration through three-dimensional porous mineralized collagen based composite:nHAC/PLA.J Bioact Comp Poly 2004;19:117-130.
31.吴慧玲,谷志远.透明质酸对关节软骨的影响及作用机制.国外医学口腔医学分册1999;26(1):30-33.
32.Godbey WT,Atala A.In vitro systems for tissue engineering.Ann N Y Acad Sci 2002;961:10-26.
33.周庆亮.聚乳酸软骨组织工程支架的制备、降解及细胞相容性研究.浙江大学硕士学位论文 2005.
34.Chu CR,Monosov AZ,Amiel D.In situ assessment of cell viability within biodegradable polylactic acid polymer matrices.Biomaterials 1995;16(18):1381-I384.
35.蔡晴,石桂欣,贝建中,王身国.聚(丙交酯-乙交酯)共聚物细胞支架降解行为的研究.第三届全国组织工程学术会议论文集 433-436.
36.俞耀庭,张兴栋.生物医用材料.天津.天津大学出版社.2003;50-51.
37.Xue JM,Tan CH,Lukito D.Biodegradable polymer-silica xerogel composite microspheres for controlled release of gentamicin.J Biomed Mater Res B Appl Biomater 2006;78(2):417-422.
38.高长有,马列.医用高分子材料.北京.化学工业出版社.2006:227-228.
39.Zhao F,Yin Y,Lu WW,Leong JC,Zhang W,Zhang J,et al.Preparation and histological evaluation of biomimetic three-dimensional hydroxyapatite/chitosan-gelatin network composite scaffolds.Biomaterials 2002;23(15):3227-3234.
40.Kim K,Yu M,Zong X,Chiu J,Fang D,Seo YS,et al.Control of degradation rate
and hydrophilicity in electrospun non-woven poly(D,L-lactide) nanofiber scaffolds
for biomedical applications.Biomaterials 2003;24(27):4977-4985.
41.Hoffrnan AS.Hydrogels for biomedical applications.Adv Drug Deliv Rev
2002;54(1):3-12.
42.Balakrishnan B,Jayakrishnan A.Self-cross-linking biopolymers as injectable in
situ forming biodegradable scaffolds.Biomaterials 2005;26(18):3941-3951.
43.Ma Z,Gao C,Gong Y,Shen J.Cartilage tissue engineering PLLA scaffold with
surface immobilized collagen and basic fibroblast growth factor.Biomaterials
2005;26(11 ):1253-1259.
44.Ma PX,Choi JW.Biodegradable polymer scaffolds with well-defined
interconnected spherical pore network.Tissue Eng 2001;7(1 ):23-33.
45.Chen G;Ushida T,Tateishi T.Preparation of poly(L-lactic acid) and
poly(DL-lactic-co-glycolic acid) foams by use of ice microparticulates.Biomaterials
2001;22(18):2563-2567.
46.Madihally SV,Matthew HW.Porous chitosan scaffolds for tissue engineering.Biomaterials 1999;20(12):1133-1142.
47.Rocha LB,Goissis G,Rossi MA.Biocompatibility of anionic collagen matrix as scaffold for bone healing.Biomaterials 2002;23(2):449-456.
48.Chen YL,Lee HP,Chan HY,Sung LY,Chen HC,Hu YC.Composite chondroitin-6-sulfate/dermatan sulfate/chitosan scaffolds for cartilage tissue engineering.Biomaterials 2007;28(14):2294-2305.
49.马列,胶原基组织工程真皮支架的构建.浙江大学博士学位论文 2004.
50.Nam YS,Park TG.Porous biodegradable polymeric scaffolds prepared by thermally induced phase separation.J Biomed Mater Res 1999;47(1):8-17.
51.Liu X,Ma PX.Polymeric scaffolds for bone tissue engineering.Ann Biomed Eng 2004;32(3):477-486.
52.高长有,胡小红,管建均,李安,沈家骢.热致相分离技术制备聚氨酯多孔膜的条件控制.高分子学报2001;19(3):351-356.
53.Li WJ,Laurencin CT,Caterson EJ,Tuan RS,Ko FK.Electrospun nanofibrous structure:a novel scaffold for tissue engineering.J Biomed Mater Res 2002;60(4):613-621.
54.Yoshimoto H,Shin YM,Terai H,Vacanti JP.A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering.Biomaterials 2003;24(12):2077-2082.
55.Zhang Y,Ouyang H,Lim CT,Ramakrishna S,Huang ZM.Electrospinning of gelatin fibers and gelatin/PCL composite fibrous scaffolds.J Biomed Mater Res B Appl Biomater 2005;72(1):156-165.
56.Mooney DJ,Mazzoni CL,Breuer C,McNamara K,Hem D,Vacanti JP,et al.Stabilized polyglycolic acid fibre-based tubes for tissue engineering.Biomaterials 1996:17(2):115-124.
57.罗丙红,卢泽俭.组织工程用高度多孔生物可降解支架的制备.国外医学生物医学工程分册 2001;24(4):154-158.
58.Hile DD,Amirpour ML,Akgerman A,Pishko MV.Active growth factor delivery from poly(D,L-lactide-co-glycolide) foams prepared in supercritical CO(2).J Control Release 2000;66(2-3):177-185.
59.Sheridan MH,Shea LD,Peters MC,Mooney DJ.Bioabsorbable polymer scaffolds for tissue engineering capable of sustained growth factor delivery.J Control Release 2000;64(1-3):91-102.
60.Khil MS,Bhattarai SR,Kim HY,Kim SZ,Lee KH.Novel fabricated matrix via electrospinning for tissue engineering.J Biomed Mater Res B Appl Biomater 2005;72(1):117-124.
61.Borden M,Attawia M,Khan Y,Laurencin CT.Tissue engineered microsphere-based matrices for bone repair:design and evaluation.Biomaterials 2002;23(2):551-559.
62.Borden M,Attawia M,Laurencin CT.The sintered microsphere matrix for bone tissue engineering:in vitro osteoconductivity studies.J Biomed Mater Res 2002;61(3):421-429.
63.Borden M,El-Amin SF,Attawia M,Laurencin CT.Structural and human cellular assessment of a novel microsphere-based tissue engineered scaffold for bone repair. Biomaterials 2003;24(4):597-609.
64.Woodfield TB,Malda J,de Wijn J,Peters F,Riesle J,van Blitterswijk CA.Design of porous scaffolds for cartilage tissue engineering using a three-dimensional fiber-deposition technique.Biomaterials 2004;25(18):4149-4161.
65.Hutmacher DW,Sittinger M,Risbud MV.Scaffold-based tissue engineering:rationale for computer-aided design and solid free-form fabrication systems.Trends Biotechnol 2004;22(7):354-362.
66.Temenoff JS,Mikos AG.Injectable biodegradable materials for orthopedic tissue engineering.Biomaterials 2000;21(23):2405-2412.
67.Xu HH,Weir MD,Simon CG.Injectable and strong nano-apatite scaffolds for cell/growth factor delivery and bone regeneration.Dent Mater 2008;24(9):1212-1222.
68.洪奕.可注射性聚乳酸细胞微载体/壳聚糖水凝胶复合支架的构建.浙江大学博士学位论文 2005.
69.Lao L,Tan H,Wang Y,Gao C.Chitosan modified poly(L-lactide) microspheres as cell microcarriers for cartilage tissue engineering.Colloids Surf B Biointerfaces 2008;66(2):218-225.
70.Hu X,Zhou J,Zhang N,Tan H,Gao C.Preparation and properties of an injectable scaffold of poly(lactic-co-glycolic acid) microparticles/chitosan hydrogel.J Mech Behav Biomed Mater 2008;1(4):352-359.
71.Elam JH,Elam M.Surface modification of intravenous catheters to reduce local tissue reactions.Biomaterials 1993;14(11):861-864.
72.Sawhney AS,Pathak CP,Hubbell JA.Interfacial photopolymerization of poly(ethylene glycol)-based hydrogels upon alginate-poly(1-lysine) microcapsules for enhanced biocompatibility.Biomaterials 1993;14(13):1008-1016.
73.Tan JS,Butterfield DE,Voycheck CL,Caldwell KD,Li JT.Surface modification of nanoparticles by PEO/PPO block copolymers to minimize interactions with blood components and prolong blood circulation in rats.Biomaterials 1993;14(11):823-833.
74.Zhu H,Ji J,Lin R,Gao C,Feng L,Shen J.Surface engineering of poly(DL-lactic acid) by entrapment of alginate-amino acid derivatives for promotion of chondrogenesis.Biomaterials 2002;23(15):3141-3148.
75. Wang DA, Ji J, Gao CY, Yu GH, Feng LX. Surface coating of stearyl poly(ethylene oxide) coupling-polymer on polyurethane guiding catheters with poly(ether urethane) film-building additive for biomedical applications. Biomaterials 2001;22(12):1549-1562.
76. Yang J, Bei J, Wang S. Enhanced cell affinity of poly (D,L-lactide) by combining plasma treatment with collagen anchorage. Biomaterials 2002;23(12):2607-2614.
77. Khang G, Jeon JH, Lee JW, Cho SC, Lee HB. Cell and platelet adhesions on plasma glow discharge-treated poly(lactide-co-glycolide). Biomed Mater Eng 1997;7(6):357-368.
78. Lee JH, Khang G, Lee JW, Lee HB. Interaction of Different Types of Cells on Polymer Surfaces with Wettability Gradient. J Colloid Interface Sci 1998;205(2):323-330.
79. Khang G, Lee SJ, Lee JH, Kim YS, Lee HB. Interaction of fibroblast cells on poly(lactide-co-glycolide) surface with wettability chemogradient. Biomed Mater Eng 1999;9(3):179-187.
80. Zhu Y, Gao C, Liu X, Shen J. Surface modification of polycaprolactone membrane via aminolysis and biomacromolecule immobilization for promoting cytocompatibility of human endothelial cells. Biomacromolecules 2002;3(6):1312-1319.
81. Durrani AA, Hayward JA, Chapman D. Biomembranes as models for polymer surfaces. II. The syntheses of reactive species for covalent coupling of phosphorylcholine to polymer surfaces. Biomaterials 1986;7(2): 121-125.
82. Hayward JA, Durrani AA, Lu Y, Clayton CR, Chapman D. Biomembranes as models for polymer surfaces. IV. ESCA analyses of a phosphorylcholine surface covalently bound to hydroxylated substrates. Biomaterials 1986;7(4):252-258.
83. Ma Z, Gao C, Gong Y, Ji J, Shen J. Immobilization of natural macromolecules on poly-L-lactic acid membrane surface in order to improve its cytocompatibility. J Biomed Mater Res 2002;63(6):838-847.
84. Ma Z, Gao C, Shen J. Surface modification of poly-L-lactic acid (PLLA) membrane by grafting acrylamide: an effective way to improve cytocompatibility for chondrocytes. J Biomater Sci Polym Ed 2003;14(1):13-25.
85. Lahann J, Klee D, Thelen H, Bienert H, Vorwerk D, Hocker.H. Improvement of haemocompatibility of metallic stents by polymer coating. J Mater Sci Mater Med 1999;10(7):443-448.
86. Alanazi A, Nojiri C, Kido T, Noguchi T, Ohgoe Y, Matsuda T, et al. Engineering analysis of diamond-like carbon coated polymeric materials for biomedical applications. Artif Organs 2000;24(8):624-627.
87. Jones MI, McColl IR, Grant DM, Parker KG, Parker TL. Protein adsorption and platelet attachment and activation, on TiN, TiC, and DLC coatings on titanium for cardiovascular applications. J Biomed Mater Res 2000;52(2):413-421.
88. Dion I, Rouais F, Trut L, Baquey C, Monties JR, Havlik P. TiN coating: surface characterization and haemocompatibility. Biomaterials 1993;14(3):169-176.
89. Sato H, Tsuji H, Ikeda S, Ikemoto N, Ishikawa J, Nishimoto S. Enhanced growth of human vascular endothelial cells on negative ion (Ag-)-implanted hydrophobic surfaces. J Biomed Mater Res 1999;44(1):22-30.
90. Svorcik V, Rybka V, Hnatowicz V, Smetana K, Jr. Structure and biocompatibility of ion beam modified polyethylene. J Mater Sci Mater Med 1997;8(7):435-440.
91. Chen G, Ushida T, Tatsuya T. Hybrid Biomaterials for Tissue Engineering: A Preparative Method for PLA or PLGA-Collagen Hybrid Sponges. Adv Mater 2000; 12:455-457.
92. Wan Y, Qu X, Lu J, Zhu C, Wan L, Yang J, et al. Characterization of surface property of poly(lactide-co-glycolide) after oxygen plasma treatment. Biomaterials 2004;25(19):4777-4783.
93. He W, Ma Z, Yong T, Teo WE, Ramakrishna S. Fabrication of collagen-coated biodegradable polymer nanofiber mesh and its potential for endothelial cells growth. Biomaterials 2005;26(36):7606-7615.
94. Griesser HJ, Chatelier RC, Gengenbach TR, Johnson G, Steele JG. Growth of human cells on plasma polymers: putative role of amine and amide groups. J Biomater Sci Polym Ed 1994;5(6):531-554.
95.李晓明,冯庆玲.骨组织工程材料发展现状及未来发展方向.生物骨科材料与临床研究2004;1(4):44-47.
96.Murugan R,Ramakrishna S.Development of nanocomposites for bone grafting.Composites Science and Technology 2005;65:2385-2406.
97.王颖俊.电纺PLGA及PLGA/羟基磷灰石纳米纤维材料研究.浙江大学硕士学位论文 2007.
98.刘舒佳,王东.骨组织工程的研究现状.实用骨科杂志 2006;12(3):232-235.
99.Rezwan K,Chen QZ,Blaker JJ,Boccaccini AR.Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering.Biomaterials 2006;27(18):3413-3431.
100.Ber S,Torun Kose G,Hasirci V.Bone tissue engineering on patterned collagen films:an in vitro study.Biomaterials 2005;26(14):1977-1986.
101.Engstrom PE,Shi XQ,Tronje G,Larsson A,Welander U,Frithiof L,et al.The effect of hyaluronan on bone and soft tissue and immune response in wound healing.J Periodontol 2001;72(9):1192-1200.
102.Karp JM,Sarraf F,Shoichet MS,Davies JE.Fibrin-filled scaffolds for bone-tissue engineering:An in vivo study.J Biomed Mater Res A 2004;71(1):162-171.
103.Seol YJ,Lee JY,Park YJ,Lee YM,Young K,Rhyu IC,et al.Chitosan sponges as tissue engineering scaffolds for bone formation.Biotechnol Lett 2004;26(13):1037-1041.
104.Wang L,Shelton RM,Cooper PR,Lawson M,Triffitt JT,Barralet JE.Evaluation of sodium alginate for bone marrow cell tissue engineering.Biomaterials 2003;24(20):3475-3481.
105.Montjovent MO,Mark S,Mathieu L,Scaletta C,Scherberich A,Delabarde C,et al.Human fetal bone cells associated with ceramic reinforced PLA scaffolds for tissue engineering.Bone 2008;42(3):554-564.
106.Kim SS,Sun Park M,Jeon O,Yong Choi C,Kim BS.Poly(lactide-co-glycolide)/hydroxyapatite composite scaffolds for bone tissue engineering.Biomaterials 2006;27(8):1399-1409.
107. Ngiam M, Liao S, Patil AJ, Cheng Z, Chan CK, Ramakrishna S. The fabrication of nano-hydroxyapatite on PLGA and PLGA/collagen nanofibrous composite scaffolds and their effects in osteoblastic behavior for bone tissue engineering. Bone 2009;45(1):4-16.
108. Wutticharoenmongkol P, Pavasant P, Supaphol P. Osteoblastic phenotype expression of MC3T3-E1 cultured on electrospun polycaprolactone fiber mats filled with hydroxyapatite nanoparticles. Biomacromolecules 2007;8(8):2602-2610.
109. Wang YW, Wu Q, Chen GQ. Attachment, proliferation and differentiation of osteoblasts on random biopolyester poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds. Biomaterials 2004;25(4):669-675.
110. Brook IM, Hatton PV. Glass-ionomers: bioactive implant materials. Biomaterials 1998;19(6):565-571.
111. Xu F, Li Y, Deng Y, Xiong J. Porous nano-hydroxyapatite/poly(vinyl alcohol) composite hydrogel as artificial cornea fringe: characterization and evaluation in vitro. J Biomater Sci Polym Ed 2008; 19(4):431-439.
112. TenHuisen KS, Brown PW. The formation of hydroxyapatite-gelatin composites at 38 degrees C. J Biomed Mater Res 1994;28(1):27-33.
113. TenHuisen KS, Martin RI, Klimkiewicz M, Brown PW. Formation and properties of a synthetic bone composite: hydroxyapatite-collagen. J Biomed Mater Res 1995;29(7):803-810.
114. Rodrigues CV, Serricella P, Linhares AB, Guerdes RM, Borojevic R, Rossi MA, et al. Characterization of a bovine collagen-hydroxyapatite composite scaffold for bone tissue engineering. Biomaterials 2003;24(27):4987-4997.
115. Marra KG, Szem JW, Kumta PN, DiMilla PA, Weiss LE. In vitro analysis of biodegradable polymer blend/hydroxyapatite composites for bone tissue engineering. J Biomed Mater Res 1999;47(3):324-335.
116. Navarro M, Ginebra MP, Planell JA, Zeppetelli S, Ambrosio L. Development and cell response of a new biodegradable composite scaffold for guided bone regeneration. J Mater Sci Mater Med 2004;15(4):419-422.
117. Liao SS, Cui FZ, Zhang W, Feng QL. Hierarchically biomimetic bone scaffold materials: nano-HA/collagen/PLA composite. J Biomed Mater Res B Appl Biomater 2004;69(2):158-165.
118. Hohling HJ. Collagen mineralization in bone, dentine, cementum and cartilage. Naturwissenschaften 1969;56(9):466.
119. Cui FZ, Li Y, Ge J. Self-assembly of mineralized collagen composites. Materials Science and Engineering R 2007;57(2)1-27.
120. Lickorish D, Guan L, Davies JE. A three-phase, fully resorbable, polyester/calcium phosphate scaffold for bone tissue engineering: Evolution of scaffold design. Biomaterials 2007;28(8):1495-1502.
121. Liu X, Smith LA, Hu J, Ma PX. Biomimetic nanofibrous gelatin/apatite composite scaffolds for bone tissue engineering. Biomaterials 2009;30(12):2252-2258.
122. Maniatopoulos C, Sodek J, Melcher AH. Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats. Cell Tissue Res 1988;254(2):317-330.
123. Lieberman JR, Daluiski A, Einhorn TA. The role of growth factors in the repair of bone. Biology and clinical applications. J Bone Joint Surg Am 2002;84-A(6): 1032-1044.
124. Gori F, Thomas T, Hicok KC, Spelsberg TC, Riggs BL. Differentiation of human marrow stromal precursor cells: bone morphogenetic protein-2 increases OSF2/CBFA1, enhances osteoblast commitment, and inhibits late adipocyte maturation. J Bone Miner Res 1999;14(9):1522-1535.
125. Chen B, Lin H, Wang J, Zhao Y, Wang B, Zhao W, et al. Homogeneous osteogenesis and bone regeneration by demineralized bone matrix loading with collagen-targeting bone morphogenetic protein-2. Biomaterials 2007;28(6):1027-1035.
126. Xie J, Li X, Xia Y. Putting Electrospun Nanofibers to Work for Biomedical Research. Macromol Rapid Commun 2008;29(22):1775-1792.
127. Liang D, Hsiao BS, Chu B. Functional electrospun nanofibrous scaffolds for biomedical applications. Adv Drug Deliv Rev 2007;59(14):1392-1412.
128.Deitzel JM,Kleinmeyer J,Harris D,Tan NCB.The effect of processing variables on the morphology of electrospun nanofibers and textiles.Polymer 2001;42:261-272.
129.Buchko JC,Chen CL,Shen Y,Martin CD.Processing and microstructural characterization of porous biocompatible protein polymer thin films.Polymer 1999;40:7397-7407.
130.Zong XH,Kim K,Fang DF,Ran SF,Hsiao SB,Chu B.Structure and process relationship of electrospun bioabsorbable nanofiber membranes.Polymer 2002;43:4403-4412.
131.Megelski S,Stephens JS,Chase DB,Rabolt JF.Micro- and nanostructured surface morphology on electrospun polymer fibers.Macromolecule 2002;35(22):8456-8466.
132.王颖俊,高长有.溶剂挥发性对PLGA电纺纤维直径及其膜动态力学性能的影响.组织工程与重建外科杂志2007:3:7-10.
133.Jaeger R,Bergshoef MM,Batlle CMI,Schonherr H,Vancso GJ.Electrospinning of ultra-thin polymer fibers.Macromol Symp 1998;127:141-150.
134.Yang F,Murugan R,Wang S,Ramakrishna S.Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissue engineering.Biomaterials 2005;26(15):2603-2610.
135.Zhong S,Teo WE,Zhu X,Beuerman RW,Ramakrishna S,Yung LY.An aligned nanofibrous collagen scaffold by electrospinning and its effects on in vitro fibroblast culture.J Biomed Mater Res A 2006;79(3):456-463.
136.Xu CY,Inai R,Kotaki M,Rarnakrishna S.Aligned biodegradable nanofibrous structure:a potential scaffold for blood vessel engineering.Biomaterials 2004;25(5):877-886.
137.Lee CH,Shin HJ,Cho IH,Kang YM,Kim IA,Park KD,et al.Nanofiber alignment and direction of mechanical strain affect the ECM production of human ACL fibroblast.Biomaterials 2005;26(11):1261-1270.
138.Yang D,Lu B,Zhao Y,Jiang X.Fabrication of aligned fibirous arrays by magnetic electrospinning.Adv Mater 2007;19:3702-3706.
139. Agarwal S, Greiner A, Wendorff JH. Electrospinning of Manmade and Biopolymer Nanofibers-Progress in Techniques, Materials, and Applications. Adv Funct Mater 2009; 19:1-17
140. Kidoaki S, Kwon IK, Matsuda T. Mesoscopic spatial designs of nano- and microfiber meshes for tissue-engineering matrix and scaffold based on newly devised multilayering and mixing electrospinning techniques. Biomaterials 2005;26(1):37-46.
141. Kim HW, Ju-Ha Song JH; Kim HE. Nanofiber generation of gelatin-hydroxyapatite biomimetics for guided tissue regeneration. Adv Funct Mater 2005;15(12):1988-1994.
142. Sun ZC, Zussman E, Yarin AL, Wendorff JH, Greiner A. Compound core-shell polymer nanofibers by co-electrospinning. Adv Mater 2003; 15:1929-1932.
143. Yu JH, Fridrikh SV, Rutledge GC. Production of submicrometer diameter fibers by two-fluid electrospinning. Adv Mater (Weinheim, Germany) 2004; 16:1562-1566.
144. Jiang H, Hu Y, Zhao P, Li Y, Zhu K. Modulation of protein release from biodegradable core-shell structured fibers prepared by coaxial electrospinning. J Biomed Mater Res B Appl Biomater 2006;79(1):50-57.
145. Townsend-Nicholson A, Jayasinghe SN. Cell electrospinning: a unique biotechnique for encapsulating living organisms for generating active biological microthreads/scaffolds. Biomacromolecules 2006;7(12):3364-3369.
146. Sanders EH, Kloefkorn R, Bowlin GL, Simpson DG, Wnek GE. Two-phase electrospinning from a single electrified jet: microencapsulation of aqueous reservoirs in poly(ethylene-co-vinyl acetate) fibers. Macromolecules 2003;36:3803-3805.
147. Baker BM, Mauck RL. The effect of nanofiber alignment on the maturation of engineered meniscus constructs. Biomaterials 2007;28(11): 1967-1977.
148. Lee YH, Lee JH, An IG, Kim C, Lee DS, Lee YK, et al. Electrospun dual-porosity structure and biodegradation morphology of Montmorillonite reinforced PLLA nanocomposite scaffolds. Biomaterials 2005;26(16):3165-3172.
149. Nam J, Huang Y, Agarwal S, Lannutti J. Improved cellular infiltration in electrospun fiber via engineered porosity. Tissue Eng 2007;13(9):2249-2257.
150. Kim TG, Chung HJ, Park TG Macroporous and nanofibrous hyaluronic acid/collagen hybrid scaffold fabricated by concurrent electrospinning and deposition/leaching of salt particles. Acta Biomater 2008;4(6): 1611-1619.
151. Baker BM, Gee AO, Metter RB, Nathan AS, Marklein RA, Burdick JA, et al. The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers. Biomaterials 2008;29(15):2348-2358.
152. Martinez E, Engel E, Planell JA, Samitier J. Effects of artificial micro- and nano-structured surfaces on cell behaviour. Ann Anat 2009; 191(1): 126-135.
153. Tian F, Hosseinkhani H, Hosseinkhani M, Khademhosseini A, Yokoyama Y, Estrada GG, et al. Quantitative analysis of cell adhesion on aligned micro- and nanofibers. J Biomed Mater Res A 2008;84(2):291-299.
154. Takahashi Y, Tabata Y. Effect of the fiber diameter and porosity of non-woven PET fabrics on the osteogenic differentiation of mesenchymal stem cells. J Biomater Sci Polym Ed 2004; 15(1):41-57.
155. Li M, Guo Y, Wei Y, MacDiarmid AG, Lelkes PI. Electrospinning polyaniline-contained gelatin nanofibers for tissue engineering applications. Biomaterials 2006;27(13):2705-2715.
156. Zong X, Bien H, Chung CY, Yin L, Fang D, Hsiao BS, et al. Electrospun fine-textured scaffolds for heart tissue constructs. Biomaterials 2005;26(26):5330-5338.
157. Venugopal J, Ramakrishna S. Biocompatible nanofiber matrices for the engineering of a dermal substitute for skin regeneration. Tissue Eng 2005;11(5-6):847-854.
158. Chong EJ, Phan TT, Lim IJ, Zhang YZ, Bay BH, Ramakrishna S, et al. Evaluation of electrospun PCL/gelatin nanofibrous scaffold for wound healing and layered dermal reconstitution. Acta Biomater 2007;3(3):321-330.
159. Kenawy el R, Layman JM, Watkins JR, Bowlin GL, Matthews JA, Simpson DG, et al. Electrospinning of poly(ethylene-co-vinyl alcohol) fibers. Biomaterials 2003;24(6):907-913.
160. Kumbar SG, James R, Nukavarapu SP, Laurencin CT. Electrospun nanofiber scaffolds: engineering soft tissues. Biomed Mater 2008;3(3):034002.
161. Liao S, Li B, Ma Z, Wei H, Chan C, Ramakrishna S. Biomimetic electrospun nanofibers for tissue regeneration. Biomed Mater 2006;1(3):R45-53.
162. Ma Z, Kotaki M, Yong T, He W, Ramakrishna S. Surface engineering of electrospun polyethylene terephthalate (PET) nanofibers towards development of a new material for blood vessel engineering. Biomaterials 2005;26(15):2527-2536.
163. Schnell E, Klinkhammer K, Balzer S, Brook G, Klee D, Dalton P, et al. Guidance of glial cell migration and axonal growth on electrospun nanofibers of poly-epsilon-caprolactone and a collagen/poly-epsilon-caprolactone blend. Biomaterials 2007;28(19):3012-3025.
164. Ahmed I, Liu HY, Mamiya PC, Ponery AS, Babu AN, Weik T, et al. Three-dimensional nanofibrillar surfaces covalently modified with tenascin-C-derived peptides enhance neuronal growth in vitro. J Biomed Mater Res A 2006;76(4):851-860.
165. Patel S, Kurpinski K, Quigley R, Gao H, Hsiao BS, Poo MM, et al. Bioactive nanofibers: synergistic effects of nanotopography and chemical signaling on cell guidance. Nano Lett 2007;7(7):2122-2128.
166. Chew SY, Mi R, Hoke A, Leong KW. Aligned Protein-Polymer Composite Fibers Enhance Nerve Regeneration: A Potential Tissue-Engineering Platform. Adv Funct Mater 2007; 17(8): 1288-1296.
167. Li WJ, Danielson KG, Alexander PG, Tuan RS. Biological response of chondrocytes cultured in three-dimensional nanofibrous poly(epsilon-caprolactone) scaffolds. J Biomed Mater Res A2003;67(4):1105-1114.
168. Subramanian A, Vu D, Larsen GF, Lin HY. Preparation and evaluation of the electrospun chitosan/PEO fibers for potential applications in cartilage tissue engineering. J Biomater Sci Polym Ed 2005;16(7):861-873.
169. Meng W, Kim SY, Yuan J, Kim JC, Kwon OH, Kawazoe N, et al. Electrospun PHBV/collagen composite nanofibrous scaffolds for tissue engineering. J Biomater Sci Polym Ed 2007;18(1):81-94.
170. Shields KJ, Beckman MJ, Bowlin GL, Wayne JS. Mechanical properties and cellular proliferation of electrospun collagen type II. Tissue Eng 2004;10(9-10):1510-1517.
171. Griffith LG, Naughton G. Tissue engineering—current challenges and expanding opportunities. Science 2002;295(5557): 1009-1014.
172. Fujihara K, Kotaki M, Ramakrishna S. Guided bone regeneration membrane made of polycaprolactone/calcium carbonate composite nano-fibers. Biomaterials 2005;26(19):4139-4147.
173. Kim HW, Lee HH, Knowles JC. Electrospinning biomedical nanocomposite fibers of hydroxyapatite/poly(lactic acid) for bone regeneration. J Biomed Mater Res A 2006;79(3):643-649.
174. Chen J, Chu B, Hsiao BS. Mineralization of hydroxyapatite in electrospun nanofibrous poly(L-lactic acid) scaffolds. J Biomed Mater Res A 2006;79(2):307-317.
175. Yu HS, Hong SJ, Kim HW. Surface-mineralized polymeric nanofiber for the population and osteogenic stimulation of rat bone-marrow stromal cell. Mater Chem Phys 2009; 113:873-877.
176. Agarwal S, Wendorff JH, Gre A. Progress in the Field of Electrospinning for Tissue Engineering Applications. Adv Mater 2009;21:3343-3351.
177. Zhao HG, Ma L, Gao CY, Wang JF, Shen JC. Fabrication and properties of injectable β-tricalcium phosphate particles/fibrin gel composite scaffolds for bone tissue engineering. Mater Sci Eng C 2009;29:836-842.
178. Li Y, Kong F, Weng W. Preparation and characterization of novel biphasic calcium phosphate powders (alpha-TCP/HA) derived from carbonated amorphous calcium phosphates. J Biomed Mater Res B Appl Biomater 2009;89B(2):508-517.
179. Jayasuriya AC, Shah C, Ebraheim NA, Jayatissa AH. Acceleration of biomimetic mineralization to apply in bone regeneration. Biomed Mater 2008;3(1):15003.
180. Kim YJ, Sah RL, Doong JY, Grodzinsky AJ. Fluorometric assay of DNA in cartilage explants using Hoechst 33258. Anal Biochem 1988;174(1):168-176.
181. Thomas V, Dean DR, Jose MV, Mathew B, Chowdhury S, Vohra YK. Nanostructured biocomposite scaffolds based on collagen coelectrospun with nanohydroxyapatite.Biomacromolecules 2007;8(2):631-637.
182.Zhang HL,Liu JS,Yao ZW,Yang J,Pan LZ,Chen ZQ.Biomimetic mineralization of electrospun poly(lactic-co-glycolic acid)/multi-walled carbon nanotubes composite scaffolds in vitro.Mater Lett 2009;63(27):2313-2316.
183.Zhang P,Hong Z,Yu T,Chen X,Jing X.In vivo mineralization and osteogenesis of nanocomposite scaffold of poly(lactide-co-glycolide) and hydroxvapatite surface-grafted with ooly(L-lactide).Biomaterials 2009;30(1):58-70.
184.胡小红.软骨修复用水凝胶的制备和性能研究.浙江大学博士学位论文2009.
185.Lee J,Tae G,Kim YH,Park IS,Kim SH.The effect of gelatin incorporation into electrospun poly(L-lactide-co-epsilon-caprolactone) fibers on mechanical properties and cytocompatibility.Biomaterials 2008;29(12):1872-1879.
186.Tan H,Wu J,Lao L,Gao C.Gelatin/chitosan/hyaluronan scaffold integrated with PLGA microspheres for cartilage tissue engineering.Acta Biomater 2009;5(1):328-337.
187.Zhang Y,Venugopal JR,El-Turki A,Ramakrishna S,Su B,Lim CT.Electrospun biomimetic nanocomposite nanofibers of hydroxyapatite/chitosan for bone tissue engineering.Biomaterials 2008;29(32):4314-4322.
188.Dulgar-Tulloch AJ,Bizios R,Siegel RW.Human mesenchymal stem cell adhesion and proliferation in response to ceramic chemistry and nanoscale topography.J Biomed Mater Res A 2009;90(2):586-594.
189.Cui Y,Liu Y,Jing X,Zhang P,Chen X.The nanocomposite scaffold of poly(lactide-co-glycolide) and hydroxyapatite surface-grafted with L-lactic acid oligomer for bone repair.Acta Biomater 2009;5(7):2680-2692.
190.Tsukamoto Y,Fukutani S,Moil M.Hydroxyapatite-induced alkaline phosphatase activity of human pulp fibroblasts.J Mater Sci-Mater Med 1992;3:180-183.
191.Ruoslahti E,Pierschbacher MD.New perspectives in cell adhesion:RGD and integrins.Science 1987;238(4826):491-497.
192.谈华平.生物活性软骨组织工程支架的制备与性能研究.浙江大学博士学位论文2007.
193.王淡兮,孙秀兰.蛋白质定量检测方法的探讨.粮食与食品工业2009;16(4):49-51&62.
194.Rhee SH,Lee JD,Tanaka J.Nucleation of hydroxyapatite crystal through chemical interaction with collagen.J Am Ceram Soc 2000;83:2890-2892.
195.Liu C,Han Z,Czernuszka JT.Gradient collagen/nanohydroxyapatite composite scaffold:development and characterization.Acta Biomater 2009;5(2):661-669.
196.Ekaputra AK,Prestwich GD,Cool SM,Hutmacher DW.Combining electrospun scaffolds with electrosprayed hydrogels leads to three-dimensional cellularization of hybrid constructs.Biomacromolecules 2008;9(8):2097-2103.
197.Pham QP,Sharma U,Mikos AG.Electrospun poly(epsilon-caprolactone)microfiber and multilayer nanofiber/microfiber scaffolds:characterization of scaffolds and measurement of cellular infiltration.Biomacromolecules 2006;7(10):2796-2805.