摘要
随着组织工程研究的深入,具有特定生物学功能的组织工程支架逐渐成为研究热点。电纺法制备的超细纤维比表面积大,孔隙率高,尤其具有与天然细胞外基质相近的纳米级结构,是理想的药物载体和组织工程支架材料;而电喷微球大小均匀可控,呈现较好的单分散性,在药物释放和生物涂层方面具有很大应用前景。本文以电纺超细纤维和电喷微球为研究对象,通过表面修饰和功能化的方法制备适用于不同应用方向的支架材料和药物载体,并考察其生物学特性。
采用乳液电纺法将蛋白酶K包载于聚乙二醇单甲醚-聚丙交酯两嵌段共聚物(PELA)超细纤维内部,体外降解实验表明,与PELA超细纤维比较,包载蛋白酶K的PELA超细纤维膜降解速度明显加快。将乳液电纺法和同轴电纺法相结合,制备芯层包载牛血清蛋白,外层包载蛋白酶K的聚氧化乙烯(PEO)/PELA超细纤维,有望成为可控释放的新型药物载体。
采用逐层自组装沉积法在聚ε-己内酯(PCL)超细纤维表面制备明胶涂层,然后在10倍浓度的人体模拟体液(10SBF)中浸泡沉积磷酸钙涂层,最终得到含有PCL、明胶和类骨磷酸钙的复合支架,前成骨细胞(MC3T3-E1)在复合支架表面表现出很好的粘附和增殖,证明此支架适用于骨组织工程。通过滴加10SBF的方法在PCL、聚(丙交酯-co-乙交酯)(PLGA)超细纤维膜表面制备类骨磷酸钙梯度涂层。对纤维膜进行力学性能测试发现,电纺膜局部杨氏模量随磷酸钙含量降低而降低;体外细胞培养发现MC3T3-E1细胞密度随电纺膜轴向磷酸钙含量降低而下降,这说明磷酸钙梯度涂层超细纤维膜是一种很有潜力的、可用于骨-肌腱界面损伤修复的支架材料。通过在接收屏上方放置可移动支撑架的方法来控制电喷过程中接收屏不同位置接收微球的时间,一步法制备了连续和不连续PLGA微球梯度涂层。在不同粗糙度的微球涂层表面进行背根神经节培养,发现适宜的表面粗糙度有利于神经突起的粘附和生长。
In the field of tissue engineering, functionalized scaffolds have gained popularity for specific engineering applications with improved biological performance. Electrospun ultrafine fibers have been investigated as promising tissue engineering scaffolds since they can mimic the nanofibrous assembled structure of extracellular matrix (ECM). Microspheres and nanospheres produced by electrospraying are uniform-sized and monodisperse, which make it a suitable candidate for drug carrier and biological coating. In this thesis, we focused on the surface modification and functionalization of electrospun fibers and electrosprayed microspheres with different applications as drug delivery and tissue engineering system.
Proteinase K was successfully loaded inside ultrafine fibers of poly(ethylene glycol)-poly(L-lactide) (PELA) by emulsion electrospinning. In vitro degradation study showed that the proteinase K-loaded PELA membranes exhibited self-accelerated biodegradability and could benefit drug controlled release and tissue regeneration. Poly(ethylene oxide) (PEO)/PELA core/shell structured ultrafine fibers, with bovine serum albumin in the core section and proteinase K in the shell section, a promising drug carrier for controlled drug release was produced by combining coaxial electrospinning and emulsion electrsospinning.
A hybrid scaffod containing poly(ε-caprolactone) (PCL), gelatin and calcium phosphate which could serve as a new class of biomimetic scaffolds for bone tissue engineering was produced by surface modification. The surfaces of the PCL fibers were coated with gelatin through layer-by-layer deposition, followed by functionalization with a uniform coating of bonelike calcium phosphate by mineralization in the 10 times concentrated simulated body fluid (10SBF). It was found that the preosteoblastic MC3T3-E1 cells attached, spread, and proliferated well with a flat morphology on the mineralized scaffolds. A continuously graded, bonelike calcium phosphate coating on a nonwoven mat of electrospun PCL and poly(lactic-co-glycolic acid) (PLGA) nanofibers was achieved by adding 10SBF at a constant rate into a glass vial, which contained the electrospun mat in a titled orientation. The results of the mechanical testing showed that Young’s modulus along the scaffolds increased with increasing levels of mineral. Preosteoblastic MC3T3-E1 cells were seeded onto a gelatin-coated PCL scaffold covered by a graded coating of calcium phosphate, and it was found that the cell density gradually decreased with decreasing mineral content. All the results indicated that this new class of nanofiber-based scaffolds can potentially be employed for repairing the tendon-to-bone insertion site via a tissue engineering approach. Continuous and discrete microsphere density gradients on underlying substrates were fabricated by spatially controlling collection time during electrospraying. A moveable paper mask was placed above the collector to control the collection time. Dorsal root ganglions were cultured on microsphere coatings of varying roughness. It was found that the optimal surface roughness cound promote neurite adhesion and extension.
引文
[1] Wu Y, Clark R. Electrohydrodynamic atomization: a versatile process for preparing materials for biomedical applications. Journal of Biomaterials Science, Polymer Edition, 2008, 19 (5): 573-601.
[2] Wong S F, Meng C K, Fenn J B. Multiple charging in electrospray ionization of poly(ethylene glycols). The Journal of Physical Chemistry, 1998, 92 (2): 546-550.
[3] Formhals A. Process and apparatus for preparing artificial threads. US Patent, 1934, 1975504.
[4] Spivak A F, Dzenis Y A, Reneker D H. A model of steady state jet in the electrospinning process. Mechanics Research Communications, 2000, 27 (1): 37-42.
[5] Reneker D H, Kataphinan W, Theron A, Zussman E, Yarin A L. Nanofiber garlands of polycaprolactone by electrospinning. Polymer, 2000, 43 (25): 6785-6794.
[6] Shin Y M, Hohman M M, Brenner M P, Rutledge G C. Experimental characterization of electrospinning: the electrically forced jet and instabilities. Polymer, 2001, 42(25): 9955-9967.
[7] Zarkoob S, Eby R, Reneker D H, Hudson S D, Ertley D, Adams W W. Structure and morphology of electrospun silk nanofibers. Polymer, 2004, 45 (11): 3973-3977
[8] Zhou S, Peng H, Yu X, et al. Preparation and characterization of a novel electrospun spider silk fibroin/poly(D,L-lactide) composite fiber. Journal of Physical Chemistry B, 2008, 112 (36): 11209-11216.
[9] Burger C, Hsiao B S, Chu B. Nanofibrous materials and their applications. Annual Review of Materials Research, 2006, 36: 333-368.
[10] Xie J, Marijnissen J C, Wang C. Microparticles developed by electrohydrodynamic atomization for the local delivery of anticancer drug to treat C6 glioma in vitro. Biomaterials, 2006, 27 (17): 3321-3332.
[11] Yeo L Y, Gagnon Z, Chang H. AC electrospray biomaterials synthesis. Biomaterials, 2005, 26 (31): 6122-6128.
[12] Liu Y, He J, Yu J, Zeng H. Controlling numbers and sizes of beads in electrospun nanofibers. Polymer International, 2008, 57 (4):632-636.
[13] Huang Z, Zhang Y, Kotaki M, Ramakrishna S. A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Composites Science and Technology, 2003, 63 (15): 2223-2253.
[14] You Y, Youk J H, Lee S W, Min B, Lee S J, Park W H. Preparation of porous ultrafine PGA fibers via selective dissolution of electrospun PGA/PLA blend fibers. Materials Letters, 2006, 60 (6): 757-760.
[15] Zhang Y Z, Feng Y, Huang Z M, Ramakrishna S, Lim C T. Fabrication of porous electrospun nanofibres. Nanotechnology, 2006, 17: 901-908.
[16] Bognitzki M, Czado W, Frese T, et al. Nanostructured fibers via electrospinning. Advanced Materials, 2001, 13 (1): 70-72.
[17] Casper C L, Stephens J S, Tassi N G, et al. Controlling surface morphology of electrospun polystyrene fibers: effect of humidity and molecular weight in the electrospinning process. Macromolecules, 2004, 37 (2): 573-578.
[18] McCann J T, Marquez M, Xia Y. Highly porous fibers by electrospinning into a cryogenic liquid. Journal of the American Chemical Society, 2006, 128 (5): 1436-1437.
[19] Li D, Xia Y. Direct fabrication of composite and ceramic hollow nanofibers by electrospinning. Nano Letters, 2004, 4 (5): 933-938.
[20] Larsen G, Velarde-Ortiz R, Minchow K, et al. A method for making inorganic and hybrid (organic/inorganic) fibers and vesicles with diameters in the submicrometer and micrometer range via sol-gel chemistry and electrically forced liquid jets. Journal of the American Chemical Society, 2003, 125 (5): 1154-1155.
[21] Zhao Y, Cao X, Jiang L. Bio-mimic multichannel microtubes by a facile method. Journal of the American Chemical Society, 2007, 129 (4): 764-765.
[22] Lin S, Cai Q, Ji J, et al. Electrospun nanofiber reinforced and toughened composites through in situ nano-interface formation. Composites Science and Technology, 2008, 68 (15-16): 3322-3329.
[23] Li X, Su Y, Liu S, Tan L, Mo X, Ramakrishna S. Encapsulation of proteins in poly(L-lactide-co-caprolactone) fibers by emulsion electrospinning. Colloids and Surface B: Biointerface, 2010, 75(2): 418-424.
[24] Yang Y, Li X, Qi M, et al. Release pattern and structural integrity of lysozyme encapsulated in core-sheath structured poly(D, L-lactide) ultrafine fibers prepared by emulsion electrospinning. European Journal of Pharmaceutics and Biopharmaceutics, 2008, 69 (1): 106-116.
[25] Xiang R, Chang C, Fann W. Electrospinning of continuous aligned polymer fibers. Applied Physics Letters, 2004, 84 (7): 1222-1224.
[26] Matthew J A, Wnek G E, Simpson D G, Bowlin G L. Electrospinning of collagen nanofibers. Biomacromolecules, 2002, 3: 232-238.
[27] Kessick R, Fenn J, Tepper G. The use of AC potentials in electrospraying and electrospinning processes. Polymer, 2004, 45 (9): 2981-2984.
[28] Xu C Y, Inai R, Kotaki M, Ramakrishna S. Aligned biodegradable nanofibrous structure: a potential scaffold for blood vessel engineering. Biomaterials, 2004, 25 (5): 877-886.
[29] Fong H, Liu W, Wang C S, Vaia R A. Generation of electrospun fibers of nylon 6 and nylon 6-montmorillonite nanocomposite. Polymer, 2002, 43 (3): 775-780.
[30] Deitzel J M, Kleinmeyer J D, Hirvonen J K, Beck Tan N C. Controlled deposition of electrospun poly(ethylene oxide) fibers. Polymer, 2001, 42 (19): 8163-8170.
[31] Li D, Wang Y, Xia Y. Electrospinning of polymeric and ceramic nanofibers as uniaxially alighed arrays. Nano Letters, 2003, 3 (8): 1167-1171.
[32] Katta P, Alessandro M, Ramsier R D, Chase G G. Continuous electrospinning of aligned polymer nanofibers onto a wire drum collector. Nano Letters, 2004, 4 (11): 2215-2218.
[33] Li D, Wang Y, Xia Y. Electrospinning nanofibers as uniaxially aligned arrays and layer-by-layer stacked films. Advanced Materials, 2004, 16 (4): 361-366.
[34] Yoo H S, Kim T G, Park T G. Surface-functionalized electrospun nanofibers for tissue engineering and drug delivery. Advanced Drug Delivery Reviews, 2009, 61 (12): 1033-1042.
[35] Park H, Lee K Y, Lee S J, et al. Plasma-treated poly(lactic-coglycolic acid) nanofibers for tissue engineering, Macromolecular Research, 2007, 15 (3): 238-243.
[36] Baek H S, Park Y H, Ki C S, et al. Enhanced chondrogenic responses of articular chondrocytes onto porous silk fibroin scaffolds treated with microwave-induced argon plasma. Surface and Coatings Technology, 2008, 202 (22-23): 5794-5797.
[37] Koh H S, Yong T, Chan C K, Ramakrishna S. Enhancement of neurite outgrowth using nano-structured scaffolds coupled with laminin. Biomaterials, 2008, 29 (26): 3574-3582.
[38] He W, Yong T, Ma Z W, et al. Biodegradable polymer nanofiber mesh to maintain functions of endothelial cells. Tissue Engineering, 2006, 12 (9): 2457-2466.
[39] Yang F, Wolke J G C, Jansen J A, Biomimetic calcium phosphate coating on electrospun poly (ε-caprolactone) scaffolds for bone tissue engineering. Chemical Engineering Journal, 2008, 137 (1): 154-161.
[40] Croll T I, O'Connor A J, Stevens G W, Cooper-White J J. Controllable surface modification of poly(lactic-co-glycolic acid) (PLGA) by hydrolysis or aminolysis I: Physical, chemical, and theoretical aspects. Biomacromolecules, 2004, 5 (2): 463-473.
[41] Yuan X Y, Mak A F T, Yao K D. Surface degradation of poly(L-lactic acid) fibres in a concentrated alkaline solution. Polymer Degradation and Stability, 2003, 79 (1): 45-52.
[42] Yanagida H, Okada M, Masuda M, et al. Cell adhesion and tissue response to hydroxyapatite nanocrystal-coated poly(L-lactic acid) fabric. Journal of Bioscience and Bioengineering, 2009, 108 (3): 235-243.
[43] Chen J, Chu B, Hsiao B S. Mineralization of hydroxyapatite in electrospun nanofibrous poly(L-lactic acid) scaffolds. Journal of Biomedical Materials Research, 2006, 79A (2): 307-317.
[44] Ma Z W, Kotaki M, Yong T, et al. Surface engineering of electrospun polyethylene terephthalate (PET) nanofibers towards development of a new material for blood vessel engineering. Biomaterials, 2005, 26 (15): 2527-2536.
[45] Venugopal J R, Low S, Choon A T, et al. Nanobioengineered electrospun composite nanofibers and osteoblasts for bone regeneration. Artificial Organs, 2008, 32(5):388-397.
[46] Choi J S, Leong K W, Yoo H S. In vivo wound healing of diabetic ulcers using electrospun nanofibers immobilized with human epidermal growth factor (EGF). Biomaterials, 2008, 29 (5): 587-596.
[47] Yoshida M, Langer R, Lendlein A, Lahann J. From advanced biomedical coatings to multi-functionalized biomaterials. Polymer Reviews, 2006, 46 (4): 347-375.
[48] Casper C L, Yamaguchi N, Kiick K L, Rabolt J F. Functionalizing electrospun fibers with biologically relevant macromolecules. Biomacromolecules, 2005, 6 (4): 1998-2007.
[49] Saurer E M, Jewell C M, Kuchenreuther J M, Lynn D M. Assembly of erodible, DNA-containing thin films on the durfaces of polymer microparticles: Toward a layer-by-layer approach to the delivery of DNA to antigenpresenting cells. Acta Biomaterialia, 2009, 5 (3): 913-924.
[50] Muller K, Quinn J F, Johnston A R, et al. Polyelectrolyte functionalization of electrospun fibers. Chemistry of Materials, 2006, 18 (9): 2397-2403.
[51] Wu Y, Clerk R L. Controllable porous polymer particles generated by electrospraying. Journal of Colloid and Interface Science, 2007, 310 (2): 529-535.
[52] Loscertales I G, Barrero A, Guerrero I, et al. Micro/nano encapsulation via electrified coaxial liquid jets. Science, 2002, 295 (5560): 1695-1698.
[53] López H J M, Barrero A, López A, et al. Coaxial jets generated from electrified Taylor cones. Scaling laws. Journal of Aerosol Science, 2003, 34 (5): 535-552.
[54] Hartman R P A, Brunner D J, Camelot D M A, et al. Electrohydrodynamic atomization in the cone-jet mode physical modeling of the liquid cone and jet. Journal of Aerosol Science, 1999, 30 (7): 823-849.
[55] Ga?án-Calvo A M, Dávila J, Barrero A. Current and droplet size in the electrospraying of liquids. Scaling laws. Journal of Aerosol Science. 1997, 28 (2): 249-275.
[56] Ahmad Z, Zhang H B, Farook U, et al. Generation of multilayered structures for biomedical applications using a novel tri-needle coaxial device and electrohydrodynamic flow. Journal of the Royal Society Interface, 2008, 5 (27): 1255-1261.
[57] He C, Huang Z, Han X. Fabrication of drug-loaded electrospun aligned fibrous threads for suture applications. Journal of Biomedical Materials Research, 2009, 89A (1): 80-95.
[58] Chew, S Y, Wen J, Yim E K, et al. Sustained release of proteins from electrospun biodegradable fibers. Biomacromolecules, 2005, 6 (4): 2017-2024.
[59] Huang Z, He C, Wang H, Mo X. Preparation of core-shell biodegradable microfibers for long-term drug delivery. Journal of Biomedical Materials Research, 2009, 90A (4): 1243-1251.
[60] Li X, Su Y, Zhou X, Mo X. Distribution of Sorbitan Monooleate in poly(L-lactide-co-ε-caprolactone) nanofibers from emulsion electrospinning. Colloids and Surfaces B: Biointerfaces, 2009, 69 (2): 221-224.
[61] Zeng J, Xu X Y, Chen X S, et al. Biodegradable electrospun fibers for drug delivery. Journal of Controlled Release, 2003, 92 (3): 227-231.
[62] Zeng J, Yang L, Liang Q, et al. Influence of the drug compatibility with polymer solution on the release kinetics of electrospun fiber formulation. Journal of Controlled Release, 2005, 105 (1-2): 43-51.
[63] Xu X L, Yang L X, Xu X Y. Ultrafine medicated fibers electrospun from W/O emulsions. Journal of Controlled Release, 2005, 108 (1): 33-42.
[64] Xu X, Chen X, Wang Z, Jing X. Ultrafine PEG-PLA fibers loaded with both paclitaxel and doxorubicin hydrochloride and their in vitro cytotoxicity. European Journal of Pharmaceutics and Biopharmaceutics, 2009, 72 (1): 18-25.
[65] Su Y, Li X, Liu S, Mo X, Seeram R. Controlled release of dual drugs from emulsion electrospun nanofibrous mats. Colloids and Surfaces B: Biointerfaces, 2009, 73 (2): 376-381.
[66] Luu Y, Kim K, Hsiao B, Chu B, Hadjiargyrou M. Development of a nanostructured DNA delivery scaffold via electrospinning of PLGA and PLA-PEG block copolymers. Journal of Controlled Release, 2003, 89 (2): 341-353.
[67] Chu B, Liang D, Hadjiargyrou M, Hsiao B S. A new pathway for developing in vitro nanostructured non-viral gene carriers. Journal of Physics: Condensed Matter, 2006, 18: S2513-S2525.
[68] Kim K H, Jeong L, Park H. Biological efficacy of silk fibroin nanofiber membranes for guided bone regeneration. Journal of Biotechnology, 2005, 120 (3): 327-339.
[69] Weiner S, Wagner H D. The material bone: Structure-mechanical function relations. Annual Review of Materials Science, 1998, 28: 271-298.
[70] Venugopal J, Vadgama P, Kumar T S S, Ramakrishna S. Biocomposite nanofibres and osteoblasts for bone tissue engineering. Nanotechnology, 2007, 18: 055101 (8pp).
[71] Taguchi T, Kishida A, Akashi M. Hydroxyapatite formation on/in hydrogels using a novel alternate soaking process. Chemistry Letters, 1998, 27 (8): 711-712.
[72] Taguchi T, Muraoka Y, Matsuyama H, Kishida A, Akashi M. Apatite coating on hydrophilic polymer-grafted poly(ethylene) films using an alternate soaking process. Biomaterials, 2001, 22 (1): 53-58.
[73] Mutsuzaki H, Sakane M, Nakajima H, Ito A, Hattori S, Miyanaga Y, Ochiai N, Tanaka J. Calcium phosphate-hybridized tendon directly promotes regeneration of tendon-bone insertion. Journal of Biomedical Materials Research. Part A, 2004, 70 (2): 319-327.
[74] Kim H M, Kishimoto K, Miyaji F, et al. Composition and structure of the apatite formed on PET substrate in SBF modified with various ionic activity products. Journal of Biomedical Materials Research, 1999, 46 (2): 228-235.
[75] Oyane A, Kawashita M, Nakanishi K, et al. Bonelike apatite formation on ethylene-vinyl alcohol copolymer modified with silane coupling agent and calcium silicate solutions. Biomaterials, 2003, 24 (10): 1729-1735.
[76] Balas F, Kawashita M, Nakamura T, Kokubo T. Formation of bone-like apatite on organic polymers treated with a silane-coupling agent and a titania solution. Biomaterials, 2006, 27 (9): 1704-1710.
[77] Kawashita M, Nakao M, Minoda M, et al. Apatite-forming ability of carboxyl group-containing polymer gels in a simulated body fluid. Biomaterials, 2003, 24 (14): 2477-2884.
[78] Li C, Vepari C, Jin H, et al. Electrospun silk-BMP-2 scaffolds for bone tissue engineering. Biomaterials, 2006, 27 (16): 3115-3124.
[79] Fu Y C,Nie H,Ho M L,et al. Optimized bone regeneration based on sustained release from three-dimensional fibrous PLGA/HAp composite scaffolds loaded with BMP-2. Biotechnology and Bioengineering, 2008, 99 (4): 996-1006.
[80] James R, Kesturu G, Balian G, Chhabra B. Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options. Journal of Hand Surgery, 2008, 33A (1): 102-112.
[81] Laurencin C T, Freeman J W. Ligament tissue engineering: an evolutionary materials science approach. Biomaterials, 2005, 26 (36): 7530-7536.
[82] Sahoo S, Ouyang H, Goh J C, et al. Characterization of a novel polymeric scaffold for potential application in tendon/ligament tissue engineering. Tissuse Engineering, 2006, 12 (1): 91-99.
[83] Moffat K L, Kwei A S, Spalazzi J P, et al. Novel nanofiber-based scaffold for rotator cuff repair and augmentation. Tissuse Engineering: Part A, 2009, 15 (1): 115-126.
[84] Molloy T, Wang Y, Murrell G. The roles of growth factors in tendon and ligament healing. Sports Medicine, 2003, 33 (55): 381-394.
[85] 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.
[86] Patel S, Kurpinski K, Quigley R, et al. Bioactive Nanofibers: Synergistic effects of nanotopography and chemical signaling on cell guidance. Nano letters, 2007, 7 (7): 2122-2128.
[87] Chew S Y, Mi R, Hoke A, Leong K W. Aligned protein-polymer composite fibers enhance nerve regeneration: a potential tissue-engineering platform. Advanced Functional Materials, 2007, 17 (8): 1288-1296.
[88] Xie J W, MacEwan M R, Willerth S M, et al. Conductive core-sheath nanofibers and their potential application in neural tissue engineering. Advanced Functional Materials, 2009, 19 (14): 2312-2318.
[89] Pareta R, Edirisinghe M J. A novel method for preparation of biodegradable microspheres for protein drug delivery. Journal of the Royal Society Interface, 2006, 3 (9): 573-582.
[90] Wu Y, MacKay J A, McDaniel J R, Chilkoti A, Clark R L. Fabrication of elastin-like polypeptide nanoparticles for drug delivery by electrospraying. Biomacromolecules, 2009, 10 (1): 19-24.
[91] Xie J, Wang C. Encapsulation of proteins in biodegradable polymeric microparticles using electrospray in the Taylor cone-jet mode. Biotechnology and Bioengineering, 2007, 97 (5): 1278-1290.
[92] Huang J, Jayasinghe N, Best S M, et al. Novel deposition of nano-sized silicon substituted hydroxyapatite by electrostatic spraying. Journal of Materials Science: Materials in Medicine, 2005, 16: 1137-1142.
[93] Morozov V N, Morozova T Y. Electrospray deposition as a method to fabricatefunctionally active protein films. Analytical Chemistry, 1999, 71 (7): 1415-1420.
[94] Stride E, Edirisinghe M. Novel preparation techniques for controlling microbubble uniformity: a comparison. Medical and Biological Engineering and Computing, 2009, 47 (8): 883-892.
[95] Farook U, Stride E, Edirisinghe M J. Preparation of suspensions of phospholipid-coated microbubbles by coaxial electrohydrodynamic atomization. Journal of the Royal Society Interface, 2009, 6 (32): 271-277.
[96] Park C H, Kim K, Lee J, Lee J. In-situ nanofabrication via electrohydrodynamic jetting of countercharged nozzles. Polymer Bulletin, 2008, 61 (4): 521-528.
[97] Gupta D, Venugopal J, Mitra S, et al. Nanostructured biocomposite substrates by electrospinning and electrospraying for the mineralization of osteoblasts. Biomaterials, 2009, 30 (11): 2085-2094.
[98] Stankus J J, Soletti L, Fujimoto K, Hong Y. Fabrication of cell microintegrated blood vessel constructs through electrohydrodynamic atomization. Biomaterials, 2007, 28 (17): 2738-2746.
[99] Lee S H, Shin H. Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering. Advanced Drug Delivery Reviews, 2007, 59 (4-5): 339-359.
[100] Huttunen M, Ashammakhi N, Tormala P, Kellomaki M. Fibre reinforced bioresorbable composites for spinal surgery. Acta Biomaterialia, 2006, 2 (5): 575-587.
[101] Liu X H, Won Y J, Ma P X. Surface modification of interconnected porous scaffolds. Journal of Biomedical Materials Research Part A, 2005, 74A (1): 84-91.
[102] Williams D F. Enzymatic hydrolysis of polylactic acid. Engineering Medical, 1981, 10 (1): 5-7.
[103] Kikkawa Y, Fujita M, Abe H, Doi Y. Effect of water on the surface molecular mobility of poly(lactide) thin films: an atomic force microscopy study. Biomacromolecules, 2004, 5 (4): 1187-1193.
[104] Yamashita K, Kikkawa Y, Kurokawa K, Doi Y. Enzymatic degradation of poly(L-lactide) film by proteinase K: quartz crystal microbalance and atomic force microscopy study. Biomacromolecules, 2005, 6 (2): 850-857.
[105] Kurokawa K J, Yamashita K C, Doi Y, Abe H. Surface properties and enzymatic degradation of end-capped poly(L-lactide). Polymer Degradation and Stability, 2006, 91 (6): 1300-1310.
[106] Li S, Tenon M, Garreau H, et al. Enzymatic degradation of stereocopolymers derived from L-, DL- and meso-lactides. Polymer Degradation and Stability, 2000, 67 (1): 85-90.
[107] Tsuji H, Miyauchi S. Enzymatic hydrolysis of poly(lactide)s: effects of molecular weight, L-lactide content, and enantiomeric and diastereoisomeric polymer blending. Biomacromolecules, 2001, 2 (2): 597-604.
[108] Tsuji H, Tezuka Y, Yamada J. Alkaline and enzymatic degradation of L-lactide copolymers. II. crystallized films of poly(L-lactide-co-D-lactide) and poly(L-lactide) with similar crystallinities. Journal of Polymer Science, Part B: Polymer Physics. 2005, 43 (9): 1064-1075.
[109] Zeng J, Chen X S, Liang Q Z, et al. Enzymatic degradation of poly(L-lactide) and poly(ε-caprolactone) electrospun fiber. Macromolecular Bioscience, 2004, 4 (12): 1118-1125.
[110] Li S, Molina I, Martinez MB, Vert M. Hydrolytic and enzymatic degradation of physically crosslinked hydrogels prepared from PLA/PEO/PLA triblock copolymers. Journal of Materials Science: Materials in Medicine, 2002, 13 (11): 81-86.
[111] Reneker D H. Bending instability of electrically charged liquid jets of polymer solutions in electrospinning. Journal of Applied Physics, 2000, 87 (9): 4531-4547.
[112] Xu X L, Zhang X L, Chen X S, et al. Preparation of core-sheath composite nanofibers by emulsion electrospinning. Macromolecular Rapid Communications, 2006, 27 (19): 1637-1642.
[113] Xu X, Che X, Ma P. et al. The release behavior of doxorubicin hydrochloride from medicated fibers prepared by emulsion-electrospinning. European Journal of Pharmaceutics and Biopharmaceutics, 2008, 70 (1): 165-170.
[114] Qi H, Hu P, Xu J, Wang A. Encapsulation of drug reservoirs in fibers by emulsion electrospinning: morphology, characterization and preliminary release assessment. Biomacromolecules, 2006, 7 (8): 2327-2330.
[115] Bazilevsky A V, Yarin A L, Megaridis C M. Co-electrospinning of core-shell fibers using a single-nozzle technique. Langmuir, 2007, 23 (5): 2311-2314.
[116] Sy J C, Klemm A S, Shastri P. Emulsion as a means of controlling electrospinning of polymers. Advanced Materials, 2009, 21 (18): 1814-1819.
[117] Yoshimoto M, Wang S, Fukunaga K, et al. Enhancement of apparent substrate selectivity of proteinase K encapsulated in liposomes through a cholate-induced alteration of the bilayer permeability. Biotechnology and Bioengineering, 2004, 85 (2): 222-233.
[118] Kim K, Yu M, Zong X, 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.
[119] Sweeney P J, Walker J M. Proteinase K in Enzymes of molecular biology (Burrell M M ed.) New Jersey: Humana Press; 1993. p. 305 (chapter 16).
[120] Jiang H, Hu Q, Zhao P, Li Y, Zhu K. Modulation of protein release from biodegradable core-shell structured fibers prepared by coaxial electrospinning. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2006, 79 (11): 50-57.
[121] Li S, Sun B, Li X, Yuan X. Characterization of electrospun core/shell poly(vinyl pyrrolidone)/poly(L-lactide-co-ε-caprolactone) fibrous membranes and their cytocompatibility in vitro. Journal of Biomaterials Science, Polymer Edition, 2008, 19 (2): 245-258.
[122] Ebeling W, Hennrich N, Klockow M, et al. Proteinase K from tritirachium album Limber. European Journal of Biochemistry, 1974, 47 (1): 91-97.
[123] Duan B, Wu L, Li X, Yuan X, Li X, Zhang Y, et al. Degradation of electrospun PLGA-chitosan/PVA membranes and their cytocompatibility in vitro. Journal of Biomaterials Science, Polymer Edition, 2007, 18 (1): 95-112.
[124] Gupta B, Revagade N, Hiborn J. In Vitro Degradation of dry-jet-wet spun poly(lactic acid) monofilament and knitted scaffold. Journal of Applied Polymer Science, 2007, 103 (3): 2006-2012.
[125] Yang Y, Li X, Cui W, et al. Structural stability and release profiles of proteins from core-shell poly (DL-lactide) ultrafine fibers prepared by emulsion electrospinning. Journal of Biomedical Materials Research, 2008, 86A (2): 374-385.
[126] He C, Huang Z, Han X, et al. Coaxial electrospun poly(L-lactic acid) ultrafine fibers for sustained drug delivery. Journal of Macromolecular Science: Physics, 2006, 45 (4): 515-524.
[127] Drew C, Wang X, Samuelson L, Kumar J. The effect of viscosity and filler on electrospun fiber morphology. Journal of Macromolecular Science: Pure and Applied Chemistry, 2003, 40 (12): 1415-1422.
[128] Hohman M M, Shin M, Rutledge G C, Brenner M P. Electrospinning and electrically forced jets. I. Stability theory. Physics of Fluids, 2001, 13 (8): 2201-2220.
[129] Koski A, Yim K, Shivkumar S. Effect of molecular weight on fibrous PVA produced by electrospinning. Materials Letters, 2004, 58 (3): 493-497.
[130] Theron S A, Zussman E, Yarin A L. Experimental investigation of the governing parameters in the electrospinning of polymer solutions. Polymer, 2004, 45 (6): 2017-2030.
[131] Boland E, Wnek G, Simpson D, et al. Tailoring tissue engineering scaffolds using electrostatic processing techniques: a study of poly(glycolic acid) electrospinning. Journal of Macromolecular Science: Pure and Applied Chemistry, 2001, 38 (12): 1231-1243.
[132] Pornsopone V, Supaphol P, Rangkupan R, Tantayanon S. Electrospinning of methacrylate-based copolymers: effects of solution concentration and applied electrical potential on morphological appearance of as-spun fibers. Polymer Engineering and Science, 2005, 45 (8): 1073-1080.
[133] Shenoy S L, Bates W D, Frisch H L, Wnek G E. Role of chain entanglements on fiber formation during electrospinning of polymer solutions: good solvent, non-specific polymer-polymer interaction limit. Polymer, 2005, 46 (10): 3372-3384.
[134] Shenoy S L, Bates W D, Wnek G. Correlations between electrospinnability and physical gelation. Polymer, 2005, 46 (21): 8990-9004.
[135] Burger C, Hsiao B S, Chu B. Nanofiberous materials and their applications. Annual Review of Materials Research, 2006, 36: 333-368.
[136] Shin Y M, Hohman M M, Brenner M P, Rutledge G C. Experimental characterization of electrospinning: the electrically forced jet and instabilities. Polymer, 2001, 42 (25): 9955-9967.
[137] Sun B, Duan B, Yuan X. Preparation of core/shell PVP/PLA ultrafine fibers by coaxial electrospinning. Journal of Applied Polymer Science, 2006, 102 (1): 39-45.
[138] Jiang H, Hu Y, Li Y, et al. A facile technique to prepare biodegradable coaxial electrospun nanofibers for controlled release of bioactive agents. Journal of controlled release, 2005, 108 (2-3): 237-243.
[139] Zhang Y Z, Venugopal J, Huang H M, et al. Characterization of the Surface Biocompatibility of the electrospun PCL-Collagen nanofibers using fibroblasts. Biomacromolecules, 2005, 6(5): 2583-2589.
[140] Li X, Zhang H, Li H, et al. Self-accelerated biodegradation of electrospun poly(ethylene glycol)-poly(L-lactide) membranes by loading proteinase K. Polymer Degradation and Stability, 2008, 93 (3): 618-626
[141] Stevens M M. Biomaterials for bone tissue engineering. Materials Today, 2008, 11 (5): 18-25.
[142] Porter A, Patel N, Skepper J, et al. Effect of sintered silicate-substituted hydroxyapatite on remodelling processes at the bone-implant interface. Biomaterials, 2004, 25 (16): 3303-3314.
[143] Badami AS, Kreke MR, Thompson MS, et al. Effect of fiber diameter on spreading, proliferation, and differentiation of osteoblastic cells on electrospun poly(lactic acid) substrates. Biomaterials, 2006, 27 (4): 596-606.
[144] Xin X, Hussain M, Mao J J. Continuing differentiation of human mesenchymal stem cells and induced chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold. Biomaterials, 2007, 28 (2): 316-325.
[145] Li W, Tuli R, Okafor C, et al. A three-dimensional nanofibrous scaffold for cartilage tissue engineering using human mesenchymal stem cells. Biomaterials, 2005, 26 (6): 599-609.
[146] Tas A C, Bhaduri S B. Rapid coating of Ti6Al4V at room temperature with a calcium phosphate solution similar to 10×simulated body fluid. Journal of Materials Research, 2004, 19 (9): 2742-2749.
[147] Bolgen N, Menceloglu Y, Acatay K, Vargel I, Piskin E. In vitro and in vivo degradation of non-woven materials made of poly(ε-caprolactone) nanofibers prepared by electrospinning under different conditions. Journal of Biomaterials Science, Polymer Edition, 2005, 16 (12): 1537-1555.
[148] Sombatmankhong K, Sanchavanakit N, Pavasant P, et al. Bone scaffolds from electrospun fiber mats of poly(3-hydroxybutyrate), poly(3-hydroxybutyrate-co-3- hydroxyvalerate) and their blend. Polymer, 2007, 48 (5): 1419-1427.
[149] Liu Z, Jiao Y, Zhang Z, et al. Surface modification of poly(L-lactic acid) by entrapment of chitosan and its derivatives to promote osteoblasts-like compatibility. Journal of biomedical materials research, 2007, 83A (4): 1110-1116.
[150] Smoukov S K, Bishop K J M, Kowalczyk B, et al. Electrostatically "patchy" coatings via cooperative adsorption of charged nanoparticles. Journal of the American Chemical Society, 2007, 129 (50): 15623-15630.
[151] Ma Z, He W, Yong T, et al. Grafting of gelatin on electrospun poly(ε-caprolactone) nanofibers to improve endothelial cell spreading and proliferation and to control cell orientation. Tissue Engineering, 2005, 11 (7-8): 1149-1158.
[152] Shin Y M, Kim K, Lim Y M, et al. Modulation of spreading, proliferation, and differentiation of human mesenchymal stem cells on gelatin-immobilized poly(L-lactide-co-ε-caprolactone) substrates. Biomacromolecules, 2008, 9 (7): 1772-1781.
[153] Nagai M, Hayakawa T, Makimura M. Fibronectin immobilization using water-soluble carbodiimide on fibroblast attachment. Journal of Biomaterials Applications, 2006, 21 (1): 33-47.
[154] Zhu A, Zhang M, Wu J, et al. Covalent immobilization of chitosan/heparin complex with a photosensitive hetero-bifunctional crosslinking reagent on PLA surface. Biomaterials, 2002, 23 (23): 4657-4665.
[155] Hammond, P. T. Form and function in multilayer assembly: new applications at the nanoscale. Advanced Materials, 2004, 16 (15): 1271-1293.
[156] Salloum D S, Olenych S G, Keller T C S, et al. Vascular smooth muscle cells on polyelectrolyte multilayers: Hydrophobicity-directed adhesion and growth. Biomacromolecules, 2005, 6 (1): 161-167.
[157] Sun J, Wu S Y, Lin F. The role of muscle-derived stem cells in bone tissue engineering. Biomaterials, 2005, 26 (18): 3953-3960.
[158] Diaspro A, Silvano D, Krol S, et al. Single living cell encapsulation in nano-organized polyelectrolyte shells. Langmuir, 2002, 18 (13): 5047-5050.
[159] Zhu Y, Gao C, He T, et al. Layer-by-layer assembly to modify poly(L-lactic acid) surface toward improving its cytocompatibility to human endothelial cells. Biomacromolecules, 2003, 4 (2): 446-452.
[160] Ma L, Zhou J, Gao C, Shen J J. Incorporation of basic fibroblast growth factor by a layer-by-layer assembly technique to produce bioactive substrates. Journal of biomedical materials research, Part B, 2007, 83B (1): 285-292.
[161] Zou C, Weng W, Deng X, et al. Preparation and characterization of porousβ-tricalcium phosphate/collagen composites with an integrated structure. Biomaterials, 2005, 26 (26): 5276-5284.
[162] Yao J, Radin S, Leboy P S, Ducheyne P. The effect of bioactive glass content on synthesis and bioactivity of composite poly (lactic-co-glycolic acid)/bioactive glass substrate for tissue engineering. Biomaterials, 2005, 26 (14):1935-1943.
[163] Ito Y, Hasuda H, Kamitakahara M. A composite of hydroxyapatite with electrospun biodegradable nanofibers as a tissue engineering material. Journal of Bioscience and Bioengineering, 2005, 100 (1): 43-49.
[164] Erisken C, Kalyon D M, Wang H. A hybrid twin screw extrusion/electrospinning method to process nanoparticle-incorporated electrospun nanofibres. Nanotechnology, 2008, 19, 165302 (8 pp).
[165] Kim H, Lee H, Knowles J C J. Electrospinning biomedical nanocomposite fibers of hydroxyapatite/poly(lactic acid) for bone regeneration. Journal of Biomedical Materials Research, 2006, 79A (3): 643-649.
[166] Yuan X, Mak A F T, Li J J. Formation of bone-like apatite on poly(L-lactic acid) fibers by a biomimetic process. Journal of Biomedical Materials Research, 2001, 57 (1): 140-150.
[167] Abe Y, Kokubo T, Yamamuro T J. Apatite coating on ceramics, metals and polymers utilizing a biological process. Journal of Materials Science: Materials in Medicine, 1990, 1 (4): 233-238.
[168] Muller F A, Müller L, Caillard D, Conforto E J. Preferred growth orientation of biomimetic apatite crystals. Journal of Crystal Growth, 2007, 304 (2): 464-471.
[169] Zhang R, Ma P X. Biomimetic polymer/apatite composite scaffolds for mineralized tissue engineering. Macromolecular Bioscience, 2004, 4 (2): 100-111.
[170] Huang S, Zhou K, Zhu W, et al. Effects of in situ biomineralization on microstructural and mechanical properties of hydroxyapatite/polyethylene composites. Journal of Applied Polymer Science, 2006, 101 (3): 1842-1847.
[171] Oyane A, Uchida M, Choong C, et al. Simple surface modification of poly(ε-caprolactone) for apatite deposition from simulated body fluid. Biomaterials, 2005, 26 (15): 2407-2413.
[172] Oyane A, Uchida M, Yokoyama Y, et al. Simple surface modification of poly(ε-caprolactone) to induce its apatite-forming ability. Journal of Biomedical Materials Research, 2005, 75A (1): 138-145.
[173] Li J, Chen Y, Yin Y, et al. Modulation of nano-hydroxyapatite size via formation on chitosan-gelatin network film in situ. Biomaterials, 2007, 28 (5): 781-790.
[174] Bigi A, Boanini E, Panzavolta S, et al. Bonelike apatite growth on hydroxyapatite-gelatin sponges from simulated body fluid. Journal of Biomedical Materials Research, 2002, 59 (4): 709-714.
[175] Wen H B, Moradian-Oldak J, Fincham A G. Dose dependent modulation of octacalcium phosphate crystal habit by amelogenins. Journal of Dental Research, 2000, 79 (11): 1902-1906.
[176] Tas A C, Bhaduri S B. Chemical processing of CaHPO4·2H2O: its conversion to hydroxyapatite. Journal of the American Ceramic Society, 2004, 87 (12): 2195-2200.
[177] Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials, 2005, 26 (27): 5474-5491.
[178] Thomopoulos S. The development of structural and mechanical anisotropy in fibroblast populated collagen gels. Journal of Biomechanical Engineering, 2005, 127 (5): 742-750.
[179] Thomopoulos S, Williams G R, Gimbel J A, et al. Variation of biomechanical, structural, and compositional properties along the tendon to bone insertion site. Journal of Orthopaedic Research, 2003, 21 (3): 413-419.
[180] Zizak, I. Roschger P, Paris O, et al. Characteristics of mineral particles in the human bone/cartilage interface. Journal of Structural Biology, 2003, 141 (3): 208-217.
[181] Katz J L, Misra A, Spencer P, et al. Multiscale mechanics of hierarchical structure/property relationships in calcified tissues and tissue/material interfaces. Materials Science and Engineering C. 2007, 27 (3): 450-468.
[182] Wopenka B, kent A, Pasteris J D, et al. The tendon-to-bone transition of the rotator cuff: a preliminary raman spectroscopic study documenting the gradual mineralization across the insertion in rat tissue samples. Applied Spectroscopy, 2008, 62 (12): 1285-1294.
[183] Thomopoulos S, Williams G R, Soslowsky L J. Tendon to bone healing: differences in biomechanical, structural, and compositional properties due to a range of activity levels. Journal of Biomechanical Engineering, 2003, 25 (1): 106-113.
[184] Erisken C, Kalyon D M, Wang H. Functionally graded electrospun polycaprolactone andβ-tricalcium phosphate nanocomposites for tissue engineering applications. Biomaterials, 2008, 29 (30): 4065-4073.
[185] Phillips J E, Burns K L, Le Doux, et al. Engineering graded tissue interfaces. Proceedings of the National Academy of Sciences, 2008, 105 (34): 12170-12175.
[186] Li X R, Xie J W, Yuan X Y, Xia Y N. Coating electrospun poly(ε-caprolactone) fibers with gelatin and calcium phosphate, and their use as biomimetic scaffolds for bone tissue engineering. Langmuir, 2008, 24 (24): 4145-14150.
[187] Birman V, Byrd LW. Modeling and analysis of functionally graded materials and structures. Applied Mechanics Review, 2007, 60 (5): 195-216.
[188] Wang S, Saadi W, Lin F, et al. Differential effects of EGF gradient profiles on MDA-MB-231 breast cancer cell chemotaxis. Experimental Cell Research, 2004, 300 (1): 180-189.
[189] Delong S A, Moon J J, West J L. Covalently immobilized gradients of bFGF on hydrogel scaffolds for directed cell migration. Biomaterials, 2005, 26(16):3227-3234.
[190] Mougin K, Ham A S, Lawrence M B, et al. Construction of a tethered poly(ethylene glycol) surface gradient for studies of cell adhesion kinetics. Langmuir, 2005, 21 (11): 4809-4812.
[191] Stefonek T J, Masters K S. Immobilized gradients of epidermal growth factor promote accelerated and directed keratinocyte migration. Wound Repair and Regeneration, 2007, 15 (6): 847-855.
[192] Barkefors, I. Le Jan S, Jakobsson L, et al. Endothelial cell migration in stable gradients of vascular endothelial growth factor A and fibroblast growth factor 2. The Journal of Biological Chemistry, 2008, 283 (20): 13905-13912.
[193] Kapur T A, Shoichet M S. Immobilized concentration gradients of nerve growth factor guide neurite outgrowth. Journal of Biomedical Materials Research, 2004, 68A (2): 235-243.
[194] Ku Y, Chung C, Jang J. The effect of the surface modification of titanium using a recombinant fragment of fibronectin and vitronectin on cell behavior. Biomaterials, 2005, 26 (25): 5153-5157.
[195] Lee K, Wang S, Yaszemski M J, Lu L. Physical properties and cellular responses to crosslinkable poly(propylene fumarate)/hydroxyapatite nanocomposites. Biomaterials, 2008, 29 (19): 2839-2848.
[196] Gurtner G C, Werner S, Barrandon Y, Longaker M T. Wound repair and regeneration. Nature, 2008, 453: 314-321.
[197] Cao X, Shoichet M S. Defining the concentration gradient of nerve growth factor for guided neurite outgrowth. Neuroscience, 2001, 103 (3): 831-840.
[198] Xie J, Tan R S, Wang C H. Biodegradable microparticles and fiber fabrics for sustained delivery of cisplatin to treat C6 glioma in vitro. Journal of Biomedical Materials Research, 2008, 85A (4): 897-908.
[199] Xie J, Tan J C, Wang C. Biodegradable films developed by electrospray deposition for sustained drug delivery. Journal of Pharmaceutical Sciences, 2008, 97 (8): 3109-3122.
[200] Xu Y, Hanna M. Electrospray encapsulation of water-soluble protein with polylactide: effects of formulations on morphology, encapsulation efficiency and release profile of particles. International Journal of Pharmaceutics, 2006, 320 (1-2): 30-36.
[201] Washburn N R, Yamada K M, Simon C G, et al. High-throughput investigation of osteoblast response to polymer crystallinity: influence of nanometer-scale roughness on proliferation. Biomaterials, 2004, 25 (7-8), 1215-1224.
[202] Kunzler T P, Drobek T, Sprecher C M, et al. Fabrication of material-independent morphology gradients for high-throughput applications. International Journal of Pharmaceutics, 2006, 253 (4): 2148-2153.
[203] Bhat R R, Fischer D A, Genzer J. Fabricating planar nanoparticle assemblies with number density gradients. Langmuir, 2002, 18 (15): 5640-5643.
[204] Kunzler TP, Huwiler C, Drobek T, et al. Systematic study of osteoblast response to nanotopography by means of nanoparticle-density gradients. Biomaterials, 2007, 28 (33): 5000-5006.
[205] Kramer S, Xie H, Gaff J, et al. Preparation of protein gradients through the controlled deposition of protein-nanoparticle conjugates onto functionalized surfaces. Journal of American Chemical Society, 2004, 126 (17): 5388-5395.
[206] Huwiler C, Kunzler T, Textor M, et al. Functionalizable nanomorphology gradients via colloidal self-assembly. Langmuir, 2007, 23 (11), 5929-5935.
[207] Miao Y, Helseth L. Adsorption of bovine serum albumin on polyelectrolyte-coated glass substrates: applications to colloidal lithography. Colloids Surf. B Biointerfaces, 2008, 66 (2): 299-303.
[208] Peret B, Murohy W. Controllable soluble protein concentration gradients in hydrogel networks. Advanced Functional Materials, 2008, 18 (21): 3410-3417.
[209] Li GN, Liu J, Ann D. Multi-molecular gradients of permissive and inhibitory cues direct neurite outgrowth. Biomedical Engineering, 2008, 36 (6): 889-904.
[210] Rosoff W J, Urbach J S, Esrick M A, et al. A new chemotaxis assay shows the extreme sensitivity of axons to molecular gradients. Nature Neuroscience, 2004, 7: 678-785.
[211] Price R, Ellison K, Haberstroh K M, Webster T J. Nanometer surface roughness increases select osteoblast adhesion on carbon nanofiber compacts. Journal of Biomedical Materials Research, 2004, 70A (1): 129-138.
[212] Kunzler T P, Drobek T, Schuler M, Spencer N D. Systematic study of osteoblast and fibroblast response to roughness by means of surface-morphology gradients. Biomaterials, 2007, 28 (13): 2175-2182.
[213] Walsh J F, Manwaring M E, Tersco P A. Directional neurite outgrowth is enhanced by engineered meningeal cell-coated substrates. Tissue Engineering, 2005, 11 (7-8): 1085-1094.
[214] Xie J, MacEwan M, Li X, et al. Neurite outgrowth on nanofiber scaffolds with different orders, structures, and surface properties. ACS Nano, 2009, 3 (5): 1151-1159.
[215] Arimura N, Kaibuchi K. Neuronal polarity: from extracellular signals to intracellular mechanisms. Nature Reviews Neuroscience, 2007, 8 (3): 194-205.
[216] Fan Y W, Cui F Z, Hou S P, et al. Culture of neural cells on silicon wafers with nano-scale surface topograph. Journal of Neuroscience Methods, 2002, 120 (1): 17-23.
[217] Khan S P, Auner G G, Newaz G M. Influence of nanoscale surface roughness on neural cell attachment on silicon. Nanomedicine: Nanotechnology, Biology and Medicine, 2005, 1 (2): 125-129.
[218] Gallo G, Letourneau P C. Axon guidance: proteins turnover in turning growth cones. Current Biology, 2002, 12 (16): R560-R562.
[219] Mattila P K, Lappalainen P. Filopodia: molecular architecture and cellular functions. Nature Reviews Molecular Cell Biology, 2008, 9 (6): 446-454.
[220] Mueller B K. Growth cone guidance: first steps towards a deeper understanding. Annual Review of Neuroscience, 1999, 22: 351-388.
[221] Dunn G A, Heath J P. A new hypothesis of contact guidance in tissue cells. Experimental Cell Research, 1976, 101: 1-14.
[222] Smeal R M, Tresco P A. The influence of substrate curvature on neurite outgrowth is cell type dependent. Experimental Neurology, 2008, 213 (2): 281-292.
[223] Smeal R M, Rabbitt R, Biran R, Tresco P A. Substrate curvature influences the direction of nerve outgrowth. Annals of Biomedical Engineering, 2005, 33 (3): 376-382.
[224] Li N, Folch A. Integration of topographical and biochemical cues by axons during growth on microfabricated 3-D substrates. Experimental Cell Research, 2005, 311 (2): 307-316.
