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Technology Report

Electrospun nanostructured scaffolds for tissue engineering applications

    Albino Martins*

    3B’s Research Group – Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, Campus de Gualtar, University of Minho, 4710–057 Braga, Portugal

    Institute for Biotechnology and Bioengineering, PT Government Associated Laboratory, Braga, Portugal.

    ,
    José V Araújo*

    3B’s Research Group – Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, Campus de Gualtar, University of Minho, 4710–057 Braga, Portugal

    Institute for Biotechnology and Bioengineering, PT Government Associated Laboratory, Braga, Portugal.

    ,
    Rui L Reis

    3B’s Research Group – Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, Campus de Gualtar, University of Minho, 4710–057 Braga, Portugal

    Institute for Biotechnology and Bioengineering, PT Government Associated Laboratory, Braga, Portugal.

    &
    Nuno M Neves

    † Author for correspondence

    3B’s Research Group – Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, Campus de Gualtar, University of Minho, 4710–057 Braga, Portugal

    Institute for Biotechnology and Bioengineering, PT Government Associated Laboratory, Braga, Portugal.

    Published Online:https://doi.org/10.2217/17435889.2.6.929

    Despite being known for decades (since 1934), electrospinning has emerged recently as a very widespread technology to produce synthetic nanofibrous structures. These structures have morphologies and fiber diameters in a range comparable with those found in the extracellular matrix of human tissues. Therefore, nanofibrous scaffolds are intended to provide improved environments for cell attachment, migration, proliferation and differentiation when compared with traditional scaffolds. In addition, the process versatility and the highly specific surface area of nanofiber meshes may facilitate their use as local drug-release systems. Common electrospun nanofiber meshes are characterized by a random orientation. However, in some special cases, aligned distributions of the fibers can be obtained, with an interconnected microporous structure. The characteristic pore sizes and the inherent planar structure of the meshes can be detrimental for the desired cell infiltration into the inner regions, and eventually compromise tissue regeneration. Several strategies can be followed to overcome these limitations, and are discussed in detail here.

    Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.

    Bibliography

    • Langer R, Vacanti JP: Tissue engineering. Science260(5110),920–926 (1993).
    • Ma ZW, Kotaki M, Inai R, Ramakrishna S: Potential of nanofiber matrix as tissue-engineering scaffolds. Tissue Eng.11(1–2),101–109 (2005).
    • Leong KF, Cheah CM, Chua CK: Solid freeform fabrication of three-dimensional scaffolds for engineering replacement tissues and organs. Biomaterials24(13),2363–2378 (2003).
    • Yang SF, Leong KF, Du ZH, Chua CK: The design of scaffolds for use in tissue engineering. Part 1. Traditional factors. Tissue Eng.7(6),679–689 (2001).
    • Salgado AJ, Coutinho OP, Reis RL: Bone tissue engineering: state of the art and future trends. Macromol. Biosci.4(8),743–765 (2004).
    • Miller DC, Thapa A, Haberstroh KM, Webster TJ: Endothelial and vascular smooth muscle cell function on poly(lactic-co-glycolic acid) with nano-structured surface features. Biomaterials25(1),53–61 (2004).
    • Lannutti J, Reneker D, Ma T, Tomasko D, Farson D: Electrospinning for tissue engineering scaffolds. Mater. Sci. Eng. C – Biomim. Supramol. Syst.27(3),504–509 (2007).
    • Chen F, Lee CN, Teoh SH: Nanofibrous modification on ultra-thin poly(ε-caprolactone) membrane via electrospinning. Mater. Sci. Eng. C – Biomim. Supramol. Syst.27(2),325–332 (2007).
    • Courtney T, Sacks MS, Stankus J, Guan J, Wagner WR: Design and analysis of tissue engineering scaffolds that mimic soft tissue mechanical anisotropy. Biomaterials27(19),3631–3638 (2006).
    • 10  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. Biomaterials26(15),2603–2610 (2005).
    • 11  Xu CY, Yang F, Wang S, Ramakrishna S: In vitro study of human vascular endothelial cell function on materials with various surface roughness. J. Biomed. Mater. Res. A71A(1),154–161 (2004).
    • 12  Fields GB: Induction of protein-like molecular architecture by self-assembly processes. Bioorgan. Med. Chem.7(1),75–81 (1999).
    • 13  Woo KM, Chen VJ, Ma PX: Nano-fibrous scaffolding architecture selectively enhances protein adsorption contributing to cell attachment. J. Biomed. Mater. Res. A67A(2),531–537 (2003).
    • 14  Matthews JA, Wnek GE, Simpson DG, Bowlin GL: Electrospinning of collagen nanofibers. Biomacromolecules3(2),232–238 (2002).• Electrospun collagen nanofibers with diameters similar to the native type I collagen fibrils were obtained.
    • 15  Ashammakhi N, Ndreu A, Piras AM et al.: Biodegradable nanomats produced by electrospinning: expanding multifunctionality and potential for tissue engineering. J. Nanosci. Nanotechnol.7(3),862–882 (2007).
    • 16  Ramakrishna S, Fujihara K, Teo WE, Yong T, Ma Z, Ramaseshan R: Electrospun nanofibers: solving global issues. Mater. Today9(3),40 (2006).
    • 17  Li D, Xia YN: Electrospinning of nanofibers: reinventing the wheel? Adv. Mater.16(14),1151–1170 (2004).
    • 18  Frenot A, Chronakis IS: Polymer nanofibers assembled by electrospinning. Curr. Opin. Coll. Interf. Sci.8(1–2),64–75 (2003).
    • 19  Taepaiboon P, Rungsardthong U, Supaphol P: Drug-loaded electrospun mats of poly(vinyl alcohol) fibers and their release characteristics of four model drugs. Nanotechnology17(9),2317–2329 (2006).
    • 20  Kim K, Luu YK, Chang C et al.: Incorporation and controlled release of a hydrophilic antibiotic using poly(lactide-co-glycolide)-based electrospun nanofibrous scaffolds. J. Control. Release98(1),47–56 (2004).
    • 21  Kenawy ER, Bowlin GL, Mansfield K et al.: Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a blend. J. Control. Release81(1–2),57–64 (2002).• First report describing the incorporation of drugs into the electrospun nanofibers.
    • 22  Baker BM, Mauck RL: The effect of nanofiber alignment on the maturation of engineered meniscus constructs. Biomaterials28(11),1967–1977 (2007).
    • 23  Pham QP, Sharma U, Mikos AG: Electrospun poly(epsilon-caprolactone) microfiber and multilayer nanofiber/microfiber scaffolds: characterization of scaffolds and measurement of cellular infiltration. Biomacromolecules7(10),2796–2805 (2006).
    • 24  Mitchell SB, Sanders JE: A unique device for controlled electrospinning. J. Biomed. Mater. Res. A78A(1),110–120 (2006).
    • 25  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. Biomaterials26(1),37–46 (2005).
    • 26  Zong XH, Kim K, Fang DF, Ran SF, Hsiao BS, Chu B: Structure and process relationship of electrospun bioabsorbable nanofiber membranes. Polymer43(16),4403–4412 (2002).
    • 27  Boland ED, Telemeco TA, Simpson DG, Wnek GE, Bowlin GL: Utilizing acid pretreatment and electrospinning to improve biocompatibility of poly(glycolic acid) for tissue engineering. J. Biomed. Mater. Res. B – Appl. Biomater.71B(1),144–152 (2004).
    • 28  Zong XH, Ran SF, Fang DF, Hsiao BS, Chu B: Control of structure, morphology and property in electrospun poly (glycolide-co-lactide) non-woven membranes via post-draw treatments. Polymer44(17),4959–4967 (2003).
    • 29  Zhong SP, Teo WE, Zhu X, Beuerman RW, Ramakrishna S, Yung LYL: An aligned nanofibrous collagen scaffold by electrospinning and its effects on in vitro fibroblast culture. J. Biomed. Mater. Res. A79A(3),456–463 (2006).
    • 30  Xu CY, Inai R, Kotaki M, Ramakrishna S: Aligned biodegradable nanofibrous structure: a potential scaffold for blood vessel engineering. Biomaterials25(5),877–86 (2004).• Simple approach to obtain aligned electrospun nanofibers, which mimic the circumferential orientation of fibrils found in the medial layer of a native artery.
    • 31  Neves NM, Campos R, Pedro A, Cunha J, Macedo F, Reis RL: Patterning of polymer nanofiber meshes by electrospinning for biomedical applications. Int. J. Nanomed.2(3),1–16 (2007).
    • 32  Xin XJ, Hussain M, Mao JJ: Continuing differentiation of human mesenchymal stem cells and induced chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold. Biomaterials28(2),316–325 (2007).
    • 33  Li WJ, Tuli R, Huang XX, Laquerriere P, Tuan RS: Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold. Biomaterials26(25),5158–5166 (2005).•• Ability of the nanofibrous scaffolds to support and maintain multilineage differentiation of bone marrow-derived human mesenchymal stem cells was studied.
    • 34  Li CM, Vepari C, Jin HJ, Kim HJ, Kaplan DL: Electrospun silk-BMP-2 scaffolds for bone tissue engineering. Biomaterials27(16),3115–3124 (2006).
    • 35  Zhang YZ, Ouyang HW, Lim CT, Ramakrishna S, Huang ZM: Electrospinning of gelatin fibers and gelatin/PCL composite fibrous scaffolds. J. Biomed. Mater. Res. B – Appl. Biomater.72B(1),156–165 (2005).
    • 36  Ohkawa K, Cha DI, Kim H, Nishida A, Yamamoto H: Electrospinning of chitosan. Macromol. Rapid Comm.25(18),1600–1605 (2004).• Electrospun nonwoven chitosan nanofiber meshes free of ‘beads’ were successfully obtained.
    • 37  Chong EJ, Phan TT, Lim IJ et al.: Evaluation of electrospun PCL/gelatin nanofibrous scaffold for wound healing and layered dermal reconstitution. Acta Biomater.3(3),321–330 (2007).
    • 38  Buttafoco L, Kolkman NG, Engbers-Buijtenhuijs P et al.: Electrospinning of collagen and elastin for tissue engineering applications. Biomaterials27(5),724–734 (2006).
    • 39  Park KE, Jung SY, Lee SJ, Min BM, Park WH: Biomimetic nanofibrous scaffolds: Preparation and characterization of chitin/silk fibroin blend nanofibers. Int. J. Biol. Macromol.38(3–5),165–173 (2006).
    • 40  Chen Z, Mo X, Qing F: Electrospinning of collagen–chitosan complex. Mater. Lett.61(16),3490 (2007).
    • 41  Kim HW, Lee HH, Knowles JC: Electrospinning biomedical nanocomposite fibers of hydroxyapatite/poly(lactic acid) for bone regeneration. J. Biomed. Mater. Res. A79(3),643–649 (2006).
    • 42  Wutticharoenmongkol P, Sanchavanakit N, Pavasant P, Supaphol P: Preparation and characterization of novel bone scaffolds based on electrospun polycaprolactone fibers filled with nanoparticles. Macromol. Biosci.6(1),70–77 (2006).
    • 43  Kim HW, Song JH, Kim HE: Nanofiber generation of gelatin–hydroxyapatite biomimetics for guided tissue regeneration. Adv. Funct. Mater.15(12),1988–1994 (2005).
    • 44  Dai XS, Shivkumar S: Electrospinning of hydroxyapatite fibrous mats. Mater. Lett.61(13),2735–2738 (2007).
    • 45  Kim HW, Kim HE, Knowles JC: Production and potential of bioactive glass nanofibers as a next-generation biomaterial. Adv. Funct. Mater.16(12),1529–1535 (2006).
    • 46  Kim HW, Kim HE: Nanofiber generation of hydroxyapatite and fluor-hydroxyapatite bioceramics. J. Biomed. Mater. Res. B – Appl. Biomater.77B(2),323–328 (2006).
    • 47  Sangsanoh P, Supaphol P: Stability improvement of electrospun chitosan nanofibrous membranes in neutral or weak basic aqueous solutions. Biomacromolecules7(10),2710–2714 (2006).
    • 48  Kim SH, Nam YS, Lee TS, Park WH: Silk fibroin nanofiber. Electrospinning, properties, and structure. Polym. J.35(2),185–190 (2003).
    • 49  Min BM, Lee G, Kim SH, Nam YS, Lee TS, Park WH: Electrospinning of silk fibroin nanofibers and its effect on the adhesion and spreading of normal human keratinocytes and fibroblasts in vitro.Biomaterials25(7–8),1289–1297 (2004).• Electrospinning was used to successfully produce silk fibroin nanofibers with the possibility of being used in wound-dressing applications.
    • 50  Nishida T, Yasumoto K, Otori T, Desaki J: The network structure of corneal fibroblasts in the rat as revealed by scanning electron-microscopy. Invest. Ophth. Vis. Sci.29(12),1887–1890 (1988).
    • 51  Tan W, Krishnaraj R, Desai TA: Evaluation of nanostructured composite collagen–chitosan matrices for tissue engineering. Tissue Eng.7(2),203–210 (2001).
    • 52  Zagris N: Extracellular matrix in development of the early embryo. Micron32(4),427–438 (2001).
    • 53  Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P: Molecular Biology of the Cell (Fourth Edition). Garland Science, London, UK, Chapter 19 (2002) (Electronic version).
    • 54  Smith LA, Ma PX: Nano-fibrous scaffolds for tissue engineering. Coll. Surf. B – Biointerf.39(3),125–131 (2004).
    • 55  Zhang YZ, Lim CT, Ramakrishna S, Huang ZM: Recent development of polymer nanofibers for biomedical and biotechnological applications. J. Mater. Sci. Mater. Med.16(10),933–946 (2005).
    • 56  Khil MS, Cha DI, Kim HY, Kim IS, Bhattarai N: Electrospun nanofibrous polyurethane membrane as wound dressing. J. Biomed. Mater. Res. B – Appl. Biomater.67B(2),675–679 (2003).• One of the first in vivo studies that demonstrated the nanofiber mesh’s integration after implantation.
    • 57  Zong XH, Li S, Chen E et al.: Prevention of postsurgery-induced abdominal adhesions by electrospun bioabsorbable nanofibrous poly(lactide-co-glycolide)-based membranes. Ann. Surg.240(5),910–915 (2004).
    • 58  Bolgen N, Vargel I, Korkusuz P, Menceloglu YZ, Piskin E: In vivo performance of antibiotic embedded electrospun PCL membranes for prevention of abdominal adhesions. J. Biomed. Mater. Res. B – Appl. Biomater.81B(2),530–543 (2007).
    • 59  Shin M, Yoshimoto H, Vacanti JP: In vivo bone tissue engineering using mesenchymal stem cells on a novel electrospun nanofibrous scaffold. Tissue Eng.10(1–2),33–41 (2004).
    • 60  Kim KH, Jeong L, Park HN et al.: Biological efficacy of silk fibroin nanofiber membranes for guided bone regeneration. J. Biotechnol.120(3),327–339 (2005).
    • 61  Bini TB, Gao SJ, Tan TC et al.: Electrospun poly(L-lactide-co-glycolide) biodegradable polymer nanofiber tubes for peripheral nerve regeneration. Nanotechnology15(11),1459–1464 (2004).
    • 62  Goldberg M, Langer R, Jia XQ: Nanostructured materials for applications in drug delivery and tissue engineering. J. Biomater. Sci. Polym. Ed.18(3),241–268 (2007).
    • 63  Tuzlakoglu K, Bolgen N, Salgado AJ, Gomes ME, Piskin E, Reis RL: Nano- and micro-fiber combined scaffolds: a new architecture for bone tissue engineering. J. Mater. Sci. Mater. Med.16(12),1099–1104 (2005).•• Shows that the presence of nanofibers on macroporous 3D scaffolds may influence cell shape and cytoskeletal organization.
    • 64  Santos MI, Tuzlakoglu K, Gomes ME et al.: Nano- and micro-fiber combined scaffolds: an innovative design for improving endothelial cell migration in bone tissue engineering approaches. Tissue Eng.12(4),986–987 (2006).
    • 65  Huang ZM, Zhang YZ, Kotaki M, Ramakrishna S: A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Compos. Sci. Technol.63(15),2223–2253 (2003).
    • 66  Martins A, Reis RL, Neves NM: Electrospinning – a processing technique for tissue engineering scaffolding. Int. Mater. Rev. (2007) (In Press).
    • 67  Murugan R, Ramakrishna S: Design strategies of tissue engineering scaffolds with controlled fiber orientation. Tissue Eng.13(8),1845–1866 (2007).
    • 68  Kim JS, Reneker DH: Polybenzimidazole nanofiber produced by electrospinning. Polym. Eng. Sci.39(5),849–854 (1999).
    • 69  Lee CH, Shin HJ, Cho IH et al.: Nanofiber alignment and direction of mechanical strain affect the ECM production of human ACL fibroblast. Biomaterials26(11),1261–1270 (2005).
    • 70  Teo WE, Kotaki M, Mo XM, Ramakrishna S: Porous tubular structures with controlled fiber orientation using a modified electrospinning method. Nanotechnology16(6),918–924 (2005).
    • 71  Nerurkar NL, Elliott DM, Mauck RL: Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering. J. Orthop. Res.25(8),1018–1028 (2007).
    • 72  Li WJ, Mauck RL, Cooper JA, Yuan X, Tuan RS: Engineering controllable anisotropy in electrospun biodegradable nanofibrous scaffolds for musculoskeletal tissue engineering. J. Biomech.40(8),1686–1693 (2007).
    • 73  Li D, Wang YL, Xia YN: Electrospinning of polymeric and ceramic nanofibers as uniaxially aligned arrays. Nano Lett.3(8),1167–1171 (2003).•• Outstanding study of the production of aligned nanofibers, varying the geometrical configuration of the collector.
    • 74  Dersch R, Liu TQ, Schaper AK, Greiner A, Wendorff JH: Electrospun nanofibers: Internal structure and intrinsic orientation. J. Polym. Sci. A – Polym. Chem.41(4),545–553 (2003).
    • 75  Li D, Wang YL, Xia YN: Electrospinning nanofibers as uniaxially aligned arrays and layer-by-layer stacked films. Adv. Mater.16(4),361–366 (2004).
    • 76  Schnell E, Klinkhammer K, Balzer S et al.: Guidance of glial cell migration and axonal growth on electrospun nanofibers of poly-ε-caprolactone and a collagen/poly-ε-caprolactone blend. Biomaterials28(19),3012–3025 (2007).
    • 77  Theron A, Zussman E, Yarin AL: Electrostatic field-assisted alignment of electrospun nanofibers. Nanotechnology12(3),384–390 (2001).
    • 78  Teo WE, Ramakrishna S: Electrospun fiber bundle made of aligned nanofibers over two fixed points. Nanotechnology16(9),1878–1884 (2005).
    • 79  Dalton PD, Klee D, Moller M: Electrospinning with dual collection rings. Polymer46(3),611–614 (2005).
    • 80  Zhang YZ, Huang ZM, Xu XJ, Lim CT, Ramakrishna S: Preparation of core–shell structured PCL-r-gelatin bi-component nanofibers by coaxial electrospinning. Chem. Mater.16(18),3406–3409 (2004).
    • 81  Li D, Xia YN: Direct fabrication of composite and ceramic hollow nanofibers by electrospinning. Nano Lett.4(5),933–938 (2004).
    • 82  Loscertales IG, Barrero A, Marquez M, Spretz R, Velarde-Ortiz R, Larsen G: Electrically forced coaxial nanojets for one-step hollow nanofiber design. J. Am. Chem. Soc.126(17),5376–5377 (2004).
    • 83  Li D, Babel A, Jenekhe SA, Xia YN: Nanofibers of conjugated polymers prepared by electrospinning with a two-capillary spinneret. Adv. Mater.16(22),2062–2066 (2004).
    • 84  Yu JH, Fridrikh SV, Rutledge GC: Production of submicrometer diameter fibers by two-fluid electrospinning. Adv. Mater.16(17),1562–1566 (2004).
    • 85  Huang ZM, Zhang Y, Ramakrishna S: Double-layered composite nanofibers and their mechanical performance. J. Polym. Sci. B – Polym. Phys.43(20),2852–2861 (2005).
    • 86  Jiang HL, Hu YQ, Zhao PC, Li Y, Zhu KJ: Modulation of protein release from biodegradable core–shell structured fibers prepared by coaxial electrospinning. J. Biomed. Mater. Res. B – Appl. Biomater.79B(1),50–57 (2006).
    • 87  Townsend-Nicholson A, Jayasinghe SN: Cell electrospinning: a unique biotechnique for encapsulating living organisms for generating active biological microthreads/scaffolds. Biomacromolecules7(12),3364–3369 (2006).••  Demonstrates the feasibility of using coaxial electrospinning technology to produce composite microthreads with living cells.
    • 88  Nam J, Huang Y, Agarwal S, Lannutti J: Improved cellular infiltration in electrospun fiber via engineered porosity. Tissue Eng.13(9),2249–2257 (2007).
    • 89  Kim G, Kim W: Highly porous 3D nanofiber scaffold using an electrospinning technique. J. Biomed. Mater. Res. B – Appl. Biomater.81(1),104–110 (2007).
    • 90  He W, Ma ZW, Yong T, Teo WE, Ramakrishna S: Fabrication of collagen-coated biodegradable polymer nanofiber mesh and its potential for endothelial cells growth. Biomaterials26(36),7606–7615 (2005).
    • 91  Zhang YZ, Venugopal J, Huang ZM, Lim CT, Ramakrishna S: Characterization of the surface biocompatibility of the electrospun PCL-collagen nanofibers using fibroblasts. Biomacromolecules6(5),2583–2589 (2005).
    • 92  Ma ZW, 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. Biomaterials26(15),2527–2536 (2005).
    • 93  Araujo JV, Martins A, Leonor IB, Pinho ED, Reis RL, Neves NM: Surface Controlled biomimetic coating of polycaprolactone nanofiber meshes to be used as bone extracellular matrix analogues. J. Biomater. Sci. – Polm. Ed. (2007) (In Press).
    • 94  Vaz CM, van Tuijl S, Bouten CVC, Baaijens FPT: Design of scaffolds for blood vessel tissue engineering using a multi-layering electrospinning technique. Acta Biomater.1(5),575–582 (2005).
    • 95  Telemeco TA, Ayres C, Bowlin GL et al.: Regulation of cellular infiltration into tissue engineering scaffolds composed of submicron diameter fibrils produced by electrospinning. Acta Biomater.1(4),377–385 (2005).
    • 96  Boland ED, Wnek GE, Simpson DG, Pawlowski KJ, Bowlin GL: Tailoring tissue engineering scaffolds using electrostatic processing techniques: a study of poly(glycolic acid) electrospinning. J. Macromol. Sci. – Pure Appl. Chem.38(12),1231–1243 (2001).
    • 97  Li WJ, Laurencin CT, Caterson EJ, Tuan RS, Ko FK: Electrospun nanofibrous structure: a novel scaffold for tissue engineering. J. Biomed. Mater. Res.60(4),613–621 (2002).•• One of the first studies on the electrospun nanofibrous structures capability of supporting cell attachment and proliferation.
    • 98  Hsu CM, Shivkumar S: N,N-dimethylformamide additions to the solution for the electrospinning of poly(ε-caprolactone) nanofibers. Macromol. Mater. Eng.289(4),334–340 (2004).
    • 99  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.72B(1),117–124 (2005).
    • 100  Ito Y, Hasuda H, Kamitakahara M et al.: A composite of hydroxyapatite with electrospun biodegradable nanofibers as a tissue engineering material. J. Biosci. Bioeng.100(1),43–49 (2005).
    • 101  Choi JS, Lee SW, Jeong L et al.: Effect of organosoluble salts on the nanofibrous structure of electrospun poly(3-hydroxybutyrate-co-3-hydroxyvalerate). Int. J. Biol. Macromol.34(4),249–256 (2004).
    • 102  Rho KS, Jeong L, Lee G et al.: Electrospinning of collagen nanofibers: effects on the behavior of normal human keratinocytes and early-stage wound healing. Biomaterials27(8),1452–1461 (2006).
    • 103  Venugopal J, Ma LL, Yong T, Ramakrishna S: In vitro study of smooth muscle cells on polycaprolactone and collagen nanofibrous matrices. Cell Biol. Int.29(10),861–867 (2005).
    • 104  Geng XY, Kwon OH, Jang JH: Electrospinning of chitosan dissolved in concentrated acetic acid solution. Biomaterials26(27),5427–5432 (2005).
    • 105  Jin HJ, Chen JS, Karageorgiou V, Altman GH, Kaplan DL: Human bone marrow stromal cell responses on electrospun silk fibroin mats. Biomaterials25(6),1039–1047 (2004).
    • 106  Um IC, Fang DF, Hsiao BS, Okamoto A, Chu B: Electro-spinning and electro-blowing of hyaluronic acid. Biomacromolecules5(4),1428–1436 (2004).
    • 107  Wang XF, Um IC, Fang DF, Okamoto A, Hsiao BS, Chu B: Formation of water-resistant hyaluronic acid nanofibers by blowing-assisted electro-spinning and non-toxic post treatments. Polymer46(13),4853–4867 (2005).
    • 108  Li MY, Mondrinos MJ, Gandhi MR, Ko FK, Weiss AS, Lelkes PI: Electrospun protein fibers as matrices for tissue engineering. Biomaterials26(30),5999–6008 (2005).• Innovative study on the electrospinning of different proteins, where recombinant human tropoelastin nanofibers were electrospun for the first time.
    • 109  Wnek GE, Carr ME, Simpson DG, Bowlin GL: Electrospinning of nanofiber fibrinogen structures. Nano Lett.3(2),213–216 (2003).
    • 110  McManus MC, Boland ED, Simpson DG, Barnes CP, Bowlin GL: Electrospun fibrinogen: feasibility as a tissue engineering scaffold in a rat cell culture model. J. Biomed. Mater. Res. A81A(2),299–309 (2007).
    • 111  Min BM, Lee SW, Lim JN et al.: Chitin and chitosan nanofibers: electrospinning of chitin and deacetylation of chitin nanofibers. Polymer45(21),7137–7142 (2004).
    • 112  Min BM, You Y, Kim JM, Lee SJ, Park WH: Formation of nanostructured poly(lactic-co-glycolic acid)/chitin matrix and its cellular response to normal human keratinocytes and fibroblasts. Carbohyd. Polym.57(3),285–292 (2004).
    • 113  Pan H, Jiang HL, Chen WL: Interaction of dermal fibroblasts with electrospun composite polymer scaffolds prepared from dextran and poly lactide-co-glycolide. Biomaterials27(17),3209–3220 (2006).
    • 114  Kenawy ER, Layman JM, Watkins JR et al.: Electrospinning of poly(ethylene-co-vinyl alcohol) fibers. Biomaterials24(6),907–913 (2003).
    • 115  Schindler M, Ahmed I, Kamal J et al.: A synthetic nanofibrillar matrix promotes in vivo-like organization and morphogenesis for cells in culture. Biomaterials26(28),5624–5631 (2005).
    • 116  Min BM, Jeong L, Nam YS, Kim JM, Kim JY, Park WH: Formation of silk fibroin matrices with different texture and its cellular response to normal human keratinocytes. Int. J. Biol. Macromol.34(5),281–288 (2004).
    • 117  Li WJ, Danielson KG, Alexander PG, Tuan RS: Biological response of chondrocytes cultured in three-dimensional nanofibrous poly(ε-caprolactone) scaffolds. J. Biomed. Mater. Res. A67A(4),1105–1114 (2003).
    • 118  Alves da Silva M, Crawford A, Mundy J et al.: Evaluation of extracellular matrix formation in PCL and SPCL nanofiber meshes when seeded with bovine articular chondrocytes. J. Biomed. Mater. Res. A (2007) (In Press).
    • 119  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.16(7),861–873 (2005).
    • 120  Bhattarai N, Edmondson D, Veiseh O, Matsen FA, Zhang MQ: Electrospun chitosan-based nanofibers and their cellular compatibility. Biomaterials26(31),6176–6184 (2005).
    • 121  Li WJ, Tuli R, Okafor C et al.: A three-dimensional nanofibrous scaffold for cartilage tissue engineering using human mesenchymal stem cells. Biomaterials26(6),599–609 (2005).
    • 122  Fujihara K, Kotaki M, Ramakrishna S: Guided bone regeneration membrane made of polycaprolactone/calcium carbonate composite nano-fibers. Biomaterials26(19),4139–4147 (2005).
    • 123  Nair LS, Bhattacharyya S, Bender JD et al.: Fabrication and optimization of methylphenoxy substituted polyphosphazene nanofibers for biomedical applications. Biomacromolecules5(6),2212–2220 (2004).
    • 124  Yoshimoto H, Shin YM, Terai H, Vacanti JP: A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering. Biomaterials24(12),2077–2082 (2003).•• Showed that electrospun polycaprolactone nanofiber meshes support mineralized-tissue formation, thus being a suitable candidate for the treatment of bone defects.
    • 125  Boudriot U, Goetz B, Dersch R, Greiner A, Wendorff JH: Role of electrospun nanofibers in stem cell technologies and tissue engineering. Macromol. Symp.225,9–16 (2005).
    • 126  Yang F, Xu CY, Kotaki M, Wang S, Ramakrishna S: Characterization of neural stem cells on electrospun poly(L-lactic acid) nanofibrous scaffold. J. Biomater. Sci. Polym. Ed.15(12),1483–1497 (2004).
    • 127  Yang Y, De Laporte L, Rives CB et al.: Neurotrophin releasing single and multiple lumen nerve conduits. J. Control. Release104(3),433–446 (2005).
    • 128  Shin M, Ishii O, Sueda T, Vacanti JP: Contractile cardiac grafts using a novel nanofibrous mesh. Biomaterials25(17),3717–3723 (2004).
    • 129  Zong XH, Bien H, Chung CY et al.: Electrospun fine-textured scaffolds for heart tissue constructs. Biomaterials26(26),5330–5338 (2005).
    • 130  Stitzel JD, Pawlowski KJ, Wnek GE, Simpson DG, Bowlin GL: Arterial smooth muscle cell proliferation on a novel biomimicking, biodegradable vascular graft scaffold. J. Biomater. Appl.16(1),22–33 (2001).
    • 131  Xu CY, Inai R, Kotaki M, Ramakrishna S: Electrospun nanofiber fabrication as synthetic extracellular matrix and its potential for vascular tissue engineering. Tissue Eng.10(7–8),1160–1168 (2004).
    • 132  Mo XM, Xu CY, Kotaki M, Ramakrishna S: Electrospun P(LLA-CL) nanofiber: a biomimetic extracellular matrix for smooth muscle cell and endothelial cell proliferation. Biomaterials25(10),1883–1890 (2004).
    • 133  Jeong SI, Kim SY, Cho SK et al.: Tissue-engineered vascular grafts composed of marine collagen and PLGA fibers using pulsatile perfusion bioreactors. Biomaterials28(6),1115–1122 (2007).
    • 134  Stitzel J, Liu L, Lee SJ et al.: Controlled fabrication of a biological vascular substitute. Biomaterials27(7),1088–1094 (2006).
    • 135  Venugopal J, Zhang YZ, Ramakrishna S: Fabrication of modified and functionalized polycaprolactone nanofiber scaffolds for vascular tissue engineering. Nanotechnology16(10),2138–2142 (2005).
    • 136  Kwon IK, Kidoaki S, Matsuda T: Electrospun nano- to microfiber fabrics made of biodegradable copolyesters: structural characteristics, mechanical properties and cell adhesion potential. Biomaterials26(18),3929–3939 (2005).
    • 137  Riboldi SA, Sampaolesi M, Neuenschwander P, Cossu G, Mantero S: Electrospun degradable polyesterurethane membranes: potential scaffolds for skeletal muscle tissue engineering. Biomaterials26(22),4606–4615 (2005).
    • 138  Sahoo S, Ouyang H, Goh JCH, Tay TE, Toh SL: Characterization of a novel polymeric scaffold for potential application in tendon/ligament tissue engineering. Tissue Eng.12(1),91–99 (2006).
    • 139  Chua KN, Lim WS, Zhang PC et al.: Stable immobilization of rat hepatocyte spheroids on galactosylated nanofiber scaffold. Biomaterials26(15),2537–2547 (2005).
    • 140  Welle A, Kroger M, Doring M, Niederer K, Pindel E, Chronakis S: Electrospun aliphatic polycarbonates as tailored tissue scaffold materials. Biomaterials28(13),2211–2219 (2007).
    • 141  Zong XH, Kim K, Chiu J et al.: Prevention of post-surgical adhesions using electrospun bioabsorbable non-woven nanofiber membranes. Abs. Pap. Am. Chem. Soc.226,U436 (2003).
    • 142  Katti DS, Robinson KW, Ko FK, Laurencin CT: Bioresorbable nanofiber-based systems for wound healing and drug delivery: optimization of fabrication parameters. J. Biomed. Mater. Res. B – Appl. Biomater.70B(2),286–296 (2004).
    • 143  Verreck G, Chun I, Rosenblatt J et al.: Incorporation of drugs in an amorphous state into electrospun nanofibers composed of a water-insoluble, nonbiodegradable polymer. J. Control. Release92(3),349–360 (2003).
    • 144  Huang ZM, He CL, Yang AZ et al.: Encapsulating drugs in biodegradable ultrafine fibers through co-axial electrospinning. J. Biomed. Mater. Res. A77A(1),169–179 (2006).
    • 145  Jing Z, Xu XY, Chen XS et al.: Biodegradable electrospun fibers for drug delivery. J. Control. Release92(3),227–231 (2003).
    • 146  Xie JW, Wang CH: Electrospun micro- and nanofibers for sustained delivery of paclitaxel to treat C6 glioma in vitro.Pharm. Res.23(8),1817–1826 (2006).
    • 147  Jiang HL, Fang DF, Hsiao BJ, Chu BJ, Chen WL: Preparation and characterization of ibuprofen-loaded poly(lactide-co-glycolide)/poly(ethylene glycol)-g-chitosan electrospun membranes. J. Biomater. Sci. Polym. Ed.15(3),279–296 (2004).
    • 148  Cui WG, Li XH, Zhu XL, Yu G, Zhou SB, Weng J: Investigation of drug release and matrix degradation of electrospun poly(dl-lactide) fibers with paracetanol inoculation. Biomacromolecules7(5),1623–1629 (2006).
    • 149  Luong-Van E, Grondahl L, Chua KN, Leong KW, Nurcombe V, Cool SM: Controlled release of heparin from poly(ε-caprolactone) electrospun fibers. Biomaterials27(9),2042–2050 (2006).
    • 150  Casper CL, Yamaguchi N, Kiick KL, Rabolt JF: Functionalizing electrospun fibers with biologically relevant macromolecules. Biomacromolecules6(4),1998–2007 (2005).
    • 151  Park YJ, Kim KH, Lee JY et al.: Immobilization of bone morphogenetic protein-2 on a nanofibrous chitosan membrane for enhanced guided bone regeneration. Biotechnol. Appl. Biochem.43,17–24 (2006).
    • 152  Chew SY, Wen J, Yim EKF, Leong KW: Sustained release of proteins from electrospun biodegradable fibers. Biomacromolecules6(4),2017–2024 (2005).
    • 153  Zeng J, Aigner A, Czubayko F, Kissel T, Wendorff JH, Greiner A: Poly(vinyl alcohol) nanofibers by electrospinning as a protein delivery system and the retardation of enzyme release by additional polymer coatings. Biomacromolecules6(3),1484–1488 (2005).
    • 154  Luu YK, Kim K, Hsiao BS, Chu B, Hadjiargyrou M: Development of a nanostructured DNA delivery scaffold via electrospinning of PLGA and PLA–PEG block copolymers. J. Control. Release89(2),341–353 (2003).
    • 155  Liang DH, Luu YK, Kim KS, Hsiao BS, Hadjiargyrou M, Chu B: In vitro non-viral gene delivery with nanofibrous scaffolds. Nucleic Acids Res.33(19),E170 (2005).