Electrospun multifunctional tissue engineering scaffolds

Abstract

Tissue engineering holds great promises in providing successful treatments of human body tissue loss that current methods are unable to treat or unable to achieve satisfactory clinical outcomes. In scaffold-based tissue engineering, a high-performance scaffold underpins the success of a tissue engineering strategy and a major direction in the field is to create multifunctional tissue engineering scaffolds for enhanced biological performance and for regenerating complex body tissues. Electrospinning can produce nanofibrous scaffolds that are highly desirable for tissue engineering. The enormous interest in electrospinning and electrospun fibrous structures by the science, engineering and medical communities has led to various developments of the electrospinning technology and wide investigations of electrospun products in many industries, including biomedical engineering, over the past two decades. It is now possible to create novel, multicomponent tissue engineering scaffolds with multiple functions. This article provides a concise review of recent advances in the R & D of electrospun multifunctional tissue engineering scaffolds. It also presents our philosophy and research in the designing and fabrication of electrospun multicomponent scaffolds with multiple functions.

Graphical abstract

Keywords

electrospinning / monocomponent / multicomponent / scaffold / core--shell / drug / biomolecule / growth factor / controlled release

References

[1] Huang Z M, Zhang Y Z, Kotaki M, . A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Composites Science and Technology, 2003, 63(15): 2223–2253

[2] Kenawy R, Bowlin G L, Mansfield K, . Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a blend. Journal of Controlled Release, 2002, 81(1–2): 57–64

[3] Wang C, Wang M, Yuan X Y. Novel electrospun bicomponent scaffolds for bone tissue engineering: fabrication, characterization and sustained release of growth factor. Cambridge University Press: Materials Research Society Symposium Proceedings, 2012, 1418: 151–162

[4] Tucker N, Stanger J J, Staiger M P, . The history of the science and technology of electrospinning from 1600 to 1995. Journal of Engineered Fabrics and Fibers, 2012, 7(3): 63–73

[5] Formhals A. Process and apparatus for preparing artificial threads. US Patent, 1 975 504, 1934

[6] Formhals A. Production of artificial fibers from fiber forming liquids. US Patent, 2 323 025, 1943

[7] The 3rd International Conference on Electrospinning, Aug. 4–7, 2014, San Francisco, CA, USA (organized by the American Ceramic Society)

[8] Ramakrishna S, Fujihara K, Teo W E, . An Introduction to Electrospinning and Nanofibers. Singapore: World Scientific, 2005

[9] Reneker D H, Yarin A L, Zussman E, . Electrospinning of nanofibers from polymer solutions and melts. Advances in Applied Mechanics, 2007, 41: 43–195

[10] Pham Q P, Sharma U, Mikos A G. Electrospinning of polymeric nanofibers for tissue engineering applications: a review. Tissue Engineering, 2006, 12(5): 1197–1211

[11] Sill T J, von Recum H A. Electrospinning: applications in drug delivery and tissue engineering. Biomaterials, 2008, 29(13): 1989–2006

[12] Schiffman J D, Schauer C L. A review: Electrospinning of biopolymer nanofibers and their applications. Polish Review, 2008, 48(2): 317–352

[13] Zhang Z, Hu J, Ma P X. Nanofiber-based delivery of bioactive agents and stem cells to bone sites. Advanced Drug Delivery Reviews, 2012, 64(12): 1129–1141

[14] Lanza R, Langer R, Vacanti J. Principles of Tissue Engineering. 3rd ed. UT, USA: Academic Press, 2007

[15] Li W-J, Laurencin C T, Caterson E J, . Electrospun nanofibrous structure: A novel scaffold for tissue engineering. Journal of Biomedical Materials Research, 2002, 60(4): 613–621

[16] Li C, Vepari C, Jin H J, . Electrospun silk-BMP-2 scaffolds for bone tissue engineering. Biomaterials, 2006, 27(16): 3115–3124

[17] 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

[18] Ji W, Yang F, van den Beucken J J P, . Fibrous scaffolds loaded with protein prepared by blend or coaxial electrospinning. Acta Biomaterialia, 2010, 6(11): 4199–4207

[19] Theron S A, Yarin A L, Zussman E, . Multiple jets in electrospinning: experiment and modeling. Polymer, 2005, 46(9): 2889–2899

[20] Wu X-F, Salkovskiy Y, Dzenis Y A. Modeling of solvent evaporation from polymer jets in electrospinning. Applied Physics Letters, 2011, 98(22): 223108 (3 pages)

[21] Yarin A L, Koombhongse S, Reneker D H. Taylor cone and jetting from liquid droplets in electrospinning of nanofibers. Journal of Applied Physics, 2001, 90(9): 4836–4846

[22] Wang M, Tong H W, Lo M. Electrospinning of polymer tissue engineering scaffolds: effects of emitting electrode polarity. In: Proceedings of the 8th World Biomaterials Congress, Amsterdam, the Netherlands. Paper #1462, 2008

[23] Tong H W, Wang M.Electrospinning of fibrous polymer scaffolds using positive voltage or negative voltage: a comparative study. Biomedical Materials, 2010, 5: 054110 (15 pages)

[24] Tong H W, Wang M, Lu W W. Enhancing the biological performance of osteoconductive nanocomposite scaffolds through negative voltage electrospinning. Nanomedicine, 2013, 8(4): 577–589

[25] Sanders E H, Kloefkorn R, Bowlin G L, . Two-phase electrospinning from a single electrified jet: Microencapsulation of aqueous reservoirs in poly(ethylene-co-vinyl acetate) fibers. Macromolecules, 2003, 36(11): 3803–3805

[26] Wang C, Wang M. Emulsion electrospinning of nanofibrous delivery vehicles for the controlled release of biomolecules and the in vitro release behaviour of biomolecules. Advanced Materials Research, 2012, 410: 98–101

[27] Maretschek S, Greiner A, Kissel T. Electrospun biodegradable nanofiber nonwovens for controlled release of proteins. Journal of Controlled Release, 2008, 127(2): 180–187

[28] Li X, Su Y, Zhou 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

[29] Sy J C, Klemm A S, Shastri V P. Emulsion as a means of controlling electrospinning of polymers. Advanced Materials, 2009, 21(18): 1814–1819

[30] Loscertales I G, Barrero A, Guerrero I, . Micro/nano encapsulation via electrified coaxial liquid jets. Science, 2002, 295(5560): 1695–1698

[31] Zhang Y, Huang Z-M, Xu X, . Preparation of core–shell structured PCL-r-gelatin bi-component nanofibers by coaxial electrospinning. Chemistry of Materials, 2004, 16(18): 3406–3409

[32] Hong Y, Chen X, Jing X, . Fabrication and drug delivery of ultrathin mesoporous bioactive glass hollow fibers. Advanced Functional Materials, 2010, 20(9): 1503–1510

[33] Fazley E, Wang L, Guan G P, . Core–shell fibers for biomedical applications — A review. Journal Bioengineer and Biomedical Science, 2013, 3(1): 1000121 (14 pages)

[34] Yarin A L, Zussman E. Upward needleless electrospinning of multiple nanofibers. Polymer, 2004, 45(9): 2977–2980

[35] Park K E, Kang H K, Lee S J, . Biomimetic nanofibrous scaffolds: preparation and characterization of PGA/chitin blend nanofibers. Biomacromolecules, 2006, 7(2): 635–643

[36] Jose M V, Thomas V, Johnson K T, . Aligned PLGA/HA nanofibrous nanocomposite scaffolds for bone tissue engineering. Acta Biomaterialia, 2009, 5(1): 305–315

[37] Kim H W, Lee H H, Knowles J C. Electrospinning biomedical nanocomposite fibers of hydroxyapatite/poly(lactic acid) for bone regeneration. Journal of Biomedical Materials Research Part A, 2006, 79A(3): 643–649

[38] Tong H W, Wang M, Li Z. Electrospinning, characterization and in vitro biological evaluation of nanocomposite fibers containing carbonated hydroxyapatite nanoparticles. Biomedical Materials, 2010, 5: 054111 (13 pages)

[39] Wang C, Wang M. Electrospun bioactive and biodegradable calcium phosphate/polymer nanocomposite scaffolds for bone tissue engineering. In: Proceedings of the 13th CCT Conference: Regenerative Nanomedicine, Tissue and Genetic Engineering, and the Role of Ceramics. Faenza, Italy, 2011 (7 pages)

[40] Hong Y, Li Y, Zhuang X, . Electrospinning of multicomponent ultrathin fibrous nonwovens for semi-occlusive wound dressings. Journal of Biomedical Materials Research Part A, 2009, 89A(2): 345–354

[41] Xu F, Cui F Z, Jiao Y P, . Improvement of cytocompatibility of electrospinning PLLA microfibers by blending PVP. Journal of Materials Science: Materials in Medicine, 2009, 20(6): 1331–1338

[42] Li M, Mondrinos M J, Chen X, . Electrospun blends of natural and synthetic polymers as scaffolds for tissue engineering. In: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society, 2005, 6: 5858–5861

[43] Meng W, Xing Z C, Jung K H, . Synthesis of gelatin-containing PHBV nanofiber mats for biomedical application. Journal of Materials Science: Materials in Medicine, 2008, 19(8): 2799–2807

[44] Duan B, Wu L, Yuan X, . Hybrid nanofibrous membranes of PLGA/chitosan fabricated via an electrospinning array. Journal of Biomedical Materials Research Part A, 2007, 83A(3): 868–878

[45] Wang C, Wang M. Dual-source dual-power electrospinning and characteristics of multifunctional scaffolds for bone tissue engineering. Journal of Materials Science: Materials in Medicine, 2012, 23(10): 2381–2397

[46] Wang C, Wang M. Electrospun osteoconductive and osteoinductive bicomponent scaffolds: controlled release of rhbmp-2 and enhanced biological performance of scaffolds. In: Transactions of the Society for Biomaterials 2013 Annual Meeting, Boston, USA, 2013

[47] Luttikhuizen D T, Harmsen M C, Van Luyn M J. Cellular and molecular dynamics in the foreign body reaction. Tissue Engineering, 2006, 12(7): 1955–1970

[48] Yilgor P, Tuzlakoglu K, Reis R L, . Incorporation of a sequential BMP-2/BMP-7 delivery system into chitosan-based scaffolds for bone tissue engineering. Biomaterials, 2009, 30(21): 3551–3559

[49] Simmons C A, Alsberg E, Hsiong S, . Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells. Bone, 2004, 35(2): 562–569

[50] Mouriño V, Boccaccini A R. Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds. Journal of the Royal Society: Interface, 2010, 7(43): 209–227

[51] Li X D, Hu Y Y. The treatment of osteomyelitis with gentamicin-reconstituted bone xenograft-composite. The Journal of Bone and Joint Surgery, 2001, 83(7): 1063–1068

[52] Stewart R L, Cox J T, Volgas D, . The use of a biodegradable, load-bearing scaffold as a carrier for antibiotics in an infected open fracture model. Journal of Orthopaedic Trauma, 2010, 24(9): 587–591

[53] Wu T, Zhang Q, Ren W, . Controlled release of gentamicin from gelatin/genipin reinforced β-tricalcium phosphate scaffold for the treatment of osteomyelitis. Journal of Materials Chemistry B, 2013, 1(26): 3304–3313

[54] Zhang H, Jia X, Han F, . Dual-delivery of VEGF and PDGF by double-layered electrospun membranes for blood vessel regeneration. Biomaterials, 2013, 34(9): 2202–2212

[55] Ono I, Akasaka Y, Kikuchi R, . Basic fibroblast growth factor reduces scar formation in acute incisional wounds. Wound Repair and Regeneration, 2007, 15(5): 617–623

[56] Uebersax L, Mattotti M, Papaloïzos M, . Silk fibroin matrices for the controlled release of nerve growth factor (NGF). Biomaterials, 2007, 28(30): 4449–4460

[57] Woo H M, Bentley E, Campbell S F, . Nerve growth factor and corneal wound healing in dogs. Experimental Eye Research, 2005, 80(5): 633–642

[58] Apfel S C, Wright D E, Wiideman A M, . Nerve growth factor regulates the expression of brain-derived neurotrophic factor mRNA in the peripheral nervous system. Molecular and Cellular Neurosciences, 1996, 7(2): 134–142

[59] Aloe L, Rocco M L, Bianchi P, . Nerve growth factor: from the early discoveries to the potential clinical use. Journal of Translational Medicine, 2012, 10(1): 239

[60] Choi-Lundberg D L, Lin Q, Chang Y N, . Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science, 1997, 275(5301): 838–841

[61] Oppenheim R W, Houenou L J, Johnson J E, . Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF. Nature, 1995, 373(6512): 344–346

[62] Liu C Y, Wang M. Incorporation and release of two growth factors for nerve tissue engineering using nanofibrous bicomponent scaffolds. In: Proceedings of the International Conference on Materials for Advanced Technologies 2013 (ICMAT 2013), Singapore, 2013-July

[63] Kontogiannopoulos K N, Assimopoulou A N, Tsivintzelis I, . Electrospun fiber mats containing shikonin and derivatives with potential biomedical applications. International Journal of Pharmaceutics, 2011, 409(1–2): 216–228

[64] Nie H, Wang C H. Fabrication and characterization of PLGA/HAp composite scaffolds for delivery of BMP-2 plasmid DNA. Journal of Controlled Release, 2007, 120(1–2): 111–121

[65] Nie H, Soh B W, Fu Y C, . Three-dimensional fibrous PLGA/HAp composite scaffold for BMP-2 delivery. Biotechnology and Bioengineering, 2008, 99(1): 223–234

[66] Su Y, Su Q, Liu W, . Controlled release of bone morphogenetic protein 2 and dexamethasone loaded in core–shell PLLACL-collagen fibers for use in bone tissue engineering. Acta Biomaterialia, 2012, 8(2): 763–771

[67] Taepaiboon P, Rungsardthong U, Supaphol P. Vitamin-loaded electrospun cellulose acetate nanofiber mats as transdermal and dermal therapeutic agents of vitamin A acid and vitamin E. European Journal of Pharmaceutics and Biopharmaceutics, 2007, 67(2): 387–397

[68] Yan S, Xiaoqiang L, Shuiping L, . Controlled release of dual drugs from emulsion electrospun nanofibrous mats. Colloids and Surfaces B: Biointerfaces, 2009, 73(2): 376–381

[69] Qi H, Hu P, Xu J, . Encapsulation of drug reservoirs in fibers by emulsion electrospinning: morphology characterization and preliminary release assessment. Biomacromolecules, 2006, 7(8): 2327–2330

[70] Xu X, Chen X, Wang Z, . 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

[71] Ye L, Wu X, Mu Q, . Heparin-conjugated PCL scaffolds fabricated by electrospinning and loaded with fibroblast growth factor 2. Journal of Biomaterials Science: Polymer Edition, 2011, 22(1–3): 389–406

[72] Kang J C, Wang M, Yuan X Y. Bicomponent fibrous scaffolds of controlled composition for tissue engineering applications. In: Proceedings of ASME International Mechanical Engineering Congress and Exposition, 2010, 2: 7–15

[73] Okuda T, Tominaga K, Kidoaki S. Time-programmed dual release formulation by multilayered drug-loaded nanofiber meshes. Journal of Controlled Release, 2010, 143(2): 258–264

[74] Ekaputra A K, Prestwich G D, Cool S M, . The three-dimensional vascularization of growth factor-releasing hybrid scaffold of poly (ε-caprolactone)/collagen fibers and hyaluronic acid hydrogel. Biomaterials, 2011, 32(32): 8108–8117

[75] Thakur R A, Florek C A, Kohn J, . Electrospun nanofibrous polymeric scaffold with targeted drug release profiles for potential application as wound dressing. International Journal of Pharmaceutics, 2008, 364(1): 87–93

[76] Wang C, Wang M. Fibrous delivery vehicles formed by dual-source dual-power electrospinning for the dual release of growth factors. In: Proceedings of the 2011 European Materials Research Society Spring Meeting, Nice, France, 2010

[77] Liu C Y, Zhang X, Wang M. Novel electrospun bicomponent scaffolds for nerve tissue repair. In: Proceedings of the 37th International Conference and Exposition on Advanced Ceramics and Composites (ICACC’13), Daytona Beach, FL, USA, 2013

[78] Du F, Wang H, Zhao W, . Gradient nanofibrous chitosan/poly ε-caprolactone scaffolds as extracellular microenvironments for vascular tissue engineering. Biomaterials, 2012, 33(3): 762–770

[79] Hou Z, Li X, Li C, . Electrospun upconversion composite fibers as dual drugs delivery system with individual release properties. Langmuir, 2013, 29(30): 9473–9482

[80] Wang C, Wang M. Bone tissue engineering scaffolds incorporated with rhVEGF for promoting vascularization. In: Proceedings of the 10th Pacific Rim Conference on Ceramics and Glass Technology (PacRim10), San Diego, CA, USA, 2013

Acknowledgements

This work was supported by the Hong Kong Research Grants Council through GRF grants (HKU 7181/09E and HKU 7177/13E). The authors thank an anonymous donor for generously providing financial support for our group’s research in biomaterials and tissue engineering at The University of Hong Kong.

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2014 Higher Education Press and Springer-Verlag Berlin Heidelberg