Electrospun 3D multi-scale fibrous scaffold for enhanced human dermal fibroblast infiltration

Wen Shing Leong, Shu Cheng Wu, KeeWoei Ng, Lay Poh Tan

Article ID: 02002
Vol 2, Issue 1, 2016, Article identifier:81-92

VIEWS - 3196 (Abstract) 897 (PDF)


Electrospun polymeric nanofibrous scaffold possesses significant potential in the field of tissue engineering due to its extracellular matrix mimicking topographical features that modulate a variety of key cellular activities. However, traditional two dimensional (2D) electrospun scaffolds are generally close-packed fiber mats which prohibit cell infiltration and proliferation. Consequently, the applications of electrospun scaffolds in regenerative medicine is limited. In this study, we detail the use of a needle collector to fabricate 3D electrospun poly-ε-caprolactone (PCL) scaffolds with multi-scale fiber dimensions. The resultant pore size is 4 times larger than conventional 2D electrospun scaffolds with interweaving micro (3.3 ± 0.6µm) and nano (240 ± 50 nm) fibers. The scaffold was surface modified by grafting with gelatin molecules. It was found that surface modification significantly improved Human Dermal Fibroblasts (HDFs) cell infiltration throughout the 3D multi-scale scaffold. Even after an extended culture period of up to 28 days, cell proliferation was well supported in the surface-modified 3D multi-scale scaffold as confirmed by Ki67 staining. Extracellular matrix proteins secreted by the HDFs was evident on the 3D multi-scale PCL scaffold showing promising potential to facilitate tissue regeneration, in particular dermal tissue engineering.


tissue engineering; 3D electrospinning scaffold; Human Dermal Fibroblasts; three dimensional scaffold; cell infiltration

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Atala A, Thomson J A and Nerem R M, 2011, Principles of Regenerative Medicine, 2nd edn, Elsevier Inc.

Jayarama R V, Radhakrishnan S, Ravichandran R, et al., 2013, Nanofibrous structured biomimetic strategies for skin tissue regeneration. Wound Repair and Regenera-tion, vol.21(1): 1–16. http://dx.doi.org/10.1111/j.1524-475X.2012.00861.x

Metcalfe A D and Ferguson M W J, 2007, Tissue engineering of replacement skin: The crossroads of biomaterials, wound healing, embryonic development, stem cells and regeneration. Journal of The Royal Society In-terface, vol.4(14): 413–417. http://dx.doi.org/10.1098/rsif.2006.0179

Xu C Y, Inai R, Kotaki M, et al., 2004, Aligned biodegradable nanofibrous structure: A potential scaffold for blood vessel engineering. Biomaterials, vol.25(5): 877–886. http://dx.doi.org/10.1016/S0142-9612(03)00593-3

Barnes C P, Sell S A, Boland E D, et al., 2007, Nanofiber technology: Designing the next generation of tissue engineering scaffolds. Advanced Drug Delivery Reviews, vol.59(14): 1413–1433. http://dx.doi.org/10.1016/j.addr.2007.04.022

Smith L A and Ma P X, 2004, Nanofibrous scaffolds for tissue engineering. Colloids and Surfaces B: Biointerfaces, vol.39(3): 125–131. http://dx.doi.org/10.1016/j.colsurfb.2003.12.004

Powell H M, Supp D M and Boyce S T, 2008, Influence of electrospun collagen on wound contraction of engineered skin substitutes. Biomaterials, vol.29(7): 834–843. http://dx.doi.org/10.1016/j.biomaterials.2007.10.036

Ayres C E, Jha B S, Sell S A, et al., 2010, Nanotechnology in the design of soft tissue scaffolds: Innovations in structure and function. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, vol.2(1): 20–34. http://dx.doi.org/10.1002/wnan.55

Lowery J L, Datta N and Rutledge G C, 2010, Effect of fiber diameter, pore size and seeding method on growth of human dermal fibroblasts in electrospun poly(ɛ-cap-rolactone) fibrous mats. Biomaterials, vol.31(3): 491–504. http://dx.doi.org/10.1016/j.biomaterials.2009.09.072

Gelain F, 2008, Novel opportunities and challenges offered by nanobiomaterials in tissue engineering. International Journal of Nanomedicine, vol.3(4): 415–424. http://dx.doi.org/10.2147/IJN.S3795

Zhong S P, Zhang Y Z and Lim C T, 2012, Fabrication of large pores in electrospun nanofibrous scaffolds for cellular infiltration: A review. Tissue Engineering Part B: Reviews, vol.18(2): 77–87. http://dx.doi.org/10.1089/ten.TEB.2011.0390

Rnjak-Kovacina J and Weiss A S, 2011, Increasing the pore size of electrospun scaffolds. Tissue Engineering Part B: Reviews, vol.17(5): 365–372. http://dx.doi.org/10.1089/ten.teb.2011.0235

Shim I K, Jung M R, Kim K H, et al., 2010, Novel three-dimensional scaffolds of poly(L-lactic acid) microfibers using electrospinning and mechanical expansion: Fabrication and bone regeneration. Journal of Biomedical Materials Research Part B: Applied Bioma-terials, vol.95(1): 150–160. http://dx.doi.org/10.1002/jbm.b.31695

Nam J, Huang Y, Agarwal S, et al., 2007, Improved cellular infiltration in electrospun fiber via engineered porosity. Tissue Engineering, vol.13(9): 2249–2257. http://dx.doi.org/10.1089/ten.2006.0306

Balguid A, Mol A, van Marion M H, et al., 2009, Tailoring fiber diameter in electrospun poly(ɛ-caprolactone) scaffolds for optimal cellular infiltration in cardiovascular tissue engineering. Tissue Engineering Part A, vol.15(2): 437–444. http://dx.doi.org/10.1089/ten.tea.2007.0294

Baker B M, Gee A O, Metter R B, et al., 2008, The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers. Biomaterials, vol.29(15): 2348–2358. http://dx.doi.org/10.1016/j.biomaterials.2008.01.032

Guimaraes A, Martins A, Pinho E D, et al., 2010, Solving cell infiltration limitations of electrospun nanofiber meshes for tissue engineering applications. Nanomedicine (London), vol.5(4): 539–554. http://dx.doi.org/10.2217/nnm.10.31

Simonet M, Schneider O D, Neuenschwander P, et al., 2007, Ultraporous 3D polymer meshes by low-temperature electrospinning: Use of ice crystals as a removable void template. Polymer Engineering and Science, vol.47(12): 2020–2026. http://dx.doi.org/10.1002/pen.20914

Pham Q P, Sharma U and Mikos A G, 2006, Electrospun poly(ε-caprolactone) microfiber and multilayer nanofiber/microfiber scaffolds: Characterization of scaffolds and measurement of cellular infiltration. Biomacromolecules, vol.7(10): 2796–2805. http://dx.doi.org/10.1021/bm060680j

Soliman S, Pagliari S, Rinaldi A, et al., 2010, Multiscale three-dimensional scaffolds for soft tissue engineering via multimodal electrospinning. Acta Biomaterialia, vol.6(4): 1227–1237. http://dx.doi.org/10.1016/j.actbio.2009.10.051

Moroni L, Hamann D, Schotel R, et al., 2008, 3D fiber-deposited electrospun intergrated scaffolds enhance cartilage tissue formation. Advanced Functional Materials, vol.18(1): 53–60. http://dx.doi.org/10.1002/adfm.200601158

Kim G, Son J, Park S, et al., 2008, Hybrid process for fabricating 3D hierarchical scaffolds combining rapid prototyping and electrospinning. Macromolecular Rapid Communications, vol.29(19): 1577–1581. http://dx.doi.org/10.1002/marc.200800277

Blakeney B A, Tambralli A, Anderson J M, et al., 2011, Cell infiltration and growth in a low density, uncom-pressed three-dimensional electrospun nanofibrous scaffold. Biomaterials, vol.32(6): 1583–1590. http://dx.doi.org/10.1016/j.biomaterials.2010.10.056

Tzezana R, Zussman E, Levenberg S, 2008, A layered ultraporous scaffold for tissue engineering, created via a hydrospinning method. Tissue Engineering Part C: Methods, vol.14(4): 281–288. http://dx.doi.org/10.1089/ten.tec.2008.0201

Ahirwal D, Hebraud A, Kadar R, et al., 2013, From self-assembly of electrospun nanofibers to 3D cm thick hierarchical foams. Soft Matter, vol.9(11): 3164–3172. http://dx.doi.org/10.1039/C2SM27543K

Lavery L A, Armstrong D G and Harkless L B, 1996, Classification of diabetic foot wounds. Journal of Foot and Ankle Surgery, vol.35(6): 528–531. http://dx.doi.org/10.1016/S1067-2516(96)80125-6

Zhu Y, Gao C, Liu X, et al., 2002, Surface modification of polycaprolactone membrane via aminolysis and biomacromolecule immobilization for promoting cyto-compatibility of human endothelial cells. Biomacromolecules, vol.3(6): 1312–1319. http://dx.doi.org/10.1021/bm020074y

ImageJ Download page, n.d., viewed March 31, 2015, http://rsb.info.nih.gov/ij/download.html

Grant P V, Tomlins P E, Mikhalovska L, et al., 2005, Physical characterization of a polycaprolactone tissue scaffold in Surface Chemistry in Biomedical and Environmental Science, Springer, Dordrecht, 215–228.

Tanaka A, Nagate T and Matsuda H, 2005, Acceleration of wound healing by gelatin film dressings with epidermal growth factor. Journal of Veterinary Medical Science, vol.67(9): 909–913. http://dx.doi.org/10.1292/jvms.67.909

Bissell M J, Hall H G and Parry G, 1982, How does the extracellular matrix direct gene expression? Journal of Theoritical Biology, vol.99(1): 31–68. http://dx.doi.org/10.1016/0022-5193(82)90388-5

Martínez E, Engel E, Planell J A, et al., 2009, Effects of artificial micro- and nano-structured surfaces on cell behaviour. Annals of Anatomy — Anatomischer Anzeiger, vol.191(1): 126–135. http://dx.doi.org/10.1016/j.aanat.2008.05.006

Tay C Y, Irvine S A, Boey F Y C, et al., 2011, Micro-/nano-engineered cellular responses for soft tissue engineering and biomedical applications. Small, vol.7(10): 1361–1378. http://dx.doi.org/10.1002/smll.201100046

Li H, Wong Y S, Wen F, et al., 2013, Human mesen-chymal stem — cell behaviour on direct laser micropatterned electrospun scaffolds with hierarchical structures. Macromolecular Bioscience, vol.13(3): 299–310. http://dx.doi.org/10.1002/mabi.201200318

Tay C Y, Koh C G, Tan N S, et al., 2013, Mechanoregulation of stem cell fate via micro-/nano-scale manipulation for regenerative medicine. Nanomedicine, vol.8(4): 623–638. http://dx.doi.org/10.2217/nnm.13.31

Yeong W Y, Yu H, Lim K P, et al., 2010, Multiscale topological guidance for cell alignment via direct laser writing on biodegradable polymer. Tissue Engineering Part C: Methods, vol.16(5): 1011–1021. http://dx.doi.org/10.1089/ten.TEC.2009.0604

Tang C C, Chen J C, Long Y Z, et al., 2011, Preparation of curled microfibers by electrospinning with tip collector. Chinese Physics Letters, vol.28(5). http://dx.doi.org/10.1088/0256-307X/28/5/056801

Kim H Y, Lee M, Park K J, et al., 2010, Nanopottery: Coiling of electrospun polymer nanofibers. Nano Letters, vol.10(6): 2138–2140. http://dx.doi.org/10.1021/nl100824d

Watt F M and Fujiwara H, 2011, Cell-extracellular matrix interactions in normal and diseased skin. Cold Spring Harbor Perspectives in Biology, vol.3(4): a005124. http://dx.doi.org/10.1101/cshperspect.a005124

DOI: http://dx.doi.org/10.18063/IJB.2016.01.002


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