Research Article

Influence of porosity and pore shape on structural, mechanical and biological properties of poly ϵ-caprolactone electro-spun fibrous scaffolds

Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), National University of Ireland, Galway (NUI Galway), Galway, Ireland

Centre for Research in Medical Devices (CÚRAM), National University of Ireland, Galway (NUI Galway), Galway, Ireland

Search for more papers by this author

Diana Gaspar

Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), National University of Ireland, Galway (NUI Galway), Galway, Ireland

Centre for Research in Medical Devices (CÚRAM), National University of Ireland, Galway (NUI Galway), Galway, Ireland

Search for more papers by this author

Luis M Delgado

Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), National University of Ireland, Galway (NUI Galway), Galway, Ireland

Centre for Research in Medical Devices (CÚRAM), National University of Ireland, Galway (NUI Galway), Galway, Ireland

Search for more papers by this author

Abhay Pandit

Centre for Research in Medical Devices (CÚRAM), National University of Ireland, Galway (NUI Galway), Galway, Ireland

Search for more papers by this author

Dimitrios I Zeugolis

*Author for correspondence:

E-mail Address: dimitrios.zeugolis@nuigalway.ie

Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), National University of Ireland, Galway (NUI Galway), Galway, Ireland

Centre for Research in Medical Devices (CÚRAM), National University of Ireland, Galway (NUI Galway), Galway, Ireland

Search for more papers by this author

Published Online:13 Apr 2016https://doi.org/10.2217/nnm.16.21

View article

Abstract

Background: Electro-spun scaffolds are utilized in a diverse spectrum of clinical targets, with an ever-increasing quantity of work progressing to clinical studies and commercialization. The limited number of conformations in which the scaffolds can be fabricated hampers their wide acceptance in clinical practice. Materials & methods: Herein, we assessed a single-strep fabrication process for predesigned electro-spun scaffold preparation and the ramifications of the introduction of porosity (0, 30, 50, 70%) and pore shape (circle, rhomboid, square) on structural, mechanical (tensile and ball burst) and biological (dermal fibroblast and THP-1) properties. Results: The collector design did not affect the fibrous nature of the scaffold. Modulation of the porosity and pore shape offered control over the mechanical properties of the scaffolds. Neither the porosity nor the pore shape affected cellular (dermal fibroblast and THP-1) response. Conclusion: Overall, herein we provide evidence that electro-spun scaffolds of controlled architecture can be fabricated with fibrous fidelity, adequate mechanical properties and acceptable cytocompatibility for a diverse range of clinical targets.

Keywords:

References

1 Lang N, Skodzek K, Hurst S et al. Biphasic response of cell invasion to matrix stiffness in three-dimensional biopolymer networks. Acta Biomater. 13, 61–67 (2015).Crossref, Medline, CAS, Google Scholar
2 Ge S, Zhao N, Wang L et al. Bone repair by periodontal ligament stem cell-seeded nanohydroxyapatite-chitosan scaffold. Int. J. Nanomed. 7, 5405–5414 (2012).Crossref, Medline, CAS, Google Scholar
3 Urciuolo F, Imparato G, Totaro A, Netti P. Building a tissue in vitro from the bottom up: implications in regenerative medicine. Houston Methodist DeBakey Cardiovascular Journal 9(4), 213–217 (2013).Crossref, Medline, Google Scholar
4 Azeem A, English A, Kumar P et al. The influence of anisotropic nano- to micro-topography on in vitro and in vivo osteogenesis. Nanomedicine 10(5), 693–711 (2015).Link, CAS, Google Scholar
5 English A, Azeem A, Spanoudes K et al. Substrate topography: a valuable in vitro tool, but a clinical red herring for in vivo tenogenesis. Acta Biomater. 27, 3–12 (2015).Crossref, Medline, CAS, Google Scholar
6 Khan O, Voice D, Leung B, Sefton M. A novel high-speed production process to create modular components for the bottom-up assembly of large-scale tissue-engineered constructs. Advanced Healthcare Materials 4(1), 113–120 (2015).Crossref, Medline, CAS, Google Scholar
7 Elbert D. Bottom-up tissue engineering. Curr. Opin. Biotechnol. 22(5), 674–680 (2011).Crossref, Medline, CAS, Google Scholar
8 Liu W, Thomopoulos S, Xia Y. Electrospun nanofibers for regenerative medicine. Advanced Healthcare Materials 1(1), 10–25 (2012).Crossref, Medline, CAS, Google Scholar
9 Chou S, Carson D, Woodrow K. Current strategies for sustaining drug release from electrospun nanofibers. J. Control. Release 220(Pt B), 584–591 (2015).Crossref, Medline, CAS, Google Scholar
10 Ryan C, Fuller K, Larrañaga A et al. An academic, clinical and industrial update on electrospun, additive manufactured and imprinted medical devices. Expert Rev. Med. Devices 12(5), 601–612 (2015).Crossref, Medline, CAS, Google Scholar
11 Fuller K, Pandit A, Zeugolis D. The multifaceted potential of electro-spinning in regenerative medicine. Pharm. Nanotechnol. 2(1), 23–34 (2014).Crossref, CAS, Google Scholar
12 Jayasinghe S. Cell electrospinning: a novel tool for functionalising fibres, scaffolds and membranes with living cells and other advanced materials for regenerative biology and medicine. Analyst 138(8), 2215–2223 (2013).Crossref, Medline, CAS, Google Scholar
13 Teo W, Ramakrishna S. A review on electrospinning design and nanofibre assemblies. Nanotechnology 17(14), R89 (2006).Crossref, Medline, CAS, Google Scholar
14 Yao L, O’Brien N, Windebank A, Pandit A. Orienting neurite growth in electrospun fibrous neural conduits. J. Biomed. Mater. Res. B 90B(2), 483–491 (2009).Crossref, CAS, Google Scholar
15 Bergmeister H, Grasl C, Walter I et al. Electrospun small-diameter polyurethane vascular grafts: ingrowth and differentiation of vascular-specific host cells. Artif. Organs 36(1), 54–61 (2012).Crossref, Medline, CAS, Google Scholar
16 Phipps M, Clem W, Grunda J, Clines G, Bellis S. Increasing the pore sizes of bone-mimetic electrospun scaffolds comprised of polycaprolactone, collagen I and hydroxyapatite to enhance cell infiltration. Biomaterials 33(2), 524–534 (2012).Crossref, Medline, CAS, Google Scholar
17 Walthers C, Nazemi A, Patel S, Wu B, Dunn J. The effect of scaffold macroporosity on angiogenesis and cell survival in tissue-engineered smooth muscle. Biomaterials 35(19), 5129–5137 (2014).Crossref, Medline, CAS, Google Scholar
18 Kim T, Chung H, Park T. Macroporous and nanofibrous hyaluronic acid/collagen hybrid scaffold fabricated by concurrent electrospinning and deposition/leaching of salt particles. Acta Biomater. 4(6), 1611–1619 (2008).Crossref, Medline, CAS, Google Scholar
19 Baker B, Gee A, Metter R et al. The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers. Biomaterials 29(15), 2348–2358 (2008).Crossref, Medline, CAS, Google Scholar
20 Vaquette C, Cooper-White J. Increasing electrospun scaffold pore size with tailored collectors for improved cell penetration. Acta Biomater. 7(6), 2544–2557 (2011).Crossref, Medline, CAS, Google Scholar
21 Cheng Q, Lee B, Komvopoulos K, Li S. Engineering the microstructure of electrospun fibrous scaffolds by microtopography. Biomacromolecules 14(5), 1349–1360 (2013).Crossref, Medline, CAS, Google Scholar
22 English A, Azeem A, Gaspar D et al. Preferential cell response to anisotropic electro-spun fibrous scaffolds under tension-free conditions. J. Mater. Sci. Mater. Med. 23(1), 137–148 (2012).Crossref, Medline, CAS, Google Scholar
23 Zeugolis D, Khew S, Yew E et al. Electro-spinning of pure collagen nano-fibres – just an expensive way to make gelatin? Biomaterials 29(15), 2293–2305 (2008).Crossref, Medline, CAS, Google Scholar
24 Zeugolis D, Li B, Lareu R, Chan C, Raghunath M. Collagen solubility testing. A quality assurance step for reproducible electro-spun nano-fibres fabrication. A technical note. J. Biomater. Sci. 19(10), 1307–1317 (2008).Crossref, CAS, Google Scholar
25 Zeugolis D, Paul R, Attenburrow G. Extruded collagen fibres for tissue-engineering applications: influence of collagen concentration and NaCl amount. J. Biomater. Sci. 20(2), 219–234 (2009).Crossref, CAS, Google Scholar
26 Peh P, Lim N, Blocki A et al. Simultaneous delivery of highly diverse bioactive compounds from blend electrospun fibers for skin wound healing. Bioconj. Chem. 26(7), 1348–1358 (2015).Crossref, Medline, CAS, Google Scholar
27 Masaeli E, Wieringa P, Morshed M et al. Peptide functionalized polyhydroxyalkanoate nanofibrous scaffolds enhance Schwann cells activity. Nanomedicine 10(7), 1559–1569 (2014).Crossref, Medline, CAS, Google Scholar
28 Orr S, Chainani A, Hippensteel K et al. Aligned multilayered electrospun scaffolds for rotator cuff tendon tissue engineering. Acta Biomater. 24, 117–126 (2015).Crossref, Medline, CAS, Google Scholar
29 Phu D, Wray L, Warren R, Haskell R, Orwin E. Effect of substrate composition and alignment on corneal cell phenotype. Tissue Eng. A 17(5–6), 799–807 (2011).Crossref, Medline, CAS, Google Scholar
30 Brown T, Dalton P, Hutmacher D. Direct writing by way of melt electrospinning. Adv. Mater. 23(47), 5651–5657 (2011).Crossref, Medline, CAS, Google Scholar
31 Wang Y, Wang G, Chen L et al. Electrospun nanofiber meshes with tailored architectures and patterns as potential tissue-engineering scaffolds. Biofabrication 1(1), 015001 (2009).Crossref, Medline, Google Scholar
32 Li H, Xu Y, Xua H, Chang J. Electrospun membranes: control of the structure and structure related applications in tissue regeneration and drug delivery. J. Mater. Chem. B 2(34), 5492–5510 (2014).Crossref, Medline, CAS, Google Scholar
33 Li D, Ouyang G, McCann J, Xia Y. Collecting electrospun nanofibers with patterned electrodes. Nano Lett. 5(5), 913–916 (2005).Crossref, Medline, CAS, Google Scholar
34 Sanders J, Bale S, Neumann T. Tissue response to microfibers of different polymers: polyester, polyethylene, polylactic acid, and polyurethane. J. Biomed. Mater. Res. 62(2), 222–227 (2002).Crossref, Medline, CAS, Google Scholar
35 Sanders J, Cassisi D, Neumann T et al. Relative influence of polymer fiber diameter and surface charge on fibrous capsule thickness and vessel density for single-fiber implants. J. Biomed. Mater. Res. A 65(4), 462–467 (2003).Crossref, Medline, CAS, Google Scholar
36 Zeugolis D, Paul R, Attenburrow G. Post-self-assembly experimentation on extruded collagen fibres for tissue engineering applications. Acta Biomater. 4(6), 1646–1656 (2008).Crossref, Medline, CAS, Google Scholar
37 Coburn J, Brody S, Billiar K, Pandit A. Biaxial mechanical evaluation of cholecyst-derived extracellular matrix: a weakly anisotropic potential tissue engineered biomaterial. J. Biomed. Mater. Res. A 81(1), 250–256 (2007).Crossref, Medline, Google Scholar
38 Saberski E, Orenstein S, Novitsky Y. Anisotropic evaluation of synthetic surgical meshes. Hernia 15(1), 47–52 (2011).Crossref, Medline, CAS, Google Scholar
39 Pu J, Komvopoulos K. Mechanical properties of electrospun bilayer fibrous membranes as potential scaffolds for tissue engineering. Acta Biomater. 10(6), 2718–2726 (2014).Crossref, Medline, CAS, Google Scholar
40 Yu H, Matthew H, Wooley P, Yang S. Effect of porosity and pore size on microstructures and mechanical properties of poly-epsilon-caprolactone-hydroxyapatite composites. J. Biomed. Mater. Res. B 86(2), 541–547 (2008).Crossref, Medline, Google Scholar
41 Kim H, Kim H, Lee S et al. Effect of pore sizes of PLGA scaffolds on mechanical properties and cell behaviour for nucleus pulposus regeneration in vivo. J. Tissue Eng. Regen. Med. doi:10.1002/term.1856 (2014) (Epub ahead of print).Google Scholar
42 Li Z, Yang L, Li Y et al. Effects of pore size on the mechanical properties of three-dimensionally ordered macroporous nickel. Mater. Design 45, 52–55 (2013).Crossref, CAS, Google Scholar
43 Charernsriwilaiwat N, Rojanarata T, Ngawhirunpat T, Opanasopit P. Electrospun chitosan/polyvinyl alcohol nanofibre mats for wound healing. Int. Wound J. 11(2), 215–222 (2014).Crossref, Medline, Google Scholar
44 Saeed M, Mirzadeh H, Zandi M, Irani S, Barzin J. Rationalization of specific structure formation in electrospinning process: study on nano-fibrous PCL- and PLGA-based scaffolds. J. Biomed. Mater. Res. A 103(12), 3927–3939 (2015).Crossref, Medline, CAS, Google Scholar
45 Kumbar S, Nukavarapu S, James R, Nair L, Laurencin C. Electrospun poly(lactic acid-co-glycolic acid) scaffolds for skin tissue engineering. Biomaterials 29(30), 4100–4107 (2008).Crossref, Medline, CAS, Google Scholar
46 Li W, Laurencin C, Caterson E, Tuan R, Ko F. Electrospun nanofibrous structure: a novel scaffold for tissue engineering. J. Biomed. Mater. Res. 60(4), 613–621 (2002).Crossref, Medline, CAS, Google Scholar
47 Lin H, Kuo Y, Chang S, Ni T. Characterization of electrospun nanofiber matrices made of collagen blends as potential skin substitutes. Biomed. Mater. 8(2), 025009 (2013).Crossref, Medline, CAS, Google Scholar
48 Chen M, Patra P, Warner S, Bhowmick S. Role of fiber diameter in adhesion and proliferation of NIH 3T3 fibroblast on electrospun polycaprolactone scaffolds. Tissue Eng. 13(3), 579–587 (2007).Crossref, Medline, CAS, Google Scholar
49 Miyoshi H, Adachi T. Topography design concept of a tissue engineering scaffold for controlling cell function and fate through actin cytoskeletal modulation. Tissue Eng. B 20(6), 609–627 (2014).Crossref, Medline, CAS, Google Scholar
50 Bettinger C, Langer R, Borenstein J. Engineering substrate topography at the micro- and nanoscale to control cell function. Angew. Chem. Int. Ed. Engl. 48(30), 5406–5415 (2009).Crossref, Medline, CAS, Google Scholar
51 Smith M, White K, Smith D, Bowlin G. In vitro evaluations of innate and acquired immune responses to electrospun polydioxanone-elastin blends. Biomaterials 30(2), 149–159 (2009).Crossref, Medline, CAS, Google Scholar
52 Pan H, Jiang H, Kantharia S, Chen W. A fibroblast/macrophage co-culture model to evaluate the biocompatibility of an electrospun Dextran/PLGA scaffold and its potential to induce inflammatory responses. Biomed. Mater. 6(6), 065002 (2011).Crossref, Medline, Google Scholar
53 Saino E, Focarete M, Gualandi C et al. Effect of electrospun fiber diameter and alignment on macrophage activation and secretion of proinflammatory cytokines and chemokines. Biomacromolecules 12(5), 1900–1911 (2011).Crossref, Medline, CAS, Google Scholar
54 Garg K, Pullen N, Oskeritzian C, Ryan J, Bowlin G. Macrophage functional polarization (M1/M2) in response to varying fiber and pore dimensions of electrospun scaffolds. Biomaterials 34(18), 4439–4451 (2013).Crossref, Medline, CAS, Google Scholar
55 Wang Z, Cui Y, Wang J et al. The effect of thick fibers and large pores of electrospun poly(ϵ-caprolactone) vascular grafts on macrophage polarization and arterial regeneration. Biomaterials 35(22), 5700–5710 (2014).Crossref, Medline, CAS, Google Scholar
56 Lively B, Kumar S, Tian L, Li B, Zhong W. Mechanical, thermal and morphological characterization of polycarbonate/oxidized carbon nanofiber composites produced with a lean 2-step manufacturing process. J. Nanosci. Nanotechnol. 11(5), 3929–3937 (2011).Crossref, Medline, CAS, Google Scholar
57 Boehler R, Graham J, Shea L. Tissue engineering tools for modulation of the immune response. BioTechniques 51(4), 239–240 (2011).Crossref, Medline, CAS, Google Scholar
58 Franz S, Rammelt S, Scharnweber D, Simon J. Immune responses to implants - A review of the implications for the design of immunomodulatory biomaterials. Biomaterials 32(28), 6692–6709 (2011).Crossref, Medline, CAS, Google Scholar

Vol. 11, No. 9

Metrics

Downloaded 256 times

History

Published online 13 April 2016

Published in print May 2016

Information

Keywords

Financial & competing interests disclosure

This work is supported by the EU FP7/2007–2013, NMP award, Green Nano Mesh Project (grant agreement number: 263289) to D Zeugolis; the Health Research Board, Health Research Awards Programme, under the grant agreement number HRA_POR/2011/84 to D Zeugolis; the Enterprise Partnership Scheme, Irish Research Council (project number: EPSPG/2011/64) to K Fuller and D Zeugolis; the Irish Research Council, EMBARK Initiative, Postgraduate Scholarship (grant agreement number: RS/2012/82) to D Gaspar and D Zeugolis. This publication has also been supported from Science Foundation Ireland and the European Regional Development Fund (grant agreement number: 13/RC/2073) to A Pandit. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

PDF download