Tunable 3D Nanofiber Architecture of Polycaprolactone by Divergence Electrospinning for Potential Tissue Engineering Applications
Corresponding Author: George Z. Tan
Nano-Micro Letters,
Vol. 10 No. 4 (2018), Article Number: 73
Abstract
The creation of biomimetic cell environments with micro and nanoscale topographical features resembling native tissues is critical for tissue engineering. To address this challenge, this study focuses on an innovative electrospinning strategy that adopts a symmetrically divergent electric field to induce rapid self-assembly of aligned polycaprolactone (PCL) nanofibers into a centimeter-scale architecture between separately grounded bevels. The 3D microstructures of the nanofiber scaffolds were characterized through a series of sectioning in both vertical and horizontal directions. PCL/collagen (type I) nanofiber scaffolds with different density gradients were incorporated in sodium alginate hydrogels and subjected to elemental analysis. Human fibroblasts were seeded onto the scaffolds and cultured for 7 days. Our studies showed that the inclination angle of the collector had significant effects on nanofiber attributes, including the mean diameter, density gradient, and alignment gradient. The fiber density and alignment at the peripheral area of the 45°-collector decreased by 21% and 55%, respectively, along the z-axis, while those of the 60°-collector decreased by 71% and 60%, respectively. By altering the geometry of the conductive areas on the collecting bevels, polyhedral and cylindrical scaffolds composed of aligned fibers were directly fabricated. By using a four-bevel collector, the nanofibers formed a matrix of microgrids with a density of 11%. The gradient of nitrogen-to-carbon ratio in the scaffold-incorporated hydrogel was consistent with the nanofiber density gradient. The scaffolds provided biophysical stimuli to facilitate cell adhesion, proliferation, and morphogenesis in 3D.
Highlights:
1 A novel 3D divergence electrospinning technique of tunable fibrous microarchitecture for tissue engineering.
2 Versatile capability of controlling both the microstructure and macroscopic shape of the scaffold.
3 Nanofiber scaffold with microstructure gradient coupled with element gradient.
Keywords
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- P.M. Mendes, Cellular nanotechnology: making biological interfaces smarter. Chem. Soc. Rev. 42(24), 9207–9218 (2013). https://doi.org/10.1039/c3cs60198f
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- J. Hu, D. Kai, H.Y. Ye, L.L. Tian, X. Ding, S. Ramakrishna, X.J. Loh, Electrospinning of poly(glycerol sebacate)-based nanofibers for nerve tissue engineering. Mater. Sci. Eng. C-Mater. 70, 1089–1094 (2017). https://doi.org/10.1016/j.msec.2016.03.035
- C.M.B. Ho, A. Mishra, P.T.P. Lin, S.H. Ng, W.Y. Yeong, Y.J. Kim, Y.J. Yoon, 3D printed polycaprolactone carbon nanotube composite scaffolds for cardiac tissue engineering. Macromol. Biosci. 17(4), 1600250 (2017). https://doi.org/10.1002/mabi.201600250
- B.B. Rothrauff, B.B. Lauro, G. Yang, R.E. Debski, V. Musahl, R.S. Tuan, Braided and stacked electrospun nanofibrous scaffolds for tendon and ligament tissue engineering. Tissue Eng. Part A 23(9–10), 378–389 (2017). https://doi.org/10.1089/ten.tea.2016.0319
- Y. Qu, B.Y. Wang, B.Y. Chu, C.L. Liu, X. Rong, H. Chen, J.R. Peng, Z.Y. Qian, Injectable and thermosensitive hydrogel and PDLLA electrospun nanofiber membrane composites for guided spinal fusion. ACS Appl. Mater. Interfaces 10(5), 4462–4470 (2018). https://doi.org/10.1021/acsami.7b17020
- Q.L. Zhao, J. Wang, H.Q. Cui, H.X. Chen, Y.L. Wang, X.M. Du, Programmed shape-morphing scaffolds enabling facile 3D endothelialization. Adv. Funct. Mater. 28(29), 1801027 (2018). https://doi.org/10.1002/adfm.201801027
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- M.E. Wright, I.C. Parrag, M. Yangc, J.P. Santerre, Electrospun polyurethane nanofiber scaffolds with ciprofloxacin oligomer versus free ciprofloxacin: effect on drug release and cell attachment. J. Control Release 250, 107–115 (2017). https://doi.org/10.1016/j.jconrel.2017.02.008
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- G. Gainza, S. Villullas, J.L. Pedraz, R.M. Hernandez, M. Igartua, Advances in drug delivery systems (DDSS) to release growth factors for wound healing and skin regeneration. Nanomed. Nanotechnol. 11(6), 1551–1573 (2015). https://doi.org/10.1016/j.nano.2015.03.002
- W. Zhu, F. Masood, J. O’Brien, L.G. Zhang, Highly aligned nanocomposite scaffolds by electrospinning and electrospraying for neural tissue regeneration. Nanomed. Nanotechnol. 11(3), 693–704 (2015). https://doi.org/10.1016/j.nano.2014.12.001
- B. Akar, B. Jiang, S.I. Somo, A.A. Appel, J.C. Larson, K.M. Tichauer, E.M. Brey, Biomaterials with persistent growth factor gradients in vivo accelerate vascularized tissue formation. Biomaterials 72, 61–73 (2015). https://doi.org/10.1016/j.biomaterials.2015.08.049
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- L.M. He, S.S. Liao, D.P. Quan, K. Ma, C. Chan, S. Ramakrishna, J.A. Lu, Synergistic effects of electrospun PLLA fiber dimension and pattern on neonatal mouse cerebellum. Acta Biomater. 6(8), 2960–2969 (2010). https://doi.org/10.1016/j.actbio.2010.02.039
- X.F. Wang, B. Ding, B.Y. Li, Biomimetic electrospun nanofibrous structures for tissue engineering. Mater. Today 16(6), 229–241 (2013). https://doi.org/10.1016/j.mattod.2013.06.005
- M.C. Lewis, B.D. MacArthur, J. Malda, G. Pettet, C.P. Please, Heterogeneous proliferation within engineered cartilaginous tissue: the role of oxygen tension. Biotechnol. Bioeng. 91(5), 607–615 (2005). https://doi.org/10.1002/bit.20508
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- F.J. O’Brien, B.A. Harley, I.V. Yannas, L.J. Gibson, The effect of pore size on cell adhesion in collagen-GAG scaffolds. Biomaterials 26(4), 433–441 (2005). https://doi.org/10.1016/j.biomaterials.2004.02.052
- T. Rinker, J. Temenoff, in Micro-and nanotechnology engineering strategies for tissue interface regeneration and repair, ed. by L.G. Zhang, A. Khademhosseini, T. Webster. Tissue and Organ Regeneration: Advances in Micro-and Nanotechnology (2014), pp. 105–155
- F.Y. Du, H. Wang, W. Zhao, D. Li, D.L. Kong, J. Yang, Y.Y. Zhang, Gradient nanofibrous chitosan/poly epsilon-caprolactone scaffolds as extracellular microenvironments for vascular tissue engineering. Biomaterials 33(3), 762–770 (2012). https://doi.org/10.1016/j.biomaterials.2011.10.037
- M. Ramalingam, M.F. Young, V. Thomas, L.M. Sun, L.C. Chow, C.K. Tison, K. Chatterjee, W.C. Miles, C.G. Simon, Nanofiber scaffold gradients for interfacial tissue engineering. J. Biomater. Appl. 27(6), 695–705 (2013). https://doi.org/10.1177/0885328211423783
- Y.J. Son, W.J. Kim, H.S. Yoo, Therapeutic applications of electrospun nanofibers for drug delivery systems. Arch. Pharm. Res. 37(1), 69–78 (2014). https://doi.org/10.1007/s12272-013-0284-2
- J. Cheng, Y. Jun, J.H. Qin, S.H. Lee, Electrospinning versus microfluidic spinning of functional fibers for biomedical applications. Biomaterials 114, 121–143 (2017). https://doi.org/10.1016/j.biomaterials.2016.10.040
- M.B. Fisher, E.A. Henning, N. Soegaard, J.L. Esterhai, R.L. Mauck, Organized nanofibrous scaffolds that mimic the macroscopic and microscopic architecture of the knee meniscus. Acta Biomater. 9(1), 4496–4504 (2013). https://doi.org/10.1016/j.actbio.2012.10.018
References
P.M. Mendes, Cellular nanotechnology: making biological interfaces smarter. Chem. Soc. Rev. 42(24), 9207–9218 (2013). https://doi.org/10.1039/c3cs60198f
B.M. Baker, C.S. Chen, Deconstructing the third dimension—how 3D culture microenvironments alter cellular cues. J. Cell Sci. 125(13), 3015–3024 (2012). https://doi.org/10.1242/jcs.079509
C.S. Chen, Mechanotransduction—a field pulling together? J. Cell Sci. 121(20), 3285–3292 (2008). https://doi.org/10.1242/jcs.023507
J. Hu, D. Kai, H.Y. Ye, L.L. Tian, X. Ding, S. Ramakrishna, X.J. Loh, Electrospinning of poly(glycerol sebacate)-based nanofibers for nerve tissue engineering. Mater. Sci. Eng. C-Mater. 70, 1089–1094 (2017). https://doi.org/10.1016/j.msec.2016.03.035
C.M.B. Ho, A. Mishra, P.T.P. Lin, S.H. Ng, W.Y. Yeong, Y.J. Kim, Y.J. Yoon, 3D printed polycaprolactone carbon nanotube composite scaffolds for cardiac tissue engineering. Macromol. Biosci. 17(4), 1600250 (2017). https://doi.org/10.1002/mabi.201600250
B.B. Rothrauff, B.B. Lauro, G. Yang, R.E. Debski, V. Musahl, R.S. Tuan, Braided and stacked electrospun nanofibrous scaffolds for tendon and ligament tissue engineering. Tissue Eng. Part A 23(9–10), 378–389 (2017). https://doi.org/10.1089/ten.tea.2016.0319
Y. Qu, B.Y. Wang, B.Y. Chu, C.L. Liu, X. Rong, H. Chen, J.R. Peng, Z.Y. Qian, Injectable and thermosensitive hydrogel and PDLLA electrospun nanofiber membrane composites for guided spinal fusion. ACS Appl. Mater. Interfaces 10(5), 4462–4470 (2018). https://doi.org/10.1021/acsami.7b17020
Q.L. Zhao, J. Wang, H.Q. Cui, H.X. Chen, Y.L. Wang, X.M. Du, Programmed shape-morphing scaffolds enabling facile 3D endothelialization. Adv. Funct. Mater. 28(29), 1801027 (2018). https://doi.org/10.1002/adfm.201801027
B. Ostrowska, J. Jaroszewicz, E. Zaczynska, W. Tomaszewski, W. Swieszkowski, K.J. Kurzydlowski, Evaluation of 3D hybrid microfiber/nanofiber scaffolds for bone tissue engineering. Bull. Pol. Acad. Sci. Tech. 62(3), 551–556 (2014). https://doi.org/10.2478/bpasts-2014-0059
F.M. Wunner, S. Florczak, P. Mieszczanek, O. Bas, E.M. De-Juan-Pardo, D.W. Hutmacher, in Electrospinning with polymer melts-state of the art and future perspectives, ed. by P. Ducheyne. Comprehensive Biomaterials II (Elsevier, 2017), pp. 217–235
W. Fu, Z.L. Liu, B. Feng, R.J. Hu, X.M. He et al., Electrospun gelatin/PCL and collagen/PLCL scaffolds for vascular tissue engineering. Int. J. Nanomed. 9, 2335–2344 (2014). https://doi.org/10.2147/Ijn.S61375
D.M. Panaitescu, A.N. Frone, C. Nicolae, Micro- and nano-mechanical characterization of polyamide 11 and its composites containing cellulose nanofibers. Eur. Polym. J. 49(12), 3857–3866 (2013). https://doi.org/10.1016/j.eurpolymj.2013.09.031
T. Ushiki, Collagen fibers, reticular fibers and elastic fibers. A comprehensive understanding from a morphological viewpoint. Arch. Histol. Cytol. 65(2), 109–126 (2002). https://doi.org/10.1679/Aohc.65.109
C.L. Zhu, S. Pongkitwitoon, J.C. Qiu, S. Thomopoulos, Y.N. Xia, Design and fabrication of a hierarchically structured scaffold for tendon-to-bone repair. Adv. Mater. 30(16), 1870116 (2018). https://doi.org/10.1002/Adma.201707306
U. D’Amora, M. D’Este, D. Eglin, F. Safari, C.M. Sprecher, A. Gloria, R. De Santis, M. Alini, L. Ambrosio, Collagen density gradient on three-dimensional printed poly(epsilon-caprolactone) scaffolds for interface tissue engineering. J. Tissue Eng. Regen. Med. 12(2), 321–329 (2018). https://doi.org/10.1002/term.2457
E. Llorens, H. Ibanez, L.J. del Valle, J. Puiggali, Biocompatibility and drug release behavior of scaffolds prepared by coaxial electrospinning of poly(butylene succinate) and polyethylene glycol. Mater. Sci. Eng. C Mater. 49, 472–484 (2015). https://doi.org/10.1016/j.msec.2015.01.039
M.E. Wright, I.C. Parrag, M. Yangc, J.P. Santerre, Electrospun polyurethane nanofiber scaffolds with ciprofloxacin oligomer versus free ciprofloxacin: effect on drug release and cell attachment. J. Control Release 250, 107–115 (2017). https://doi.org/10.1016/j.jconrel.2017.02.008
M.S. Kang, J.H. Kim, R.K. Singh, J.H. Jang, H.W. Kim, Therapeutic-designed electrospun bone scaffolds: mesoporous bioactive nanocarriers in hollow fiber composites to sequentially deliver dual growth factors. Acta Biomater. 16, 103–116 (2015). https://doi.org/10.1016/j.actbio.2014.12.028
G. Gainza, S. Villullas, J.L. Pedraz, R.M. Hernandez, M. Igartua, Advances in drug delivery systems (DDSS) to release growth factors for wound healing and skin regeneration. Nanomed. Nanotechnol. 11(6), 1551–1573 (2015). https://doi.org/10.1016/j.nano.2015.03.002
W. Zhu, F. Masood, J. O’Brien, L.G. Zhang, Highly aligned nanocomposite scaffolds by electrospinning and electrospraying for neural tissue regeneration. Nanomed. Nanotechnol. 11(3), 693–704 (2015). https://doi.org/10.1016/j.nano.2014.12.001
B. Akar, B. Jiang, S.I. Somo, A.A. Appel, J.C. Larson, K.M. Tichauer, E.M. Brey, Biomaterials with persistent growth factor gradients in vivo accelerate vascularized tissue formation. Biomaterials 72, 61–73 (2015). https://doi.org/10.1016/j.biomaterials.2015.08.049
T.M. Dinis, R. Elia, G. Vidal, A. Auffret, D.L. Kaplan, C. Egles, Method to form a fiber/growth factor dual-gradient along electrospun silk for nerve regeneration. ACS Appl. Mater. Interfaces 6(19), 16817–16826 (2014). https://doi.org/10.1021/am504159j
S.Y. Chew, R. Mi, A. Hoke, K.W. Leong, The effect of the alignment of electrospun fibrous scaffolds on schwann cell maturation. Biomaterials 29(6), 653–661 (2008). https://doi.org/10.1016/j.biomaterials.2007.10.025
L.M. He, S.S. Liao, D.P. Quan, K. Ma, C. Chan, S. Ramakrishna, J.A. Lu, Synergistic effects of electrospun PLLA fiber dimension and pattern on neonatal mouse cerebellum. Acta Biomater. 6(8), 2960–2969 (2010). https://doi.org/10.1016/j.actbio.2010.02.039
X.F. Wang, B. Ding, B.Y. Li, Biomimetic electrospun nanofibrous structures for tissue engineering. Mater. Today 16(6), 229–241 (2013). https://doi.org/10.1016/j.mattod.2013.06.005
M.C. Lewis, B.D. MacArthur, J. Malda, G. Pettet, C.P. Please, Heterogeneous proliferation within engineered cartilaginous tissue: the role of oxygen tension. Biotechnol. Bioeng. 91(5), 607–615 (2005). https://doi.org/10.1002/bit.20508
Q.L. Loh, C. Choong, Three-dimensional scaffolds for tissue engineering applications: role of porosity and pore size. Tissue Eng. Part B Rev. 19(6), 485–502 (2013). https://doi.org/10.1089/ten.teb.2012.0437
F.J. O’Brien, B.A. Harley, I.V. Yannas, L.J. Gibson, The effect of pore size on cell adhesion in collagen-GAG scaffolds. Biomaterials 26(4), 433–441 (2005). https://doi.org/10.1016/j.biomaterials.2004.02.052
T. Rinker, J. Temenoff, in Micro-and nanotechnology engineering strategies for tissue interface regeneration and repair, ed. by L.G. Zhang, A. Khademhosseini, T. Webster. Tissue and Organ Regeneration: Advances in Micro-and Nanotechnology (2014), pp. 105–155
F.Y. Du, H. Wang, W. Zhao, D. Li, D.L. Kong, J. Yang, Y.Y. Zhang, Gradient nanofibrous chitosan/poly epsilon-caprolactone scaffolds as extracellular microenvironments for vascular tissue engineering. Biomaterials 33(3), 762–770 (2012). https://doi.org/10.1016/j.biomaterials.2011.10.037
M. Ramalingam, M.F. Young, V. Thomas, L.M. Sun, L.C. Chow, C.K. Tison, K. Chatterjee, W.C. Miles, C.G. Simon, Nanofiber scaffold gradients for interfacial tissue engineering. J. Biomater. Appl. 27(6), 695–705 (2013). https://doi.org/10.1177/0885328211423783
Y.J. Son, W.J. Kim, H.S. Yoo, Therapeutic applications of electrospun nanofibers for drug delivery systems. Arch. Pharm. Res. 37(1), 69–78 (2014). https://doi.org/10.1007/s12272-013-0284-2
J. Cheng, Y. Jun, J.H. Qin, S.H. Lee, Electrospinning versus microfluidic spinning of functional fibers for biomedical applications. Biomaterials 114, 121–143 (2017). https://doi.org/10.1016/j.biomaterials.2016.10.040
M.B. Fisher, E.A. Henning, N. Soegaard, J.L. Esterhai, R.L. Mauck, Organized nanofibrous scaffolds that mimic the macroscopic and microscopic architecture of the knee meniscus. Acta Biomater. 9(1), 4496–4504 (2013). https://doi.org/10.1016/j.actbio.2012.10.018