Hydrogels, electrospun fiber mats (EFMs), and their composites have been extensively studied for tissue engineering because of their physical and chemical similarity to native biological systems. However, while chemically similar, hydrogels and electrospun fiber mats display very different topographical features. Here, we examine the influence of surface topography and composition of hydrogels, EFMs, and hydrogel-EFM composites on cell behavior. Materials studied were composed of synthetic poly(ethylene glycol) (PEG) and poly(ethylene glycol)-poly(ε-caprolactone) (PEGPCL) hydrogels and electrospun poly(caprolactone) (PCL) and core/shell PCL/PEGPCL constituent materials. The number of adherent cells and cell circularity were most strongly influenced by the fibrous nature of materials (e.g., topography), whereas cell spreading was more strongly influenced by material composition (e.g., chemistry). These results suggest that cell attachment and proliferation to hydrogel-EFM composites can be tuned by varying these properties to provide important insights for the future design of such composite materials.
References
[1]
Kashyap, N.; Kumar, N.; Kumar, M.N. Hydrogels for pharmaceutical and biomedical applications. Crit. Rev. Ther. Drug Carrier Syst. 2005, 22, 107–149, doi:10.1615/CritRevTherDrugCarrierSyst.v22.i2.10.
[2]
Sill, T.J.; von Recum, H.A. Electro spinning: Applications in drug delivery and tissue engineering. Biomaterials 2008, 29, 1989–2006, doi:10.1016/j.biomaterials.2008.01.011.
[3]
Peppas, N.A.; Hilt, J.Z.; Khademhosseini, A.; Langer, R. Hydrogels in biology and medicine: From molecular principles to bionanotechnology. Adv. Mater. 2006, 18, 1345–1360.
[4]
Chew, S.Y.; Wen, Y.; Dzenis, Y.; Leong, K.W. The role of electrospinning in the emerging field of nanomedicine. Curr. Pharm. Des. 2006, 12, 4751–4770, doi:10.2174/138161206779026326.
[5]
Murugan, R.; Ramakrishna, S. Nano-featured scaffolds for tissue engineering: A review of spinning methodologies. Tissue Eng. 2006, 12, 435–447, doi:10.1089/ten.2006.12.435.
[6]
Liang, D.; Hsiao, B.S.; Chu, B. Functional electrospun nanofibrous scaffolds for biomedical applications. Adv. Drug Deliv. Rev. 2007, 59, 1392–1412, doi:10.1016/j.addr.2007.04.021.
[7]
Yoo, H.S.; Kim, T.G.; Park, T.G. Surface-functionalized electrospun nanofibers for tissue engineering and drug delivery. Adv. Drug Deliv. Rev. 2009, 61, 1033–1042, doi:10.1016/j.addr.2009.07.007.
Hayami, J.W.; Surrao, D.C.; Waldman, S.D.; Amsden, B.G. Design and characterization of a biodegradable composite scaffold for ligament tissue engineering. J. Biomed. Mater. Res. A 2010, 92, 1407–1420.
[11]
Hong, Y.; Huber, A.; Takanari, K.; Amoroso, N.J.; Hashizume, R.; Badylak, S.F.; Wagner, W.R. Mechanical properties and in vivo behavior of a biodegradable synthetic polymer microfiber-extracellular matrix hydrogel biohybrid scaffold. Biomaterials 2011, 32, 3387–3394.
[12]
McMahon, R.E.; Qu, X.; Jimenez-Vergara, A.C.; Bashur, C.A.; Guelcher, S.A.; Goldstein, A.S.; Hahn, M.S. Hydrogel-electrospun mesh composites for coronary artery bypass grafts. Tissue Eng. Part C Methods 2011, 17, 451–461, doi:10.1089/ten.tec.2010.0427.
[13]
Rnjak, J.; Li, Z.; Maitz, P.K.; Wise, S.G.; Weiss, A.S. Primary human dermal fibroblast interactions with open weave three-dimensional scaffolds prepared from synthetic human elastin. Biomaterials 2009, 30, 6469–6477.
[14]
Xu, W.; Ma, J.; Jabbari, E. Material properties and osteogenic differentiation of marrow stromal cells on fiber-reinforced laminated hydrogel nanocomposites. Acta Biomater. 2010, 6, 1992–2002, doi:10.1016/j.actbio.2009.12.003.
[15]
Abidian, M.R.; Corey, J.M.; Kipke, D.R.; Martin, D.C. Conducting-polymer nanotubes improve electrical properties, mechanical adhesion, neural attachment, and neurite outgrowth of neural electrodes. Small 2010, 6, 421–429.
[16]
Alberts, B.; Bray, D.; Lewis, B.; Raff, M.; Roberts, K.; Watson, J.D. Molecular Biology of the Cell; Garland Publishing, Inc.: New York, NY, USA, 1996.
[17]
Anderson, J.M. Inflammation, wound healing, and the foreign-body response. In Biomaterials Science: An Introduction to Materials in Medicine, 2nd; Ratner, B.D., Hoffman, A.S., Schoen, F.J., Lemons, J.E., Eds.; Elsevier: London, UK, 2004; pp. 296–304.
[18]
Anderson, J.M. Biological responses to materials. Ann. Rev. Mater. Res. 2001, 31, 81–110, doi:10.1146/annurev.matsci.31.1.81.
[19]
Anderson, J.M.; Rodriguez, A.; Chang, D.T. Foreign body reaction to biomaterials. Semin. Immunol. 2008, 20, 86–100, doi:10.1016/j.smim.2007.11.004.
Berthiaume, F.; Moghe, P.V.; Toner, M.; Yarmush, M.L. Effect of extracellular matrix topology on cell structure, function, and physiological responsiveness: Hepatocytes cultured in a sandwich configuration. FASEB J. 1996, 10, 1471–1484.
Eugene, M. Polyethyleneglycols and immunocamouflage of the cells tissues and organs for transplantation. Cell Mol. Biol. (Noisy-le-grand) 2004, 50, 209–215.
[24]
Zhu, Y.B.; Gao, C.Y.; Shen, J.C. Surface modification of polycaprolactone with poly(methacrylic acid) and gelatin covalent immobilization for promoting its cytocompatibility. Biomaterials 2002, 23, 4889–4895, doi:10.1016/S0142-9612(02)00247-8.
[25]
Koh, H.S.; Yong, T.; Chan, C.K.; Ramakrishna, S. Enhancement of neurite outgrowth using nano-structured scaffolds coupled with laminin. Biomaterials 2008, 29, 3574–3582.
[26]
Moxon, K.A.; Kalkhoran, N.M.; Markert, M.; Sambito, M.A.; McKenzie, J.L.; Webster, J.T. Nanostructured surface modification of ceramic-based microelectrodes to enhance biocompatibility for a direct brain-machine interface. IEEE Trans. Biomed. Eng. 2004, 51, 881–889, doi:10.1109/TBME.2004.827465.
[27]
Biedler, J.L.; Helson, L.; Spengler, B.A. Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Res. 1973, 33, 2643–2652.
[28]
Eichhorn, S.J.; Sampson, W.W. Statistical geometry of pores and statistics of porous nanofibrous assemblies. J. R. Soc. Interface 2005, 2, 309–318, doi:10.1098/rsif.2005.0039.
Nam, J.; Johnson, J.K.; Lannutti, J.J.; Agarwal, S. Modulation of embryonic mesenchymal progenitor cell differentiation via control over pure mechanical modulus in electrospun nanofibers. Acta Biomater. 2011, 7, 1516–1524, doi:10.1016/j.actbio.2010.11.022.
[31]
Wang, J.H.; Thampatty, B.P. An introductory review of cell mechanobiology. Biomech. Model. Mechanobiol. 2006, 5, 1–16, doi:10.1007/s10237-005-0012-z.
[32]
Peyton, S.R.; Ghajar, C.M.; Khatiwala, C.B.; Putnam, A.J. The emergence of ECM mechanics and cytoskeletal tension as important regulators of cell function. Cell Biochem. Biophys. 2007, 47, 300–320, doi:10.1007/s12013-007-0004-y.
[33]
Rao, S.S.; Han, N.; Winter, J.O. Polylysine-modified PEG-based hydrogels to enhance the neuro-electrode interface. J. Biomater. Sci. Polym. Ed. 2011, 22, 611–625, doi:10.1163/092050610X488241.
[34]
Zhu, X.L.; Cui, W.G.; Li, X.H.; Jin, Y. Electrospun fibrous mats with high porosity as potential scaffolds for skin tissue engineering. Biomacromolecules 2008, 9, 1795–1801, doi:10.1021/bm800476u.
[35]
Guan, J.; Fujimoto, K.L.; Sacks, M.S.; Wagner, W.R. Preparation and characterization of highly porous, biodegradable polyurethane scaffolds for soft tissue applications. Biomaterials 2005, 26, 3961–3971, doi:10.1016/j.biomaterials.2004.10.018.
[36]
Sawhney, A.S.; Pathak, C.P.; Hubbell, J.A. Bioerodible hydrogels based on photopolymerized poly(ethylene glycol)-co-poly(alpha-hydroxy acid) diacrylate macromers. Macromolecules 1993, 26, 581–587.
[37]
Han, N.; Johnson, J.; Lannutti, J.J.; Winter, J.O. Hydrogel-electrospun fiber composite materials for hydrophilic protein release. J. Control. Release 2012, 158, 165–170, doi:10.1016/j.jconrel.2011.09.094.
[38]
Stichel, C.C.; Muller, H.W. Dissociated cell-culture of rat cerebral cortical-neurons in serum-free, conditioned media- gaba-immunopositive neurons. Dev. Brain Res. 1991, 64, 145–154, doi:10.1016/0165-3806(91)90218-8.
[39]
Dichter, M.A. Rat cortical-neurons in cell-culture—culture methods, cell morphology, electrophysiology, and synapse formation. Brain Res. 1978, 149, 279–293, doi:10.1016/0006-8993(78)90476-6.
[40]
Chung, T.W.; Liu, D.Z.; Wang, S.Y.; Wang, S.S. Enhancement of the growth of human endothelial cells by surface roughness at nanometer scale. Biomaterials 2003, 24, 4655–4661, doi:10.1016/S0142-9612(03)00361-2.
[41]
Kim, D.H.; Kim, P.; Song, I.; Cha, J.M.; Lee, S.H.; Kim, B.; Suh, K.Y. Guided three-dimensional growth of functional cardiomyocytes on polyethylene glycol nanostructures. Langmuir 2006, 22, 5419–5426.
[42]
Huang, Y.; Siewe, M.; Madihally, S.V. Effect of spatial architecture on cellular colonization. Biotechnol. Bioeng. 2006, 93, 64–75, doi:10.1002/bit.20703.
[43]
Curtis, A.; Wilkinson, C. New depths in cell behaviour: reactions of cells to nanotopography. Biochem. Soc. Symp. 1999, 65, 15–26.
[44]
Ma, Z.W.; Kotaki, M.; Inai, R.; Ramakrishna, S. Potential of nanofiber matrix as tissue-engineering scaffolds. Tissue Eng. 2005, 11, 101–109, doi:10.1089/ten.2005.11.101.
[45]
Matsuzawa, M.; Potember, R.S.; Stenger, D.A.; Krauthamer, V. Containment and growth of neuroblastoma-cells on chemically patterned substrates. J. Neurosci. Meth. 1993, 50, 253–260, doi:10.1016/0165-0270(93)90014-I.