Advertisement

Journal of Biological Physics

, Volume 44, Issue 3, pp 245–271 | Cite as

Mesenchymal stem cell cultivation in electrospun scaffolds: mechanistic modeling for tissue engineering

  • Ágata PaimEmail author
  • Isabel C. Tessaro
  • Nilo S. M. Cardozo
  • Patricia Pranke
Review
First Online:

Abstract

Tissue engineering is a multidisciplinary field of research in which the cells, biomaterials, and processes can be optimized to develop a tissue substitute. Three-dimensional (3D) architectural features from electrospun scaffolds, such as porosity, tortuosity, fiber diameter, pore size, and interconnectivity have a great impact on cell behavior. Regarding tissue development in vitro, culture conditions such as pH, osmolality, temperature, nutrient, and metabolite concentrations dictate cell viability inside the constructs. The effect of different electrospun scaffold properties, bioreactor designs, mesenchymal stem cell culture parameters, and seeding techniques on cell behavior can be studied individually or combined with phenomenological modeling techniques. This work reviews the main culture and scaffold factors that affect tissue development in vitro regarding the culture of cells inside 3D matrices. The mathematical modeling of the relationship between these factors and cell behavior inside 3D constructs has also been critically reviewed, focusing on mesenchymal stem cell culture in electrospun scaffolds.

Keywords

Stem cells Tissue development Electrospun scaffolds Phenomenological modeling 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgements

The authors wish to thank the Stem Cell Research Institute, the Coordination for the Improvement of Higher Level Personnel (CAPES), and the Study and Project Financer (FINEP) for financial support.

Compliance with ethical standards

This work does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Langer, R., Vacanti, J.P.: Tissue engineering. Science 260, 920–926 (1993).  https://doi.org/10.1126/science.8493529 ADSGoogle Scholar
  2. 2.
    O’Brien, F.J.: Biomaterials & scaffolds for tissue engineering. Mater. Today 14, 88–95 (2011).  https://doi.org/10.1016/S1369-7021(11)70058-X Google Scholar
  3. 3.
    Chua, A.W.C., Khoo, Y.C., Tan, B.K., Tan, K.C., Foo, C.L., Chong, S.J.: Skin tissue engineering advances in severe burns: review and therapeutic applications. Burn. Trauma. 4, 3 (2016).  https://doi.org/10.1186/s41038-016-0027-y Google Scholar
  4. 4.
    Place, E.S., Evans, N.D., Stevens, M.M.: Complexity in biomaterials for tissue engineering. Nat. Mater. 8, 457–470 (2009).  https://doi.org/10.1038/nmat2441 ADSGoogle Scholar
  5. 5.
    Oryan, A., Alidadi, S., Moshiri, A., Maffulli, N.: Bone regenerative medicine: classic options , novel strategies , and future directions. J. Orthop. Surg. Res. 9, 18 (2014).  https://doi.org/10.1186/1749-799X-9-18 Google Scholar
  6. 6.
    Fitzpatrick, L.E., McDevitt, T.C.: Cell-derived matrices for tissue engineering and regenerative medicine applications. Biomater. Sci. 3, 12–24 (2015).  https://doi.org/10.1039/C4BM00246F Google Scholar
  7. 7.
    Ku, D., Braddon, L., Wooton, D.: Poly(Vinyl Alcohol) Cryogel, (1999)Google Scholar
  8. 8.
    Kumar, R.J., Kimble, R.M., Boots, R., Pegg, S.P.: Treatment of partial-thickness burns: a prospective, randomized trial using transcyte (TM). ANZ J. Surg. 74, 622–626 (2004).  https://doi.org/10.1111/j.1445-1433.2004.03106.x Google Scholar
  9. 9.
    Walsh, W.R., Bertollo, N., Heuberer, P., Christou, C., Stanton, R., Poggie, R.: Evaluation of a PLLA device in-vitro and in an ovine model of acute rupture of the rotator cuff. In: Proceedings of the Orthopaedic Research Society Annual Meeting, Las Vegas, Nevada, 2015Google Scholar
  10. 10.
    Khojasteh, A., Behnia, H., Hosseini, F.S., Dehghan, M.M., Abbasnia, P., Abbas, F.M.: The effect of PCL-TCP scaffold loaded with mesenchymal stem cells on vertical bone augmentation in dog mandible: a preliminary report. J. Biomed. Mater. Res. Part B 101, 848–854 (2013).  https://doi.org/10.1002/jbm.b.32889 Google Scholar
  11. 11.
    Flasza, M., Kemp, P., Shering, D., Qiao, J., Marshall, D., Bokta, A., Johnson, P.A.: Development and manufacture of an investigational human living dermal equivalent (ICX-SKN). Regen. Med. 2, 903–918 (2007).  https://doi.org/10.2217/17460751.2.6.903 Google Scholar
  12. 12.
    Baskin, D.S., Ryan, P., Sonntag, V., Westmark, R., Widmayer, M.A.: A prospective, randomized, controlled cervical fusion study using recombinant human bone morphogenetic protein-2 with the CORNERSTONE-SR allograft ring and the ATLANTIS anterior cervical plate. Spine (Phila Pa 1976) 28, 1219–1224; discussion 1225 (2003).  https://doi.org/10.1097/01.BRS.0000065486.22141.CA Google Scholar
  13. 13.
    Kreuz, P.C., Müller, S., Ossendorf, C., Kaps, C., Erggelet, C.: Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results. Arthritis Res. Ther. 11, R33 (2009).  https://doi.org/10.1186/ar2638 Google Scholar
  14. 14.
    Stone, P.A., AbuRahma, A.F., Mousa, A.Y., Phang, D., Hass, S.M., Modak, A., Dearing, D.: Prospective randomized trial of ACUSEAL versus Vascu-Guard patching in carotid endarterectomy. Ann. Vasc. Surg. 28, 1530–1538 (2014).  https://doi.org/10.1016/j.avsg.2014.02.017 Google Scholar
  15. 15.
    Kehoe, S., Zhang, X.F., Boyd, D.: FDA approved guidance conduits and wraps for peripheral nerve injury: a review of materials and efficacy. Injury 43, 553–572 (2012).  https://doi.org/10.1016/j.injury.2010.12.030 Google Scholar
  16. 16.
    Olson, J.L., Atala, A., Yoo, J.J.: Tissue engineering: current strategies and future directions. Chonnam Med. J. 47, 1–13 (2011).  https://doi.org/10.4068/cmj.2011.47.1.1 Google Scholar
  17. 17.
    Chatterjea, A., Meijer, G., van Blitterswijk, C., de Boer, J.: Clinical application of human mesenchymal stromal cells for bone tissue engineering. Stem Cells Int. 2010, 215625 (2010).  https://doi.org/10.4061/2010/215625 Google Scholar
  18. 18.
    Koh, C.J., Atala, A.: Tissue engineering, stem cells, and cloning: opportunities for regenerative medicine. J. Am. Soc. Nephrol. 15, 1113–1125 (2004).  https://doi.org/10.1097/01.ASN.0000119683.59068.F0 Google Scholar
  19. 19.
    Tay, L.X., Ahmad, R.E., Dashtdar, H., Tay, K.W., Masjuddin, T., Ab-Rahim, S., Chong, P.P., Selvaratnam, L., Kamarul, T.: Treatment outcomes of alginate-embedded allogenic mesenchymal stem cells versus autologous chondrocytes for the repair of focal articular cartilage defects in a rabbit model. Am. J. Sports Med. 40, 83–90 (2012).  https://doi.org/10.1177/0363546511420819 Google Scholar
  20. 20.
    Wong, K.L., Lee, K.B.L., Tai, B.C., Law, P., Lee, E.H., Hui, J.H.P.: Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years’ follow-up. Arthrosc. - J. Arthrosc. Relat. Surg. 29, 2020–2028 (2013).  https://doi.org/10.1016/j.arthro.2013.09.074 Google Scholar
  21. 21.
    Cook, C.A., Huri, P.Y., Ginn, B.P., Gilbert-Honick, J., Somers, S.M., Temple, J.P., Mao, H.Q., Grayson, W.L.: Characterization of a novel bioreactor system for 3D cellular mechanobiology studies. Biotechnol. Bioeng. 113, 1825–1837 (2016).  https://doi.org/10.1002/bit.25946 Google Scholar
  22. 22.
    Maidhof, R., Tandon, N., Lee, E.J., Luo, J., Duan, Y., Yeager, K., Konofagou, E., Vunjak-Novakovic, G.: Biomimetic perfusion and electrical stimulation applied in concert improved the assembly of engineered cardiac tissue. J. Tissue Eng. Regen. Med. 6, e12–e23 (2012).  https://doi.org/10.1002/term.525.Biomimetic Google Scholar
  23. 23.
    Wang, Z., Teoh, S.H., Johana, N.B., Khoon Chong, M.S., Teo, E.Y., Hong, M., Yen Chan, J.K., San Thian, E.: Enhancing mesenchymal stem cell response using uniaxially stretched poly(ε-caprolactone) film micropatterns for vascular tissue engineering application. J. Mater. Chem. B 2, 5898–5909 (2014).  https://doi.org/10.1039/C4TB00522H Google Scholar
  24. 24.
    Knight, E., Przyborski, S.: Advances in 3D cell culture technologies enabling tissue-like structures to be created in vitro. J. Anat. 227, 746–756 (2015).  https://doi.org/10.1111/joa.12257 Google Scholar
  25. 25.
    Lawrence, B.J.: Mass Transfer in Porous Tissue Engineering Scaffolds (PhD Thesis), Oklahoma State University (2008)Google Scholar
  26. 26.
    Romagnoli, C., Zonefrati, R., Galli, G., Puppi, D., Pirosa, A., Chiellini, F., Martelli, F.S., Tanini, A., Brandi, M.L.: In vitro behavior of human adipose tissue-derived stem cells on poly(ε-caprolactone) film for bone tissue engineering applications. Biomed. Res. Int. 2015, 323571 (2015).  https://doi.org/10.1155/2015/323571 Google Scholar
  27. 27.
    Lawrence, B.J., Devarapalli, M., Madihally, S.: V: flow dynamics in bioreactors containing tissue engineering scaffolds. Biotechnol. Bioeng. 102, 935–947 (2009).  https://doi.org/10.1002/bit.22106 Google Scholar
  28. 28.
    Asaoka, T., Ohtake, S., Furukawa, K.S., Tamura, A., Ushida, T.: Development of bioactive porous α-TCP/HAp beads for bone tissue engineering. J. Biomed. Mater. Res. Part A. 101, 3295–3300 (2013).  https://doi.org/10.1002/jbm.a.34517 Google Scholar
  29. 29.
    Matsuno, T., Hashimoto, Y., Adachi, S., Omata, K., Yoshitaka, Y., Ozeki, Y., Umezu, Y., Tabata, Y., Nakamura, M., Satoh, T.: Preparation of injectable 3D-formed beta-tricalcium phosphate bead/alginate composite for bone tissue engineering. Dent. Mater. J. 27, 827–834 (2008).  https://doi.org/10.4012/dmj.27.827 Google Scholar
  30. 30.
    Matsunaga, Y.T., Morimoto, Y., Takeuchi, S.: Molding cell beads for rapid construction of macroscopic 3D tissue architecture. Adv. Mater. 23, 90–94 (2011).  https://doi.org/10.1002/adma.201004375 Google Scholar
  31. 31.
    Wang, J.: Porous Microbeads as Three-Dimensional Scaffolds for Tissue Engineering. In: NNIN REU Research Accomplishments. pp. 32–33 (2010)Google Scholar
  32. 32.
    Takeuchi, S.: Cell-laden hydrogel beads, fibers and plates for 3D tissue construction. In: 17th International Conference on Solid-State Sensors, Actuators and Microsystems, Transducers and Eurosensors, Barcelona, Spain (2013). doi: https://doi.org/10.1109/Transducers.2013.6627069
  33. 33.
    Young, D.A., Christman, K.L.: Injectable biomaterials for adipose tissue engineering. Biomed. Mater. 7, 24104 (2012).  https://doi.org/10.1088/1748-6041/7/2/024104 Google Scholar
  34. 34.
    Lee, D.A., Reisler, T., Bader, D.L.: Expansion of chondrocytes for tissue engineering in alginate beads enhances chondrocytic phenotype compared to conventional monolayer techniques. Acta Orthop. Scand. 74, 6–15 (2003).  https://doi.org/10.1080/00016470310013581 Google Scholar
  35. 35.
    Yan, S., Wang, T., Li, X., Jian, Y., Zhang, K., Li, G., Yin, J.: Fabrication of injectable hydrogels based on poly(l-glutamic acid) and chitosan. RSC Adv. 7, 17005–17019 (2017).  https://doi.org/10.1039/C7RA01864A Google Scholar
  36. 36.
    Xue, B., Kozlovskaya, V., Kharlampieva, E.: Shaped stimuli-responsive hydrogel particles: syntheses, properties and biological responses. J. Mater. Chem. B 5, 9–35 (2017).  https://doi.org/10.1039/C6TB02746F Google Scholar
  37. 37.
    El-Sherbiny, I., Yacoub, M.: Hydrogel scaffolds for tissue engineering: progress and challenges. Glob. Cardiol. Sci. Pract. 2013, 316–342 (2013).  https://doi.org/10.5339/gcsp.2013.38 Google Scholar
  38. 38.
    Teixeira, S., Fernandes, H., Leusink, A., Van Blitterswijk, C., Ferraz, M.P., Monteiro, F.J., De Boer, J.: In vivo evaluation of highly macroporous ceramic scaffolds for bone tissue engineering. J. Biomed. Mater. Res. Part A. 93, 567–575 (2010).  https://doi.org/10.1002/jbm.a.32532 Google Scholar
  39. 39.
    Blanco, J.F., Sánchez-Guijo, F.M., Carrancio, S., Muntion, S., García-Briñon, J., del Cañizo, M.C.: Titanium and tantalum as mesenchymal stem cell scaffolds for spinal fusion: an in vitro comparative study. Eur. Spine J. 20, 1–8 (2011).  https://doi.org/10.1007/s00586-011-1901-8 Google Scholar
  40. 40.
    Wise, J.K., Yarin, A.L., Megaridis, C.M., Cho, M.: Chondrogenic differentiation of human mesenchymal stem cells on oriented nanofibrous scaffolds: engineering the superficial zone of articular cartilage. Tissue Eng. Part A. 15, 913–921 (2009).  https://doi.org/10.1089/ten.tea.2008.0109 Google Scholar
  41. 41.
    Awaji, H., Matsunaga, T., Choi, S.-M.: Relation between strength, fracture toughness, and critical frontal process zone size in ceramics. Mater. Trans. 47, 1532–1539 (2006).  https://doi.org/10.2320/matertrans.47.1532 Google Scholar
  42. 42.
    Sadiasa, A., Nguyen, T.H., Lee, B.-T.: In vitro and in vivo evaluation of porous PCL-PLLA 3D polymer scaffolds fabricated via salt leaching method for bone tissue engineering applications. J. Biomater. Sci. Polym. Ed. 25, 150–167 (2014).  https://doi.org/10.1080/09205063.2013.846633 Google Scholar
  43. 43.
    Baker, S.C., Rohman, G., Southgate, J., Cameron, N.R.: The relationship between the mechanical properties and cell behaviour on PLGA and PCL scaffolds for bladder tissue engineering. Biomaterials 30, 1321–1328 (2009).  https://doi.org/10.1016/j.biomaterials.2008.11.033 Google Scholar
  44. 44.
    Asran, A.S., Razghandi, K., Aggarwal, N.H.M.G., Groth, T.: Nanofibers from blends of polyvinyl alcohol and polyhydroxy butyrate as a potensional scaffold materail.pdf. Biomacromolecules 11, 3413–3421 (2010)Google Scholar
  45. 45.
    Siparsky, G.L., Voorhees, K.J., Miao, F.: Hydrolysis of Polylactic acid (PLA) and Polycaprolactone (PCL) in aqueous Acetonitrile solutions: autocatalysis. J. Environ. Polym. Degrad. 6, 31–41 (1998).  https://doi.org/10.1023/A:1022826528673 Google Scholar
  46. 46.
    Barbanti, S.H., Carvalho Zavaglia, C.A., De Rezende Duek, E.A.: Effect of salt leaching on PCL and PLGA (50/50) resorbable scaffolds 2. Material and Methods. Mater. Res. 11, 75–80 (2008).  https://doi.org/10.1590/S1516-14392008000100014
  47. 47.
    Sung, H.-J., Meredith, C., Johnson, C., Galis, Z.S.: The effect of scaffold degradation rate on three-dimensional cell growth and angiogenesis. Biomaterials 25, 5735–5742 (2004).  https://doi.org/10.1016/j.biomaterials.2004.01.066 Google Scholar
  48. 48.
    An, J., Leeuwenburgh, S.C.G., Wolke, J.G.C., Jansen, J.A.: Effects of stirring and fluid perfusion on the in vitro degradation of calcium phosphate cement/PLGA composites. Tissue Eng. Part C. 21, 1171–1177 (2015).  https://doi.org/10.1089/ten.tec.2015.0016 Google Scholar
  49. 49.
    Loh, Q.L., Choong, C.: Three-dimensional scaffolds for tissue engineering applications: role of porosity and pore size. Tissue Eng. Part B. Rev. 19, 485–502 (2013).  https://doi.org/10.1089/ten.TEB.2012.0437 Google Scholar
  50. 50.
    Pulikkot, S., Greish, Y.E., Mourad, A.H.I., Karam, S.M.: Establishment of a three-dimensional culture system of gastric stem cells supporting mucous cell differentiation using microfibrous polycaprolactone scaffolds. Cell Prolif. 47, 553–563 (2014).  https://doi.org/10.1111/cpr.12141 Google Scholar
  51. 51.
    Emma Campiglio, C., Marcolin, C., Draghi, L.: Electrospun ECM macromolecules as biomimetic scaffold for regenerative medicine: challenges for preserving conformation and bioactivity. AIMS Mater. Sci. 4, 638–669 (2017).  https://doi.org/10.3934/matersci.2017.3.638 Google Scholar
  52. 52.
    Wendorff, J.H., Agarwal, S., Greiner, A.: Materials, Processing, and Applications. Wiley-VCH Verlag GmbH & Co., Weinheim, Germany (2012)Google Scholar
  53. 53.
    Bye, F.J., Wang, L., Bullock, A.J., Blackwood, K.A., Ryan, A.J., MacNeil, S.: Postproduction processing of electrospun fibres for tissue engineering. J. Vis. Exp. (2012).  https://doi.org/10.3791/4172
  54. 54.
    Moon, S., Gil, M., Lee, K.J.: Syringeless electrospinning toward versatile fabrication of nanofiber web. Sci. Rep. 7, 41424 (2017).  https://doi.org/10.1038/srep41424 ADSGoogle Scholar
  55. 55.
    Niu, H., Lin, T.: Fiber generators in needleless electrospinning. J. Nanomater. 2012, 1–13 (2012).  https://doi.org/10.1155/2012/725950 Google Scholar
  56. 56.
    Kwon, S.-M., Kim, Y.-J., Hong, J.K., Bang, J.Y., Xu, G., Lee, J.-H., Lee, H.-J., Kim, H.S.: Thickness-controllable electrospun fibers promote tubular structure formation by endothelial progenitor cells. Int. J. Nanomedicine 10, 1189–1200 (2015).  https://doi.org/10.2147/IJN.S73096 Google Scholar
  57. 57.
    Aghajanpoor, M., Hashemi-Najafabadi, S., Baghaban-Eslaminejad, M., Bagheri, F., Mohammad Mousavi, S., Azam Sayyahpour, F.: The effect of increasing the pore size of nanofibrous scaffolds on the osteogenic cell culture using a combination of sacrificial agent electrospinning and ultrasonication. J. Biomed. Mater. Res. Part A. 105, 1887–1899 (2017).  https://doi.org/10.1002/jbm.a.36052 Google Scholar
  58. 58.
    Vaquette, C., Cooper-White, J.J.: Increasing electrospun scaffold pore size with tailored collectors for improved cell penetration. Acta Biomater. 7, 2544–2557 (2011).  https://doi.org/10.1016/j.actbio.2011.02.036 Google Scholar
  59. 59.
    Pham, Q.P., Sharma, U., Mikos, A.G.: Electrospun poly(ε-caprolactone) microfiber and multilayer nanofiber/microfiber scaffolds: characterization of scaffolds and measurement of cellular infiltration. Biomacromolecules 7, 2796–2805 (2006).  https://doi.org/10.1021/bm060680j Google Scholar
  60. 60.
    Phipps, M.C., Clem, W.C., Catledge, S.A., Xu, Y., Hennessy, K.M., Thomas, V., Jablonsky, M.J., Chowdhury, S., Stanishevsky, A.V., Vohra, Y.K., Bellis, S.L.: Mesenchymal stem cell responses to bone-mimetic electrospun matrices composed of polycaprolactone, collagen I and nanoparticulate hydroxyapatite. PLoS One 6, 1–8 (2011).  https://doi.org/10.1371/journal.pone.0016813 Google Scholar
  61. 61.
    Francis, M.P., Moghaddam-White, Y.M., Sachs, P.C., Beckman, M.J., Chen, S.M., Bowlin, G.L., Elmore, L.W., Holt, S.E.: Modeling early stage bone regeneration with biomimetic electrospun fibrinogen nanofibers and adipose-derived mesenchymal stem cells. Electrospinning 1, 10–19 (2016).  https://doi.org/10.1515/esp-2016-0002 Google Scholar
  62. 62.
    Yao, Q., Cosme, J.G.L., Xu, T., Miszuk, J.M., Picciani, P.H.S., Fong, H., Sun, H.: Three-dimensional electrospun PCL/PLA blend nanofibrous scaffolds with significantly improved stem cells osteogenic differentiation and cranial bone formation. Biomaterials 115, 115–127 (2017).  https://doi.org/10.1016/j.biomaterials.2016.11.018 Google Scholar
  63. 63.
    Chen, H., Peng, Y., Wu, S., Tan, L.P.: Electrospun 3D fibrous scaffolds for chronic wound repair. Materials (Basel). 9(1–12), (2016).  https://doi.org/10.3390/ma9040272
  64. 64.
    Fazili, A., Gholami, S., Zangi, B.M., Seyedjafari, E., Gholami, M.: In vivo differentiation of mesenchymal stem cells into insulin producing cells on electrospun poly-L-Lactide acid scaffolds coated with Matricaria chamomilla L. Oil. Cell J. 18, 310–321 (2016)Google Scholar
  65. 65.
    Silva, S.Y., Rueda, L.C., López, M., Vélez, I.D., Rueda-Clausen, C.F., Smith, D.J., Muñoz, G., Mosquera, H., Silva, F.A., Buitrago, A., Díaz, H., López-Jaramillo, P.: Double-blind, randomized controlled trial, to evaluate the effectiveness of a controlled nitric oxide releasing patch versus meglumine antimoniate in the treatment of cutaneous leishmaniasis [NCT00317629]. Trials 7, 14 (2006).  https://doi.org/10.1186/1745-6215-7-14 Google Scholar
  66. 66.
    Silva, S.Y., Rueda, L.C., Márquez, G.A., López, M., Smith, D.J., Calderón, C.A., Castillo, J.C., Matute, J., Rueda-Clausen, C.F., Orduz, A., Silva, F.A., Kampeerapappun, P., Bhide, M., López-Jaramillo, P.: Double blind, randomized, placebo-controlled clinical trial for the treatment of diabetic foot ulcers, using a nitric oxide releasing patch: PATHON. Trials 8, 26 (2007).  https://doi.org/10.1186/1745-6215-8-26 Google Scholar
  67. 67.
    Wu, X., Wang, Y., Zhu, C., Tong, X., Yang, M., Yang, L., Liu, Z., Huang, W., Wu, F., Zong, H., Li, H., He, H.: Preclinical animal study and human clinical trial data of co-electrospun poly(l-lactide-co-caprolactone) and fibrinogen mesh for anterior pelvic floor reconstruction. Int. J. Nanomedicine 11, 389–397 (2016).  https://doi.org/10.2147/IJN.S88803 Google Scholar
  68. 68.
    Hutmacher, D.W., Singh, H.: Computational fluid dynamics for improved bioreactor design and 3D culture. Trends Biotechnol. 26, 166–172 (2008).  https://doi.org/10.1016/j.tibtech.2007.11.012 Google Scholar
  69. 69.
    Chang, H., Wang, Y.: Cell responses to surface and architecture of tissue engineering scaffolds. In: Eberli, D. (ed.) Regenerative medicine and tissue engineering - Cells and biomaterials. pp. 569–588. InTech, Rijeka, Croatia (2011)Google Scholar
  70. 70.
    Aarvold, A., Smith, J.O., Tayton, E.R., Lanham, S.A., Chaudhuri, J.B., Turner, I.G., Oreffo, R.O.C.: The effect of porosity of a biphasic ceramic scaffold on human skeletal stem cell growth and differentiation in vivo. J. Biomed. Mater. Res. Part A. 101, 3431–3437 (2013)Google Scholar
  71. 71.
    Gomes, M.E., Holtorf, H.L., Reis, R.L., Mikos, A.G.: Influence of the porosity of starch-based fiber mesh scaffolds on the proliferation and osteogenic differentiation of bone marrow stromal cells cultured in a flow perfusion bioreactor. Tissue Eng. 12, 801–809 (2006).  https://doi.org/10.1089/ten.2006.12.801 Google Scholar
  72. 72.
    Ikeda, R., Fujioka, H., Nagura, I., Kokubu, T., Toyokawa, N., Inui, A., Makino, T., Kaneko, H., Doita, M., Kurosaka, M.: The effect of porosity and mechanical property of a synthetic polymer scaffold on repair of osteochondral defects. Int. Orthop. 33, 821–828 (2008).  https://doi.org/10.1007/s00264-008-0532-0 Google Scholar
  73. 73.
    Lee, B.L.-P., Tang, Z., Wang, A., Huang, F., Yan, Z., Wang, D., Chu, J.S., Dixit, N., Yang, L., Li, S.: Synovial stem cells and their responses to the porosity of microfibrous scaffold. Acta Biomater. 9, 7264–7275 (2013).  https://doi.org/10.1016/j.actbio.2013.03.009 Google Scholar
  74. 74.
    Fu, X., Wang, H.: Rapid fabrication of biomimetic nanofiber-enabled skin grafts. In: Webster, T.J. (ed.) Nanomedicine: Technologies and Applications. p. 428. Woodhead Publishing, Cambridge, UK (2012)Google Scholar
  75. 75.
    Sabree, I., Gough, J.E., Derby, B.: Mechanical properties of porous ceramic scaffolds: influence of internal dimensions. Ceram. Int. 41, 8425–8432 (2015).  https://doi.org/10.1016/j.ceramint.2015.03.044 Google Scholar
  76. 76.
    Lowery, J.L., Datta, N., Rutledge, G.C.: Effect of fiber diameter, pore size and seeding method on growth of human dermal fibroblasts in electrospun poly(epsilon-caprolactone) fibrous mats. Biomaterials 31, 491–504 (2010).  https://doi.org/10.1016/j.biomaterials.2009.09.072 Google Scholar
  77. 77.
    Milleret, V., Hefti, T., Hall, H., Vogel, V., Eberli, D.: Influence of the fiber diameter and surface roughness of electrospun vascular grafts on blood activation. Acta Biomater. 8, 4349–4356 (2012).  https://doi.org/10.1016/j.actbio.2012.07.032 Google Scholar
  78. 78.
    Jabur, A.R., Al-Hassani, E.S., Al-Shammari, A.M., Najim, M.A., Hassan, A.A., Ahmed, A.A.: Evaluation of stem cells’ growth on electrospun polycaprolactone (PCL) scaffolds used for soft tissue applications. Energy Procedia 119, 61–71 (2017).  https://doi.org/10.1016/j.egypro.2017.07.048 Google Scholar
  79. 79.
    Vashaghian, M., Zandieh-Doulabi, B., Roovers, J.-P., Smit, T.H.: Electrospun matrices for pelvic floor repair: effect of fiber diameter on mechanical properties and cell behavior. Tissue Eng. Part A. 22, 1305–1316 (2016).  https://doi.org/10.1089/ten.tea.2016.0194 Google Scholar
  80. 80.
    Elsayed, Y., Lekakou, C., Labeed, F., Tomlins, P.: Smooth muscle tissue engineering in crosslinked electrospun gelatin scaffolds. J. Biomed. Mater. Res. Part A. 104, 313–321 (2016).  https://doi.org/10.1002/jbm.a.35565 Google Scholar
  81. 81.
    Bergmeister, H., Schreiber, C., Grasl, C., Walter, I., Plasenzotti, R., Stoiber, M., Bernhard, D., Schima, H.: Healing characteristics of electrospun polyurethane grafts with various porosities. Acta Biomater. 9, 6032–6040 (2013).  https://doi.org/10.1016/j.actbio.2012.12.009 Google Scholar
  82. 82.
    Pham, Q.P., Sharma, U., Mikos, A.G.: Electrospinning of polymeric nanofibers for tissue engineering applications: a review. Tissue Eng. 12, 60509065116001 (2006).  https://doi.org/10.1089/ten.2006.12.ft-65 Google Scholar
  83. 83.
    Soliman, S., Pagliari, S., Rinaldi, A., Forte, G., Fiaccavento, R., Pagliari, F., Franzese, O., Minieri, M., Di Nardo, P., Licoccia, S., Traversa, E.: Multiscale three-dimensional scaffolds for soft tissue engineering via multimodal electrospinning. Acta Biomater. 6, 1227–1237 (2010).  https://doi.org/10.1016/j.actbio.2009.10.051 Google Scholar
  84. 84.
    Gluck, J.M.: Electrospun Nanofibrous Poly(ε-Caprolactone) (PCL) Scaffolds for Liver Tissue Engineering (Master Thesis), Graduate Faculty of North Carolina State University (2007)Google Scholar
  85. 85.
    Cardwell, R.D., Dahlgren, L.A., Goldstein, A.S.: Electrospun fibre diameter, not alignment, affects mesenchymal stem cell differentiation into the tendon/ligament lineage. J. Tissue Eng. Regen. Med. 8, 937–945 (2014).  https://doi.org/10.1002/term.1589 Google Scholar
  86. 86.
    Tatapudy, S., Aloisio, F., Barber, D., Nystul, T.: Cell fate decisions: emerging roles for metabolic signals and cell morphology. EMBO Rep. 18, 2105–2118 (2017).  https://doi.org/10.15252/embr.201744816 Google Scholar
  87. 87.
    Aghamohseni, H., Ohadi, K., Spearman, M., Krahn, N., Moo-young, M., Scharer, J.M., Butler, M., Budman, H.M.: Effects of nutrient levels and average culture pH on the glycosylation pattern of camelid-humanized monoclonal antibody. J. Biotechnol. 186, 98–109 (2014).  https://doi.org/10.1016/j.jbiotec.2014.05.024 Google Scholar
  88. 88.
    Monfoulet, L.-E., Becquart, P., Marchat, D., Vandamme, K., Bourguignon, M., Pacard, E., Viateau, V., Petite, H., Logeart-Avramoglou, D.: The pH in the microenvironment of human mesenchymal stem cells is a critical factor for optimal osteogenesis in tissue-engineered constructs. Tissue Eng. Part A. 20, 1827–1840 (2014).  https://doi.org/10.1089/ten.tea.2013.0500 Google Scholar
  89. 89.
    Ham, R.G., Mckeehan, W.L.: Media and growth requirements. In: Jakoby, W.B., Pastan, I.H. (eds.) Methods in Enzymology Vol. 58: Cell Culture, pp. 47–93. Academic Press, New York (1979)Google Scholar
  90. 90.
    Sivakumar, S., Daum, J.R., Gorbsky, G.J.: Live-cell fluorescence imaging for phenotypic analysis of mitosis. In: Noguchi, E., Gadaleta, M. (eds.) Cell Cycle Control Vol. 1170: Methods in Molecular Biology (Methods and Protocols), pp. 549–562. Humana Press, New York, NY (2014)Google Scholar
  91. 91.
    Negoro, K., Kobayashi, S., Takeno, K., Uchida, K., Baba, H.: Effect of osmolarity on glycosaminoglycan production and cell metabolism of articular chondrocyte under three-dimensional culture system. Clin. Exp. Rheumatol. 26, 534–541 (2008)Google Scholar
  92. 92.
    Potočar, U., Hudoklin, S., Kreft, M.E., Završnik, J., Božikov, K., Fröhlich, M.: Adipose-derived stem cells respond to increased osmolarities. PLoS One 11, e0163870 (2016).  https://doi.org/10.1371/journal.pone.0163870 Google Scholar
  93. 93.
    Koay, E.J., Athanasiou, K.A.: Hypoxic chondrogenic differentiation of human embryonic stem cells enhances cartilage protein synthesis and biomechanical functionality. Osteoarthr. Cartil. 16, 1450–1456 (2008).  https://doi.org/10.1016/j.joca.2008.04.007 Google Scholar
  94. 94.
    Ma, T., Grayson, W.L., Fröhlich, M., Vunjak-Novakovic, G.: Hypoxia and stem cell-based engineering of mesenchymal tissues. Biotechnol. Prog. 25, 32–42 (2009).  https://doi.org/10.1002/btpr.128 Google Scholar
  95. 95.
    Dos Santos, F., Andrade, P.Z., Boura, J.S., Abecasis, M.M., Da Silva, C.L., Cabral, J.M.S.: Ex vivo expansion of human mesenchymal stem cells: a more effective cell proliferation kinetics and metabolism under hypoxia. J. Cell. Physiol. 223, 27–35 (2010).  https://doi.org/10.1002/jcp.21987 Google Scholar
  96. 96.
    Deschepper, M., Oudina, K., David, B., Myrtil, V., Collet, C., Bensidhoum, M., Logeart-Avramoglou, D., Petite, H.: Survival and function of mesenchymal stem cells (MSCs) depend on glucose to overcome exposure to long-term, severe and continuous hypoxia. J. Cell. Mol. Med. 15, 1505–1514 (2011).  https://doi.org/10.1111/j.1582-4934.2010.01138.x Google Scholar
  97. 97.
    Adesida, A.B., Mulet-sierra, A., Jomha, N.M.: Hypoxia mediated isolation and expansion enhances the chondrogenic capacity of bone marrow mesenchymal stromal cells. Stem Cell Res Ther 3, 9 (2012).  https://doi.org/10.1186/scrt100 Google Scholar
  98. 98.
    Freshney, R.I., Obradovic, B., Grayson, W., Cannizzaro, C., Vunjak-Novakovic, G.: Principles of tissue culture and bioreactor design. In: Lanza, R., Langer, R., Vacanti, J. (eds.) Principles of Tissue Engineering, pp. 155–183. Academic Press, San Diego (2007)Google Scholar
  99. 99.
    Nuschke, A., Rodrigues, M., Wells, A.W., Sylakowski, K., Wells, A.: Mesenchymal stem cells/multipotent stromal cells (MSCs) are glycolytic and thus glucose is a limiting factor of in vitro models of MSC starvation. Stem Cell Res. Ther. 1–9 (2016). doi: https://doi.org/10.1186/s13287-016-0436-7
  100. 100.
    Machado, N.M.: Glicose e Glutamina na Proliferação e Viabilidade de Células-Tronco Dentais Humanas (Master Thesis), Universidade Federal de São Paulo (2014)Google Scholar
  101. 101.
    Heywood, H.K., Bader, D.L., Lee, D.A.: Rate of oxygen consumption by isolated articular chondrocytes is sensitive to medium glucose concentration. J. Cell. Physiol. 206, 402–410 (2006).  https://doi.org/10.1002/jcp.20491 Google Scholar
  102. 102.
    Kasinskas, R.W., Venkatasubramanian, R., Forbes, N.S.: Rapid uptake of glucose and lactate, and not hypoxia, induces apoptosis in three-dimensional tumor tissue culture. Integr. Biol. (Camb). 6, 399–410 (2014).  https://doi.org/10.1039/c4ib00001c Google Scholar
  103. 103.
    Farrell, M.J., Shin, J.I., Smith, L.J., Mauck, R.L.: Functional consequences of glucose and oxygen deprivation on engineered mesenchymal stem cell-based cartilage constructs. Osteoarthr. Cartil. 23, 134–142 (2015).  https://doi.org/10.1016/j.joca.2014.09.012 Google Scholar
  104. 104.
    Zhang, B., Liu, N., Shi, H., Wu, H., Gao, Y., He, H., Gu, B., Liu, H.: High-glucose microenvironments inhibit the proliferation and migration of bone mesenchymal stem cells by activating GSK3β. J. Bone Miner. Metab. 34, 140–150 (2016).  https://doi.org/10.1007/s00774-015-0662-6 Google Scholar
  105. 105.
    Rogatzki, M.J., Ferguson, B.S., Goodwin, M.L., Gladden, L.B.: Lactate is always the end product of glycolysis. Front. Neurosci. 9, 1–7 (2015).  https://doi.org/10.3389/fnins.2015.00022 Google Scholar
  106. 106.
    Schop, D., Janssen, F.W., van Rijn, L.D.S., Fernandes, H., Bloem, R.M., de Bruijn, J.D., van Dijkhuizen-Radersma, R.: Growth, metabolism, and growth inhibitors of mesenchymal stem cells. Tissue Eng. Part A. 15, 1877–1886 (2009).  https://doi.org/10.1089/ten.tea.2008.0345 Google Scholar
  107. 107.
    Chen, T., Zhou, Y., Tan, W.: Effects of low temperature and lactate on osteogenic differentiation of human amniotic mesenchymal stem cells. Biotechnol. Bioprocess Eng. 14, 708–715 (2009).  https://doi.org/10.1007/s12257-009-0034-y Google Scholar
  108. 108.
    Rödling, L., Schwedhelm, I., Kraus, S., Bieback, K., Hansmann, J., Lee-Thedieck, C.: 3D models of the hematopoietic stem cell niche under steady-state and active conditions. Sci. Rep. 7, 4625 (2017).  https://doi.org/10.1038/s41598-017-04808-0 ADSGoogle Scholar
  109. 109.
    Burdick, J A, Vunjak-Novakovic, G.: Engineered microenvironments for controlled stem cell differentiation. Tissue Eng. Part A. 15, 205–219 (2009). doi: https://doi.org/10.1089/ten.tea.2008.0131
  110. 110.
    Ferrari, C., Olmos, E., Balandras, F., Tran, N., Chevalot, I., Guedon, E., Marc, A.: Investigation of growth conditions for the expansion of porcine mesenchymal stem cells on microcarriers in stirred cultures. Appl. Biochem. Biotechnol. 172, 1004–1017 (2014).  https://doi.org/10.1007/s12010-013-0586-3 Google Scholar
  111. 111.
    Sart, S., Errachid, A., Schneider, Y.-J., Agathos, S.N.: Modulation of mesenchymal stem cell actin organization on conventional microcarriers for proliferation and differentiation in stirred bioreactors. J. Tissue Eng. Regen. Med. 7, 537–551 (2013).  https://doi.org/10.1002/term.545 Google Scholar
  112. 112.
    Mizukami, A., Fernandes-Platzgummer, A., Carmelo, J.G., Swiech, K., Covas, D.T., Cabral, J.M.S., da Silva, C.L.: Stirred tank bioreactor culture combined with serum−/xenogeneic-free culture medium enables an efficient expansion of umbilical cord-derived mesenchymal stem/stromal cells. Biotechnol. J. 11, 1048–1059 (2016).  https://doi.org/10.1002/biot.201500532 Google Scholar
  113. 113.
    Rosa, F., Sales, K.C., Carmelo, J.G., Fernandes-Platzgummer, A., da Silva, C.L., Lopes, M.B., Calado, C.R.C.: Monitoring the ex-vivo expansion of human mesenchymal stem/stromal cells in xeno-free microcarrier-based reactor systems by MIR spectroscopy. Biotechnol. Prog. 32, 447–455 (2016).  https://doi.org/10.1002/btpr.2215 Google Scholar
  114. 114.
    Grein, T.A., Leber, J., Blumenstock, M., Petry, F., Weidner, T., Salzig, D., Czermak, P.: Multiphase mixing characteristics in a microcarrier-based stirred tank bioreactor suitable for human mesenchymal stem cell expansion. Process Biochem. 51, 1109–1119 (2016).  https://doi.org/10.1016/j.procbio.2016.05.010 Google Scholar
  115. 115.
    Wu, X., Li, S., Lou, L., Chen, Z.: The effect of the microgravity rotating culture system on the chondrogenic differentiation of bone marrow mesenchymal stem cells. Mol. Biotechnol. 54, 331–336 (2013).  https://doi.org/10.1007/s12033-012-9568-x Google Scholar
  116. 116.
    Bancroft, G.N., Sikavitsas, V.I., Mikos, A.G.: Design of a flow perfusion bioreactor system for bone tissue-engineering applications. Tissue Eng. 9, 549–554 (2003).  https://doi.org/10.1089/107632703322066723 Google Scholar
  117. 117.
    Yeatts, A.B., Tubular perfusion system bioreactor for the dynamic culture of human mesenchymal stem cells (PhD Thesis), College Park (2012)Google Scholar
  118. 118.
    Cartmell, S.H., Porter, B.D., García, A.J., Guldberg, R.E.: Effects of medium perfusion rate on cell-seeded three-dimensional bone constructs in vitro. Tissue Eng. 9, 1197–1203 (2003).  https://doi.org/10.1089/10763270360728107 Google Scholar
  119. 119.
    de Peppo, G.M., Sladkova, M., Sjövall, P., Palmquist, A., Oudina, K., Hyllner, J., Thomsen, P., Petite, H., Karlsson, C.: Human embryonic stem cell-derived mesodermal progenitors display substantially increased tissue formation compared to human mesenchymal stem cells under dynamic culture conditions in a packed bed/column bioreactor. Tissue Eng. Part A. 19, 175–187 (2013).  https://doi.org/10.1089/ten.tea.2011.0412 Google Scholar
  120. 120.
    Ban, Y., Wu, Y., Yu, T., Geng, N., Wang, Y., Liu, X., Gong, P.: Response of osteoblasts to low fluid shear stress is time dependent. Tissue Cell. 43, 311–317 (2011).  https://doi.org/10.1016/j.tice.2011.06.003 Google Scholar
  121. 121.
    Markhoff, J., Wieding, J., Weissmann, V., Pasold, J., Jonitz-Heincke, A., Bader, R.: Influence of different three-dimensional open porous titanium scaffold designs on human osteoblasts behavior in static and dynamic cell investigations. Materials (Basel). 8, 5490–5507 (2015).  https://doi.org/10.3390/ma8085259 ADSGoogle Scholar
  122. 122.
    Yang, Z., Tang, Y., Li, J., Zhang, Y., Hu, X.: Facile synthesis of tetragonal columnar-shaped TiO2 nanorods for the construction of sensitive electrochemical glucose biosensor. Biosens. Bioelectron. 54, 528–533 (2014).  https://doi.org/10.1016/j.bios.2013.11.043 Google Scholar
  123. 123.
    Zhang, Z., Yuan, L., Lee, P.D., Jones, E., Jones, J.R.: Modeling of time-dependent localized flow shear stress and its impact on cellular growth within additive manufactured titanium implants. J. Biomed. Mater. Res. Part B Appl. Biomater. 102, 1689–1699 (2014).  https://doi.org/10.1002/jbm.b.33146 Google Scholar
  124. 124.
    Moore, M., Moore, R., McFetridge, P.S.: Directed oxygen gradients initiate a robust early remodeling response in engineered vascular grafts. Tissue Eng. Part A. 19, 2005–2013 (2013).  https://doi.org/10.1089/ten.TEA.2012.0592 Google Scholar
  125. 125.
    Janssen, F.W., Oostra, J., Van Oorschot, A., Van Blitterswijk, C.A.: A perfusion bioreactor system capable of producing clinically relevant volumes of tissue-engineered bone: In vivo bone formation showing proof of concept. Biomaterials 27, 315–323 (2006).  https://doi.org/10.1016/j.biomaterials.2005.07.044 Google Scholar
  126. 126.
    Liao, J., Guo, X., Grande-Allen, K.J., Kasper, F.K., Mikos, A.G.: Bioactive polymer/extracellular matrix scaffolds fabricated with a flow perfusion bioreactor for cartilage tissue engineering. Biomaterials 31, 8911–8920 (2010).  https://doi.org/10.1016/j.biomaterials.2010.07.110 Google Scholar
  127. 127.
    Thibault, R.A., Mikos, A.G., Kasper, F.K.: Protein and mineral composition of osteogenic extracellular matrix constructs generated with a flow perfusion bioreactor. Biomacromolecules 12, 4204–4212 (2011).  https://doi.org/10.1021/bm200975a Google Scholar
  128. 128.
    Alves da Silva, M.L., Martins, A., Costa-Pinto, A.R., Costa, P., Faria, S., Gomes, M., Reis, R.L., Neves, N.M.: Cartilage tissue engineering using electrospun PCL nanofiber meshes and MSCs. Biomacromolecules 11, 3228–3236 (2010).  https://doi.org/10.1021/bm100476r Google Scholar
  129. 129.
    Gugerell, A., Neumann, A., Kober, J., Tammaro, L., Hoch, E., Schnabelrauch, M., Kamolz, L., Kasper, C., Keck, M.: Adipose-derived stem cells cultivated on electrospun l-lactide/glycolide copolymer fleece and gelatin hydrogels under flow conditions – aiming physiological reality in hypodermis tissue engineering. Burns 41, 163–171 (2015).  https://doi.org/10.1016/j.burns.2014.06.010 Google Scholar
  130. 130.
    Weyand, B., Kasper, C., Israelowitz, M., Gille, C., von Schroeder, H.P., Reimers, K., Vogt, P.M.: A differential pressure laminar flow reactor supports osteogenic differentiation and extracellular matrix formation from adipose mesenchymal stem cells in a macroporous ceramic scaffold. Biores. Open Access 1, 145–156 (2012).  https://doi.org/10.1089/biores.2012.9901 Google Scholar
  131. 131.
    Tsai, A.-C., Liu, Y., Ma, T.: Expansion of human mesenchymal stem cells in fibrous bed bioreactor. Biochem. Eng. J. 108, 51–57 (2016).  https://doi.org/10.1016/j.bej.2015.09.002 Google Scholar
  132. 132.
    Yeatts, A.B., Both, S.K., Yang, W., Alghamdi, H.S., Yang, F., Fisher, J.P., Jansen, J.A.: In vivo bone regeneration using tubular perfusion system bioreactor cultured nanofibrous scaffolds. Tissue Eng. Part A. 20, 139–146 (2014).  https://doi.org/10.1089/ten.tea.2013.0168
  133. 133.
    Kim, J., Ma, T.: Regulation of autocrine fibroblast growth factor-2 signaling by perfusion flow in 3D human mesenchymal stem cell constructs. Biotechnol. Prog. 28, 1384–1388 (2012).  https://doi.org/10.1002/btpr.1604 Google Scholar
  134. 134.
    Grayson, W.L., Marolt, D., Bhumiratana, S., Fröhlich, M., Guo, X.E., Vunjak-Novakovic, G.: Optimizing the medium perfusion rate in bone tissue engineering bioreactors. Biotechnol. Bioeng. 108, 1159–1170 (2011).  https://doi.org/10.1002/bit.23024 Google Scholar
  135. 135.
    Dahlin, R.L., Meretoja, V.V., Ni, M., Kasper, F.K., Mikos, A.G.: Design of a high-throughput flow perfusion bioreactor system for tissue engineering. Tissue Eng. Part C Methods. 18, 817–820 (2012).  https://doi.org/10.1089/ten.tec.2012.0037 Google Scholar
  136. 136.
    Santoro, M., Lamhamedi-Cherradi, S.-E., Menegaz, B.A., Ludwig, J.A., Mikos, A.G.: Flow perfusion effects on three-dimensional culture and drug sensitivity of Ewing sarcoma. Proc. Natl. Acad. Sci. 112, 10304–10309 (2015).  https://doi.org/10.1073/pnas.1506684112 ADSGoogle Scholar
  137. 137.
    Diederichs, S., Röker, S., Marten, D., Peterbauer, A., Scheper, T., van Griensven, M., Kasper, C.: Dynamic cultivation of human mesenchymal stem cells in a rotating bed bioreactor system based on the Z®RP platform. Biotechnol. Prog. 25, 1762–1771 (2009).  https://doi.org/10.1002/btpr.258 Google Scholar
  138. 138.
    Neumann, A., Lavrentieva, A., Heilkenbrinker, A., Loenne, M., Kasper, C.: Characterization and application of a disposable rotating bed bioreactor for mesenchymal stem cell expansion. Bioengineering 1, 231–245 (2014).  https://doi.org/10.3390/bioengineering1040231 Google Scholar
  139. 139.
    Stefani, I., Asnaghi, M.A., Cooper-White, J.J., Mantero, S.: A double chamber rotating bioreactor for enhanced tubular tissue generation from human mesenchymal stem cells. J. Tissue Eng. Regen. Med. (2017).  https://doi.org/10.1002/term.2341
  140. 140.
    De Napoli, I.E., Scaglione, S., Giannoni, P., Quarto, R., Catapano, G.: Mesenchymal stem cell culture in convection-enhanced hollow fibre membrane bioreactors for bone tissue engineering. J. Memb. Sci. 379, 341–352 (2011).  https://doi.org/10.1016/j.memsci.2011.06.001 Google Scholar
  141. 141.
    Li, S., Liu, Y., Zhou, Q., Lue, R., Song, L., Dong, S.-W., Guo, P., Kopjar, B.: A novel axial-stress bioreactor system combined with a substance exchanger for tissue engineering of 3D constructs. Tissue Eng. Part C. Methods. 20, 205–214 (2014).  https://doi.org/10.1089/ten.TEC.2013.0173 Google Scholar
  142. 142.
    Holy, C.E., Shoichet, M.S., Davies, J.E.: Engineering three-dimensional bone tissue in vitro using biodegradable scaffolds: investigating initial cell-seeding density and culture period. J. Biomed. Mater. Res. 51, 376–382 (2000).  https://doi.org/10.1002/1097 Google Scholar
  143. 143.
    Griffon, D.J., Abulencia, J.P., Ragetly, G.R., Fredericks, L.P., Chaieb, S.: A comparative study of seeding techniques and three-dimensional matrices for mesenchymal cell attachment. J. Tissue Eng. Regen. Med. 5, 169–179 (2011).  https://doi.org/10.1002/term.302 Google Scholar
  144. 144.
    Yamanaka, K., Yamamoto, K., Sakai, Y., Suda, Y., Shigemitsu, Y., Kaneko, T., Kato, K., Kumagai, T., Kato, Y.: Seeding of mesenchymal stem cells into inner part of interconnected porous biodegradable scaffold by a new method with a filter paper. Dent. Mater. J. 34, 78–85 (2015).  https://doi.org/10.4012/dmj.2013-330 Google Scholar
  145. 145.
    Solchaga, L.A., Tognana, E., Penick, K., Baskaran, H., Goldberg, V.M., Caplan, A.I., Welter, J.F.: A rapid seeding technique for the assembly of large cell/scaffold composite constructs. Tissue Eng. 12, 1851–1863 (2006).  https://doi.org/10.1089/ten.2006.12.1851 Google Scholar
  146. 146.
    Godbey, W.T., Stacey Hindy, B.S., Sherman, M.E., Atala, A.: A novel use of centrifugal force for cell seeding into porous scaffolds. Biomaterials 25, 2799–2805 (2004).  https://doi.org/10.1016/j.biomaterials.2003.09.056 Google Scholar
  147. 147.
    Ng, R., Gurm, J.S., Yang, S.-T.: Centrifugal seeding of mammalian cells in nonwoven fibrous matrices. Biotechnol. Prog. 26, n/a-n/a (2009). doi: https://doi.org/10.1002/btpr.317
  148. 148.
    Buizer, A.T., Veldhuizen, A.G., Bulstra, S.K., Kuijer, R.: Static versus vacuum cell seeding on high and low porosity ceramic scaffolds. J. Biomater. Appl. 29, 3–13 (2014).  https://doi.org/10.1177/0885328213512171 Google Scholar
  149. 149.
    Wanasekara, N.D., Ghosh, S., Chen, M., Chalivendra, V.B., Bhowmick, S.: Effect of stiffness of micron/sub-micron electrospun fibers in cell seeding. J. Biomed. Mater. Res. Part A. 103, 2289–2299 (2015).  https://doi.org/10.1002/jbm.a.35362 Google Scholar
  150. 150.
    Fu, W.-J., Xu, Y.-D., Wang, Z.-X., Li, G., Shi, J.-G., Cui, F.-Z., Zhang, Y., Zhang, X.: New ureteral scaffold constructed with composite poly(l-lactic acid)-collagen and urothelial cells by new centrifugal seeding system. J. Biomed. Mater. Res. Part A. 100A, 1725–1733 (2012).  https://doi.org/10.1002/jbm.a.34134 Google Scholar
  151. 151.
    Kim, B.-S., Putnam, A.J., Kulik, T.J., Mooney, D.J.: Optimizing seeding and culture methods to engineer smooth muscle tissue on biodegradable polymer matrices. Biotechnol. Bioeng. 57, 46–54 (1998).  https://doi.org/10.1002/(SICI)1097-0290(19980105)57:1<46::AID-BIT6>3.0.CO;2-V Google Scholar
  152. 152.
    Wendt, D., Marsano, A., Jakob, M., Heberer, M., Martin, I.: Oscillating perfusion of cell suspensions through three-dimensional scaffolds enhances cell seeding efficiency and uniformity. Biotechnol. Bioeng. 84, 205–214 (2003).  https://doi.org/10.1002/bit.10759 Google Scholar
  153. 153.
    Zhao, F., Ma, T.: Perfusion bioreactor system for human mesenchymal stem cell tissue engineering: dynamic cell seeding and construct development. Biotechnol. Bioeng. 91, 482–493 (2005).  https://doi.org/10.1002/bit.20532 Google Scholar
  154. 154.
    Ajalloueian, F., Lim, M.L., Lemon, G., Haag, J.C., Gustafsson, Y., Sjöqvist, S., Beltrán-Rodríguez, A., Del Gaudio, C., Baiguera, S., Bianco, A., Jungebluth, P., Macchiarini, P.: Biomechanical and biocompatibility characteristics of electrospun polymeric tracheal scaffolds. Biomaterials 35, 5307–5315 (2014).  https://doi.org/10.1016/j.biomaterials.2014.03.015 Google Scholar
  155. 155.
    Ladd, M.R., Hill, T.K., Yoo, J.J., Lee, S.J.: Electrospun Nanofibers. In: Lin, T. (ed.) Tissue Engineering, Nanofibers - Production, Properties and Functional Applications. InTech (2011)Google Scholar
  156. 156.
    Barker, D.A., Bowers, D.T., Hughley, B., Chance, E.W., Klembczyk, K.J., Brayman, K.L., Park, S.S., Botchwey, E.: A: multilayer cell-seeded polymer nanofiber constructs for soft-tissue reconstruction. JAMA Otolaryngol. Head Neck Surg. 139, 914–922 (2013).  https://doi.org/10.1001/jamaoto.2013.4119 Google Scholar
  157. 157.
    Dunn, J.C.Y., Chan, W.-Y., Cristini, V., Kim, J.S., Lowengrub, J., Singh, S., Wu, B.M.: Analysis of cell growth in three-dimensional scaffolds. Tissue Eng. 12, 705–716 (2006).  https://doi.org/10.1089/ten.2006.12.705 Google Scholar
  158. 158.
    Papenburg, B.J., Liu, J., Higuera, G.A., Barradas, A.M.C., de Boer, J., van Blitterswijk, C.A., Wessling, M., Stamatialis, D.: Development and analysis of multi-layer scaffolds for tissue engineering. Biomaterials 30, 6228–6239 (2009).  https://doi.org/10.1016/j.biomaterials.2009.07.057 Google Scholar
  159. 159.
    Srouji, S., Kizhner, T., Suss-Tobi, E., Livne, E., Zussman, E.: 3-D Nanofibrous electrospun multilayered construct is an alternative ECM mimicking scaffold. J. Mater. Sci. Mater. Med. 19, 1249–1255 (2008).  https://doi.org/10.1007/s10856-007-3218-z Google Scholar
  160. 160.
    Gugerell, A., Neumann, A., Kober, J., Tammaro, L., Hoch, E., Schnabelrauch, M., Kamolz, L., Kasper, C., Keck, M.: Adipose-derived stem cells cultivated on electrospun l-lactide/glycolide copolymer fleece and gelatin hydrogels under flow conditions – aiming physiological reality in hypodermis tissue engineering. Burns 41, 163–171 (2014).  https://doi.org/10.1016/j.burns.2014.06.010 Google Scholar
  161. 161.
    Ardakani, A.G., Cheema, U., Brown, R.A., Shipley, R.J.: Quantifying the correlation between spatially defined oxygen gradients and cell fate in an engineered three-dimensional culture model. J. R. Soc. Interface 11, 20140501–20140501 (2014).  https://doi.org/10.1098/rsif.2014.0501 Google Scholar
  162. 162.
    Coletti, F., Macchietto, S., Elvassore, N.: Mathematical modeling of three-dimensional cell cultures in perfusion bioreactors. Ind. Eng. Chem. Res. 45, 8158–8169 (2006).  https://doi.org/10.1021/ie051144v Google Scholar
  163. 163.
    Decuzzi, P., Ferrari, M.: Modulating cellular adhesion through nanotopography. Biomaterials 31, 173–179 (2010).  https://doi.org/10.1016/j.biomaterials.2009.09.018 Google Scholar
  164. 164.
    Gómez-Pachón, E.Y., Sánchez-Arévalo, F.M., Sabina, F.J., Maciel-Cerda, A., Campos, R.M., Batina, N., Morales-Reyes, I., Vera-Graziano, R.: Characterisation and modelling of the elastic properties of poly(lactic acid) nanofibre scaffolds. J. Mater. Sci. 48, 8308–8319 (2013).  https://doi.org/10.1007/s10853-013-7644-7 ADSGoogle Scholar
  165. 165.
    Jungreuthmayer, C., Jaasma, M.J., Al-Munajjed, A.A., Zanghellini, J., Kelly, D.J., O’Brien, F.J.: Deformation simulation of cells seeded on a collagen-GAG scaffold in a flow perfusion bioreactor using a sequential 3D CFD-elastostatics model. Med. Eng. Phys. 31, 420–427 (2009).  https://doi.org/10.1016/j.medengphy.2008.11.003 Google Scholar
  166. 166.
    Ma, C.Y.J., Kumar, R., Xu, X.Y., Mantalaris, A.: A combined fluid dynamics, mass transport and cell growth model for a three-dimensional perfused bioreactor for tissue engineering of haematopoietic cells. Biochem. Eng. J. 35, 1–11 (2007).  https://doi.org/10.1016/j.bej.2006.11.024 Google Scholar
  167. 167.
    McCoy, R.J., O’Brien, F.J.: Visualizing feasible operating ranges within tissue engineering systems using a “windows of operation” approach: a perfusion-scaffold bioreactor case study. Biotechnol. Bioeng. 109, 3161–3171 (2012).  https://doi.org/10.1002/bit.24566 Google Scholar
  168. 168.
    Santamaría, V.A.A., Malvè, M., Duizabo, A., Mena Tobar, A., Gallego Ferrer, G., García Aznar, J.M., Doblaré, M., Ochoa, I.: Computational methodology to determine fluid related parameters of non regular three-dimensional scaffolds. Ann. Biomed. Eng. 41, 2367–2380 (2013).  https://doi.org/10.1007/s10439-013-0849-8 Google Scholar
  169. 169.
    Truscello, S., Kerckhofs, G., Van Bael, S., Pyka, G., Schrooten, J., Van Oosterwyck, H.: Prediction of permeability of regular scaffolds for skeletal tissue engineering: a combined computational and experimental study. Acta Biomater. 8, 1648–1658 (2012).  https://doi.org/10.1016/j.actbio.2011.12.021 Google Scholar
  170. 170.
    Yan, X., Bergstrom, D.J., Chen, X.B.: Modeling of cell cultures in perfusion bioreactors. IEEE Trans. Biomed. Eng. 59, 2568–2575 (2012).  https://doi.org/10.1109/TBME.2012.2206077 Google Scholar
  171. 171.
    Akalp, U., Bryant, S.J., Vernerey, F.J.: Tuning tissue growth with scaffold degradation in enzyme-sensitive hydrogels: a mathematical model. Soft Matter 12, 7505–7520 (2016).  https://doi.org/10.1039/c6sm00583g ADSGoogle Scholar
  172. 172.
    Chen, Y., Zhou, S., Li, Q.: Mathematical modeling of degradation for bulk-erosive polymers: Applications in tissue engineering scaffolds and drug delivery systems. Acta Biomater. 7, 1140–1149 (2011).  https://doi.org/10.1016/j.actbio.2010.09.038 Google Scholar
  173. 173.
    Ferdous, J., Kolachalama, V.B., Shazly, T.: Impact of polymer structure and composition on fully resorbable endovascular scaffold performance. Acta Biomater. 9, 6052–6061 (2013).  https://doi.org/10.1016/j.actbio.2012.12.011 Google Scholar
  174. 174.
    Heljak, M., Swieszkowski, W., Kurzydlowski, K.J.: A phenomenological model for the degradation of polymeric tissue engineering scaffolds. In: Proceedings of the International Conference on Computer Methods in Mechanics, Warsaw, Poland (2011)Google Scholar
  175. 175.
    Heljak, M., Swieszkowski, W., Kurzydlowski, K.J.: Modeling of the degradation kinetics of biodegradable scaffolds: the effects of the environmental conditions. J. Appl. Polym. Sci. 131, 1–7 (2014).  https://doi.org/10.1002/app.40280 Google Scholar
  176. 176.
    Shazly, T., Kolachalama, V.B., Ferdous, J., Oberhauser, J.P., Hossainy, S., Edelman, E.R.: Assessment of material by-product fate from bioresorbable vascular scaffolds. Ann. Biomed. Eng. 40, 955–965 (2012).  https://doi.org/10.1007/s10439-011-0445-8 Google Scholar
  177. 177.
    Devarapalli, M., Lawrence, B.J., Madihally, S.V.: Modeling nutrient consumptions in large flow-through bioreactors for tissue engineering. Biotechnol. Bioeng. 103, 1003–1015 (2009).  https://doi.org/10.1002/bit.22333 Google Scholar
  178. 178.
    Hidalgo-Bastida, L.A., Thirunavukkarasu, S., Griffiths, S., Cartmell, S.H., Naire, S.: Modeling and design of optimal flow perfusion bioreactors for tissue engineering applications. Biotechnol. Bioeng. 109, 1095–1099 (2012).  https://doi.org/10.1002/bit.24368 Google Scholar
  179. 179.
    Pathi, P., Ma, T., Locke, B.R.: Role of nutrient supply on cell growth in bioreactor design for tissue engineering of hematopoietic cells. Biotechnol. Bioeng. 89, 743–758 (2005).  https://doi.org/10.1002/bit.20367 Google Scholar
  180. 180.
    Schirmaier, C., Jossen, V., Kaiser, S.C., Jüngerkes, F., Brill, S., Safavi-Nab, A., Siehoff, A., van den Bos, C., Eibl, D., Eibl, R.: Scale-up of adipose tissue-derived mesenchymal stem cell production in stirred single-use bioreactors under low-serum conditions. Eng. Life Sci. 14, 292–303 (2014).  https://doi.org/10.1002/elsc.201300134 Google Scholar
  181. 181.
    Singh, H., Teoh, S.H., Low, H.T., Hutmacher, D.W.: Flow modelling within a scaffold under the influence of uni-axial and bi-axial bioreactor rotation. J. Biotechnol. 119, 181–196 (2005).  https://doi.org/10.1016/j.jbiotec.2005.03.021 Google Scholar
  182. 182.
    Chung, C.A., Lin, T.-H., Chen, S.-D., Huang, H.-I.: Hybrid cellular automaton modeling of nutrient modulated cell growth in tissue engineering constructs. J. Theor. Biol. 262, 267–278 (2010).  https://doi.org/10.1016/j.jtbi.2009.09.031 Google Scholar
  183. 183.
    Doagǎ, I.O., Savopol, T., Neagu, M., Neagu, A., Kovács, E.: The kinetics of cell adhesion to solid scaffolds: an experimental and theoretical approach. J. Biol. Phys. 34, 495–509 (2008).  https://doi.org/10.1007/s10867-008-9108-x Google Scholar
  184. 184.
    Jeong, D., Yun, A., Kim, J.: Mathematical model and numerical simulation of the cell growth in scaffolds. Biomech. Model. Mechanobiol. 11, 677–688 (2012).  https://doi.org/10.1007/s10237-011-0342-y Google Scholar
  185. 185.
    Campolo, M., Curcio, F., Soldati, A.: Minimal perfusion flow for osteogenic growth of mesenchymal stem cells on lattice scaffolds. AICHE J. 59, 3131–3144 (2013).  https://doi.org/10.1002/aic.14084 Google Scholar
  186. 186.
    Causin, P., Sacco, R.: A computational model for biomass growth simulation in tissue engineering. Commun. Appl. Ind. Math. 2, (2011).  https://doi.org/10.1685/journal.caim.370
  187. 187.
    Chung, C.A., Chen, C.W., Chen, C.P., Tseng, C.S.: Enhancement of cell growth in tissue-engineering constructs under direct perfusion: modeling and simulation. Biotechnol. Bioeng. 97, 1603–1616 (2007).  https://doi.org/10.1002/bit.21378 Google Scholar
  188. 188.
    Flaibani, M., Magrofuoco, E., Elvassore, N.: Computational modeling of cell growth heterogeneity in a perfused 3D scaffold. Ind. Eng. Chem. Res. 49, 859–869 (2010).  https://doi.org/10.1021/ie900418g Google Scholar
  189. 189.
    Lesman, A., Blinder, Y., Levenberg, S.: Modeling of flow-induced shear stress applied on 3D cellular scaffolds: implications for vascular tissue engineering. Biotechnol. Bioeng. 105, 645–654 (2010).  https://doi.org/10.1002/bit.22555 Google Scholar
  190. 190.
    Liu, D., Chua, C.K., Leong, K.F.: A mathematical model for fluid shear-sensitive 3D tissue construct development. Biomech. Model. Mechanobiol. 12, 19–31 (2013).  https://doi.org/10.1007/s10237-012-0378-7 Google Scholar
  191. 191.
    Porter, B., Zauel, R., Stockman, H., Guldberg, R., Fyhrie, D.: 3-D computational modeling of media flow through scaffolds in a perfusion bioreactor. J. Biomech. 38, 543–549 (2005).  https://doi.org/10.1016/j.jbiomech.2004.04.011 Google Scholar
  192. 192.
    Raimondi, M.T., Boschetti, F., Falcone, L., Fiore, G.B., Remuzzi, A., Marinoni, E., Marazzi, M., Pietrabissa, R.: Mechanobiology of engineered cartilage cultured under a quantified fluid-dynamic environment. Biomech. Model. Mechanobiol. 1, 69–82 (2002).  https://doi.org/10.1007/s10237-002-0007-y Google Scholar
  193. 193.
    Zhao, F., Chella, R., Ma, T.: Effects of shear stress on 3-D human mesenchymal stem cell construct development in a perfusion bioreactor system: experiments and hydrodynamic modeling. Biotechnol. Bioeng. 96, 584–595 (2007).  https://doi.org/10.1002/bit.21184 Google Scholar
  194. 194.
    Doagă, I.O., Savopol, T., Neagu, M., Neagu, A., Kovács, E.: The kinetics of cell adhesion to solid scaffolds: an experimental and theoretical approach. J. Biol. Phys. 34, 495–509 (2008).  https://doi.org/10.1007/s10867-008-9108-x Google Scholar
  195. 195.
    Sacco, R., Causin, P., Zunino, P., Raimondi, M.T.: A multiphysics/multiscale 2D numerical simulation of scaffold-based cartilage regeneration under interstitial perfusion in a bioreactor. Biomech. Model. Mechanobiol. 10, 577–589 (2011).  https://doi.org/10.1007/s10237-010-0257-z Google Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Chemical EngineeringUniversidade Federal do Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  2. 2.Faculty of PharmacyUniversidade Federal do Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  3. 3.Stem Cell Research InstitutePorto AlegreBrazil

Personalised recommendations

Cite article

Buy options