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The control of stem cell morphology and differentiation using three-dimensional printed scaffold architecture

  • Biomaterials for 3D Cell Biology Prospective Article
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Abstract

In this work, we investigated the interactions of human mesenchymal stem cells (hMSCs) with three-dimensional (3D) printed scaffolds displaying different scaffold architectures. Pressure-assisted microsyringe system was used to fabricate scaffolds with square (SQR), hexagonal (HEX), and octagonal (OCT) architectures defined by various degrees of curvatures. OCT represents the highest degree of curvature followed by HEX, and SQR is composed of linear struts without curvature. Scaffolds were fabricated from poly(L-lactic acid) and poly(tyrosol carbonate). We found that hMSCs attached and spread by taking the shape of the individual struts, exhibiting high aspect ratios (ARs) and mean cell area when cultured on OCT scaffolds as compared with those cultured on HEX and SQR scaffolds. In contrast, cells appeared bulkier with low AR on SQR scaffolds. These significant changes in cell morphology directly correlate with the stem cell lineage commitment, such that 80 ± 1% of the hMSCs grown on OCT scaffolds differentiated into osteogenic lineage, compared with 70 ± 4% and 62 ± 2% of those grown on HEX and SQR scaffolds, respectively. Cells on OCT scaffolds also showed 2.5 times more alkaline phosphatase activity compared with cells on SQR scaffolds. This study demonstrates the importance of scaffold design to direct stem cell differentiation, and aids in the development of novel 3D scaffolds for bone regeneration.

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References

  1. A.J. Engler, S. Sen, H.L. Sweeney, and D.E. Discher: Matrix elasticity directs stem cell lineage specification. Cell 126, 677 (2006).

    Article  CAS  Google Scholar 

  2. T.S. Stappenbeck and H. Miyoshi: The role of stromal stem cells in tissue regeneration and wound repair. Science 324, 1666 (2009).

    Article  CAS  Google Scholar 

  3. M. Sasaki, R. Abe, Y. Fujita, S. Ando, D. Inokuma, and H. Shimizu: Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. J. Immunol. 180, 2581 (2008).

    Article  CAS  Google Scholar 

  4. M.F. Pittenger, A.M. Mackay, S.C. Beck, R.K. Jaiswal, R. Douglas, J.D. Mosca, M.A. Moorman, D.W. Simonetti, S. Craig, and D.R. Marshak: Multilineage potential of adult human mesenchymal stem cells. Science 284, 143 (1999).

    Article  CAS  Google Scholar 

  5. A.E. Grigoriadis, J.N.M. Heersche, and J.E. Aubin: Differentiation of muscle, fat, cartilage, and bone from progenitor cells present in a bone-derived clonal cell population: effect of dexamethasone. J. Cell Biol. 106, 2139 (1988).

    Article  CAS  Google Scholar 

  6. M. Guvendiren and J.A. Burdick: Stiffening hydrogels to probe short-and long-term cellular responses to dynamic mechanics. Nat. Commun. 3, 792 (2012).

    Article  Google Scholar 

  7. J.A. Burdick and G. Vunjak-Novakovic: Engineered microenvironments for controlled stem cell differentiation. Tissue Eng. A 15, 205 (2009).

    Article  CAS  Google Scholar 

  8. R.A. Marklein and J.A. Burdick: Controlling stem cell fate with material design. Adv. Mater. 22, 175 (2010).

    Article  CAS  Google Scholar 

  9. D.E. Discher, D.J. Mooney, and P.W. Zandstra: Growth factors, matrices, and forces combine and control stem cells. Science 324, 1673 (2009).

    Article  CAS  Google Scholar 

  10. D.E. Discher, P. Janmey, and Y.L. Wang: Tissue cells feel and respond to the stiffness of their substrate. Science 310, 1139 (2005).

    Article  CAS  Google Scholar 

  11. B.G. Keselowsky, D.M. Collard, and A.J. García: Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiation. Proc. Natl. Acad. Sci. U. S. A. 102, 5953 (2005).

    Article  CAS  Google Scholar 

  12. A.J. García, M.D. Vega, and D. Boettiger: Modulation of cell proliferation and differentiation through substrate- dependent changes in fibronectin conformation. Mol. Biol. Cell 10, 785 (1999).

    Article  Google Scholar 

  13. W.G. Brodbeck, M.S. Shive, E. Colton, Y. Nakayama, T. Matsuda, and J.M. Anderson: Influence of biomaterial surface chemistry on the apoptosis of adherent cells. J. Biomed. Mater. Res. 55, 661 (2001).

    Article  CAS  Google Scholar 

  14. M. Guvendiren and J.A. Burdick: The control of stem cell morphology and differentiation by hydrogel surface wrinkles. Biomaterials 31, 6511 (2010).

    Article  CAS  Google Scholar 

  15. S.A. Ruiz and C.S. Chen: Emergence of patterned stem cell differentiation within multicellular structures. Stem Cells 26, 2921 (2008).

    Article  Google Scholar 

  16. R. McBeath, D.M. Pirone, C.M. Nelson, K. Bhadriraju, and C.S. Chen: Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev. Cell 6, 483 (2004).

    Article  CAS  Google Scholar 

  17. C.H. Thomas, J.H. Collier, C.S. Sfeir, and K.E. Healy: Engineering gene expression and protein synthesis by modulation of nuclear shape. Proc. Natl. Acad. Sci. U. S. A. 99, 1972 (2002).

    Article  CAS  Google Scholar 

  18. A.I. Teixeira, G.A. Abrams, P.J. Bertics, C.J. Murphy, and P.F. Nealey: Epithelial contact guidance on well-defined micro- and nanostructured substrates. J. Cell Sci. 116, 1881 (2003).

    Article  CAS  Google Scholar 

  19. S. Oh, K.S. Brammer, Y.S.J. Li, D. Teng, A.J. Engler, S. Chien, and S. Jin: Stem cell fate dictated solely by altered nanotube dimension. Proc. Natl. Acad. Sci. U. S. A. 106, 2130 (2009).

    Article  CAS  Google Scholar 

  20. R.G. Flemming, C.J. Murphy, G.A. Abrams, S.L. Goodman, and P.F. Nealey: Effects of synthetic micro- and nano-structured surfaces on cell behavior. Biomaterials 20, 573 (1999).

    Article  CAS  Google Scholar 

  21. M. Guvendiren and J.A. Burdick: Engineering synthetic hydrogel microenvironments to instruct stem cells. Curr. Opin. Biotechnol. 24, 841 (2013).

    Article  CAS  Google Scholar 

  22. F.M. Gregoire, C.M. Smas, and H.S. Sul: Understanding adipocyte differentiation. Physiol. Rev. 78, 783 (1998).

    Article  CAS  Google Scholar 

  23. V.I. Sikavitsas, J.S. Temenoff, and A.G. Mikos: Biomaterials and bone mechanotransduction. Biomaterials 22, 2581 (2001).

    Article  CAS  Google Scholar 

  24. K.A. Kilian, B. Bugarija, B.T. Lahn, and M. Mrksich: Geometric cues for directing the differentiation of mesenchymal stem cells. Proc. Natl. Acad. Sci. U. S. A. 107, 4872 (2010).

    Article  CAS  Google Scholar 

  25. M.D. Treiser, E.H. Yang, S. Gordonov, D.M. Cohen, I.P. Androulakis, J. Kohn, C.S. Chen, and P.V. Moghe: Cytoskeleton-based forecasting of stem cell lineage fates. Proc. Natl Acad. Sci. U. S. A. 107, 610 (2010).

    Article  CAS  Google Scholar 

  26. P. Viswanathan, M.G. Ondeck, S. Chirasatitsin, K. Ngamkham, G.C. Reilly, A.J. Engler, and G. Battaglia: 3D surface topology guides stem cell adhesion and differentiation. Biomaterials 52, 140 (2015).

    Article  CAS  Google Scholar 

  27. M. Guvendiren, J. Molde, R.M.D. Soares, and J. Kohn: Designing biomaterials for 3D printing. ACS Biomater. Sci. Eng. 2, 1679 (2016).

    Article  CAS  Google Scholar 

  28. S. Ji and M. Guvendiren: Recent advances in bioink design for 3D bioprinting of tissues and organs. Front. Bioeng. Biotechnol. 5, 23 (2017).

    Article  Google Scholar 

  29. S. Bose, S. Vahabzadeh, and A. Bandyopadhyay: Bone tissue engineering using 3D printing. Mater. Today 16, 496 (2013).

    Article  CAS  Google Scholar 

  30. S.J. Hollister: Porous scaffold design for tissue engineering. Nat. Mater. 4, 518 (2005).

    Article  CAS  Google Scholar 

  31. G. Jürgen, B. Thomas, B. Torsten, A.B. Jason, C. Dong-Woo, D.D. Paul, D. Brian, F. Gabor, L. Qing, A.M. Vladimir, M. Lorenzo, N. Makoto, S. Wenmiao, T. Shoji, V. Giovanni, B.F.W. Tim, X. Tao, J.Y. James, and M. Jos: Biofabrication: reappraising the definition of an evolving field. Biofabrication 8, 013001 (2016).

    Article  Google Scholar 

  32. V. Tangpasuthadol, S.M. Pendharkar, and J. Kohn: Hydrolytic degradation of tyrosine-derived polycarbonates, a class of new biomaterials. Part I: study of model compounds. Biomaterials 21, 2371 (2000).

    Article  CAS  Google Scholar 

  33. V. Tangpasuthadol, S.M. Pendharkar, R.C. Peterson, and J. Kohn: Hydrolytic degradation of tyrosine-derived polycarbonates, a class of new biomaterials. Part II: 3-yr study of polymeric devices. Biomaterials 21, 2379 (2000).

    Article  CAS  Google Scholar 

  34. S.I. Ertel and J. Kohn: Evaluation of a series of tyrosine-derived polycarbonates as degradable biomaterials. J. Biomed. Mater. Res. 28, 919 (1994).

    Article  CAS  Google Scholar 

  35. S.D. Sommerfeld, Z. Zhang, M.C. Costache, S.L. Vega, and J. Kohn: Enzymatic surface erosion of high tensile strength polycarbonates based on natural phenols. Biomacromolecules 15, 830 (2014).

    Article  CAS  Google Scholar 

  36. G. Vozzi, A. Previti, D. De Rossi, and A. Ahluwalia: Microsyringe-based deposition of two-dimensional and three-dimensional polymer scaffolds with a well-defined geometry for application to tissue engineering. Tissue Eng. 8, 1089 (2002).

    Article  CAS  Google Scholar 

  37. M. Mariani, F. Rosatini, G. Vozzi, A. Previti, and A. Ahluwalia: Characterization of tissue-engineered scaffolds microfabricated with PAM. Tissue Eng. 12, 547 (2006).

    Article  CAS  Google Scholar 

  38. G. Criscenti, C. De Maria, E. Sebastiani, M. Tei, G. Placella, A. Speziali, G. Vozzi and G. Cerulli: Material and structural tensile properties of the human medial patello-femoral ligament. J. Mech. Behav. Biomed. Mater. 54, 141 (2016).

    Article  CAS  Google Scholar 

  39. M. Mattioli-Belmonte, C. De Maria, C. Vitale-Brovarone, F. Baino, M. Dicarlo, and G. Vozzi: Pressure-activated microsyringe (PAM) fabrication of bioactive glass–poly (lactic-co-glycolic acid) composite scaffolds for bone tissue regeneration. J. Tissue Eng. Regen. Med. 11, 1986 (2015).

    Article  Google Scholar 

  40. S. Dobbenga, L.E. Fratila-Apachitei, and A.A. Zadpoor: Nanopattern-induced osteogenic differentiation of stem cells—a systematic review. Acta Biomater. 46, 3 (2016).

    Article  CAS  Google Scholar 

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Acknowledgments

Authors would like to thank Tyler Hoffman for his assistance on cell culture assays. This study was supported by RESBIO, the “Resource for polymeric biomaterials”, funded by the National Institute of Health, National Institute of Biomedical Imaging and Bioengineering Award Number P41EB001046, and by the National Science Foundation under Grant No. 1714882.

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Correspondence to Joachim Kohn.

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The supplementary material for this article can be found at https://doi.org/10.1557/mrc.2017.73.

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Guvendiren, M., Fung, S., Kohn, J. et al. The control of stem cell morphology and differentiation using three-dimensional printed scaffold architecture. MRS Communications 7, 383–390 (2017). https://doi.org/10.1557/mrc.2017.73

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