Hostname: page-component-745bb68f8f-v2bm5 Total loading time: 0 Render date: 2025-01-14T10:22:01.988Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  29 August 2017

Murat Guvendiren ,
Stephanie Fung ,
Joachim Kohn Open the ORCID record for Joachim Kohn [Opens in a new window] ,
Carmelo De Maria ,
Francesca Montemurro  and
Giovanni Vozzi
Murat Guvendiren
Affiliation:
Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, Department of Bioengineering, New Jersey Institute of Technology, University Heights, Newark, NJ 07102, USA New Jersey Center for Biomaterials, Rutgers University, Piscataway, NJ 08854, USA
Stephanie Fung
Affiliation:
New Jersey Center for Biomaterials, Rutgers University, Piscataway, NJ 08854, USA
Joachim Kohn*
Affiliation:
New Jersey Center for Biomaterials, Rutgers University, Piscataway, NJ 08854, USA
Carmelo De Maria
Affiliation:
Department of Ingegneria dell'Informazione, Research Center “E. Piaggio”, University of Pisa, 56100 Pisa, Italy
Francesca Montemurro
Affiliation:
Department of Ingegneria dell'Informazione, Research Center “E. Piaggio”, University of Pisa, 56100 Pisa, Italy
Giovanni Vozzi
Affiliation:
Department of Ingegneria dell'Informazione, Research Center “E. Piaggio”, University of Pisa, 56100 Pisa, Italy
*
Address all correspondence to Joachim Kohn at kohn@rutgers.edu
Get access

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.

Type
Biomaterials for 3D Cell Biology Prospective Articles
Information
MRS Communications , Volume 7 , Issue 3 , September 2017 , pp. 383 - 390
Copyright
Copyright © Materials Research Society 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Engler, A.J., Sen, S., Sweeney, H.L., and Discher, D.E.: Matrix elasticity directs stem cell lineage specification. Cell 126, 677 (2006).Google Scholar
2.Stappenbeck, T.S. and Miyoshi, H.: The role of stromal stem cells in tissue regeneration and wound repair. Science 324, 1666 (2009).Google Scholar
3.Sasaki, M., Abe, R., Fujita, Y., Ando, S., Inokuma, D., and Shimizu, H.: 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).Google Scholar
4.Pittenger, M.F., Mackay, A.M., Beck, S.C., Jaiswal, R.K., Douglas, R., Mosca, J.D., Moorman, M.A., Simonetti, D.W., Craig, S., and Marshak, D.R.: Multilineage potential of adult human mesenchymal stem cells. Science 284, 143 (1999).Google Scholar
5.Grigoriadis, A.E., Heersche, J.N.M., and Aubin, J.E.: 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).Google Scholar
6.Guvendiren, M. and Burdick, J.A.: Stiffening hydrogels to probe short-and long-term cellular responses to dynamic mechanics. Nat. Commun. 3, 792 (2012).Google Scholar
7.Burdick, J.A. and Vunjak-Novakovic, G.: Engineered microenvironments for controlled stem cell differentiation. Tissue Eng. A 15, 205 (2009).Google Scholar
8.Marklein, R.A. and Burdick, J.A.: Controlling stem cell fate with material design. Adv. Mater. 22, 175 (2010).Google Scholar
9.Discher, D.E., Mooney, D.J., and Zandstra, P.W.: Growth factors, matrices, and forces combine and control stem cells. Science 324, 1673 (2009).Google Scholar
10.Discher, D.E., Janmey, P., and Wang, Y.L.: Tissue cells feel and respond to the stiffness of their substrate. Science 310, 1139 (2005).Google Scholar
11.Keselowsky, B.G., Collard, D.M., and García, A.J.: Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiation. Proc. Natl. Acad. Sci. U. S. A. 102, 5953 (2005).Google Scholar
12.García, A.J., Vega, M.D., and Boettiger, D.: Modulation of cell proliferation and differentiation through substrate- dependent changes in fibronectin conformation. Mol. Biol. Cell 10, 785 (1999).Google Scholar
13.Brodbeck, W.G., Shive, M.S., Colton, E., Nakayama, Y., Matsuda, T., and Anderson, J.M.: Influence of biomaterial surface chemistry on the apoptosis of adherent cells. J. Biomed. Mater. Res. 55, 661 (2001).Google Scholar
14.Guvendiren, M. and Burdick, J.A.: The control of stem cell morphology and differentiation by hydrogel surface wrinkles. Biomaterials 31, 6511 (2010).Google Scholar
15.Ruiz, S.A. and Chen, C.S.: Emergence of patterned stem cell differentiation within multicellular structures. Stem Cells 26, 2921 (2008).Google Scholar
16.McBeath, R., Pirone, D.M., Nelson, C.M., Bhadriraju, K., and Chen, C.S.: Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev. Cell 6, 483 (2004).Google Scholar
17.Thomas, C.H., Collier, J.H., Sfeir, C.S., and Healy, K.E.: Engineering gene expression and protein synthesis by modulation of nuclear shape. Proc. Natl. Acad. Sci. U. S. A. 99, 1972 (2002).Google Scholar
18.Teixeira, A.I., Abrams, G.A., Bertics, P.J., Murphy, C.J., and Nealey, P.F.: Epithelial contact guidance on well-defined micro- and nanostructured substrates. J. Cell Sci. 116, 1881 (2003).Google Scholar
19.Oh, S., Brammer, K.S., Li, Y.S.J., Teng, D., Engler, A.J., Chien, S., and Jin, S.: Stem cell fate dictated solely by altered nanotube dimension. Proc. Natl. Acad. Sci. U. S. A. 106, 2130 (2009).Google Scholar
20.Flemming, R.G., Murphy, C.J., Abrams, G.A., Goodman, S.L., and Nealey, P.F.: Effects of synthetic micro- and nano-structured surfaces on cell behavior. Biomaterials 20, 573 (1999).Google Scholar
21.Guvendiren, M. and Burdick, J.A.: Engineering synthetic hydrogel microenvironments to instruct stem cells. Curr. Opin. Biotechnol. 24, 841 (2013).Google Scholar
22.Gregoire, F.M., Smas, C.M., and Sul, H.S.: Understanding adipocyte differentiation. Physiol. Rev. 78, 783 (1998).Google Scholar
23.Sikavitsas, V.I., Temenoff, J.S., and Mikos, A.G.: Biomaterials and bone mechanotransduction. Biomaterials 22, 2581 (2001).Google Scholar
24.Kilian, K.A., Bugarija, B., Lahn, B.T., and Mrksich, M.: Geometric cues for directing the differentiation of mesenchymal stem cells. Proc. Natl. Acad. Sci. U. S. A. 107, 4872 (2010).Google Scholar
25.Treiser, M.D., Yang, E.H., Gordonov, S., Cohen, D.M., Androulakis, I.P., Kohn, J., Chen, C.S., and Moghe, P.V.: Cytoskeleton-based forecasting of stem cell lineage fates. Proc. Natl Acad. Sci. U. S. A. 107, 610 (2010).Google Scholar
26.Viswanathan, P., Ondeck, M.G., Chirasatitsin, S., Ngamkham, K., Reilly, G.C., Engler, A.J., and Battaglia, G.: 3D surface topology guides stem cell adhesion and differentiation. Biomaterials 52, 140 (2015).Google Scholar
27.Guvendiren, M., Molde, J., Soares, R.M.D., and Kohn, J.: Designing biomaterials for 3D printing. ACS Biomater. Sci. Eng. 2, 1679 (2016).Google Scholar
28.Ji, S. and Guvendiren, M.: Recent advances in bioink design for 3D bioprinting of tissues and organs. Front. Bioeng. Biotechnol. 5, 23 (2017).Google Scholar
29.Bose, S., Vahabzadeh, S., and Bandyopadhyay, A.: Bone tissue engineering using 3D printing. Mater. Today 16, 496 (2013).Google Scholar
30.Hollister, S.J.: Porous scaffold design for tissue engineering. Nat. Mater. 4, 518 (2005).Google Scholar
31.Jürgen, G., Thomas, B., Torsten, B., Jason, A.B., Dong-Woo, C., Paul, D.D., Brian, D., Gabor, F., Qing, L., Vladimir, A.M., Lorenzo, M., Makoto, N., Wenmiao, S., Shoji, T., Giovanni, V., Tim, B.F.W., Tao, X., James, J.Y., and Jos, M.: Biofabrication: reappraising the definition of an evolving field. Biofabrication 8, 013001 (2016).Google Scholar
32.Tangpasuthadol, V., Pendharkar, S.M., and Kohn, J.: Hydrolytic degradation of tyrosine-derived polycarbonates, a class of new biomaterials. Part I: study of model compounds. Biomaterials 21, 2371 (2000).Google Scholar
33.Tangpasuthadol, V., Pendharkar, S.M., Peterson, R.C., and Kohn, J.: Hydrolytic degradation of tyrosine-derived polycarbonates, a class of new biomaterials. Part II: 3-yr study of polymeric devices. Biomaterials 21, 2379 (2000).Google Scholar
34.Ertel, S.I. and Kohn, J.: Evaluation of a series of tyrosine-derived polycarbonates as degradable biomaterials. J. Biomed. Mater. Res. 28, 919 (1994).Google Scholar
35.Sommerfeld, S.D., Zhang, Z., Costache, M.C., Vega, S.L., and Kohn, J.: Enzymatic surface erosion of high tensile strength polycarbonates based on natural phenols. Biomacromolecules 15, 830 (2014).Google Scholar
36.Vozzi, G., Previti, A., De Rossi, D., and Ahluwalia, A.: 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).Google Scholar
37.Mariani, M., Rosatini, F., Vozzi, G., Previti, A., and Ahluwalia, A.: Characterization of tissue-engineered scaffolds microfabricated with PAM. Tissue Eng. 12, 547 (2006).Google Scholar
38.Criscenti, G., De Maria, C., Sebastiani, E., Tei, M., Placella, G., Speziali, A., Vozzi, G. and Cerulli, G.: Material and structural tensile properties of the human medial patello-femoral ligament. J. Mech. Behav. Biomed. Mater. 54, 141 (2016).Google Scholar
39.Mattioli-Belmonte, M., De Maria, C., Vitale-Brovarone, C., Baino, F., Dicarlo, M., and Vozzi, G.: 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).Google Scholar
40.Dobbenga, S., Fratila-Apachitei, L.E., and Zadpoor, A.A.: Nanopattern-induced osteogenic differentiation of stem cells—a systematic review. Acta Biomater. 46, 3 (2016).Google Scholar
Supplementary material: File

Guvendiren et al supplementary material 1

Guvendiren et al supplementary material

Download Guvendiren et al supplementary material 1(File)
File 449.8 KB