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Coupling synthetic biology and programmable materials to construct complex tissue ecosystems

Published online by Cambridge University Press:  27 May 2019

Catherine S. Millar-Haskell ,
Allyson M. Dang  and
Jason P. Gleghorn
Catherine S. Millar-Haskell
Affiliation:
Departments of Biomedical Engineering, University of Delaware, Newark, DE 19716, USA
Allyson M. Dang
Affiliation:
Departments of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA
Jason P. Gleghorn*
Affiliation:
Departments of Biomedical Engineering, University of Delaware, Newark, DE 19716, USA
*
Address all correspondence to Jason P. Gleghorn at gleghorn@udel.edu
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Abstract

Synthetic biology combines engineering and biology to produce artificial systems with programmable features. Specifically, engineered microenvironments have advanced immensely over the past few decades, owing in part to the merging of materials with biologic mimetic structures. In this review, the authors adapt a traditional definition of community ecology to describe “cellular ecology,” or the study of the distribution of cell populations and interactions within their microenvironment. The authors discuss two exemplar hydrogel platforms: (1) self-assembling peptide hydrogels and (2) poly(ethylene) glycol hydrogels and describe future opportunities for merging smart material design and synthetic biology within the scope of multicellular platforms.

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Type
Synthetic Biology Prospective
Information
MRS Communications , Volume 9 , Issue 2 , June 2019 , pp. 421 - 432
Copyright
Copyright © Materials Research Society 2019 

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References

1.Benner, S.A. and Sismour, A.M.: Synthetic biology. Nat. Rev. Genet. 6, 533–543 (2005).Google Scholar
2.Roberts, M.A.J., Cranenburgh, R.M., Stevens, M.P., and Oyston, P.C.F.: Synthetic biology: biology by design. Microbiol. Read. Engl. 159, 1219–1220 (2013).Google Scholar
3.Rosano, G.L. and Ceccarelli, E.A.: Recombinant protein expression in Escherichia coli: advances and challenges. Front. Microbiol. 5, 172 (2014).Google Scholar
4.Yu, J., Vodyanik, M.A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J.L., Tian, S., Nie, J., Jonsdottir, G.A., Ruotti, V., Stewart, R., Slukvin, I.I., and Thomson, J.A.: Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917–1920 (2007).Google Scholar
5.Hsu, P.D., Lander, E.S., and Zhang, F.: Development and applications of CRISPR-Cas9 for genome engineering. Cell 157, 1262–1278 (2014).Google Scholar
6.Sia, S.K., Gillette, B.M., and Yang, G.J.: Synthetic tissue biology: tissue engineering meets synthetic biology. Birth Defects Res. Part C Embryo Today Rev. 81, 354–361 (2007).Google Scholar
7.Bianconi, E., Piovesan, A., Facchin, F., Beraudi, A., Casadei, R., Frabetti, F., Vitale, L., Pelleri, M.C., Tassani, S., Piva, F., Perez-Amodio, S., Strippoli, P., and Canaider, S.: An estimation of the number of cells in the human body. Ann. Hum. Biol. 40, 463–471 (2013).Google Scholar
8.Bokka, K.K., Jesudason, E.C., Lozoya, O.A., Guilak, F., Warburton, D., and Lubkin, S.R.: Morphogenetic implications of peristalsis-driven fluid flow in the embryonic lung. PLoS ONE 10, e0132015 (2015).Google Scholar
9.George, U.Z., Bokka, K.K., Warburton, D., and Lubkin, S.R.: Quantifying stretch and secretion in the embryonic lung: implications for morphogenesis. Mech. Dev. 138, 356–363 (2015).Google Scholar
10.Kim, H.Y., Pang, M.-F., Varner, V.D., Kojima, L., Miller, E., Radisky, D.C., and Nelson, C. M.: Localized smooth muscle differentiation is essential for epithelial bifurcation during branching morphogenesis of the mammalian lung. Dev. Cell 34, 719–726 (2015).Google Scholar
11.Patel, A.: The primary cilium calcium channels and their role in flow sensing. Pflüg. Arch.––Eur. J. Physiol. 467, 157–165 (2015).Google Scholar
12.Kalluri, R.: The biology and function of fibroblasts in cancer. Nat. Rev. Cancer 16, 582–598 (2016).Google Scholar
13.Boghaert, E., Gleghorn, J.P., Lee, K., Gjorevski, N., Radisky, D.C., and Nelson, C.M.: Host epithelial geometry regulates breast cancer cell invasiveness. Proc. Natl. Acad. Sci. 109, 19632–19637 (2012).Google Scholar
14.Ameis, D., Khoshgoo, N., and Keijzer, R.: Abnormal lung development in congenital diaphragmatic hernia. Semin. Pediatr. Surg. 26, 123–128 (2017).Google Scholar
15.Zhang, W., Yu, X., Li, Y., Su, Z., Jandt, K.D., and Wei, G.: Protein-mimetic peptide nanofibers: motif design, self-assembly synthesis, and sequence-specific biomedical applications. Prog. Polym. Sci. 80, 94–124 (2018).Google Scholar
16.Coin, I., Beyermann, M., and Bienert, M.: Solid-phase peptide synthesis: from standard procedures to the synthesis of difficult sequences. Nat. Protoc. 2, 3247 (2007).Google Scholar
17.Tsukamoto, J., Naruse, K., Nagai, Y., Kan, S., Nakamura, N., Hata, M., Omi, M., Hayashi, T., Kawai, T., and Matsubara, T.: Efficacy of a self-assembling peptide hydrogel, SPG-178-Gel, for bone regeneration and three-dimensional osteogenic induction of dental pulp stem cells. Tissue Eng. Part A 23, 1394–1402 (2017).Google Scholar
18.Tsutsumi, H., Kawamura, M., and Mihara, H.: Osteoblastic differentiation on hydrogels fabricated from Ca 2+-responsive self-assembling peptides functionalized with bioactive peptides. Bioorg. Med. Chem. 26, 3126–3132 (2018).Google Scholar
19.Li, R., Xu, J., Wong, D.S.H., Li, J., Zhao, P., and Bian, L.: Self-assembled N-cadherin mimetic peptide hydrogels promote the chondrogenesis of mesenchymal stem cells through inhibition of canonical Wnt/β-catenin signaling. Biomaterials 145, 33–43 (2017).Google Scholar
20.Liu, X., Wang, X., Wang, X., Ren, H., He, J., Qiao, L., and Cui, F.-Z.: Functionalized self-assembling peptide nanofiber hydrogels mimic stem cell niche to control human adipose stem cell behavior in vitro. Acta Biomater. 9, 6798–6805 (2013).Google Scholar
21.Chen, S., Zhou, A., He, B., Zhao, W., Chen, X., and Jiang, D.: Designer D-form self-assembling peptide scaffolds promote the proliferation and migration of rat bone marrow-derived mesenchymal stem cells. Int. J. Mol. Med. 40, 679–688 (2017).Google Scholar
22.Shi, J., Du, X., Yuan, D., Zhou, J., Zhou, N., Huang, Y., and Xu, B.: d-amino acids modulate the cellular response of enzymatic-instructed supramolecular nanofibers of small peptides. Biomacromolecules 15, 3559–3568 (2014).Google Scholar
23.Zhou, J., Du, X., Wang, J., Yamagata, N., and Xu, B.: Enzyme-instructed self-assembly of peptides containing phosphoserine to form supramolecular hydrogels as potential soft biomaterials. Front. Chem. Sci. Eng. 11, 509–515 (2017).Google Scholar
24.Hogrebe, N.J., Reinhardt, J.W., Tram, N.K., Debski, A.C., Agarwal, G., Reilly, M.A., and Gooch, K.J.: Independent control of matrix adhesiveness and stiffness within a 3D self-assembling peptide hydrogel. Acta Biomater. 70, 110–119 (2018).Google Scholar
25.Hogrebe, N.J. and Gooch, K.J.: Direct influence of culture dimensionality on human mesenchymal stem cell differentiation at various matrix stiffnesses using a fibrous self-assembling peptide hydrogel: effect of culture dimensionality on HMSC differentiation. J. Biomed. Mater. Res. A 104, 2356–2368 (2016).Google Scholar
26.Tavakol, S., Mousavi, S.M.M., Tavakol, B., Hoveizi, E., Ai, J., and Sorkhabadi, S.M.R.: Erratum to: mechano-transduction signals derived from self-assembling peptide nanofibers containing long motif of laminin influence neurogenesis in in-vitro and in-vivo. Mol. Neurobiol. 54, 2497–2497 (2017).Google Scholar
27.Tavakol, S., Saber, R., Hoveizi, E., Tavakol, B., Aligholi, H., Ai, J., and Rezayat, S.M.: Self-assembling peptide nanofiber containing long motif of laminin induces neural differentiation, tubulin polymerization, and neurogenesis: in vitro, ex vivo, and in vivo studies. Mol. Neurobiol. 53, 5288–5299 (2016).Google Scholar
28.Lu, C., Wang, Y., Yang, S., Wang, C., Sun, X., Lu, J., Yin, H., Jiang, W., Meng, H., Rao, F., Wang, X., and Peng, J.: Bioactive self-assembling peptide hydrogels functionalized with brain-derived neurotrophic factor and nerve growth factor mimicking peptides synergistically promote peripheral nerve regeneration. ACS Biomater. Sci. Eng. 4, 2994–3005 (2018).Google Scholar
29.Maude, S., Ingham, E., and Aggeli, A.: Biomimetic self-assembling peptides as scaffolds for soft tissue engineering. Nanomed. 8, 823–847 (2013).Google Scholar
30.Cheng, T.-Y., Wu, H.-C., Huang, M.-Y., Chang, W.-H., Lee, C.-H., and Wang, T.-W.: Self-assembling functionalized nanopeptides for immediate hemostasis and accelerative liver tissue regeneration. Nanoscale 5, 2734 (2013).Google Scholar
31.Saini, A., Serrano, K., Koss, K., and Unsworth, L.D.: Evaluation of the hemocompatibility and rapid hemostasis of (RADA) 4 peptide-based hydrogels. Acta Biomater. 31, 71–79 (2016).Google Scholar
32.Yang, S., Wei, S., Mao, Y., Zheng, H., Feng, J., Cui, J., Xie, X., Chen, F., and Li, H.: Novel hemostatic biomolecules based on elastin-like polypeptides and the self-assembling peptide RADA-16. BMC Biotechnol. 18, 12 (2018).Google Scholar
33.Altunbas, A., Lee, S.J., Rajasekaran, S.A., Schneider, J.P., and Pochan, D.J.: Encapsulation of curcumin in self-assembling peptide hydrogels as injectable drug delivery vehicles. Biomaterials 32, 5906–5914 (2011).Google Scholar
34.Gelain, F., Unsworth, L.D., and Zhang, S.: Slow and sustained release of active cytokines from self-assembling peptide scaffolds. J. Controlled Release 145, 231–239 (2010).Google Scholar
35.Pugliese, R., Marchini, A., Saracino, G.A.A., Zuckermann, R.N., and Gelain, F.: Cross-linked self-assembling peptide scaffolds. Nano Res. 11, 586–602 (2018).Google Scholar
36.Jansen, L.E., Birch, N.P., Schiffman, J.D., Crosby, A.J., and Peyton, S.R.: Mechanics of intact bone marrow. J. Mech. Behav. Biomed. Mater. 50, 299–307 (2015).Google Scholar
37.Zhang, Z., Wu, G., Cao, Y., Liu, C., Jin, Y., Wang, Y., Yang, L., Guo, J., and Zhu, L.: Self-assembling peptide and nHA/CTS composite scaffolds promote bone regeneration through increasing seed cell adhesion. Mater. Sci. Eng. C 93, 445–454 (2018).Google Scholar
38.Hou, T., Li, Z., Luo, F., Xie, Z., Wu, X., Xing, J., Dong, S., and Xu, J.: A composite demineralized bone matrix––self assembling peptide scaffold for enhancing cell and growth factor activity in bone marrow. Biomaterials 35, 5689–5699 (2014).Google Scholar
39.Li, K., Zhang, Z., Li, D., Zhang, W., Yu, X., Liu, W., Gong, C., Wei, G., and Su, Z.: Biomimetic ultralight, highly porous, shape-adjustable, and biocompatible 3D graphene minerals via incorporation of self-assembled peptide nanosheets. Adv. Funct. Mater. 28, 1801056 (2018).Google Scholar
40.Wu, G., Pan, M., Wang, X., Wen, J., Cao, S., Li, Z., Li, Y., Qian, C., Liu, Z., Wu, W., Zhu, L., and Guo, J.: Osteogenesis of peripheral blood mesenchymal stem cells in self assembling peptide nanofiber for healing critical size calvarial bony defect. Sci. Rep. 5, 16681 (2015).Google Scholar
41.Schiele, N.R., Marturano, J.E., and Kuo, C.K.: Mechanical factors in embryonic tendon development: potential cues for stem cell tenogenesis. Curr. Opin. Biotechnol. 24, 834–840 (2013).Google Scholar
42.Annabi, N., Nichol, J.W., Zhong, X., Ji, C., Koshy, S., Khademhosseini, A., and Dehghani, F.: Controlling the porosity and microarchitecture of hydrogels for tissue engineering. Tissue Eng. Part B Rev. 16, 371–383 (2010).Google Scholar
43.Peyton, S.R., Raub, C.B., Keschrumrus, V.P., and Putnam, A.J.: The use of poly(ethylene glycol) hydrogels to investigate the impact of ECM chemistry and mechanics on smooth muscle cells. Biomaterials 27, 4881–4893 (2006).Google Scholar
44.Huettner, N., Dargaville, T.R., and Forget, A.: Discovering cell-adhesion peptides in tissue engineering: beyond RGD. Trends Biotechnol. 36, 372–383 (2018).Google Scholar
45.Visser, R., Rico-Llanos, G.A., Pulkkinen, H., and Becerra, J.: Peptides for bone tissue engineering. J. Controlled Release 244, 122–135 (2016).Google Scholar
46.Naba, A., Clauser, K.R., Hoersch, S., Liu, H., Carr, S.A., and Hynes, R.O.: The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. Mol. Cell. Proteomics 11, M111.014647 (2012).Google Scholar
47.Jansen, L., McCarthy, T., Lee, M., and Peyton, S.: A synthetic, three-dimensional bone marrow hydrogel. University of Massachusetts Medical School Faculty Publications. 1528 (2018).Google Scholar
48.Anjum, F., Lienemann, P.S., Metzger, S., Biernaskie, J., Kallos, M.S., and Ehrbar, M.: Enzyme responsive GAG-based natural-synthetic hybrid hydrogel for tunable growth factor delivery and stem cell differentiation. Biomaterials 87, 104–117 (2016).Google Scholar
49.Lv, H., Li, L., Sun, M., Zhang, Y., Chen, L., Rong, Y., and Li, Y.: Mechanism of regulation of stem cell differentiation by matrix stiffness. Stem Cell Res. Ther. 6, 103 (2015).Google Scholar
50.Rehmann, M.S., Luna, J.I., Maverakis, E., and Kloxin, A.M.: Tuning microenvironment modulus and biochemical composition promotes human mesenchymal stem cell tenogenic differentiation: human mesenchymal stem cell tenogenic differentiation. J. Biomed. Mater. Res. A 104, 1162–1174 (2016).Google Scholar
51.Blache, U., Metzger, S., Vallmajo-Martin, Q., Martin, I., Djonov, V., and Ehrbar, M.: Dual role of mesenchymal stem cells allows for microvascularized bone tissue-like environments in PEG hydrogels. Adv. Healthc. Mater. 5, 489–498 (2016).Google Scholar
52.Mahadevaiah, S., Robinson, K.G., Kharkar, P.M., Kiick, K.L., and Akins, R.E.: Decreasing matrix modulus of PEG hydrogels induces a vascular phenotype in human cord blood stem cells. Biomaterials 62, 24–34 (2015).Google Scholar
53.Peters, E.B., Christoforou, N., Leong, K.W., Truskey, G.A., and West, J.L.: Poly(ethylene glycol) hydrogel scaffolds containing cell-adhesive and protease-sensitive peptides support microvessel formation by endothelial progenitor cells. Cell. Mol. Bioeng. 9, 38–54 (2016).Google Scholar
54.Mabry, K.M., Lawrence, R.L., and Anseth, K.S.: Dynamic stiffening of poly(ethylene glycol)-based hydrogels to direct valvular interstitial cell phenotype in a three-dimensional environment. Biomaterials 49, 47–56 (2015).Google Scholar
55.Singh, S.P., Schwartz, M.P., Lee, J.Y., Fairbanks, B.D., and Anseth, K.S.: A peptide functionalized poly(ethylene glycol) (PEG) hydrogel for investigating the influence of biochemical and biophysical matrix properties on tumor cell migration. Biomater. Sci. 2, 1024 (2014).Google Scholar
56.Soman, P., Kelber, J.A., Lee, J.W., Wright, T.N., Vecchio, K.S., Klemke, R.L., and Chen, S.: Cancer cell migration within 3D layer-by-layer microfabricated photocrosslinked PEG scaffolds with tunable stiffness. Biomaterials 33, 7064–7070 (2012).Google Scholar
57.Sunyer, R., Jin, A.J., Nossal, R., and Sackett, D.L.: Fabrication of hydrogels with steep stiffness gradients for studying cell mechanical response. PLoS ONE 7, e46107 (2012).Google Scholar
58.Yang, C., DelRio, F.W., Ma, H., Killaars, A.R., Basta, L.P., Kyburz, K.A., and Anseth, K.S.: Spatially patterned matrix elasticity directs stem cell fate. Proc. Natl. Acad. Sci. 113, E4439–E4445 (2016).Google Scholar
59.Hahn, M.S., Miller, J.S., and West, J.L.: Three-dimensional biochemical and biomechanical patterning of hydrogels for guiding cell behavior. Adv. Mater. 18, 2679–2684 (2006).Google Scholar
60.Nemir, S., Hayenga, H.N., and West, J.L.: PEGDA hydrogels with patterned elasticity: novel tools for the study of cell response to substrate rigidity. Biotechnol. Bioeng. 105, 636–644 (2010).Google Scholar
61.Ma, Y., Lin, M., Huang, G., Li, Y., Wang, S., Bai, G., Lu, T.J., and Xu, F.: 3D spatiotemporal mechanical microenvironment: a hydrogel-based platform for guiding stem cell fate. Adv. Mater. 30, 1705911 (2018).Google Scholar
62.Kloxin, A.M., Kloxin, C.J., Bowman, C.N., and Anseth, K.S.: Mechanical properties of cellularly responsive hydrogels and their experimental determination. Adv. Mater. 22, 3484–3494 (2010).Google Scholar
63.Kloxin, A.M., Tibbitt, M.W., Kasko, A.M., Fairbairn, J.A., and Anseth, K.S.: Tunable hydrogels for external manipulation of cellular microenvironments through controlled photodegradation. Adv. Mater. 22, 61–66 (2010).Google Scholar
64.Sletten, E.M. and Bertozzi, C.R.: Bioorthogonal chemistry: fishing for selectivity in a sea of functionality. Angew. Chem. Int. Ed. 48, 6974–6998 (2009).Google Scholar
65.Wu, X., Huang, W., Wu, W.-H., Xue, B., Xiang, D., Li, Y., Qin, M., Sun, F., Wang, W., Zhang, W.-B., and Cao, Y.: Reversible hydrogels with tunable mechanical properties for optically controlling cell migration. Nano Res. 11, 5556–5565 (2018).Google Scholar
66.Norris, S.C.P., Tseng, P., and Kasko, A.M.: Direct gradient photolithography of photodegradable hydrogels with patterned stiffness control with submicrometer resolution. ACS Biomater. Sci. Eng. 2, 1309–1318 (2016).Google Scholar
67.Desmouliere, A., Darby, I.A., Laverdet, B., and Bonté, F.: Fibroblasts and myofibroblasts in wound healing. Clin. Cosmet. Investig. Dermatol. 7, 301 (2014).Google Scholar
68.Hughes, A.J., Miyazaki, H., Coyle, M.C., Zhang, J., Laurie, M.T., Chu, D., Vavrušová, Z., Schneider, R.A., Klein, O.D., and Gartner, Z.J.: Engineered tissue folding by mechanical compaction of the mesenchyme. Dev. Cell 44, 165–178.e6 (2018).Google Scholar
69.Merceron, T.K., Burt, M., Seol, Y.-J., Kang, H.-W., Lee, S.J., Yoo, J.J., and Atala, A.: A 3D bioprinted complex structure for engineering the muscle–tendon unit. Biofabrication. 7, 035003 (2015).Google Scholar
70.Skardal, A., Devarasetty, M., Kang, H.-W., Mead, I., Bishop, C., Shupe, T., Lee, S.J., Jackson, J., Yoo, J., Soker, S., and Atala, A.: A hydrogel bioink toolkit for mimicking native tissue biochemical and mechanical properties in bioprinted tissue constructs. Acta Biomater. 25, 24–34 (2015).Google Scholar
71.Kolesky, D.B., Truby, R.L., Gladman, A.S., Busbee, T.A., Homan, K.A., and Lewis, J.A.: 3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs. Adv. Mater. 26, 3124–3130 (2014).Google Scholar
72.Ma, X., Qu, X., Zhu, W., Li, Y.-S., Yuan, S., Zhang, H., Liu, J., Wang, P., Lai, C.S.E., Zanella, F., Feng, G.-S., Sheikh, F., Chien, S., and Chen, S.: Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting. Proc. Natl. Acad. Sci. 113, 2206–2211 (2016).Google Scholar
73.Soman, P., Chung, P.H., Zhang, A.P., and Chen, S.: Digital microfabrication of user-defined 3D microstructures in cell-laden hydrogels: 3D microstructures in cell-laden hydrogels. Biotechnol. Bioeng. 110, 3038–3047 (2013).Google Scholar
74.Randall, C.L., Gultepe, E., and Gracias, D.H.: Self-folding devices and materials for biomedical applications. Trends Biotechnol. 30, 138–146 (2012).Google Scholar
75.Guan, J., He, H., Hansford, D.J., and Lee, L.J.: Self-Folding of three-dimensional hydrogel microstructures. J. Phys. Chem. B 109, 23134–23137 (2005).Google Scholar
76.Yoon, C., Xiao, R., Park, J., Cha, J., Nguyen, T.D., and Gracias, D.H.: Functional stimuli responsive hydrogel devices by self-folding. Smart Mater. Struct. 23, 094008 (2014).Google Scholar
77.Naficy, S., Gately, R., Gorkin, R., Xin, H., and Spinks, G.M.: 4D printing of reversible shape morphing hydrogel structures. Macromol. Mater. Eng. 302, 1600212 (2017).Google Scholar
78.Kwag, H.R., Serbo, J.V., Korangath, P., Sukumar, S., Romer, L.H., and Gracias, D.H.: A self-folding hydrogel in vitro model for ductal carcinoma. Tissue Eng. Part C Methods 22, 398–407 (2016).Google Scholar
79.Kuribayashi-Shigetomi, K., Onoe, H., and Takeuchi, S.: Cell origami: self-folding of three-dimensional cell-laden microstructures driven by cell traction force. PLoS ONE 7, e51085 (2012).Google Scholar
80.Bassik, N., Stern, G.M., Jamal, M., and Gracias, D.H.: Patterning thin film mechanical properties to drive assembly of complex 3D structures. Adv. Mater. 20, 4760–4764 (2008).Google Scholar
81.Bae, J., Na, J.-H., Santangelo, C.D., and Hayward, R.C.: Edge-defined metric buckling of temperature-responsive hydrogel ribbons and rings. Polymer 55, 5908–5914 (2014).Google Scholar
82.Li, T., Wang, J., Zhang, L., Yang, J., Yang, M., Zhu, D., Zhou, X., Handschuh-Wang, S., Liu, Y., and Zhou, X.: “Freezing”, morphing, and folding of stretchy tough hydrogels. J. Mater. Chem. B 5, 5726–5732 (2017).Google Scholar
83.Jeon, S.-J., Hauser, A.W., and Hayward, R.C.: Shape-morphing materials from stimuli-responsive hydrogel hybrids. Acc. Chem. Res. 50, 161–169 (2017).Google Scholar
84.Park, S.-J., Gazzola, M., Park, K.S., Park, S., Di Santo, V., Blevins, E.L., Lind, J.U., Campbell, P.H., Dauth, S., Capulli, A.K., Pasqualini, F.S., Ahn, S., Cho, A., Yuan, H., Maoz, B.M., Vijaykumar, R., Choi, J.-W., Deisseroth, K., Lauder, G.V., Mahadevan, L., and Parker, K.K.: Phototactic guidance of a tissue-engineered soft-robotic ray. Science 353, 158–162 (2016).Google Scholar