Rising influence of synthetic biology in regenerative medicine

Angharad Evans; Elizabeth Ratcliffe

Rising influence of synthetic biology in regenerative medicine

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Author(s): Angharad Evans ¹ and Elizabeth Ratcliffe ¹
- Affiliations: 1: Centre for Biological Engineering, Department of Chemical Engineering, Loughborough University, Loughborough, Leicestershire, UK
Source: Volume 1, Issue 1, June 2017, p. 24 – 29
DOI: 10.1049/enb.2017.0007 , Online ISSN 2398-6182

This is an open access article published by the IET under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/)

Received 07/03/2017, Accepted 12/04/2017, Revised 10/04/2017, Published 22/06/2017

Synthetic biology is an emerging area of research that combines the investigative nature of biology with the constructive nature of engineering. Despite the field being in its infancy, it has already aided the development of a myriad of industrially and pharmaceutically useful compounds, devices and therapies and is now being applied within the field of regenerative medicine. By combining synthetic biology with regenerative medicine, the engineering of cells and organisms offers potential avenues for applications in tissue engineering, bioprocessing, biomaterial and scaffold development, stem cell therapies and even gene therapies. This review aims to discuss how synthetic biology has been applied within these distinct areas of regenerative medicine, the challenges it faces and any future possibilities this exciting new field may hold.

References

1. 1)
  - 31. Paddon, C.J., Westfall, D.J., Pitera, K., et al: ‘High-level semi-synthetic production of the potent antimalarial artemisinin’, Nature, 2013, 496, (7446), pp. 528–532, (doi: 10.1038/nature12051).
2. 2)
  - 18. Deans, T.L., Cantor, C.R., Collins, J.J.: ‘A tunable genetic switch based on RNAi and repressor proteins for regulating gene expression in mammalian cells’, Cell, 2007, 130, pp. 363–372 (doi: 10.1016/j.cell.2007.05.045).
3. 3)
  - 2. Abil, Z., Xiong, X., Zhao, H.: ‘Synthetic biology for therapeutic applications’, Mol. Pharm., 2015, 12, (2), pp. 322–331 (doi: 10.1021/mp500392q).
4. 4)
  - 5. Kramer, B., Viretta, A., Daoud-El-Baba, M., et al: ‘An engineered epigenetic transgene switch in mammalian cells’, Nat. Biotechnol., 2004, 22, (7), pp. 867–870 (doi: 10.1038/nbt980).
5. 5)
  - 23. Baiguera, S., Jungebluth, P., Burns, A., et al: ‘Tissue engineered human tracheas for implantation’, Biomaterials, 2010, 31, (34), pp. 8931–8938, (doi: 10.1016/j.biomaterials.2010.08.005).
6. 6)
  - 69. Mairhofer, J., Wittwer, A., Cserjan-Puschmann, M., et al: ‘Preventing T7 RNA polymerase read-through transcription – a synthetic termination signal capable of improving bioprocess stability’, ACS Synthetic Biol., 2015, 4, (3), pp. 265–273, (doi: 10.1021/sb5000115).
7. 7)
  - 16. Anderson, J.C., Clarke, E.J., Arkin, A.P., et al: ‘Environmentally controlled invasion of cancer cells by engineered bacteria’, J. Mol. Biol., 2006, 355, pp. 619–627 (doi: 10.1016/j.jmb.2005.10.076).
8. 8)
  - 50. Lutolf, M.P., Hubbell, J.A.: ‘Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering: abstract: nature biotechnology’, Nat. Biotechnol., 2005, 23, (1), pp. 47–55, (doi: 10.1038/nbt1055).
9. 9)
  - 11. Yokobayashi, Y., Weiss, R., Arnold, F.H.: ‘Directed evolution of a genetic circuit’, Proc. Natl Acad. Sci. USA, 2002, 99, pp. 16587–16591 (doi: 10.1073/pnas.252535999).
10. 10)
  - 53. O'Brien, F.J.: ‘Biomaterials & scaffolds for tissue engineering’, Mater. Today, 2011, 14, (3), pp. 88–95, (doi: 10.1016/S1369-7021(11)70058-X).
11. 11)
  - 78. Chen, M., Przyborowski, M., Berthiaume, F.: ‘Stem cells for skin tissue engineering and wound healing’, Crit. Rev. Biomed. Eng., 2009, 37, (4–5), pp. 399–421 (doi: 10.1615/CritRevBiomedEng.v37.i4-5.50).
12. 12)
  - 80. MacDonald, C.I., Deans, T.L.: ‘Tools and applications in synthetic biology’, Adv. Drug Deliv. Rev., 2016, 105, pp. 20–34, (doi: 10.1016/j.addr.2016.08.008).
13. 13)
  - 75. Squillaro, T., Peluso, G., Galderisi, U.: ‘Clinical trials with mesenchymal stem cells: an update’, Cell Transplant, 2016, 25, (5), pp. 829–848, (doi: 10.3727/096368915X689622).
14. 14)
  - 14. Basu, S., Gerchman, Y., Collins, C.H., et al: ‘A synthetic multicellular system for programmed pattern formation’, Nature, 2005, 434, pp. 1130–1134, (doi: 10.1038/nature03461).
15. 15)
  - 34. Booth, M.J., Schild, V.R., Graham, A.D., et al: ‘Light-activated communication in synthetic tissues’, Sci. Adv., 2016, 2, (4), (doi: 10.1126/sciadv.1600056).
16. 16)
  - 83. Culler, S.J., Hoff, K.G., Smolke, C.D.: ‘Reprogramming cellular behavior with RNA controllers responsive to endogenous proteins’, Science, 2010, 330, (6008), pp. 1251–1255, (doi: 10.1126/science.1192128).
17. 17)
  - 94. Cachat, E., Martin, K.C., Davies, J.A.: ‘Synthetic biology approaches for regenerative medicine’, Rev. Cell Biol. Mol. Med., 2014, pp. 523–539.
18. 18)
  - 93. Gaj, T., Gersbach, C.A., Barbas, C.F.: ‘ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering’, Cell, 2013, 31, (7), pp. 397–405, doi: 10.1016/j.tibtech.2013.04.004.
19. 19)
  - 73. Kis, Z., Pereira, H.S.A., Homma, T., et al: ‘Mammalian synthetic biology: emerging medical applications’, J. R. Soc. Interface, 2015, 12, p. 20141000, (doi: 10.1098/rsif.2014.1000).
20. 20)
  - 89. Hsu, P.D., Lander, E.S., Zhang, F.: ‘Development and applications of CRISPR-Cas9 for genome engineering’, Cell Press., 2014, 157, (6), pp. 1262–1278, http://dx.doi.org/10.1016/j.cell.2014.05.010.
21. 21)
  - 49. Wilkinson, D.C., Alva-Ornelas, J.A., Sucre, J.M.S., et al: ‘Development of a three-dimensional bioengineering technology to generate lung tissue for personalized disease modelling’, Stem Cells Trans. Med., 2016, 5, (12), pp. 1–12, doi: 10.5966/sctm.2016-0192.
22. 22)
  - 19. Win, M.N., Smolke, C.D.: ‘A modular and extensible RNA-based gene-regulatory platform for engineering cellular function’, Proc. Natl. Acad. Sci. USA, 2007, 104, (36), pp. 14283–14288 (doi: 10.1073/pnas.0703961104).
23. 23)
  - 43. Ritter, T., Nosov, M., Griffin, M.D.: ‘Gene therapy in transplantation: toward clinical trials’, Curr. Opin. Mol. Ther., 2009, 11, (5), pp. 504–512.
24. 24)
  - 40. Choumerianou, D.M., Dimitriou, H., Kalmanti, M.: ‘Stem cells: promises versus limitations’, Tissue Eng. B Rev., 2008, 14, (1), pp. 53–60 (doi: 10.1089/teb.2007.0216).
25. 25)
  - 24. Gibson, D.G., Glass, J.L., Lartique, C., et al: ‘Creation of a bacterial cell controlled by a chemically synthesized genome’, Science, 2010, 329, (5987), pp. 52–56 (doi: 10.1126/science.1190719).
26. 26)
  - 84. Kemmer, C., Gitzinger, M., Daoud-El Baba, M., et al: ‘Self-sufficient control of urate homeostasis in mice by a synthetic circuit’, Nat. Biotechnol., 2010, 28, (4), pp. 355–360, (doi: 10.1038/nbt.1617).
27. 27)
  - 67. Alimperti, S., Lei, P., Wen, Y., et al: ‘Serum-free spheroid suspension culture maintains mesenchymal stem cell proliferation and differentiation potential’, Biotechnol. Progr., 2014, 30, (4), pp. 974–983, (doi: 10.1002/btpr.1904).
28. 28)
  - 82. O'Shaughnessy, E.C., Palani, S., Collins, J.J., et al: ‘Tunable signal processing in synthetic MAP Kinase cascades’, Cell, 2011, 144, (1), pp. 119–131, (doi: 10.1016/j.cell.2010.12.014).
29. 29)
  - 27. Callaway, E.: ‘Nature News: Stem cells that are pure enough for the clinic’, Nature, 2011, doi: 10.1038/nature.2011.9566.
30. 30)
  - 58. Gübeli, R.J., Burger, K., Weber, W.: ‘Synthetic biology for mammalian cell technology and materials sciences’, Biotechnol. Adv., 2013, 31, (1), pp. 68–78, (doi: 10.1016/j.biotechadv.2012.01.007).
31. 31)
  - 92. Esvelt, K.M., Wang, H.H.: ‘Genome-scale engineering for systems and synthetic biology’, Mol. Syst. Biol., 2013, 9, p. 641, (doi: 10.1038/msb.2012.66).
32. 32)
  - 88. Premsrirut, P.K., Martin, G., Dow, L., et al: ‘Abstract 4188: RNAi and CRISPR/Cas9 based in vivo models for drug discovery’, Cancer Res., 2016, (76), (14 Supplement), p. 4188, doi: 10.1158/1538-7445.AM2016-4188.
33. 33)
  - 25. Graham, T.G.W., Tabei, S.M.A., Dinner, A.R., et al: ‘Modelling bistable cell-fate choices in the Drosophila qualitative and quantitative perspectives’, Development, 2010, 137, pp. 2265–2278, (doi: 10.1242/dev.044826).
34. 34)
  - 76. Trounson, A., DeWitt, N.D.: ‘Pluripotent stem cells progressing to the clinic’, Nat. Rev. Mol. Biol., 2016, 17, (3), pp. 194–200, (doi: 10.1038/nrm.2016.10).
35. 35)
  - 90. Doudna, J.A.: ‘Genomic engineering and the future of medicine’, JAMA, 2015, 313, (8), pp. 791–792, (doi: 10.1001/jama.2015.287).
36. 36)
  - 62. Highley, C.B., Prestwich, G.D., Burdick, J.A.: ‘Recent advances in hyaluronic acid hydrogels for biomedical applications’, Curr. Opin. Biotechnol., 2016, 40, pp. 35–40, (doi: 10.1016/j.copbio.2016.02.008).
37. 37)
  - 72. Bhatia, P., Chugh, A.: ‘Synthetic biology based biosensors and the emerging governance issues’, Curr. Synthetic Syst. Biol., 2013, 01, (01), doi: 10.4172/2332-0737.1000108.
38. 38)
  - 85. Ye, H., Baba, M.D.-E., Peng, R.-W., et al: ‘A synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice’, Science, 2011, 332, (6037), pp. 1565–1568, (doi: 10.1126/science.1203535).
39. 39)
  - 6. Win, M.N., Smolke, C.D.: ‘Higher-order cellular information processing with synthetic RNA devices’, Science, 2008, 322, (5900), pp. 456–460 (doi: 10.1126/science.1160311).
40. 40)
  - 12. Isaacs, F.J., Dwyer, D.J., Ding, C., et al: ‘Engineered riboregulators enable post-transcriptional control of gene expression’, Nat. Biotechnol., 2004, 22, pp. 841–847 (doi: 10.1038/nbt986).
41. 41)
  - 5. Morse, M.A., Saltzman, M.W., Domb, A.J., et al: ‘Selective cell transplantation using bioabsorbable artificial polymers as matrices’, J. Pediatr. Surg., 1988, 23, (1), pp. 3–9 (doi: 10.1016/S0022-3468(88)80544-X).
42. 42)
  - 33. Heng, B.C., Aubel, D., Fussenegger, M.: ‘G protein-coupled receptors revisited: therapeutic application inspired by synthetic biology’, Annu. Rev. Pharm. Toxicol., 2014, 54, pp. 227–249, (doi: 10.1146/annurev-pharmtox-011613-135921).
43. 43)
  - 191. Tigges, M., Marquez-Lago, T.T., Stelling, J., et al: ‘A tunable synthetic mammalian oscillator’, Nature, 2009, 457, (7227), pp. 309–312 (doi: 10.1038/nature07616).
44. 44)
  - 41. Heng, B.C., Cao, T.: ‘Incorporating protein transduction domains (PTD) within intracellular proteins associated with the ‘stemness’ phenotype. Novel use of such recombinant ‘fusion’ proteins to overcome current limitations of applying autologous adult stem cells in regenerative medicine?’, Med. Hypotheses, 2005, 64, (5), pp. 992–996 (doi: 10.1016/j.mehy.2004.11.003).
45. 45)
  - 46. Macchiarini, P., Jungebluth, P., Go, T., , et al: ‘Clinical transplantation of a tissue-engineered airway’, The Lancet, 2008, 372, (9655), pp. 2023–2030, (doi: 10.1016/S0140-6736(08)61598-6).
46. 46)
  - 30. Hou, P., Li, Y., Zhang, X., et al: ‘Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds’, Science, 2013, 341, (6146), pp. 651–654, (doi: 10.1126/science.1239278).
47. 47)
  - 70. Polizzi, K.M., Kontoravdi, C.: ‘Genetically-encoded biosensors for monitoring cellular stress in bioprocessing’, Curr. Opin. Biotechnol., 2015, 31, pp. 50–56, (doi: 10.1016/j.copbio.2014.07.011).
48. 48)
  - 52. Metavarayuth, K., Sitasuwan, P., Zhao, X., et al: ‘Influence of surface topographical cues on the differentiation of Mesenchymal stem cells in vitro’, ACS Biomater. Sci. Eng., 2016, 2, (2), pp. 142–151, (doi: 10.1021/acsbiomaterials.5b00377).
49. 49)
  - 81. Levskaya, A., Weiner, O.D., Lim, W.A., et al: ‘Spatiotemporal control of cell signalling using a light-switchable protein interaction: abstract: nature’, Nature, 2009, 461, (7266), pp. 1001–1997, (doi: 10.1038/nature08446).
50. 50)
  - 32. Annaluru, N., Muller, H., Mitchell, L.A., et al: ‘Total synthesis of a functional designer eukaryotic chromosome’, Science, 2014, 344, (6179), pp. 55–58, (doi: 10.1126/science.1249252).
51. 51)
  - 65. Li, Y., Ma, T.: ‘Bioprocessing of cryopreservation for large-scale banking of human pluripotent stem cells’, BioResearch Open Access, 2012, 1, (5), pp. 205–214, (doi: 10.1089/biores.2012.0224).
52. 52)
  - 96. Wichterle, H.: ‘What can pluripotent stem cells teach us about neurodegenerative diseases?’, Nat. Neurosci., 2010, 13, (7), pp. 800–804, (doi: 10.1038/nn.2577).
53. 53)
  - 63. Hirschi, K., Li, S., Roy, K.: ‘Induced pluripotent stem cells for regenerative medicine’, Annu. Rev. Biomed. Eng., 2014, 16, pp. 277–294 (doi: 10.1146/annurev-bioeng-071813-105108).
54. 54)
  - 4. Bell, E., Ivarsson, B., Merrill, C.: ‘Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro’, Cell Biol., Proc. Natl. Acad. Sci. USA, 1979, 76, (3), pp. 1274–1278 (doi: 10.1073/pnas.76.3.1274).
55. 55)
  - 10. Guet, C.C., Elowitz, M.B., Hsing, W., et al: ‘Combinatorial synthesis of genetic networks’, Science, 2002, 296, pp. 1466–1470 (doi: 10.1126/science.1067407).
56. 56)
  - 42. Heng, B.C., Cao, T.: ‘Milieu-based versus gene-modulatory strategies for directing stem cell differentiation – a major issue of contention in transplantation medicine’, In Vitro, Cell. Dev. Biol. Anim., 2006, 42, (3–4), pp. 51–53 (doi: 10.1290/0504025.1).
57. 57)
  - 35. Daar, A.S., Greenwood, H.L.: ‘A proposed definition of regenerative medicine’, J. Tissue Eng. Regener. Med., 2007, 1, pp. 179–184 (doi: 10.1002/term.20).
58. 58)
  - 66. Schnitzler, A.C., Verma, A., Kehoe, D.E., et al: ‘Bioprocessing of human mesenchymal stem/stromal cells for therapeutic use: current technologies and challenges’, Biochem. Eng. J., 2016, 108, pp. 3–13, (doi: 10.1016/j.bej.2015.08.014).
59. 59)
  - 45. Davies, J.A.: ‘Synthetic biology: rational pathway design for regenerative medicine’, Gerontology, 2016, 62, (5), pp. 564–570, (doi: 10.1159/000440721).
60. 60)
  - 28. Bacchus, W., Lang, M., El-Baba, M.D., et al: ‘Synthetic two-way communication between mammalian cells’, Nat. Biotechnol., 2012, 30, pp. 991–996, (doi: 10.1038/nbt.2351).
61. 61)
  - 48. Pan, T., Song, W., Cao, X.: ‘3D bioplotting of gelatin/alginate scaffolds for tissue engineering: influence of crosslinking degree and pore architecture on physicochemical properties’, J. Mater. Sci. Technol., 2016, 32, (9), pp. 889–900, (doi: 10.1016/j.jmst.2016.01.007).
62. 62)
  - 64. Liang, G., Zhang, Y.: ‘Embryonic stem cell and induced pluripotent stem cell: an epigenetic perspective’, Cell Res., 2012, 23, (1), pp. 49–69 (doi: 10.1038/cr.2012.175).
63. 63)
  - 68. National Research Council (US) Committee on Bioprocess Engineering. Putting Biotechnology to Work: Bioprocess Engineering. Washington (DC): National Academies Press (US); 1992. 4, Current Bioprocess Technology, Products, and Opportunities, https://www.ncbi.nlm.nih.gov/books/NBK236005/ [accessed 06/01/2017].
64. 64)
  - 91. Heidari, R., Shaw, D.M., Elger, B.S.: ‘CRISPR and the rebirth of synthetic biology’, Sci. Eng. Ethics, 2016, 23, (2), pp. 1–13, article. doi: org/10.1007/s11948-016-9768-z.
65. 65)
  - 17. Rinaudo, K., Bleris, L., Maddamsetti, R., et al: ‘A universal RNAi-based logic evaluator that operates in mammalian cells’, Nat. Biotechnol., 2007, 25, (7), pp. 795–801 (doi: 10.1038/nbt1307).
66. 66)
  - 55. Tan, J., Saltzman, W.M.: ‘Micro-engineered biomineralized materials for bone tissue engineering’ (IEEE, Houston, TX, 2002), pp. 807–808.
67. 67)
  - 59. Kämpf, M.M., Christen, E.H., Ehrbar, M., et al: ‘A gene therapy technology-based biomaterial for the trigger-inducible release of biopharmaceuticals in mice’, Adv. Funct. Mater., 2010, 20, (15), pp. 2534–2538, (doi: 10.1002/adfm.200902377).
68. 68)
  - 37. Heng, B.C., Fussenegger, M.: ‘The synthetic biology approach to stem cells and regenerative medicine’, in Meyers, R.A.: ‘Encyclopedia of molecular cell biology and molecular medicine’ (Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, 2015), pp. 1–17.
69. 69)
  - 1. Gardner, T.S., Cantor, C.R., Collins, J.J.: ‘Construction of a genetic toggle switch in Escherichia coli’, Nature, 2000, 403, pp. 339–342 (doi: 10.1038/35002131).
70. 70)
  - 44. Sykova, E., Forostyak, S.: ‘Stem cells in regenerative medicine’, Laser Ther., 2013, 22, (2), pp. 87–92, (doi: 10.5978/islsm.13-RE-01).
71. 71)
  - 57. Ehrbar, M., Schoenmakers, R., Christen, E.H., et al: ‘Drug-sensing hydrogels for the inducible release of biopharmaceuticals: abstract: nature materials’, Nature Mater., 2008, 7, (10), pp. 800–804, (doi: 10.1038/nmat2250).
72. 72)
  - 6. Naughton, G., Mansbridge, J., Gentzkow, G.: ‘A metabolically active human dermal replacement for the treatment of diabetic foot ulcers’, Artif. Organs, 1998, 21, (11), pp. 1203–1210 (doi: 10.1111/j.1525-1594.1997.tb00476.x).
73. 73)
  - 36. Cachat, E., Davies, J.: ‘Application of synthetic biology to regenerative medicine’, J. Bioeng. Biomed. Sci., 2011, S2, doi: 10.4172/2155- 9538.S2-003.
74. 74)
  - 16. Becskei, A., Serrano, L.: ‘Engineering stability in gene networks by autoregulation’, Nature, 2000, 405, pp. 590–593 (doi: 10.1038/35014651).
75. 75)
  - 79. Chakravarti, D., Wong, W.W.: ‘Review: synthetic biology in cell-based cancer immunotherapy’, Trends Biotechnol., 2015, 33, (8), pp. 449–461, (doi: 10.1016/j.tibtech.2015.05.001).
76. 76)
  - 61. Wirostko, B., Mann, B.K., Prestwich, G.D.: ‘Clinical development of hyaluronan-based semisynthetic extracellular matrices’, Adv. Wound Care, 2014, 3, pp. 708–716 (doi: 10.1089/wound.2014.0572).
77. 77)
  - 95. Hug, K.: ‘Sources of human embryos for stem cell research: ethical problems and their possible solutions’, Medicina (Kaunas), 2005, 41, (12), pp. 1002–1010.
78. 78)
  - 15. Takahashi, K., Yamanaka, S.: ‘Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors’, Cell, 2006, 126, (4), pp. 663–676 (doi: 10.1016/j.cell.2006.07.024).
79. 79)
  - 77. Barfoot, J.: ‘What diseases and conditions can be treated with stem cells’, 2017. Available from www.eurostemcell.org, accessed 01/02/2017.
80. 80)
  - 38. Liu, J.S., Gartner, Z.J.: ‘Directing the assembly of spatially organized multicomponent tissues from the bottom up’, Trends Cell Biol., 2012, 22, (12), pp. 683–691 (doi: 10.1016/j.tcb.2012.09.004).
81. 81)
  - 30. Moon, T.S., Lou, C., Tamsir, A., et al: ‘Genetic programs constructed from layered logic gates in single cells’, Nature, 2012, 491, (7423), pp. 249–252 (doi: 10.1038/nature11516).
82. 82)
  - 26. Bone, H.K., Nelson, A.S., Goldring, C.E., et al: ‘A novel chemically directed route for the generation of definitive endoderm from human embryonic stem cells based on inhibition of GSK-3’, J. Cell Sci., 2011, 124, pp. 1992–2000, (doi: 10.1242/jcs.081679).
83. 83)
  - 87. Ausländer, D., Ausländer, S., Hamri, G.C.-E., et al: ‘A synthetic multifunctional mammalian pH sensor and CO transgene-control device’, Mol. cell, 2014, 55, (3), pp. 397–408, (doi: 10.1016/j.molcel.2014.06.007).
84. 84)
  - 3. Gurdon, J.B.: ‘Adult frogs derived from the nuclei of single somatic cells’, J. Embryol. Exp. Morphol., 1962, 10, pp. 622–640.
85. 85)
  - 54. Kessler, M.W., Grande, D.A.: ‘Tissue engineering and cartilage’, Organogenesis, 2008, 4, (1), pp. 28–32 (doi: 10.4161/org.6116).
86. 86)
  - 56. Holmes, T.C.: ‘Novel peptide-based biomaterial scaffolds for tissue engineering’, Trends Biotechnol., 2002, 20, (1), pp. 16–21, (doi: 10.1016/S0167-7799(01)01840-6).
87. 87)
  - 9. Weiss, R., Knight, T.F.Jr.: DNA6: Sixth Int. Workshop on DNA-Based Computers, DNA2000, Leiden, The Netherlands, 2000, pp. 1–16.
88. 88)
  - 39. Basu, S., Mehreja, R., Thiberge, S., et al: ‘Spatiotemporal control of gene expression with pulse-generating networks’. Proc. of the National Academy of Sciences of the United States of America, 27 April 2004, vol. 101, (17), pp. 6355–6360.
89. 89)
  - 74. Trounson, A., McDonald, C.: ‘Stem cell therapies in clinical trials: progress and challenges’, Cell Stem Cell, 2015, 17, (1), pp. 11–22, (doi: 10.1016/j.stem.2015.06.007).
90. 90)
  - 86. Rössger, K., Charpin-El-Hamri, G., Fussenegger, M.: ‘A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice’, Nat. Commun., 2013, 4, p. 2825, (doi: 10.1038/ncomms3825).
91. 91)
  - 1. Lienert, F., Lohmueller, J.J., Garg, A., et al: ‘Synthetic biology in mammalian cells: next generation research tools and therapeutics’, Nat. Rev. Mol. Cell Biol., 2014, 15, (2), pp. 95–107, (doi: 10.1038/nrm3738).
92. 92)
  - 71. Schmidt, M., Pei, L.: ‘Synthetic toxicology: where engineering meets biology and toxicology’, Toxicol. Sci., 2011, 120, (suppl 1), pp. 204–224, (doi: 10.1093/toxsci/kfq339).
93. 93)
  - 47. Johnson, C., Sheshadri, P., Ketchum, J.M., et al: ‘In vitro characterization of design and compressive properties of 3D-biofabricated/decellularized hybrid grafts for tracheal tissue engineering’, J. Mech. Behav. Biomed. Mater., 2016, 59, pp. 572–585, (doi: 10.1016/j.jmbbm.2016.03.024).
94. 94)
  - 51. Hubbell, J.A.: ‘Biomaterials in tissue engineering’, Biotechnology, 1995, 13, (6), pp. 565–576.
95. 95)
  - 60. Prestwich, G.D.: ‘Engineering a clinically-useful matrix for cell therapy’, Organogenesis, 2008, 4, (1), pp. 42–47 (doi: 10.4161/org.6152).
96. 96)
  - 20. Yao, G., Lee, T.J., Mori, S., et al: ‘A bistable Rb-E2F underlies the restriction point’, Nat. Cell Biol., 2008, 10, pp. 476–482 (doi: 10.1038/ncb1711).

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