Skip to main content
SpringerLink
Log in

Physical Non-Viral Gene Delivery Methods for Tissue Engineering

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

The integration of gene therapy into tissue engineering to control differentiation and direct tissue formation is not a new concept; however, successful delivery of nucleic acids into primary cells, progenitor cells, and stem cells has proven exceptionally challenging. Viral vectors are generally highly effective at delivering nucleic acids to a variety of cell populations, both dividing and non-dividing, yet these viral vectors are marred by significant safety concerns. Non-viral vectors are preferred for gene therapy, despite lower transfection efficiencies, and possess many customizable attributes that are desirable for tissue engineering applications. However, there is no single non-viral gene delivery strategy that “fits-all” cell types and tissues. Thus, there is a compelling opportunity to examine different non-viral vectors, especially physical vectors, and compare their relative degrees of success. This review examines the advantages and disadvantages of physical non-viral methods (i.e., microinjection, ballistic gene delivery, electroporation, sonoporation, laser irradiation, magnetofection, and electric field-induced molecular vibration), with particular attention given to electroporation because of its versatility, with further special emphasis on Nucleofection™. In addition, attributes of cellular character that can be used to improve differentiation strategies are examined for tissue engineering applications. Ultimately, electroporation exhibits a high transfection efficiency in many cell types, which is highly desirable for tissue engineering applications, but electroporation and other physical non-viral gene delivery methods are still limited by poor cell viability. Overcoming the challenge of poor cell viability in highly efficient physical non-viral techniques is the key to using gene delivery to enhance tissue engineering applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Adler, A. F., and K. W. Leong. Emerging links between surface nanotechnology and endocytosis: impact on nonviral gene delivery. Nano Today. 5:553–569, 2010.

    Article  PubMed  CAS  Google Scholar 

  2. Adler, A. F., A. T. Speidel, N. Christoforou, K. Kolind, M. Foss, and K. W. Leong. High-throughput screening of microscale pitted substrate topographies for enhanced nonviral transfection efficiency in primary human fibroblasts. Biomaterials 32:3611–3619, 2011.

    Article  PubMed  CAS  Google Scholar 

  3. Aihara, H., and J. Miyazaki. Gene transfer into muscle by electroporation in vivo. Nat. Biotechnol. 16:867–870, 1998.

    Article  PubMed  CAS  Google Scholar 

  4. Akinc, A., M. Thomas, A. M. Klibanov, and R. Langer. Exploring polyethylenimine-mediated DNA transfection and the proton sponge hypothesis. J. Gene Med. 7:657–663, 2005.

    Article  PubMed  CAS  Google Scholar 

  5. Alberts, B., D. Bray, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, and A. Campbell. Essential Cell Biology. New York: Garland Science, 2004.

    Google Scholar 

  6. Aluigi, M., M. Fogli, A. Curti, A. Isidori, E. Gruppioni, C. Chiodoni, M. P. Colombo, P. Versura, A. D’Errico-Grigioni, E. Ferri, M. Baccarani, and R. M. Lemoli. Nucleofection is an efficient nonviral transfection technique for human bone marrow derived mesenchymal stem cells. Stem Cells. 24:454–461, 2006.

    Article  PubMed  Google Scholar 

  7. Andre, F. M., and L. M. Mir. Nucleic acids electrotransfer in vivo: mechanisms and practical aspects. Curr. Gene Ther. 10:267–280, 2010.

    Article  PubMed  CAS  Google Scholar 

  8. Aslan, H., Y. Zilberman, V. Arbeli, D. Sheyn, Y. Matan, M. Liebergall, J. Li, G. Helm, D. Gazit, and Z. Gazit. Nucleofection-based ex vivo nonviral gene delivery to human stem cells as a platform for tissue regeneration. Tissue Eng. 12:877–889, 2006.

    Article  PubMed  CAS  Google Scholar 

  9. Baertschi, A. J. Antisense oligonucleotide strategies in physiology. Mol. Cell. Endocrinol. 101:R15–R24, 1994.

    Article  PubMed  CAS  Google Scholar 

  10. Baksh, D., R. Yao, and R. Tuan. Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells. 25:1384–1392, 2007.

    Article  PubMed  CAS  Google Scholar 

  11. Baoum, A. A., and C. Berkland. Calcium condensation of DNA complexed with cell-penetrating peptides offers efficient, noncytotoxic gene delivery. J. Pharm. Sci. 100:1637–1642, 2011.

    Article  PubMed  CAS  Google Scholar 

  12. Baoum, A., N. Dhillon, S. Buch, and C. Berkland. Cationic surface modification of PLG nanoparticles offers sustained gene delivery to pulmonary epithelial cells. J. Pharm. Sci. 99:2413–2422, 2010.

    PubMed  CAS  Google Scholar 

  13. Baoum, A., D. Ovcharenko, and C. Berkland. Calcium condensed cell penetrating peptide complexes offer highly efficient, low toxicity gene silencing. Int. J. Pharm. 427(1):134–142, 2011.

    Article  PubMed  CAS  Google Scholar 

  14. Bier, M., S. M. Hammer, D. J. Canaday, and R. C. Lee. Kinetics of sealing for transient electropores in isolated mammalian skeletal muscle cells. Bioelectromagnetics. 20:194–201, 1999.

    Article  PubMed  CAS  Google Scholar 

  15. Bittman, K. S., J. A. Panzer, and R. J. Balice-Gordon. Patterns of cell–cell coupling in embryonic spinal cord studied via ballistic delivery of gap-junction-permeable dyes. J. Comp. Neurol. 477:273–285, 2004.

    Article  PubMed  CAS  Google Scholar 

  16. Bolliet, C., M. C. Bohn, and M. Spector. Non-viral delivery of the gene for glial cell line-derived neurotrophic factor to mesenchymal stem cells in vitro via a collagen scaffold. Tissue Eng. C 14:207–219, 2008.

    Article  CAS  Google Scholar 

  17. Bowles, R., S. Patil, H. Pincas, and S. C. Sealfon. Validation of efficient high-throughput plasmid and siRNA transfection of human monocyte-derived dendritic cells without cell maturation. J. Immunol. Methods 363:21–28, 2010.

    Article  PubMed  CAS  Google Scholar 

  18. Bradburne, C., K. Robertson, and D. Thach. Assessment of methods and analysis of outcomes for comprehensive optimization of nucleofection. Genet. Vaccines Ther. 7:6, 2009.

    Article  PubMed  CAS  Google Scholar 

  19. Buerli, T., C. Pellegrino, K. Baer, B. Lardi-Studler, I. Chudotvorova, J. M. Fritschy, I. Medina, and C. Fuhrer. Efficient transfection of DNA or shRNA vectors into neurons using magnetofection. Nat. Protoc. 2:3090–3101, 2007.

    Article  PubMed  CAS  Google Scholar 

  20. Campbell, N., L. Mitchell, and J. Reece. Biology: Concepts & Connections. New York: Benjamin Cummings, 2003.

    Google Scholar 

  21. Cemazar, M., M. Golzio, G. Sersa, M. P. Rols, and J. Teissie. Electrically-assisted nucleic acids delivery to tissues in vivo: where do we stand? Curr. Pharm. Des. 12:3817–3825, 2006.

    Article  PubMed  CAS  Google Scholar 

  22. Cesnulevicius, K., M. Timmer, M. Wesemann, T. Thomas, T. Barkhausen, and C. Grothe. Nucleofection is the most efficient nonviral transfection method for neuronal stem cells derived from ventral mesencephali with no changes in cell composition or dopaminergic fate. Stem Cells. 24:2776–2791, 2006.

    Article  PubMed  CAS  Google Scholar 

  23. Chalut, K. J., K. Kulangara, M. G. Giacomelli, A. Wax, and K. W. Leong. Deformation of stem cell nuclei by nanotopographical cues. Soft Matter 6:1675–1681, 2010.

    Article  PubMed  CAS  Google Scholar 

  24. Check, E. Gene therapy put on hold as third child develops cancer. Nature 433:561, 2005.

    Google Scholar 

  25. Chew, S. A., J. D. Kretlow, P. P. Spicer, A. W. Edwards, L. S. Baggett, Y. Tabata, F. K. Kasper, and A. G. Mikos. Delivery of plasmid DNA encoding bone morphogenetic protein-2 with a biodegradable branched polycationic polymer in a critical-size rat cranial defect model. Tissue Eng. Part A 17:751–763, 2011.

    Article  PubMed  CAS  Google Scholar 

  26. Choi, S. O., Y. C. Kim, J. H. Park, J. Hutcheson, H. S. Gill, Y. K. Yoon, M. R. Prausnitz, and M. G. Allen. An electrically active microneedle array for electroporation. Biomed. Microdevices 12:263–273, 2010.

    Article  PubMed  Google Scholar 

  27. Cinkornpumin, J. K., and R. L. Hong. RNAi mediated gene knockdown and transgenesis by microinjection in the necromenic nematode Pristionchus pacificus. J. Vis. Exp. 16:e3270, 2011.

    Google Scholar 

  28. Clackson, T. Regulated gene expression systems. Gene Ther. 7:120–125, 2000.

    Article  PubMed  CAS  Google Scholar 

  29. Clements, B. A., V. Incani, C. Kucharski, A. Lavasanifar, B. Ritchie, and H. Uludag. A comparative evaluation of poly-l-lysine-palmitic acid and Lipofectamine 2000 for plasmid delivery to bone marrow stromal cells. Biomaterials 28:4693–4704, 2007.

    Article  PubMed  CAS  Google Scholar 

  30. Conner, S. D., and S. L. Schmid. Regulated portals of entry into the cell. Nature 422:37–44, 2003.

    Article  PubMed  CAS  Google Scholar 

  31. Cui, M., Y. Wan, D. G. Anderson, F. H. Shen, B. M. Leo, C. T. Laurencin, G. Balian, and X. Li. Mouse growth and differentiation factor-5 protein and DNA therapy potentiates intervertebral disc cell aggregation and chondrogenic gene expression. Spine J. 8:287–295, 2008.

    Article  PubMed  Google Scholar 

  32. Dahlhoff, M., M. Grzech, F. A. Habermann, E. Wolf, and M. R. Schneider. A transgenic mouse line expressing cre recombinase in pancreatic beta-cells. Genesis 50(5):437–442, 2011.

    Article  PubMed  CAS  Google Scholar 

  33. Dang, J. M., and K. W. Leong. Natural polymers for gene delivery and tissue engineering. Adv. Drug Deliv. Rev. 58:487–499, 2006.

    Article  PubMed  CAS  Google Scholar 

  34. Daugimont, L., N. Baron, G. Vandermeulen, N. Pavselj, D. Miklavcic, M. C. Jullien, G. Cabodevila, L. M. Mir, and V. Preat. Hollow microneedle arrays for intradermal drug delivery and DNA electroporation. J. Membr. Biol. 236:117–125, 2010.

    Article  PubMed  CAS  Google Scholar 

  35. del Pino, P., A. Munoz-Javier, D. Vlaskou, P. Rivera Gil, C. Plank, and W. J. Parak. Gene silencing mediated by magnetic lipospheres tagged with small interfering RNA. Nano Lett 10:3914–3921, 2010.

    Article  PubMed  CAS  Google Scholar 

  36. Denet, A. R., R. Vanbever, and V. Preat. Skin electroporation for transdermal and topical delivery. Adv. Drug Deliv. Rev. 56:659–674, 2004.

    Article  PubMed  CAS  Google Scholar 

  37. Dichek, D. A., R. F. Neville, J. A. Zwiebel, S. M. Freeman, M. B. Leon, and W. F. Anderson. Seeding of intravascular stents with genetically engineered endothelial cells. Circulation 80:1347–1353, 1989.

    Article  PubMed  CAS  Google Scholar 

  38. Doherty, G. J., and H. T. McMahon. Mechanisms of endocytosis. Annu. Rev. Biochem. 78:857–902, 2009.

    Article  PubMed  CAS  Google Scholar 

  39. Donnelly, R. F., T. R. Raj Singh, and A. D. Woolfson. Microneedle-based drug delivery systems: microfabrication, drug delivery, and safety. Drug Deliv. 17:187–207, 2010.

    Article  PubMed  CAS  Google Scholar 

  40. Dormer, N. H., Y. Qiu, A. M. Lydick, N. D. Allen, N. Mohan, C. J. Berkland, and M. S. Detamore. Osteogenic differentiation of human bone marrow stromal cells in hydroxyapatite-loaded microsphere-based scaffolds. Tissue Eng. A. 18(7–8):757–767, 2011.

    Google Scholar 

  41. Duffy, G. P., S. D’Arcy, T. Ahsan, R. M. Nerem, T. O’Brien, and F. Barry. Mesenchymal stem cells overexpressing ephrin-b2 rapidly adopt an early endothelial phenotype with simultaneous reduction of osteogenic potential. Tissue Eng. Part A 16:2755–2768, 2010.

    Article  PubMed  CAS  Google Scholar 

  42. Ear, T., P. Giguere, A. Fleury, J. Stankova, M. D. Payet, and G. Dupuis. High efficiency transient transfection of genes in human umbilical vein endothelial cells by electroporation. J. Immunol. Methods 257:41–49, 2001.

    Article  PubMed  CAS  Google Scholar 

  43. Ensenauer, R., D. Hartl, J. Vockley, A. A. Roscher, and U. Fuchs. Efficient and gentle siRNA delivery by magnetofection. Biotech. Histochem. 86:226–231, 2011.

    Article  PubMed  CAS  Google Scholar 

  44. Faurie, C., M. Rebersek, M. Golzio, M. Kanduser, J. M. Escoffre, M. Pavlin, J. Teissie, D. Miklavcic, and M. P. Rols. Electro-mediated gene transfer and expression are controlled by the life-time of DNA/membrane complex formation. J. Gene Med. 12:117–125, 2010.

    Article  PubMed  CAS  Google Scholar 

  45. Favard, C., D. S. Dean, and M. P. Rols. Electrotransfer as a non viral method of gene delivery. Curr. Gene Ther. 7:67–77, 2007.

    Article  PubMed  CAS  Google Scholar 

  46. Flanagan, M. B., J. M. Gimble, G. Yu, X. Xia, B. Bunnell, and S. Li. Competitive DNA transfection formulation via electroporation for human adipose stem cells and mesenchymal stem cells. Biol Proced Online 14:7, 2012.

    Article  PubMed  CAS  Google Scholar 

  47. Frantescu, A., S. Kakorin, K. Toensing, and E. Neumann. Adsorption of DNA and electric fields decrease the rigidity of lipid vesicle membranes. Phys. Chem. Chem. Phys. 7:4126–4131, 2005.

    Article  PubMed  CAS  Google Scholar 

  48. Frenkel, V., and K. C. Li. Potential role of pulsed-high intensity focused ultrasound in gene therapy. Future Oncol. 2:111–119, 2006.

    Article  PubMed  CAS  Google Scholar 

  49. Gersting, S. W., U. Schillinger, J. Lausier, P. Nicklaus, C. Rudolph, C. Plank, D. Reinhardt, and J. Rosenecker. Gene delivery to respiratory epithelial cells by magnetofection. J. Gene Med. 6:913–922, 2004.

    Article  PubMed  CAS  Google Scholar 

  50. Gill, H. S., and M. R. Prausnitz. Coated microneedles for transdermal delivery. J. Control Release 117:227–237, 2007.

    Article  PubMed  CAS  Google Scholar 

  51. Godbey, W. T., and A. G. Mikos. Recent progress in gene delivery using non-viral transfer complexes. J. Control Release 72:115–125, 2001.

    Article  PubMed  CAS  Google Scholar 

  52. Godbey, W. T., K. K. Wu, and A. G. Mikos. Poly(ethylenimine) and its role in gene delivery. J. Control Release 60:149–160, 1999.

    Article  PubMed  CAS  Google Scholar 

  53. Godbey, W. T., K. K. Wu, and A. G. Mikos. Tracking the intracellular path of poly(ethylenimine)/DNA complexes for gene delivery. Proc. Natl Acad. Sci. USA 96:5177–5181, 1999.

    Article  PubMed  CAS  Google Scholar 

  54. Godbey, W. T., K. K. Wu, and A. G. Mikos. Poly(ethylenimine)-mediated gene delivery affects endothelial cell function and viability. Biomaterials 22:471–480, 2001.

    Article  PubMed  CAS  Google Scholar 

  55. Golzio, M., J. M. Escoffre, T. Portet, C. Mauroy, J. Teissie, D. S. Dean, and M. P. Rols. Observations of the mechanisms of electromediated DNA uptake–from vesicles to tissues. Curr. Gene Ther. 10:256–266, 2010.

    Article  PubMed  CAS  Google Scholar 

  56. Golzio, M., S. Mazeres, and J. Teissie. Electrodes for in vivo localised subcutaneous electropulsation and associated drug and nucleic acid delivery. Expert Opin. Drug Deliv. 6:1323–1331, 2009.

    Article  PubMed  CAS  Google Scholar 

  57. Golzio, M., M. P. Rols, B. Gabriel, and J. Teissie. Optical imaging of in vivo gene expression: a critical assessment of the methodology and associated technologies. Gene Ther. 11(Suppl 1):S85–S91, 2004.

    Article  PubMed  CAS  Google Scholar 

  58. Golzio, M., J. Teissie, and M. P. Rols. Direct visualization at the single-cell level of electrically mediated gene delivery. Proc. Natl Acad. Sci. USA 99:1292–1297, 2002.

    Article  PubMed  CAS  Google Scholar 

  59. Gonzalez, F., M. Barragan Monasterio, G. Tiscornia, N. Montserrat Pulido, R. Vassena, L. Batlle Morera, I. Rodriguez Piza, and J. C. Izpisua Belmonte. Generation of mouse-induced pluripotent stem cells by transient expression of a single nonviral polycistronic vector. Proc. Natl Acad. Sci. USA 106:8918–8922, 2009.

    Article  PubMed  CAS  Google Scholar 

  60. Green, J. J., E. Chiu, E. S. Leshchiner, J. Shi, R. Langer, and D. G. Anderson. Electrostatic ligand coatings of nanoparticles enable ligand-specific gene delivery to human primary cells. Nano Lett. 7:874–879, 2007.

    Article  PubMed  CAS  Google Scholar 

  61. Green, J. J., R. Langer, and D. G. Anderson. A combinatorial polymer library approach yields insight into nonviral gene delivery. Acc. Chem. Res. 106(22):8918–8922, 2008.

    Google Scholar 

  62. Green, J. J., J. Shi, E. Chiu, E. S. Leshchiner, R. Langer, and D. G. Anderson. Biodegradable polymeric vectors for gene delivery to human endothelial cells. Bioconjug. Chem. 17:1162–1169, 2006.

    Article  PubMed  CAS  Google Scholar 

  63. Green, J. J., B. Y. Zhou, M. M. Mitalipova, C. Beard, R. Langer, R. Jaenisch, and D. G. Anderson. Nanoparticles for gene transfer to human embryonic stem cell colonies. Nano Lett. 8:3126–3130, 2008.

    Article  PubMed  CAS  Google Scholar 

  64. Gwak, S. J., and B. S. Kim. Poly(lactic-co-glycolic acid) nanosphere as a vehicle for gene delivery to human cord blood-derived mesenchymal stem cells: comparison with polyethylenimine. Biotechnol. Lett. 30:1177–1182, 2008.

    Article  PubMed  CAS  Google Scholar 

  65. Haberl, S., D. Miklavcic, and M. Pavlin. Effect of Mg ions on efficiency of gene electrotransfer and on cell electropermeabilization. Bioelectrochemistry 79:265–271, 2010.

    Article  PubMed  CAS  Google Scholar 

  66. Hay, J. C. Calcium: a fundamental regulator of intracellular membrane fusion? EMBO Rep. 8:236–240, 2007.

    Article  PubMed  CAS  Google Scholar 

  67. He, C. X., Y. Tabata, and J. Q. Gao. Non-viral gene delivery carrier and its three-dimensional transfection system. Int. J. Pharm. 386:232–242, 2010.

    Article  PubMed  CAS  Google Scholar 

  68. Heller, L. C., and R. Heller. In vivo electroporation for gene therapy. Hum. Gene Ther. 17:890–897, 2006.

    Article  PubMed  CAS  Google Scholar 

  69. Heller, R., M. Jaroszeski, A. Atkin, D. Moradpour, R. Gilbert, J. Wands, and C. Nicolau. In vivo gene electroinjection and expression in rat liver. FEBS Lett. 389:225–228, 1996.

    Article  PubMed  CAS  Google Scholar 

  70. Henshaw, J., B. Mossop, and F. Yuan. Enhancement of electric field-mediated gene delivery through pretreatment of tumors with a hyperosmotic mannitol solution. Cancer Gene Ther. 18:26–33, 2011.

    Article  PubMed  CAS  Google Scholar 

  71. Henshaw, J. W., and F. Yuan. Field distribution and DNA transport in solid tumors during electric field-mediated gene delivery. J. Pharm. Sci. 97:691–711, 2008.

    Article  PubMed  CAS  Google Scholar 

  72. Holladay, C. A., T. O’Brien, and A. Pandit. Non-viral gene therapy for myocardial engineering. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2:232–248, 2010.

    Article  PubMed  CAS  Google Scholar 

  73. Huth, S., J. Lausier, S. W. Gersting, C. Rudolph, C. Plank, U. Welsch, and J. Rosenecker. Insights into the mechanism of magnetofection using PEI-based magnetofectins for gene transfer. J. Gene Med. 6:923–936, 2004.

    Article  PubMed  CAS  Google Scholar 

  74. Hutson, T. H., W. J. Buchser, J. L. Bixby, V. P. Lemmon, and L. D. Moon. Optimization of a 96-well electroporation assay for postnatal rat CNS neurons suitable for cost-effective medium-throughput screening of genes that promote neurite outgrowth. Front. Mol. Neurosci. 4:55, 2011.

    Article  PubMed  CAS  Google Scholar 

  75. Ino, K., T. Kawasumi, A. Ito, and H. Honda. Plasmid DNA transfection using magnetite cationic liposomes for construction of multilayered gene-engineered cell sheet. Biotechnol. Bioeng. 100:168–176, 2008.

    Article  PubMed  CAS  Google Scholar 

  76. Jang, J. H., T. L. Houchin, and L. D. Shea. Gene delivery from polymer scaffolds for tissue engineering. Expert Rev. Med. Devices 1:127–138, 2004.

    Article  PubMed  CAS  Google Scholar 

  77. Jang, J. H., and L. D. Shea. Controllable delivery of non-viral DNA from porous scaffolds. J. Control Release 86:157–168, 2003.

    Article  PubMed  CAS  Google Scholar 

  78. Jo, J., and Y. Tabata. Non-viral gene transfection technologies for genetic engineering of stem cells. Eur. J. Pharm. Biopharm. 68:90–104, 2008.

    Article  PubMed  CAS  Google Scholar 

  79. Jordan, E. T., M. Collins, J. Terefe, L. Ugozzoli, and T. Rubio. Optimizing electroporation conditions in primary and other difficult-to-transfect cells. J. Biomol. Tech. 19:328–334, 2008.

    PubMed  Google Scholar 

  80. Kaneda, Y. Update on non-viral delivery methods for cancer therapy: possibilities of a drug delivery system with anticancer activities beyond delivery as a new therapeutic tool. Expert Opin. Drug Deliv. 7:1079–1093, 2010.

    Article  PubMed  CAS  Google Scholar 

  81. Kasper, F. K., S. K. Seidlits, A. Tang, R. S. Crowther, D. H. Carney, M. A. Barry, and A. G. Mikos. In vitro release of plasmid DNA from oligo(poly(ethylene glycol) fumarate) hydrogels. J. Control Release 104:521–539, 2005.

    Article  PubMed  CAS  Google Scholar 

  82. Kay, M. A., J. C. Glorioso, and L. Naldini. Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics. Nat. Med. 7:33–40, 2001.

    Article  PubMed  CAS  Google Scholar 

  83. Kendall, M., T. Mitchell, and P. Wrighton-Smith. Intradermal ballistic delivery of micro-particles into excised human skin for pharmaceutical applications. J. Biomech. 37:1733–1741, 2004.

    Article  PubMed  Google Scholar 

  84. Kendall, M., S. Rishworth, F. Carter, and T. Mitchell. Effects of relative humidity and ambient temperature on the ballistic delivery of micro-particles to excised porcine skin. J. Invest. Dermatol. 122:739–746, 2004.

    Article  PubMed  CAS  Google Scholar 

  85. Kettunen, P., J. Demas, C. Lohmann, N. Kasthuri, Y. Gong, R. O. Wong, and W. B. Gan. Imaging calcium dynamics in the nervous system by means of ballistic delivery of indicators. J. Neurosci. Methods 119:37–43, 2002.

    Article  PubMed  CAS  Google Scholar 

  86. Khalil, I. A., K. Kogure, H. Akita, and H. Harashima. Uptake pathways and subsequent intracellular trafficking in nonviral gene delivery. Pharmacol. Rev. 58:32–45, 2006.

    Article  PubMed  CAS  Google Scholar 

  87. Khondee, S., A. Baoum, T. J. Siahaan, and C. Berkland. Calcium condensed LABL-TAT complexes effectively target gene delivery to ICAM-1 expressing cells. Mol. Pharm. 8:788–798, 2011.

    Article  PubMed  CAS  Google Scholar 

  88. Kirkham, M., and R. G. Parton. Clathrin-independent endocytosis: new insights into caveolae and non-caveolar lipid raft carriers. Biochim. Biophys. Acta 1746:349–363, 2005.

    Article  PubMed  CAS  Google Scholar 

  89. Kobayashi, N., J. D. Rivas-Carrillo, A. Soto-Gutierrez, T. Fukazawa, Y. Chen, N. Navarro-Alvarez, and N. Tanaka. Gene delivery to embryonic stem cells. Birth Defects Res. C Embryo Today 75:10–18, 2005.

    Article  PubMed  CAS  Google Scholar 

  90. Kofron, M. D., and C. T. Laurencin. Bone tissue engineering by gene delivery. Adv. Drug Deliv. Rev. 58:555–576, 2006.

    Article  PubMed  CAS  Google Scholar 

  91. Krotz, F., H. Y. Sohn, T. Gloe, C. Plank, and U. Pohl. Magnetofection potentiates gene delivery to cultured endothelial cells. J. Vasc. Res. 40:425–434, 2003.

    Article  PubMed  CAS  Google Scholar 

  92. Kucherlapati, R., and A. I. Skoultchi. Introduction of purified genes into mammalian cells. CRC Crit. Rev. Biochem. 16:349–379, 1984.

    Article  PubMed  CAS  Google Scholar 

  93. Kurata, S., M. Tsukakoshi, T. Kasuya, and Y. Ikawa. The laser method for efficient introduction of foreign DNA into cultured cells. Exp. Cell Res. 162:372–378, 1986.

    Article  PubMed  CAS  Google Scholar 

  94. Lamb, N. J., C. Gauthier-Rouviere, and A. Fernandez. Microinjection strategies for the study of mitogenic signaling in mammalian cells. Front. Biosci. 1:d19–d29, 1996.

    PubMed  CAS  Google Scholar 

  95. Langer, R., and M. Moses. Biocompatible controlled release polymers for delivery of polypeptides and growth factors. J. Cell. Biochem. 45:340–345, 1991.

    Article  PubMed  CAS  Google Scholar 

  96. Leipzig, N. D., and K. A. Athanasiou. Static compression of single chondrocytes catabolically modifies single-cell gene expression. Biophys. J. 94:2412–2422, 2008.

    Article  PubMed  CAS  Google Scholar 

  97. Liang, D., Y. K. Luu, K. Kim, B. S. Hsiao, M. Hadjiargyrou, and B. Chu. In vitro non-viral gene delivery with nanofibrous scaffolds. Nucleic Acids Res. 33:e170, 2005.

    Article  PubMed  CAS  Google Scholar 

  98. Liang, H. D., J. Tang, and M. Halliwell. Sonoporation, drug delivery, and gene therapy. Proc. Inst. Mech. Eng. H 224:343–361, 2010.

    PubMed  Google Scholar 

  99. Lim, S. H., I. C. Liao, and K. W. Leong. Nonviral gene delivery from nonwoven fibrous scaffolds fabricated by interfacial complexation of polyelectrolytes. Mol. Ther. 13:1163–1172, 2006.

    Article  PubMed  CAS  Google Scholar 

  100. Lo, H., S. Kadiyala, S. E. Guggino, and K. W. Leong. Poly(l-lactic acid) foams with cell seeding and controlled-release capacity. J. Biomed. Mater. Res. 30:475–484, 1996.

    Article  PubMed  CAS  Google Scholar 

  101. Lohr, F., D. Y. Lo, D. A. Zaharoff, K. Hu, X. Zhang, Y. Li, Y. Zhao, M. W. Dewhirst, F. Yuan, and C. Y. Li. Effective tumor therapy with plasmid-encoded cytokines combined with in vivo electroporation. Cancer Res. 61:3281–3284, 2001.

    PubMed  CAS  Google Scholar 

  102. Long, X., S. D. Xiong, W. N. Xiong, and Y. J. Xu. Effect of intramuscular injection of hepatocyte growth factor plasmid DNA with electroporation on bleomycin-induced lung fibrosis in rats. Chin. Med. J. (Engl.) 120:1432–1437, 2007.

    CAS  Google Scholar 

  103. Lukacs, G. L., P. Haggie, O. Seksek, D. Lechardeur, N. Freedman, and A. S. Verkman. Size-dependent DNA mobility in cytoplasm and nucleus. J. Biol. Chem. 275:1625–1629, 2000.

    Article  PubMed  CAS  Google Scholar 

  104. Marine, S., J. Freeman, A. Riccio, M. L. Axenborg, J. Pihl, R. Ketteler, and S. Aspengren. High-throughput transfection of differentiated primary neurons from rat forebrain. J. Biomol. Screen. 17:692–696, 2012.

    Article  PubMed  CAS  Google Scholar 

  105. Mark Saltzman, W., and S. P. Baldwin. Materials for protein delivery in tissue engineering. Adv. Drug Deliv. Rev. 33:71–86, 1998.

    Article  PubMed  Google Scholar 

  106. Martinek, V., F. H. Fu, and J. Huard. Gene therapy and tissue engineering in sports medicine. Phys. Sportsmed. 28:34–51, 2000.

    Article  PubMed  CAS  Google Scholar 

  107. McCall, J., L. Nicholson, N. Weidner, and A. Blesch. Optimization of adult sensory neuron electroporation to study mechanisms of neurite growth. Front. Mol. Neurosci. 5:11, 2012.

    Article  PubMed  CAS  Google Scholar 

  108. Mehier-Humbert, S., and R. H. Guy. Physical methods for gene transfer: improving the kinetics of gene delivery into cells. Adv. Drug Deliv. Rev. 57:733–753, 2005.

    Article  PubMed  CAS  Google Scholar 

  109. Mercer, J., M. Schelhaas, and A. Helenius. Virus entry by endocytosis. Annu. Rev. Biochem. 79:803–833, 2010.

    Article  PubMed  CAS  Google Scholar 

  110. Merdan, T., J. Kopecek, and T. Kissel. Prospects for cationic polymers in gene and oligonucleotide therapy against cancer. Adv. Drug Deliv. Rev. 54:715–758, 2002.

    Article  PubMed  CAS  Google Scholar 

  111. Merkerova, M., H. Klamova, R. Brdicka, and H. Bruchova. Targeting of gene expression by siRNA in CML primary cells. Mol. Biol. Rep. 34:27–33, 2007.

    Article  PubMed  CAS  Google Scholar 

  112. Middaugh, C. R., and J. D. Ramsey. Analysis of cationic–lipid–plasmid–DNA complexes. Anal. Chem. 79:7240–7248, 2007.

    Article  PubMed  Google Scholar 

  113. Midoux, P., C. Pichon, J. J. Yaouanc, and P. A. Jaffres. Chemical vectors for gene delivery: a current review on polymers, peptides and lipids containing histidine or imidazole as nucleic acids carriers. Br. J. Pharmacol. 157:166–178, 2009.

    Article  PubMed  CAS  Google Scholar 

  114. Mir, L. M. Nucleic acids electrotransfer-based gene therapy (electrogenetherapy): past, current, and future. Mol. Biotechnol. 43:167–176, 2009.

    Article  PubMed  CAS  Google Scholar 

  115. Mir, L. M., M. F. Bureau, J. Gehl, R. Rangara, D. Rouy, J. M. Caillaud, P. Delaere, D. Branellec, B. Schwartz, and D. Scherman. High-efficiency gene transfer into skeletal muscle mediated by electric pulses. Proc. Natl Acad. Sci. USA 96:4262–4267, 1999.

    Article  PubMed  CAS  Google Scholar 

  116. Mitchell, T. J., M. A. F. Kendall, and B. J. Bellhouse. A ballistic study of micro-particle penetration to the oral mucosa. Int. J. Impact Eng. 28:581–599, 2003.

    Article  Google Scholar 

  117. Mo, D., B. A. Potter, C. A. Bertrand, J. D. Hildebrand, J. R. Bruns, and O. A. Weisz. Nucleofection disrupts tight junction fence function to alter membrane polarity of renal epithelial cells. Am. J. Physiol. Renal Physiol. 299:F1178–F1184, 2010.

    Article  PubMed  CAS  Google Scholar 

  118. Moore, J. C., K. Atze, P. L. Yeung, A. J. Toro-Ramos, C. Camarillo, K. Thompson, C. L. Ricupero, M. A. Brenneman, R. I. Cohen, and R. P. Hart. Efficient, high-throughput transfection of human embryonic stem cells. Stem Cell Res. Ther. 1:23, 2010.

    Article  PubMed  CAS  Google Scholar 

  119. Motoyama, H., S. Ogawa, A. Kubo, S. Miwa, J. Nakayama, Y. Tagawa, and S. Miyagawa. In vitro reprogramming of adult hepatocytes into insulin-producing cells without viral vectors. Biochem. Biophys. Res. Commun. 385:123–128, 2009.

    Article  PubMed  CAS  Google Scholar 

  120. Nabi, I. R., and P. U. Le. Caveolae/raft-dependent endocytosis. J. Cell Biol. 161:673–677, 2003.

    Article  PubMed  CAS  Google Scholar 

  121. Nathwani, A. C., K. M. Gale, K. D. Pemberton, D. C. Crossman, E. G. Tuddenham, and J. H. McVey. Efficient gene transfer into human umbilical vein endothelial cells allows functional analysis of the human tissue factor gene promoter. Br. J. Haematol. 88:122–128, 1994.

    Article  PubMed  CAS  Google Scholar 

  122. Netti, P. A., D. A. Berk, M. A. Swartz, A. J. Grodzinsky, and R. K. Jain. Role of extracellular matrix assembly in interstitial transport in solid tumors. Cancer Res. 60:2497–2503, 2000.

    PubMed  CAS  Google Scholar 

  123. Neu, W. K., and J. C. Neu. Mechanism of irreversible electroporation in cells: insight from the models. In: Irreversible electroporation, edited by B. Rubinsky. Berlin: Springer, 2010, pp. 85–122.

    Chapter  Google Scholar 

  124. Neumann, E., M. Schaefer-Ridder, Y. Wang, and P. H. Hofschneider. Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO J. 1:841–845, 1982.

    PubMed  CAS  Google Scholar 

  125. Newman, C. M., and T. Bettinger. Gene therapy progress and prospects: ultrasound for gene transfer. Gene Ther. 14:465–475, 2007.

    Article  PubMed  CAS  Google Scholar 

  126. Nie, H., and C. H. Wang. Fabrication and characterization of PLGA/HAp composite scaffolds for delivery of BMP-2 plasmid DNA. J. Control Release 120:111–121, 2007.

    Article  PubMed  CAS  Google Scholar 

  127. Nomikou, N., and A. P. McHale. Exploiting ultrasound-mediated effects in delivering targeted, site-specific cancer therapy. Cancer Lett. 296:133–143, 2010.

    Article  PubMed  CAS  Google Scholar 

  128. O’Neill, B. E., and K. C. Li. Augmentation of targeted delivery with pulsed high intensity focused ultrasound. Int. J. Hyperthermia 24:506–520, 2008.

    Article  PubMed  Google Scholar 

  129. Ogura, M., S. Sato, K. Nakanishi, M. Uenoyama, T. Kiyozumi, D. Saitoh, T. Ikeda, H. Ashida, and M. Obara. In vivo targeted gene transfer in skin by the use of laser-induced stress waves. Lasers Surg. Med. 34:242–248, 2004.

    Article  PubMed  Google Scholar 

  130. Palumbo, G., M. Caruso, E. Crescenzi, M. F. Tecce, G. Roberti, and A. Colasanti. Targeted gene transfer in eucaryotic cells by dye-assisted laser optoporation. J. Photochem. Photobiol., B 36:41–46, 1996.

    Article  CAS  Google Scholar 

  131. Park, J. H., M. G. Allen, and M. R. Prausnitz. Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. J. Control Release 104:51–66, 2005.

    Article  PubMed  CAS  Google Scholar 

  132. Park, T. G., J. H. Jeong, and S. W. Kim. Current status of polymeric gene delivery systems. Adv. Drug Deliv. Rev. 58:467–486, 2006.

    Article  PubMed  CAS  Google Scholar 

  133. Partridge, K. A., and R. O. Oreffo. Gene delivery in bone tissue engineering: progress and prospects using viral and nonviral strategies. Tissue Eng. 10:295–307, 2004.

    Article  PubMed  CAS  Google Scholar 

  134. Pearton, M., C. Allender, K. Brain, A. Anstey, C. Gateley, N. Wilke, A. Morrissey, and J. Birchall. Gene delivery to the epidermal cells of human skin explants using microfabricated microneedles and hydrogel formulations. Pharm. Res. 25:407–416, 2008.

    Article  PubMed  CAS  Google Scholar 

  135. Pederson, T. Movement and localization of RNA in the cell nucleus. FASEB J. 13(Suppl 2):S238–S242, 1999.

    PubMed  CAS  Google Scholar 

  136. Phez, E., C. Faurie, M. Golzio, J. Teissie, and M. P. Rols. New insights in the visualization of membrane permeabilization and DNA/membrane interaction of cells submitted to electric pulses. Biochim. Biophys. Acta 1724:248–254, 2005.

    Article  PubMed  CAS  Google Scholar 

  137. Pickard, M. R., P. Barraud, and D. M. Chari. The transfection of multipotent neural precursor/stem cell transplant populations with magnetic nanoparticles. Biomaterials 32:2274–2284, 2011.

    Article  PubMed  CAS  Google Scholar 

  138. Pimpha, N., P. Sunintaboon, S. Inphonlek, and Y. Tabata. Gene delivery efficacy of polyethyleneimine-introduced chitosan shell/poly(methyl methacrylate) core nanoparticles for rat mesenchymal stem cells. J. Biomater. Sci. Polym. Ed. 21:205–223, 2010.

    Article  PubMed  CAS  Google Scholar 

  139. Plank, C., M. Anton, C. Rudolph, J. Rosenecker, and F. Krotz. Enhancing and targeting nucleic acid delivery by magnetic force. Expert Opin. Biol. Ther. 3:745–758, 2003.

    Article  PubMed  CAS  Google Scholar 

  140. Plank, C., U. Schillinger, F. Scherer, C. Bergemann, J. S. Remy, F. Krotz, M. Anton, J. Lausier, and J. Rosenecker. The magnetofection method: using magnetic force to enhance gene delivery. Biol. Chem. 384:737–747, 2003.

    Article  PubMed  CAS  Google Scholar 

  141. Plank, C., O. Zelphati, and O. Mykhaylyk. Magnetically enhanced nucleic acid delivery. Ten years of magnetofection-progress and prospects. Adv. Drug Deliv. Rev. 63:1300–1331, 2011.

    Article  PubMed  CAS  Google Scholar 

  142. Pluen, A., Y. Boucher, S. Ramanujan, T. D. McKee, T. Gohongi, E. di Tomaso, E. B. Brown, Y. Izumi, R. B. Campbell, D. A. Berk, and R. K. Jain. Role of tumor-host interactions in interstitial diffusion of macromolecules: cranial versus subcutaneous tumors. Proc. Natl Acad. Sci. USA 98:4628–4633, 2001.

    Article  PubMed  CAS  Google Scholar 

  143. Postema, M., and O. H. Gilja. Ultrasound-directed drug delivery. Curr. Pharm. Biotechnol. 8:355–361, 2007.

    Article  PubMed  CAS  Google Scholar 

  144. Prausnitz, M. R. Microneedles for transdermal drug delivery. Adv. Drug Deliv. Rev. 56:581–587, 2004.

    Article  PubMed  CAS  Google Scholar 

  145. Prausnitz, M. R., J. D. Corbett, J. A. Gimm, D. E. Golan, R. Langer, and J. C. Weaver. Millisecond measurement of transport during and after an electroporation pulse. Biophys. J. 68:1864–1870, 1995.

    Article  PubMed  CAS  Google Scholar 

  146. Prausnitz, M. R., and R. Langer. Transdermal drug delivery. Nat. Biotechnol. 26:1261–1268, 2008.

    Article  PubMed  CAS  Google Scholar 

  147. Ramos, C., and J. Teissie. Electrofusion: a biophysical modification of cell membrane and a mechanism in exocytosis. Biochimie 82:511–518, 2000.

    Article  PubMed  CAS  Google Scholar 

  148. Rejman, J., A. Bragonzi, and M. Conese. Role of clathrin- and caveolae-mediated endocytosis in gene transfer mediated by lipo- and polyplexes. Mol. Ther. 12:468–474, 2005.

    Article  PubMed  CAS  Google Scholar 

  149. Rols, M. P., C. Delteil, M. Golzio, P. Dumond, S. Cros, and J. Teissie. In vivo electrically mediated protein and gene transfer in murine melanoma. Nat. Biotechnol. 16:168–171, 1998.

    Article  PubMed  CAS  Google Scholar 

  150. Rols, M. P., P. Femenia, and J. Teissie. Long-lived macropinocytosis takes place in electropermeabilized mammalian cells. Biochem. Biophys. Res. Commun. 208:26–35, 1995.

    Article  PubMed  CAS  Google Scholar 

  151. Russell, S. J. Science, medicine, and the future. Gene therapy. BMJ 315:1289–1292, 1997.

    Article  PubMed  CAS  Google Scholar 

  152. Sagi, S., T. Knoll, L. Trojan, A. Schaaf, P. Alken, and M. S. Michel. Gene delivery into prostate cancer cells by holmium laser application. Prostate Cancer Prostatic Dis. 6:127–130, 2003.

    Article  PubMed  CAS  Google Scholar 

  153. Saijilafu, E., M. Hur, and F. Q. Zhou. Genetic dissection of axon regeneration via in vivo electroporation of adult mouse sensory neurons. Nat. Commun. 2:543, 2011.

    Article  PubMed  CAS  Google Scholar 

  154. Sanford, J. C., M. K. Theodore, D. Edward, and N. Allen. Delivery of substances into cells and tissues using a particle bombardment process. Part. Sci. Technol. 5:27–37, 1987.

    Article  CAS  Google Scholar 

  155. Sapet, C., N. Laurent, A. de Chevigny, L. Le Gourrierec, E. Bertosio, O. Zelphati, and C. Beclin. High transfection efficiency of neural stem cells with magnetofection. Biotechniques 50:187–189, 2011.

    PubMed  CAS  Google Scholar 

  156. Saraf, A., and A. G. Mikos. Gene delivery strategies for cartilage tissue engineering. Adv. Drug Deliv. Rev. 58:592–603, 2006.

    Article  PubMed  CAS  Google Scholar 

  157. Satkauskas, S., M. F. Bureau, A. Mahfoudi, and L. M. Mir. Slow accumulation of plasmid in muscle cells: supporting evidence for a mechanism of DNA uptake by receptor-mediated endocytosis. Mol. Ther. 4:317–323, 2001.

    Article  PubMed  CAS  Google Scholar 

  158. Saul, J. M., M. P. Linnes, B. D. Ratner, C. M. Giachelli, and S. H. Pun. Delivery of non-viral gene carriers from sphere-templated fibrin scaffolds for sustained transgene expression. Biomaterials 28:4705–4716, 2007.

    Article  PubMed  CAS  Google Scholar 

  159. Saurer, E. M., R. M. Flessner, S. P. Sullivan, M. R. Prausnitz, and D. M. Lynn. Layer-by-layer assembly of DNA- and protein-containing films on microneedles for drug delivery to the skin. Biomacromolecules 11:3136–3143, 2010.

    Article  CAS  Google Scholar 

  160. Scherer, F., M. Anton, U. Schillinger, J. Henke, C. Bergemann, A. Kruger, B. Gansbacher, and C. Plank. Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo. Gene Ther. 9:102–109, 2002.

    Article  PubMed  CAS  Google Scholar 

  161. Schnoor, M., I. Buers, A. Sietmann, M. F. Brodde, O. Hofnagel, H. Robenek, and S. Lorkowski. Efficient non-viral transfection of THP-1 cells. J. Immunol. Methods 344:109–115, 2009.

    Article  PubMed  CAS  Google Scholar 

  162. Schwachtgen, J. L., V. Ferreira, D. Meyer, and D. Kerbiriou-Nabias. Optimization of the transfection of human endothelial cells by electroporation. Biotechniques 17:882–887, 1994.

    PubMed  CAS  Google Scholar 

  163. Schwerdt, J. I., G. F. Goya, M. P. Calatayud, C. B. Herenu, P. C. Reggiani, and R. G. Goya. Magnetic field-assisted gene delivery: achievements and therapeutic potential. Curr. Gene Ther. 12:116–126, 2012.

    Article  PubMed  CAS  Google Scholar 

  164. Sersa, G., M. Cemazar, C. S. Parkins, and D. J. Chaplin. Tumour blood flow changes induced by application of electric pulses. Eur. J. Cancer 35:672–677, 1999.

    Article  PubMed  CAS  Google Scholar 

  165. Sersa, G., T. Jarm, T. Kotnik, A. Coer, M. Podkrajsek, M. Sentjurc, D. Miklavcic, M. Kadivec, S. Kranjc, A. Secerov, and M. Cemazar. Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma. Br. J. Cancer 98:388–398, 2008.

    Article  PubMed  CAS  Google Scholar 

  166. Sheyn, D., G. Pelled, Y. Zilberman, F. Talasazan, J. M. Frank, D. Gazit, and Z. Gazit. Nonvirally engineered porcine adipose tissue-derived stem cells: use in posterior spinal fusion. Stem Cells. 26:1056–1064, 2008.

    Article  PubMed  Google Scholar 

  167. Shirahata, Y., N. Ohkohchi, H. Itagak, and S. Satomi. New technique for gene transfection using laser irradiation. J. Investig. Med. 49:184–190, 2001.

    Article  PubMed  CAS  Google Scholar 

  168. Smith, R. L., J. Lin, M. C. Trindade, J. Shida, G. Kajiyama, T. Vu, A. R. Hoffman, M. C. van der Meulen, S. B. Goodman, D. J. Schurman, and D. R. Carter. Time-dependent effects of intermittent hydrostatic pressure on articular chondrocyte type II collagen and aggrecan mRNA expression. J. Rehabil. Res. Dev. 37:153–161, 2000.

    PubMed  CAS  Google Scholar 

  169. Sohn, R. L., M. T. Murray, K. Schwarz, J. Nyitray, P. Purray, A. P. Franko, K. C. Palmer, L. N. Diebel, and S. A. Dulchavsky. In vivo particle mediated delivery of mRNA to mammalian tissues: ballistic and biologic effects. Wound Repair Regen. 9:287–296, 2001.

    Article  PubMed  CAS  Google Scholar 

  170. Song, L., L. Chau, Y. Sakamoto, J. Nakashima, M. Koide, and R. S. Tuan. Electric field-induced molecular vibration for noninvasive, high-efficiency DNA transfection. Mol. Ther. 9:607–616, 2004.

    Article  PubMed  CAS  Google Scholar 

  171. Storrie, H., and D. J. Mooney. Sustained delivery of plasmid DNA from polymeric scaffolds for tissue engineering. Adv. Drug Deliv. Rev. 58:500–514, 2006.

    Article  PubMed  CAS  Google Scholar 

  172. Tao, W., J. Wilkinson, E. J. Stanbridge, and M. W. Berns. Direct gene transfer into human cultured cells facilitated by laser micropuncture of the cell membrane. Proc. Natl Acad. Sci. USA 84:4180–4184, 1987.

    Article  PubMed  CAS  Google Scholar 

  173. Teifel, M., L. T. Heine, S. Milbredt, and P. Friedl. Optimization of transfection of human endothelial cells. Endothelium 5:21–35, 1997.

    Article  PubMed  CAS  Google Scholar 

  174. Teissie, J., M. Golzio, and M. P. Rols. Mechanisms of cell membrane electropermeabilization: a minireview of our present (lack of ?) knowledge. Biochim. Biophys. Acta 1724:270–280, 2005.

    Article  PubMed  CAS  Google Scholar 

  175. ter Haar, G. Therapeutic applications of ultrasound. Prog. Biophys. Mol. Biol. 93:111–129, 2007.

    Article  PubMed  Google Scholar 

  176. Thomas, C. E., A. Ehrhardt, and M. A. Kay. Progress and problems with the use of viral vectors for gene therapy. Nat. Rev. Genet. 4:346–358, 2003.

    Article  PubMed  CAS  Google Scholar 

  177. Udvardi, A., I. Kufferath, H. Grutsch, K. Zatloukal, and B. Volc-Platzer. Uptake of exogenous DNA via the skin. J. Mol. Med. (Berl.) 77:744–750, 1999.

    Article  CAS  Google Scholar 

  178. van der Aa, M. A., U. S. Huth, S. Y. Hafele, R. Schubert, R. S. Oosting, E. Mastrobattista, W. E. Hennink, R. Peschka-Suss, G. A. Koning, and D. J. Crommelin. Cellular uptake of cationic polymer-DNA complexes via caveolae plays a pivotal role in gene transfection in COS-7 cells. Pharm. Res. 24:1590–1598, 2007.

    Article  PubMed  CAS  Google Scholar 

  179. Vaughan, E. E., and D. A. Dean. Intracellular trafficking of plasmids during transfection is mediated by microtubules. Mol. Ther. 13:422–428, 2006.

    Article  PubMed  CAS  Google Scholar 

  180. Verreault, M., and M. B. Bally. siRNA-mediated integrin-linked kinase suppression: nonspecific effects of siRNA/cationic liposome complexes trigger changes in the expression of phosphorylated-AKT and mTOR independently of ILK silencing. Oligonucleotides 19:129–140, 2009.

    Article  PubMed  CAS  Google Scholar 

  181. Waehler, R., S. J. Russell, and D. T. Curiel. Engineering targeted viral vectors for gene therapy. Nat. Rev. Genet. 8:573–587, 2007.

    Article  PubMed  CAS  Google Scholar 

  182. Walton, J. R., J. D. Murray, J. T. Marshall, and C. D. Nancarrow. Zygote viability in gene transfer experiments. Biol. Reprod. 37:957–967, 1987.

    Article  PubMed  CAS  Google Scholar 

  183. Wang, L., L. Ott, K. Seshareddy, M. L. Weiss, and M. S. Detamore. Musculoskeletal tissue engineering with human umbilical cord mesenchymal stromal cells. Regen. Med. 6:95–109, 2011.

    Article  PubMed  CAS  Google Scholar 

  184. Weaver, J. C. Electroporation: a general phenomenon for manipulating cells and tissues. J. Cell. Biochem. 51:426–435, 1993.

    PubMed  CAS  Google Scholar 

  185. Weaver, J. C., and Y. A. Chizmadzhev. Theory of electroporation: a review. Bioelectrochem. Bioenerg. 41:135–160, 1996.

    Article  CAS  Google Scholar 

  186. Wells, J. M., L. H. Li, A. Sen, G. P. Jahreis, and S. W. Hui. Electroporation-enhanced gene delivery in mammary tumors. Gene Ther. 7:541–547, 2000.

    Article  PubMed  CAS  Google Scholar 

  187. Wiethoff, C. M., and C. R. Middaugh. Barriers to nonviral gene delivery. J. Pharm. Sci. 92:203–217, 2003.

    Article  PubMed  CAS  Google Scholar 

  188. Williams, S. K., and R. C. Wagner. Regulation of micropinocytosis in capillary endothelium by multivalent cations. Microvasc. Res. 21:175–182, 1981.

    Article  PubMed  CAS  Google Scholar 

  189. Wu, J. Shear stress in cells generated by ultrasound. Prog. Biophys. Mol. Biol. 93:363–373, 2007.

    Article  PubMed  Google Scholar 

  190. Wu, M., and F. Yuan. Membrane binding of plasmid DNA and endocytic pathways are involved in electrotransfection of mammalian cells. PLoS ONE 6:e20923, 2011.

    Article  PubMed  CAS  Google Scholar 

  191. Xie, T. D., and T. Y. Tsong. Study of mechanisms of electric field-induced DNA transfection. V. Effects of DNA topology on surface binding, cell uptake, expression, and integration into host chromosomes of DNA in the mammalian cell. Biophys. J. 65:1684–1689, 1993.

    Article  PubMed  CAS  Google Scholar 

  192. Xu, Y., and F. C. Szoka, Jr. Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection. Biochemistry 35:5616–5623, 1996.

    Article  PubMed  CAS  Google Scholar 

  193. Yamamoto, F., M. Furusawa, I. Furusawa, and M. Obinata. The ‘pricking’ method. A new efficient technique for mechanically introducing foreign DNA into the nuclei of culture cells. Exp. Cell Res. 142:79–84, 1982.

    Article  PubMed  CAS  Google Scholar 

  194. Yang, N. S., J. Burkholder, B. Roberts, B. Martinell, and D. McCabe. In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment. Proc. Natl Acad. Sci. USA 87:9568–9572, 1990.

    Article  PubMed  CAS  Google Scholar 

  195. Yang, C., K. Cheng, and W. Weng. Immobilization of RGD peptide on HA coating through a chemical bonding approach. J. Mater. Sci. Mater. Med. 20(11):2349–2352, 2009.

    Article  PubMed  CAS  Google Scholar 

  196. Yang, S. Y., J. S. Sun, C. H. Liu, Y. H. Tsuang, L. T. Chen, C. Y. Hong, H. C. Yang, and H. E. Horng. Ex vivo magnetofection with magnetic nanoparticles: a novel platform for nonviral tissue engineering. Artif. Organs 32:195–204, 2008.

    Article  PubMed  CAS  Google Scholar 

  197. Yao, C. P., Z. X. Zhang, R. Rahmanzadeh, and G. Huettmann. Laser-based gene transfection and gene therapy. IEEE Trans. Nanobiosci. 7:111–119, 2008.

    Article  CAS  Google Scholar 

  198. Yockell-Lelievre, J., V. Riendeau, S. N. Gagnon, C. Garenc, and M. Audette. Efficient transfection of endothelial cells by a double-pulse electroporation method. DNA Cell Biol. 28:561–566, 2009.

    Article  PubMed  CAS  Google Scholar 

  199. Yoon, C. S., and J. H. Park. Ultrasound-mediated gene delivery. Expert Opin. Drug Deliv. 7:321–330, 2010.

    Article  PubMed  CAS  Google Scholar 

  200. Zaharoff, D. A., J. W. Henshaw, B. Mossop, and F. Yuan. Mechanistic analysis of electroporation-induced cellular uptake of macromolecules. Exp. Biol. Med. (Maywood) 233:94–105, 2008.

    Article  CAS  Google Scholar 

  201. Zefirov, A. L., M. M. Abdrakhmanov, M. A. Mukhamedyarov, and P. N. Grigoryev. The role of extracellular calcium in exo- and endocytosis of synaptic vesicles at the frog motor nerve terminals. Neuroscience 143:905–910, 2006.

    Article  PubMed  CAS  Google Scholar 

  202. Zeira, E., A. Manevitch, A. Khatchatouriants, O. Pappo, E. Hyam, M. Darash-Yahana, E. Tavor, A. Honigman, A. Lewis, and E. Galun. Femtosecond infrared laser-an efficient and safe in vivo gene delivery system for prolonged expression. Mol. Ther. 8:342–350, 2003.

    Article  PubMed  CAS  Google Scholar 

  203. Zelenin, A. V., V. A. Kolesnikov, O. A. Tarasenko, R. A. Shafei, I. A. Zelenina, V. V. Mikhailov, M. L. Semenova, D. V. Kovalenko, O. V. Artemyeva, T. E. Ivaschenko, O. V. Evgrafov, G. Dickson, and V. S. Baranovand. Bacterial beta-galactosidase and human dystrophin genes are expressed in mouse skeletal muscle fibers after ballistic transfection. FEBS Lett. 414:319–322, 1997.

    Article  PubMed  CAS  Google Scholar 

  204. Zelphati, O., and F. C. Szoka, Jr. Mechanism of oligonucleotide release from cationic liposomes. Proc. Natl Acad. Sci. USA 93:11493–11498, 1996.

    Article  PubMed  CAS  Google Scholar 

  205. Zhang, X., and W. T. Godbey. Viral vectors for gene delivery in tissue engineering. Adv. Drug Deliv. Rev. 58:515–534, 2006.

    Article  PubMed  CAS  Google Scholar 

  206. Zhang, Z., A. Slobodianski, W. D. Ito, A. Arnold, J. Nehlsen, S. Weng, N. Lund, J. Liu, J. T. Egana, J. A. Lohmeyer, D. F. Muller, and H. G. Machens. Enhanced collateral growth by double transplantation of gene-nucleofected fibroblasts in ischemic hindlimb of rats. PLoS ONE 6:e19192, 2011.

    Article  PubMed  CAS  Google Scholar 

  207. Zhou, Y., J. Shi, J. Cui, and C. X. Deng. Effects of extracellular calcium on cell membrane resealing in sonoporation. J. Control Release 126:34–43, 2008.

    Article  PubMed  CAS  Google Scholar 

  208. Zimmermann, U. Electric field-mediated fusion and related electrical phenomena. Biochim. Biophys. Acta 694:227–277, 1982.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Bioengineering Program, University of Kansas, Lawrence, KS, 66045, USA

    Adam J. Mellott & Michael S. Detamore

  2. Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, 66047, USA

    M. Laird Forrest

  3. Department of Chemical and Petroleum Engineering, University of Kansas, 4132 Learned Hall, 1530 W 15th St., Lawrence, KS, 66045, USA

    Michael S. Detamore

Authors
  1. Adam J. Mellott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Laird Forrest
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael S. Detamore
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael S. Detamore.

Additional information

Associate Editor Kent Leach oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mellott, A.J., Forrest, M.L. & Detamore, M.S. Physical Non-Viral Gene Delivery Methods for Tissue Engineering. Ann Biomed Eng 41, 446–468 (2013). https://doi.org/10.1007/s10439-012-0678-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-012-0678-1

Keywords

Search

Navigation