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Gene therapy in wound healing: present status and future directions

Gene Therapy volume 14, pages 1–10 (2007)Cite this article

Abstract

Gene therapy was traditionally considered a treatment modality for patients with congenital defects of key metabolic functions or late-stage malignancies. The realization that gene therapy applications were much vaster has opened up endless opportunities for therapeutic genetic manipulations, especially in the skin and external wounds. Cutaneous wound healing is a complicated, multistep process with numerous mediators that act in a network of activation and inhibition processes. Gene delivery in this environment poses a particular challenge. Numerous models of gene delivery have been developed, including naked DNA application, viral transfection, high-pressure injection, liposomal delivery, and more. Of the various methods for gene transfer, cationic cholesterol-containing liposomal constructs are emerging as a method with great potential for non-viral gene transfer in the wound. This article aims to review the research on gene therapy in wound healing and possible future directions in this exciting field.

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References

  1. Hernandez A, Evers BM . Functional genomics: clinical effect and the evolving role of the surgeon. Arch Surg 1999; 134: 1209–1215.

    CAS  PubMed  Google Scholar 

  2. Khavari PA, Rollman O, Vahlquist A . Cutaneous gene transfer for skin and systemic diseases. J Intern Med 2002; 252: 1–10.

    CAS  PubMed  Google Scholar 

  3. Brigham PA, McLoughlin E . Burn incidence and medical care use in the United States: estimates, trends, and data sources. J Burn Care Rehab 1996; 17: 95–107.

    CAS  Google Scholar 

  4. Singer AJ, Clark RA . Cutaneous wound healing. N Engl J Med 1999; 341: 738–746.

    Article  CAS  PubMed  Google Scholar 

  5. Werner S, Grose R . Regulation of wound healing by growth factors and cytokines. Physiol Rev 2003; 83: 835–870.

    CAS  PubMed  Google Scholar 

  6. Clark RAF . The Molecular and Cellular Biology of Wound Repair. Plenum: New York, 1996.

    Google Scholar 

  7. Eming SA, Krieg T, Davidson JM . Gene transfer in tissue repair: status, challenges and future directions. Expert Opin Biol Ther 2004; 4: 1373–1386.

    CAS  PubMed  Google Scholar 

  8. Hunt TK, Knighton DR, Thakral KK, Goodson III WH, Andrews WS . Studies on inflammation and wound healing: angiogenesis and collagen synthesis stimulated in vivo by resident and activated wound macrophages. Surgery 1984; 96: 48–54.

    CAS  PubMed  Google Scholar 

  9. Bennett NT, Schultz GS . Growth factors and wound healing: biochemical properties of growth factors and their receptors. Am J Surg 1993; 165: 728–737.

    CAS  PubMed  Google Scholar 

  10. Fahey III TJ, Sadaty A, Jones II WG, Barber A, Smoller B, Shires GT . Diabetes impairs the late inflammatory response to wound healing. J Surg Res 1991; 50: 308–313.

    PubMed  Google Scholar 

  11. Falanga V, Eaglstein WH . The ‘trap’ hypothesis of venous ulceration. Lancet 1993; 341: 1006–1008.

    CAS  PubMed  Google Scholar 

  12. LeGrand EK . Preclinical promise of becaplermin (rhPDGF-BB) in wound healing. Am J Surg 1998; 176: 48S–54S.

    CAS  PubMed  Google Scholar 

  13. Mast BA, Schultz GS . Interactions of cytokines, growth factors, and proteases in acute and chronic wounds. Wound Rep Reg 1996; 4: 411–420.

    CAS  Google Scholar 

  14. Steed DL . Modifying the wound healing response with exogenous growth factors. Clin Plast Surg 1998; 25: 397–405.

    CAS  PubMed  Google Scholar 

  15. Robson MC, Mustoe TA, Hunt TK . The future of recombinant growth factors in wound healing. Am J Surg 1998; 176: 80S–82S.

    CAS  PubMed  Google Scholar 

  16. Robson MC, Smith PD . Topical use of growth factors to enhance healing. In: Falanga V (ed). Cutaneous Wound Healing. Taylor & Francis: London, 2001, pp 379–398.

    Google Scholar 

  17. Lynch SE, Nixon JC, Colvin RB, Antoniades HN . Role of platelet-derived growth factor in wound healing: synergistic effects with other growth factors. Proc Natl Acad Sci USA 1987; 84: 7696–7700.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Morgan RA, Anderson WF . Human gene therapy. Annu Rev Biochem 1993; 62: 191–217.

    CAS  PubMed  Google Scholar 

  19. Sprugel KH, McPherson JM, Clowes AW, Ross R . Effects of growth factors in vivo. I. Cell ingrowth into porous subcutaneous chambers. Am J Pathol 1987; 129: 601–613.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Gardlik R, Palffy R, Hodosy J, Lukacs J, Turna J, Celec P . Vectors and delivery systems in gene therapy. Med Sci Monit 2005; 11: RA110–RA121.

    CAS  PubMed  Google Scholar 

  21. Lundstrom K . Latest development in viral vectors for gene therapy. Trends Biotechnol 2003; 21: 117–122.

    CAS  PubMed  Google Scholar 

  22. Dando JS, Roncarolo MG, Bordignon C, Aiuti A . A novel human packaging cell line with hematopoietic supportive capacity increases gene transfer into early hematopoietic progenitors. Hum Gene Ther 2001; 12: 1979–1988.

    CAS  PubMed  Google Scholar 

  23. Gu DL, Nguyen T, Gonzalez AM, Printz MA, Pierce GF, Sosnowski BA et al. Adenovirus encoding human platelet-derived growth factor-B delivered in collagen exhibits safety, biodistribution, and immunogenicity profiles favorable for clinical use. Mol Ther 2004; 9: 699–711.

    CAS  PubMed  Google Scholar 

  24. Kozarsky KF, Wilson JM . Gene therapy: adenovirus vectors. Curr Opin Genet Dev 1993; 3: 499–503.

    CAS  PubMed  Google Scholar 

  25. Lu B, Federoff HJ, Wang Y, Goldsmith LA, Scott G . Topical application of viral vectors for epidermal gene transfer. J Invest Dermatol 1997; 108: 803–808.

    CAS  PubMed  Google Scholar 

  26. Silman NJ, Fooks AR . Biophysical targeting of adenovirus vectors for gene therapy. Curr Opin Mol Ther 2000; 2: 524–531.

    CAS  PubMed  Google Scholar 

  27. Bett AJ, Prevec L, Graham FL . Packaging capacity and stability of human adenovirus type 5 vectors. J Virol 1993; 67: 5911–5921.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Liechty KW, Nesbit M, Herlyn M, Radu A, Adzick NS, Crombleholme TM . Adenoviral-mediated overexpression of platelet-derived growth factor-B corrects ischemic impaired wound healing. J Invest Dermatol 1999; 113: 375–383.

    CAS  PubMed  Google Scholar 

  29. Ritter T, Lehmann M, Volk HD . Improvements in gene therapy: averting the immune response to adenoviral vectors. BioDrugs 2002; 16: 3–10.

    CAS  PubMed  Google Scholar 

  30. Flotte TR, Brantly ML, Spencer LT, Byrne BJ, Spencer CT, Baker DJ et al. Phase I trial of intramuscular injection of a recombinant adeno-associated virus alpha 1-antitrypsin (rAAV2-CB-hAAT) gene vector to AAT-deficient adults. Hum Gene Ther 2004; 15: 93–128.

    PubMed  Google Scholar 

  31. Flotte TR, Zeitlin PL, Reynolds TC, Heald AE, Pedersen P, Beck S et al. Phase I trial of intranasal and endobronchial administration of a recombinant adeno-associated virus serotype 2 (rAAV2)-CFTR vector in adult cystic fibrosis patients: a two-part clinical study. Hum Gene Ther 2003; 14: 1079–1088.

    CAS  PubMed  Google Scholar 

  32. Deodato B, Arsic N, Zentilin L, Galeano M, Santoro D, Torre V et al. Recombinant AAV vector encoding human VEGF165 enhances wound healing. Gene Therapy 2002; 9: 777–785.

    CAS  PubMed  Google Scholar 

  33. Galeano M, Deodato B, Altavilla D, Squadrito G, Seminara P, Marini H et al. Effect of recombinant adeno-associated virus vector-mediated vascular endothelial growth factor gene transfer on wound healing after burn injury. Crit Care Med 2003; 31: 1017–1025.

    CAS  PubMed  Google Scholar 

  34. Chen S, Kapturczak M, Loiler SA, Zolotukhin S, Glushakova OY, Madsen KM et al. Efficient transduction of vascular endothelial cells with recombinant adeno-associated virus serotype 1 and 5 vectors. Hum Gene Ther 2005; 16: 235–247.

    CAS  PubMed  Google Scholar 

  35. Braun-Falco M, Eisenried A, Buning H, Ring J . Recombinant adeno-associated virus type 2-mediated gene transfer into human keratinocytes is influenced by both the ubiquitin/proteasome pathway and epidermal growth factor receptor tyrosine kinase. Arch Dermatol Res 2005; 296: 528–535.

    CAS  PubMed  Google Scholar 

  36. Yao F, Eriksson E . Gene therapy in wound repair and regeneration. Wound Repair Regen 2000; 8: 443–451.

    CAS  PubMed  Google Scholar 

  37. Quinonez R, Sutton RE . Lentiviral vectors for gene delivery into cells. DNA Cell Biol 2002; 21: 937–951.

    CAS  PubMed  Google Scholar 

  38. Morgan JR, Barrandon Y, Green H, Mulligan RC . Expression of an exogenous growth hormone gene by transplantable human epidermal cells. Science 1987; 237: 1476–1479.

    CAS  PubMed  Google Scholar 

  39. Vogel JC . Nonviral skin gene therapy. Hum Gene Ther 2000; 11: 2253–2259.

    CAS  PubMed  Google Scholar 

  40. Hengge UR, Chan EF, Foster RA, Walker PS, Vogel JC . Cytokine gene expression in epidermis with biological effects following injection of naked DNA. Nat Genet 1995; 10: 161–166.

    CAS  PubMed  Google Scholar 

  41. Slama J, Davidson JM, Eriksson E . Gene therapy of wounds. In: Falanga V (ed). Cutaneous Wound Healing. Taylor & Francis: London, 2001, pp. 123–140.

    Google Scholar 

  42. Eming SA, Whitsitt JS, He L, Krieg T, Morgan JR, Davidson JM . Particle-mediated gene transfer of PDGF isoforms promotes wound repair. J Invest Dermatol 1999; 112: 297–302.

    CAS  PubMed  Google Scholar 

  43. Cheng L, Ziegelhoffer PR, Yang NS . In vivo promoter activity and transgene expression in mammalian somatic tissues evaluated by using particle bombardment. Proc Natl Acad Sci USA 1993; 90: 4455–4459.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Yang NS, Sun WH . Gene gun and other non-viral approaches for cancer gene therapy. Nat Med 1995; 1: 481–483.

    CAS  PubMed  Google Scholar 

  45. Li L, Hoffman RM . The feasibility of targeted selective gene therapy of the hair follicle. Nat Med 1995; 1: 705–706.

    PubMed  Google Scholar 

  46. Nanney LB, Paulsen S, Davidson MK, Cardwell NL, Whitsitt JS, Davidson JM . Boosting epidermal growth factor receptor expression by gene gun transfection stimulates epidermal growth in vivo. Wound Repair Regen 2000; 8: 117–127.

    CAS  PubMed  Google Scholar 

  47. Dileo J, Miller Jr TE, Chesnoy S, Huang L . Gene transfer to subdermal tissues via a new gene gun design. Hum Gene Ther 2003; 14: 79–87.

    CAS  PubMed  Google Scholar 

  48. Eriksson E, Yao F, Svensjo T, Winkler T, Slama J, Macklin MD et al. In vivo gene transfer to skin and wound by microseeding. J Surg Res 1998; 78: 85–91.

    CAS  PubMed  Google Scholar 

  49. Baker LL, Chambers R, DeMuth SK, Villar F . Effects of electrical stimulation on wound healing in patients with diabetic ulcers. Diabetes Care 1997; 20: 405–412.

    CAS  PubMed  Google Scholar 

  50. Gardner SE, Frantz RA, Schmidt FL . Effect of electrical stimulation on chronic wound healing: a meta-analysis. Wound Repair Regen 1999; 7: 495–503.

    CAS  PubMed  Google Scholar 

  51. Lee PY, Chesnoy S, Huang L . Electroporatic delivery of TGF-beta1 gene works synergistically with electric therapy to enhance diabetic wound healing in db/db mice. J Invest Dermatol 2004; 123: 791–798.

    CAS  PubMed  Google Scholar 

  52. Marti G, Ferguson M, Wang J, Byrnes C, Dieb R, Qaiser R et al. Electroporative transfection with KGF-1 DNA improves wound healing in a diabetic mouse model. Gene Therapy 2004; 11: 1780–1785.

    CAS  PubMed  Google Scholar 

  53. Noguchi A, Furuno T, Kawaura C, Nakanishi M . Membrane fusion plays an important role in gene transfection mediated by cationic liposomes. FEBS Lett 1998; 433: 169–173.

    CAS  PubMed  Google Scholar 

  54. Miller CR, Bondurant B, McLean SD, McGovern KA, O'Brien DF . Liposome–cell interactions in vitro: effect of liposome surface charge on the binding and endocytosis of conventional and sterically stabilized liposomes. Biochemistry 1998; 37: 12875–12883.

    CAS  PubMed  Google Scholar 

  55. Williams RS, Johnston SA, Riedy M, DeVit MJ, McElligott SG, Sanford JC . Introduction of foreign genes into tissues of living mice by DNA-coated microprojectiles. Proc Natl Acad Sci USA 1991; 88: 2726–2730.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Felgner PL, Ringold GM . Cationic liposome-mediated transfection. Nature 1989; 337: 387–388.

    CAS  PubMed  Google Scholar 

  57. Jeschke MG, Barrow RE, Hawkins HK, Tao Z, Perez-Polo JR, Herndon DN . Biodistribution and feasibility of non-viral IGF-I gene transfers in thermally injured skin. Lab Invest 2000; 80: 151–158.

    CAS  PubMed  Google Scholar 

  58. Felgner PL, Tsai YJ, Sukhu L, Wheeler CJ, Manthorpe M, Marshall J et al. Improved cationic lipid formulations for in vivo gene therapy. Ann N Y Acad Sci 1995; 772: 126–139.

    CAS  PubMed  Google Scholar 

  59. Eriksson E . Gene transfer in wound healing. Adv Skin Wound Care 2000; 13: 20–22.

    CAS  PubMed  Google Scholar 

  60. Alexander MY, Akhurst RJ . Liposome-medicated gene transfer and expression via the skin. Hum Mol Genet 1995; 4: 2279–2285.

    CAS  PubMed  Google Scholar 

  61. Jeschke MG, Schubert T, Klein D . Exogenous liposomal IGF-I cDNA gene transfer leads to endogenous cellular and physiological responses in an acute wound. Am J Physiol Regul Integr Comp Physiol 2004; 286: R958–R966.

    CAS  PubMed  Google Scholar 

  62. Shea LD, Smiley E, Bonadio J, Mooney DJ . DNA delivery from polymer matrices for tissue engineering. Nat Biotechnol 1999; 17: 551–554.

    CAS  PubMed  Google Scholar 

  63. Fu H, Hu Y, McNelis T, Hollinger JO . A calcium phosphate-based gene delivery system. J Biomed Mater Res A 2005; 74: 40–48.

    PubMed  Google Scholar 

  64. Lawrie A, Brisken AF, Francis SE, Cumberland DC, Crossman DC, Newman CM . Microbubble-enhanced ultrasound for vascular gene delivery. Gene Therapy 2000; 7: 2023–2027.

    CAS  PubMed  Google Scholar 

  65. Jeschke MG, Barrow RE, Hawkins HK, Yang K, Hayes RL, Lichtenbelt BJ et al. IGF-I gene transfer in thermally injured rats. Gene Therapy 1999; 6: 1015–1020.

    CAS  PubMed  Google Scholar 

  66. Sun L, Xu L, Chang H, Henry FA, Miller RM, Harmon JM et al. Transfection with aFGF cDNA improves wound healing. J Invest Dermatol 1997; 108: 313–318.

    CAS  PubMed  Google Scholar 

  67. Rodriguez JL, Miller CG, Garner WL, Till GO, Guerrero P, Moore NP et al. Correlation of the local and systemic cytokine response with clinical outcome following thermal injury. J Trauma 1993; 34: 684–695.

    CAS  PubMed  Google Scholar 

  68. Herndon DN, Barrow RE, Rutan RL, Rutan TC, Desai MH, Abston S . A comparison of conservative versus early excision. Therapies in severely burned patients. Ann Surg 1989; 209: 547–553.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Jeschke MG, Barrow RE, Hawkins HK, Chrysopoulo MT, Perez-Polo JR, Herndon DN . Effect of multiple gene transfers of insulin like growth factor I complementary DNA gene constructs in rats after thermal injury. Arch Surg 1999; 134: 1137–1141.

    CAS  PubMed  Google Scholar 

  70. Gao X, Huang L . Cationic liposome-mediated gene transfer. Gene Therapy 1995; 2: 710–722.

    CAS  PubMed  Google Scholar 

  71. Jeschke MG, Klein D . Liposomal gene transfer of multiple genes is more effective than gene transfer of a single gene. Gene Therapy 2004; 11: 847–855.

    CAS  PubMed  Google Scholar 

  72. National Institute of Health www.clinicaltrials.gov Clinical Trials Overview. National Institute of Health, 2006.

  73. Vogt PM, Thompson S, Andree C, Liu P, Breuing K, Hatzis D et al. Genetically modified keratinocytes transplanted to wounds reconstitute the epidermis. Proc Natl Acad Sci USA 1994; 91: 9307–9311.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Gossen M, Bujard H . Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci USA 1992; 89: 5547–5551.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Chandler LA, Gu DL, Ma C, Gonzalez AM, Doukas J, Nguyen T et al. Matrix-enabled gene transfer for cutaneous wound repair. Wound Repair Regen 2000; 8: 473–479.

    CAS  PubMed  Google Scholar 

  76. Shi Y, Reitmaier B, Regenbogen J, Slowey RM, Opalenik SR, Wolf E et al. CARP, a cardiac ankyrin repeat protein, is up-regulated during wound healing and induces angiogenesis in experimental granulation tissue. Am J Pathol 2005; 166: 303–312.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. de Crombrugghe B, Lefebvre V, Behringer RR, Bi W, Murakami S, Huang W . Transcriptional mechanisms of chondrocyte differentiation. Matrix Biol 2000; 19: 389–394.

    CAS  PubMed  Google Scholar 

  78. Schreiber J, Efron PA, Park JE, Moldawer LL, Barbul A . Adenoviral gene transfer of an NF-kappaB super-repressor increases collagen deposition in rodent cutaneous wound healing. Surgery 2005; 138: 940–946.

    PubMed  Google Scholar 

  79. Yamasaki K, Edington HD, McClosky C, Tzeng E, Lizonova A, Kovesdi I et al. Reversal of impaired wound repair in iNOS-deficient mice by topical adenoviral-mediated iNOS gene transfer. J Clin Invest 1998; 101: 967–971.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Ashcroft GS, Yang X, Glick AB, Weinstein M, Letterio JL, Mizel DE et al. Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat Cell Biol 1999; 1: 260–266.

    CAS  PubMed  Google Scholar 

  81. Liu X, Zhang E, Li P, Liu J, Zhou P, Gu DY et al. Expression and possible mechanism of c-ski, a novel tissue repair-related gene during normal and radiation-impaired wound healing. Wound Repair Regen 2006; 14: 162–171.

    PubMed  Google Scholar 

  82. Liu W, Cai Z, Wang D, Wu X, Cui L, Shang Q et al. Blocking transforming growth factor-beta receptor signaling down-regulates transforming growth factor-beta1 autoproduction in keloid fibroblasts. Chin J Traumatol 2002; 5: 77–81.

    CAS  PubMed  Google Scholar 

  83. Cutroneo KR, Chiu JF . Comparison and evaluation of gene therapy and epigenetic approaches for wound healing. Wound Repair Regen 2000; 8: 494–502.

    CAS  PubMed  Google Scholar 

  84. Breuing K, Eriksson E, Liu P, Miller DR . Healing of partial thickness porcine skin wounds in a liquid environment. J Surg Res 1992; 52: 50–58.

    CAS  PubMed  Google Scholar 

  85. Voigt M, Schauer M, Schaefer DJ, Andree C, Horch R, Stark GB . Cultured epidermal keratinocytes on a microspherical transport system are feasible to reconstitute the epidermis in full-thickness wounds. Tissue Eng 1999; 5: 563–572.

    CAS  PubMed  Google Scholar 

  86. Bellocq NC, Kang DW, Wang X, Jensen GS, Pun SH, Schluep T et al. Synthetic biocompatible cyclodextrin-based constructs for local gene delivery to improve cutaneous wound healing. Bioconjug Chem 2004; 15: 1201–1211.

    CAS  PubMed  Google Scholar 

  87. Rosenthal FM, Cao L, Tanczos E, Kopp J, Andree C, Stark GB et al. Paracrine stimulation of keratinocytes in vitro and continuous delivery of epidermal growth factor to wounds in vivo by genetically modified fibroblasts transfected with a novel chimeric construct. In Vivo 1997; 11: 201–208.

    CAS  PubMed  Google Scholar 

  88. Jeschke MG, Schubert T, Krickhahn M, Polykandriotis E, Klein D, Perez-Polo JR et al. Interaction of exogenous liposomal insulin-like growth factor-I cDNA gene transfer with growth factors on collagen expression in acute wounds. Wound Repair Regen 2005; 13: 269–277.

    PubMed  Google Scholar 

  89. Lee PY, Li Z, Huang L . Thermosensitive hydrogel as a Tgf-beta1 gene delivery vehicle enhances diabetic wound healing. Pharm Res 2003; 20: 1995–2000.

    CAS  PubMed  Google Scholar 

  90. Taub PJ, Marmur JD, Zhang WX, Senderoff D, Nhat PD, Phelps R et al. Locally administered vascular endothelial growth factor cDNA increases survival of ischemic experimental skin flaps. Plast Reconstr Surg 1998; 102: 2033–2039.

    CAS  PubMed  Google Scholar 

  91. Mesri EA, Federoff HJ, Brownlee M . Expression of vascular endothelial growth factor from a defective herpes simplex virus type 1 amplicon vector induces angiogenesis in mice. Circ Res 1995; 76: 161–167.

    CAS  PubMed  Google Scholar 

  92. Kunugiza Y, Tomita N, Taniyama Y, Tomita T, Osako MK, Tamai K et al. Acceleration of wound healing by combined gene transfer of hepatocyte growth factor and prostacyclin synthase with Shima Jet. Gene Therapy 2006; 13: 1143–1152.

    CAS  PubMed  Google Scholar 

  93. Liu PY, Liu K, Wang XT, Badiavas E, Rieger-Christ KM, Tang JB et al. Efficacy of combination gene therapy with multiple growth factor cDNAs to enhance skin flap survival in a rat model. DNA Cell Biol 2005; 24: 751–757.

    CAS  PubMed  Google Scholar 

  94. Eming SA, Lee J, Snow RG, Tompkins RG, Yarmush ML, Morgan JR . Genetically modified human epidermis overexpressing PDGF-A directs the development of a cellular and vascular connective tissue stroma when transplanted to athymic mice – implications for the use of genetically modified keratinocytes to modulate dermal regeneration. J Invest Dermatol 1995; 105: 756–763.

    CAS  PubMed  Google Scholar 

  95. Machens HG, Morgan JR, Berthiaume F, Stefanovich P, Reimer R, Berger AC . Genetically modified fibroblasts induce angiogenesis in the rat epigastric island flap. Langenbecks Arch Surg 1998; 383: 345–350.

    CAS  PubMed  Google Scholar 

  96. Breitbart AS, Mason JM, Urmacher C, Barcia M, Grant RT, Pergolizzi RG et al. Gene-enhanced tissue engineering: applications for wound healing using cultured dermal fibroblasts transduced retrovirally with the PDGF-B gene. Ann Plast Surg 1999; 43: 632–639.

    CAS  PubMed  Google Scholar 

  97. Keswani SG, Katz AB, Lim FY, Zoltick P, Radu A, Alaee D et al. Adenoviral mediated gene transfer of PDGF-B enhances wound healing in type I and type II diabetic wounds. Wound Repair Regen 2004; 12: 497–504.

    PubMed  Google Scholar 

  98. Choi BM, Kwak HJ, Jun CD, Park SD, Kim KY, Kim HR et al. Control of scarring in adult wounds using antisense transforming growth factor-beta 1 oligodeoxynucleotides. Immunol Cell Biol 1996; 74: 144–150.

    CAS  PubMed  Google Scholar 

  99. Benn SI, Whitsitt JS, Broadley KN, Nanney LB, Perkins D, He L et al. Particle-mediated gene transfer with transforming growth factor-beta1 cDNAs enhances wound repair in rat skin. J Clin Invest 1996; 98: 2894–2902.

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Ha X, Li Y, Lao M, Yuan B, Wu CT . Effect of human hepatocyte growth factor on promoting wound healing and preventing scar formation by adenovirus-mediated gene transfer. Chin Med J (Engl) 2003; 116: 1029–1033.

    CAS  Google Scholar 

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Acknowledgements

We thank Liz Cook, Eileen Figueroa, and Steve Schuenke, Publications Office, Department of Surgery, The University of Texas Medical Branch, Galveston Texas, for their help in the preparation of this manuscript. We acknowledge the Postdoctoral Training in Trauma and Burns (T32-GM08256) and the Clayton Foundation for Research.

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  1. L K Branski and C T Pereira: These two authors contributed equally to the present work.

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  1. Department of Surgery, The University of Texas Medical Branch and Shriners Hospitals for Children, Galveston, TX, USA

    L K Branski, C T Pereira, D N Herndon & M G Jeschke

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Branski, L., Pereira, C., Herndon, D. et al. Gene therapy in wound healing: present status and future directions. Gene Ther 14, 1–10 (2007). https://doi.org/10.1038/sj.gt.3302837

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