Table of Contents
ISRN Dermatology
Volume 2012, Article ID 698034, 9 pages
http://dx.doi.org/10.5402/2012/698034
Review Article

A Review of Fetal Scarless Healing

Institute for Plastic Surgery Research and Education, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK

Received 9 February 2012; Accepted 13 March 2012

Academic Editors: G. Chodorowska and L. A. Laurent-Applegate

Copyright © 2012 K. J. Rolfe and A. O. Grobbelaar. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. U. Rowlatt, “Intrauterine wound healing in a 20 week human fetus,” Virchows Archiv, vol. 381, no. 3, pp. 353–361, 1979. View at Google Scholar · View at Scopus
  2. J. R. Armstrong and M. W. J. Ferguson, “Ontogeny of the skin and the transition from scar-free to scarring phenotype during wound healing in the pouch young of a marsupial, Monodelphis domestica,” Developmental Biology, vol. 169, no. 1, pp. 242–260, 1995. View at Publisher · View at Google Scholar · View at Scopus
  3. H. P. Lorenz, M. T. Longaker, L. A. Perkocha, R. W. Jennings, M. R. Harrison, and N. S. Adzick, “Scarless wound repair: a human fetal skin model,” Development, vol. 114, no. 1, pp. 253–259, 1992. View at Google Scholar · View at Scopus
  4. M. T. Longaker, D. J. Whitby, M. W. J. Ferguson, H. P. Lorenz, M. R. Harrison, and N. S. Adzick, “Adult skin wounds in the fetal environment heal with scar formation,” Annals of Surgery, vol. 219, no. 1, pp. 65–72, 1994. View at Google Scholar · View at Scopus
  5. A. J. Cowin, M. P. Brosnan, T. M. Holmes, and M. W. Ferguson, “Endogenous inflammatory response to dermal wound healing in the fetal and adult mouse,” Developmental Dynamics, vol. 212, no. 3, pp. 385–393, 1998. View at Google Scholar
  6. J. Hopkinson-Woolley, D. Hughes, S. Gordon, and P. Martin, “Macrophage recruitment during limb development and wound healing in the embryonic and foetal mouse,” Journal of Cell Science, vol. 107, no. 5, pp. 1159–1167, 1994. View at Google Scholar · View at Scopus
  7. B. C. Wulff, A. E. Parent, M. A. Meleski, L. A. Dipietro, M. E. Schrementi, and T. A. Wilgus, “Mast cells contribute to scar formation during fetal wound healing,” Journal of Investigative Dermatology, vol. 132, no. 2, pp. 458–465, 2012. View at Google Scholar
  8. A. J. Cowin, T. M. Holmes, P. Brosnan, and M. W. J. Ferguson, “Expression of TGF-β and its receptors in murine fetal and adult dermal wounds,” European Journal of Dermatology, vol. 11, no. 5, pp. 424–431, 2001. View at Google Scholar · View at Scopus
  9. T. A. Wilgus, A. M. Ferreira, T. M. Oberyszyn, V. K. Bergdall, and L. A. DiPietro, “Regulation of scar formation by vascular endothelial growth factor,” Laboratory Investigation, vol. 88, no. 6, pp. 579–590, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. F. W. Frantz, D. A. Bettinger, J. H. Haynes et al., “Biology of fetal repair: the presence of bacteria in fetal wounds induces an adult-like healing response,” Journal of Pediatric Surgery, vol. 28, no. 3, pp. 428–434, 1993. View at Publisher · View at Google Scholar · View at Scopus
  11. S. Öztürk, M. Deveci, M. Sengezer, and Ö. Günhan, “Results of artificial inflammation in scarless foetal wound healing: an experimental study in foetal lambs,” British Journal of Plastic Surgery, vol. 54, no. 1, pp. 47–52, 2001. View at Publisher · View at Google Scholar · View at Scopus
  12. E. I. Egozi, A. M. Ferreira, A. L. Burns, R. L. Gamelli, and L. A. DiPietro, “Mast cells modulate the inflammatory but not the proliferative response in healing wounds,” Wound Repair and Regeneration, vol. 11, no. 1, pp. 46–54, 2003. View at Publisher · View at Google Scholar · View at Scopus
  13. A. M. Szpaderska, E. I. Egozi, R. L. Gamelli, and L. A. DiPietro, “The effect of thrombocytopenia on dermal wound healing,” Journal of Investigative Dermatology, vol. 120, no. 6, pp. 1130–1137, 2003. View at Publisher · View at Google Scholar · View at Scopus
  14. J. V. Dovi, L. K. He, and L. A. DiPietro, “Accelerated wound closure in neutrophil-depleted mice,” Journal of Leukocyte Biology, vol. 73, no. 4, pp. 448–455, 2003. View at Publisher · View at Google Scholar · View at Scopus
  15. P. Martin, D. D'Souza, J. Martin et al., “Wound healing in the PU.1 null mouse—tissue repair is not dependent on inflammatory cells,” Current Biology, vol. 13, no. 13, pp. 1122–1128, 2003. View at Publisher · View at Google Scholar · View at Scopus
  16. K. W. Liechty, T. M. Crombleholme, D. L. Cass, B. Martin, and N. S. Adzick, “Diminished interleukin-8 (IL-8) production in the fetal wound healing response,” Journal of Surgical Research, vol. 77, no. 1, pp. 80–84, 1998. View at Publisher · View at Google Scholar · View at Scopus
  17. K. W. Liechty, N. S. Adzick, and T. M. Crombleholme, “Diminished interleukin 6 (IL-6) production during scarless human fetal wound repair,” Cytokine, vol. 12, no. 6, pp. 671–676, 2000. View at Publisher · View at Google Scholar · View at Scopus
  18. R. Alam, D. Kumar, D. Anderson-Walters, and P. A. Forsythe, “Macrophage inflammatory protein-1α and monocyte chemoattractant peptide- 1 elicit immediate and late cutaneous reactions and activate murine mast cells in vivo,” Journal of Immunology, vol. 152, no. 3, pp. 1298–1303, 1994. View at Google Scholar · View at Scopus
  19. L. A. DiPietro, P. J. Polverini, S. M. Rahbe, and E. J. Kovacs, “Modulation of JE/MCP-1 expression in dermal wound repair,” American Journal of Pathology, vol. 146, no. 4, pp. 868–875, 1995. View at Google Scholar · View at Scopus
  20. L. A. DiPietro, M. Burdick, Q. E. Low, S. L. Kunkel, and R. M. Strieter, “Mip-1α as a critical macrophage chemoattractant in murine wound repair,” Journal of Clinical Investigation, vol. 101, no. 8, pp. 1693–1698, 1998. View at Google Scholar · View at Scopus
  21. S. J. Fortunato, R. Menon, K. F. Swan, and S. J. Lombardi, “Interleukin-10 inhibition of interleukin-6 in human amniochorionic membrane: transcriptional regulation,” American Journal of Obstetrics and Gynecology, vol. 175, no. 4, pp. 1057–1065, 1996. View at Publisher · View at Google Scholar · View at Scopus
  22. S. J. Fortunato, R. Menon, and S. J. Lombardi, “The effect of transforming growth factor and interleukin-10 on interleukin-8 release by human amniochorion may regulate histologic chorioamnionitis,” American Journal of Obstetrics and Gynecology, vol. 179, no. 3, pp. 794–799, 1998. View at Publisher · View at Google Scholar · View at Scopus
  23. K. W. Liechty, H. B. Kim, N. S. Adzick, and T. M. Crombleholme, “Fetal wound repair results in scar formation in interleukin-10-deficient mice in a syngeneic murine model of scarless fetal wound repair,” Journal of Pediatric Surgery, vol. 35, no. 6, pp. 866–873, 2000. View at Google Scholar · View at Scopus
  24. W. H. Peranteau, L. Zhang, N. Muvarak et al., “IL-10 overexpression decreases inflammatory mediators and promotes regenerative healing in an adult model of scar formation,” Journal of Investigative Dermatology, vol. 128, no. 7, pp. 1852–1860, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. T. A. Wilgus, V. K. Bergdall, K. L. Tober et al., “The impact of cyclooxygenase-2 mediated inflammation on scarless fetal wound healing,” American Journal of Pathology, vol. 165, no. 3, pp. 753–761, 2004. View at Google Scholar · View at Scopus
  26. T. A. Wilgus, Y. Vodovotz, E. Vittadini, E. A. Clubbs, and T. M. Oberyszyn, “Reduction of scar formation in full-thickness wounds with topical celecoxib treatment,” Wound Repair and Regeneration, vol. 11, no. 1, pp. 25–34, 2003. View at Publisher · View at Google Scholar · View at Scopus
  27. V. C. Sandulache, A. Parekh, H. S. Li-Korotky, J. E. Dohar, and P. A. Hebda, “Prostaglandin E2 differentially modulates human fetal and adult dermal fibroblast migration and contraction: implication for wound healing,” Wound Repair and Regeneration, vol. 14, no. 5, pp. 633–643, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. A. Parekh, V. C. Sandulache, A. S. Lieb, J. E. Dohar, and P. A. Hebda, “Differential regulation of free-floating collagen gel contraction by human fetal and adult dermal fibroblasts in response to prostaglandin E2 mediated by an EP2/cAMP-dependent mechanism,” Wound Repair and Regeneration, vol. 15, no. 3, pp. 390–398, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. G. S. Schultz and A. Wysocki, “Interactions between extracellular matrix and growth factors in wound healing,” Wound Repair and Regeneration, vol. 17, no. 2, pp. 153–162, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. M. T. Longaker, E. S. Chiu, N. S. Adzick, M. Stern, M. R. Harrison, and R. Stern, “Studies in fetal wound healing: V. A prolonged presence of hyaluronic acid characterizes fetal wound fluid,” Annals of Surgery, vol. 213, no. 4, pp. 292–296, 1991. View at Google Scholar · View at Scopus
  31. T. Sawai, N. Usui, K. Sando et al., “Hyaluronic acid of wound fluid in adult and fetal rabbits,” Journal of Pediatric Surgery, vol. 32, no. 1, pp. 41–43, 1997. View at Publisher · View at Google Scholar · View at Scopus
  32. D. C. West, D. M. Shaw, P. Lorenz, N. S. Adzick, and M. T. Longaker, “Fibrotic healing of adult and late gestation fetal wounds correlates with increased hyaluronidase activity and removal of hyaluronan,” International Journal of Biochemistry and Cell Biology, vol. 29, no. 1, pp. 201–210, 1997. View at Publisher · View at Google Scholar · View at Scopus
  33. S. M. Alaish, D. Yager, R. F. Diegelmann, I. K. Cohen, and N. S. Adzick, “Biology of fetal wound healing: hyaluronate receptor expression in fetal fibroblasts,” Journal of Pediatric Surgery, vol. 29, no. 8, pp. 1040–1043, 1994. View at Publisher · View at Google Scholar · View at Scopus
  34. M. Hu, E. E. Sabelman, Y. Cao, J. Chang, and V. R. Hentz, “Three-dimensional hyaluronic acid grafts promote healing and reduce scar formation in skin incision wounds,” Journal of Biomedical Materials Research, vol. 67, no. 1, pp. 586–592, 2003. View at Google Scholar · View at Scopus
  35. J. A. Iocono, H. P. Ehrlich, K. A. Keefer, and T. M. Krummel, “Hyaluronan induces scarless repair in mouse limb organ culture,” Journal of Pediatric Surgery, vol. 33, no. 4, pp. 564–567, 1998. View at Publisher · View at Google Scholar · View at Scopus
  36. B. A. Mast, R. F. Diegelmann, T. M. Krummel, and I. K. Cohen, “Hyaluronic acid modulates proliferation, collagen and protein synthesis of cultured fetal fibroblasts,” Matrix, vol. 13, no. 6, pp. 441–446, 1993. View at Google Scholar · View at Scopus
  37. B. P. Toole, T. N. Wight, and M. I. Tammi, “Hyaluronan-cell interactions in cancer and vascular disease,” Journal of Biological Chemistry, vol. 277, no. 7, pp. 4593–4596, 2002. View at Publisher · View at Google Scholar · View at Scopus
  38. R. S. Cotran, V. Kumar, and T. Collins, Pathologic Basis of Disease, WB Saunders Company, Philadelphia, Pa, USA, 1999.
  39. J. E. Schwarzbauer, “Alternative splicing of fibronectin: three variants, three functions,” BioEssays, vol. 13, no. 10, pp. 527–533, 1991. View at Google Scholar · View at Scopus
  40. F. Pagani, L. Zagato, C. Vergani, G. Casari, A. Sidoli, and F. E. Baralle, “Tissue-specific splicing pattern of fibronectin messenger RNA precursor during development and aging in rat,” Journal of Cell Biology, vol. 113, no. 5, pp. 1223–1229, 1991. View at Google Scholar · View at Scopus
  41. A. F. Muro, A. K. Chauhan, S. Gajovic et al., “Regulated splicing of the fibronectin EDA exon is essential for proper skin wound healing and normal lifespan,” Journal of Cell Biology, vol. 162, no. 1, pp. 149–160, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. D. J. Whitby and M. W. J. Ferguson, “The extracellular matrix of lip wounds in fetal, neonatal and adult mice,” Development, vol. 112, no. 2, pp. 651–668, 1991. View at Google Scholar · View at Scopus
  43. D. J. Whitby, M. T. Longaker, M. R. Harrison, N. S. Adzick, and M. W. J. Ferguson, “Rapid epithelialisation of fetal wounds is associated with the early deposition of tenascin,” Journal of Cell Science, vol. 99, no. 3, pp. 583–586, 1991. View at Google Scholar · View at Scopus
  44. M. T. Longaker, D. J. Whitby, M. W. J. Ferguson et al., “Studies in fetal wound healing: III. Early deposition of fibronectin distinguishes fetal from adult wound healing,” Journal of Pediatric Surgery, vol. 24, no. 8, pp. 799–805, 1989. View at Google Scholar · View at Scopus
  45. D. L. Cass, K. M. Bullard, K. G. Sylvester et al., “Epidermal integrin expression is upregulated rapidly in human fetal wound repair,” Journal of Pediatric Surgery, vol. 33, no. 2, pp. 312–316, 1998. View at Publisher · View at Google Scholar · View at Scopus
  46. S. R. Beanes, C. Dang, C. Soo et al., “Down-regulation of decorin, a transforming growth factor-beta modulator, is associated with scarless fetal wound healing,” Journal of Pediatric Surgery, vol. 36, no. 11, pp. 1666–1671, 2001. View at Publisher · View at Google Scholar · View at Scopus
  47. P. G. Scott, C. M. Dodd, A. Ghahary, Y. J. Shen, and E. E. Tredget, “Fibroblasts from post-burn hypertrophic scar tissue synthesize less decorin than normal dermal fibroblasts,” Clinical Science, vol. 94, no. 5, pp. 541–547, 1998. View at Google Scholar · View at Scopus
  48. K. Sayani, C. M. Dodd, B. Nedelec et al., “Delayed appearance of decorin in healing burn scars,” Histopathology, vol. 36, no. 3, pp. 262–272, 2000. View at Publisher · View at Google Scholar · View at Scopus
  49. C. Soo, F. Y. Hu, X. Zhang et al., “Differential expression of fibromodulin, a transforming growth factor-β modulator, in fetal skin development and scarless repair,” American Journal of Pathology, vol. 157, no. 2, pp. 423–433, 2000. View at Google Scholar · View at Scopus
  50. Z. Zhang, T. M. Garron, X. J. Li et al., “Recombinant human decorin inhibits TGF-β1-induced contraction of collagen lattice by hypertrophic scar fibroblasts,” Burns, vol. 35, no. 4, pp. 527–537, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. K. R. Knight, D. A. Lepore, R. S. C. Horne et al., “Collagen content of uninjured skin and scar tissue in foetal and adult sheep,” International Journal of Experimental Pathology, vol. 74, no. 6, pp. 583–591, 1993. View at Google Scholar · View at Scopus
  52. H. N. Lovvorn, D. T. Cheung, M. E. Nimni, N. Perelman, J. M. Estes, and N. S. Adzick, “Relative distribution and crosslinking of collagen distinguish fetal from adult sheep wound repair,” Journal of Pediatric Surgery, vol. 34, no. 1, pp. 218–223, 1999. View at Publisher · View at Google Scholar · View at Scopus
  53. J. R. Merkel, B. R. DiPaolo, G. G. Hallock, and D. C. Rice, “Type I and Type III collagen content of healing wounds in fetal and adult rats,” Proceedings of the Society for Experimental Biology and Medicine, vol. 187, no. 4, pp. 493–497, 1988. View at Google Scholar · View at Scopus
  54. S. R. Goldberg, R. P. McKinstry, V. Sykes, and D. A. Lanning, “Rapid closure of midgestational excisional wounds in a fetal mouse model is associated with altered transforming growth factor-β isoform and receptor expression,” Journal of Pediatric Surgery, vol. 42, no. 6, pp. 966–973, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. R. Carter, K. Jain, V. Sykes, and D. Lanning, “Differential expression of procollagen genes between mid- and late-gestational fetal fibroblasts,” Journal of Surgical Research, vol. 156, no. 1, pp. 90–94, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. A. S. Colwell, T. M. Krummel, M. T. Longaker, and H. P. Lorenz, “Early-gestation fetal scarless wounds have less lysyl oxidase expression,” Plastic and Reconstructive Surgery, vol. 118, no. 5, pp. 1125–1129, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. G. S. Chin, S. Lee, M. Hsu et al., “Discoidin domain receptors and their ligand, collagen, are temporally regulated in fetal rat fibroblasts in vitro,” Plastic and Reconstructive Surgery, vol. 107, no. 3, pp. 769–776, 2001. View at Google Scholar · View at Scopus
  58. E. Y. Huang, H. Wu, E. R. Island et al., “Differential expression of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in early and late gestational mouse skin and skin wounds,” Wound Repair and Regeneration, vol. 10, no. 6, pp. 387–396, 2002. View at Publisher · View at Google Scholar · View at Scopus
  59. Z. M. Peled, E. D. Phelps, D. L. Updike et al., “Matrix metalloproteinases and the ontogeny of scarless repair: the other side of the wound healing balance,” Plastic and Reconstructive Surgery, vol. 110, no. 3, pp. 801–811, 2002. View at Google Scholar · View at Scopus
  60. C. M. Dang, S. R. Beanes, C. Soo et al., “Decreased expression of fibroblast and keratinocyte growth factor isoforms and receptors during scarless repair,” Plastic and Reconstructive Surgery, vol. 111, no. 6, pp. 1969–1979, 2003. View at Publisher · View at Google Scholar · View at Scopus
  61. P. Martin and J. Lewis, “Actin cables and epidermal movement in embryonic wound healing,” Nature, vol. 360, no. 6400, pp. 179–183, 1992. View at Publisher · View at Google Scholar · View at Scopus
  62. J. Brock, K. Midwinter, J. Lewis, and P. Martin, “Healing of incisional wounds in the embryonic chick wing bud: characterization of the actin purse-string and demonstration of a requirement for Rho activation,” Journal of Cell Biology, vol. 135, no. 4, pp. 1097–1107, 1996. View at Google Scholar · View at Scopus
  63. A. J. Cowin, N. Hatzirodos, J. T. Teusner, and D. A. Belford, “Differential effect of wounding on actin and its associated proteins, paxillin and gelsolin, in fetal skin explants,” Journal of Investigative Dermatology, vol. 120, no. 6, pp. 1118–1129, 2003. View at Publisher · View at Google Scholar · View at Scopus
  64. S. Nodder and P. Martin, “Wound healing in embryos: a review,” Anatomy and Embryology, vol. 195, no. 3, pp. 215–228, 1997. View at Publisher · View at Google Scholar · View at Scopus
  65. J. McCluskey and P. Martin, “Analysis of the tissue movements of embryonic wound healing—DiI studies in the limb bud stage mouse embryo,” Developmental Biology, vol. 170, no. 1, pp. 102–114, 1995. View at Publisher · View at Google Scholar · View at Scopus
  66. J. M. Estes, J. S. Vande Berg, N. S. Adzick, T. E. MacGillivray, A. Desmouliere, and G. Gabbiani, “Phenotypic and functional features of myofibroblasts in sheep fetal wounds,” Differentiation, vol. 56, no. 3, pp. 173–181, 1994. View at Publisher · View at Google Scholar · View at Scopus
  67. D. L. Cass, K. G. Sylvester, E. Y. Yang, T. M. Crombleholme, and N. S. Adzick, “Myofibroblast persistence in fetal sheep wounds is associated with scar formation,” Journal of Pediatric Surgery, vol. 32, no. 7, pp. 1017–1022, 1997. View at Publisher · View at Google Scholar · View at Scopus
  68. K. J. Rolfe, J. Richardson, C. Vigor, L. M. Irvine, A. O. Grobbelaar, and C. Linge, “A role for TGF-β1-induced cellular responses during wound healing of the non-scarring early human fetus?” Journal of Investigative Dermatology, vol. 127, no. 11, pp. 2656–2667, 2007. View at Publisher · View at Google Scholar · View at Scopus
  69. C. Soo, S. R. Beanes, F. Y. Hu et al., “Ontogenetic transition in fetal wound transforming growth factor-β regulation correlates with collagen organization,” American Journal of Pathology, vol. 163, no. 6, pp. 2459–2476, 2003. View at Google Scholar · View at Scopus
  70. P. Martin, M. C. Dickson, F. A. Millan, and R. J. Akhurst, “Rapid induction and clearance of TGFβ1 is an early response to wounding in the mouse embryo,” Developmental Genetics, vol. 14, no. 3, pp. 225–238, 1993. View at Google Scholar · View at Scopus
  71. J. H. Levine, H. L. Moses, L. I. Gold, and L. B. Nanney, “Spatial and temporal patterns of immunoreactive transforming growth factor β1, β2, and β3 during excisiona wound repair,” American Journal of Pathology, vol. 143, no. 2, pp. 368–380, 1993. View at Google Scholar · View at Scopus
  72. M. Shah, D. M. Foreman, and M. W. J. Ferguson, “Control of scarring in adult wounds by neutralising antibody to transforming growth factor β,” The Lancet, vol. 339, no. 8787, pp. 213–214, 1992. View at Publisher · View at Google Scholar · View at Scopus
  73. M. Shah, D. M. Foreman, and M. W. J. Ferguson, “Neutralising antibody to TGF-β1,2 reduces cutaneous scarring in adult rodents,” Journal of Cell Science, vol. 107, no. 5, pp. 1137–1157, 1994. View at Google Scholar · View at Scopus
  74. M. Shah, D. M. Foreman, and M. W. J. Ferguson, “Neutralisation of TGF-β1 and TGF-β2 or exogenous addition of TGF-β3 to cutaneous rat wounds reduces scarring,” Journal of Cell Science, vol. 108, no. 3, pp. 985–1002, 1995. View at Google Scholar · View at Scopus
  75. M. W. Ferguson, J. Duncan, J. Bond et al., “Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, phase I/II studies,” The Lancet, vol. 373, no. 9671, pp. 1264–1274, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. L. Wu, A. Siddiqui, D. E. Morris, D. A. Cox, S. I. Roth, and T. A. Mustoe, “Transforming growth factor β3 (TGFβ3) accelerates wound healing without alteration of scar prominence: histologic and competitive reverse- transcription-polymerase chain reaction studies,” Archives of Surgery, vol. 132, no. 7, pp. 753–760, 1997. View at Google Scholar · View at Scopus
  77. W. Chen, X. Fu, S. Ge et al., “Ontogeny of expression of transforming growth factor-β and its receptors and their possible relationship with scarless healing in human fetal skin,” Wound Repair and Regeneration, vol. 13, no. 1, pp. 68–75, 2005. View at Publisher · View at Google Scholar · View at Scopus
  78. Z. M. Peled, S. J. Rhee, M. Hsu, J. Chang, T. M. Krummel, and M. T. Longaker, “The ontogeny of scarless healing II: EGF and PDGF-B gene expression in fetal rat skin and fibroblasts as a function of gestational age,” Annals of Plastic Surgery, vol. 47, no. 4, pp. 417–424, 2001. View at Google Scholar · View at Scopus
  79. J. H. Haynes, D. E. Johnson, B. A. Mast et al., “Platelet-derived growth factor induces fetal wound fibrosis,” Journal of Pediatric Surgery, vol. 29, no. 11, pp. 1405–1408, 1994. View at Publisher · View at Google Scholar · View at Scopus
  80. D. M. Ornitz and N. Itoh, “Fibroblast growth factors,” Genome Biology, vol. 2, no. 3, article 3005, 2001. View at Google Scholar · View at Scopus
  81. W. Chen, X. B. Fu, S. L. Ge, T. Z. Sun, and Z. Y. Sheng, “Ontogeny of expression of basic fibroblast growth factor and its receptors in human fetal skin,” Chinese Journal of Traumatology, vol. 8, no. 6, pp. 332–338, 2005. View at Google Scholar · View at Scopus
  82. S. Ihara, Y. Motobayashi, E. Nagao, and A. Kistler, “Ontogenetic transition of wound healing pattern in rat skin occurring at the fetal stage,” Development, vol. 110, no. 3, pp. 671–680, 1990. View at Google Scholar · View at Scopus
  83. A. S. Colwell, S. R. Beanes, C. Soo et al., “Increased angiogenesis and expression of vascular endothelial growth factor during scarless repair,” Plastic and Reconstructive Surgery, vol. 115, no. 1, pp. 204–212, 2005. View at Publisher · View at Google Scholar · View at Scopus
  84. J. I. Jones and D. R. Clemmons, “Insulin-like growth factors and their binding proteins: biological actions,” Endocrine Reviews, vol. 16, no. 1, pp. 3–34, 1995. View at Google Scholar · View at Scopus
  85. S. Beckert, S. Haack, H. Hierlemann et al., “Stimulation of steroid-suppressed cutaneous healing by repeated topical application of IGF-I: different mechanisms of action based upon the mode of IGF-I delivery,” Journal of Surgical Research, vol. 139, no. 2, pp. 217–221, 2007. View at Publisher · View at Google Scholar · View at Scopus
  86. T. T. Phan, I. J. Lim, B. H. Bay et al., “Role of IGF system of mitogens in the induction of fibroblast proliferation by keloid-derived keratinocytes in vitro,” American Journal of Physiology, vol. 284, no. 4, pp. C860–C869, 2003. View at Google Scholar · View at Scopus
  87. A. Ghahary, Y. J. Shen, R. Wang, P. G. Scott, and E. E. Tredget, “Expression and localization of insulin-like growth factor-1 in normal and post-burn hypertrophic scar tissue in human,” Molecular and Cellular Biochemistry, vol. 183, no. 1-2, pp. 1–9, 1998. View at Publisher · View at Google Scholar · View at Scopus
  88. K. J. Rolfe, A. D. Cambrey, J. Richardson, L. M. Irvine, A. O. Grobbelaar, and C. Linge, “Dermal fibroblasts derived from fetal and postnatal humans exhibit distinct responses to insulin like growth factors,” BMC Developmental Biology, vol. 7, article 124, 2007. View at Publisher · View at Google Scholar · View at Scopus
  89. G. S. Chin, W. J. H. Kim, T. Y. Lee et al., “Differential expression of receptor tyrosine kinases and Shc in fetal and adult rat fibroblasts: toward defining scarless versus scarring fibroblast phenotypes,” Plastic and Reconstructive Surgery, vol. 105, no. 3, pp. 972–979, 2000. View at Google Scholar · View at Scopus
  90. H. Pratsinis, C. C. Giannouli, I. Zervolea, S. Psarras, D. Stathakos, and D. Kletsas, “Differential proliferative response of fetal and adult human skin fibroblasts to transforming growth factor-β,” Wound Repair and Regeneration, vol. 12, no. 3, pp. 374–383, 2004. View at Publisher · View at Google Scholar · View at Scopus
  91. A. S. Colwell, T. M. Krummel, M. T. Longaker, and H. P. Lorenz, “Fetal and adult fibroblasts have similar TGF-β-mediated, Smad-dependent signaling pathways,” Plastic and Reconstructive Surgery, vol. 117, no. 7, pp. 2277–2283, 2006. View at Publisher · View at Google Scholar · View at Scopus
  92. P. Martin and C. D. Nobes, “An early molecular component of the wound healing response in rat embryos—induction of c-fos protein in cell at the epidermal wound margin,” Mechanisms of Development, vol. 38, no. 3, pp. 209–216, 1992. View at Publisher · View at Google Scholar · View at Scopus
  93. S. Gangnuss, A. J. Cowin, I. S. Daehn et al., “Regulation of MAPK activation, AP-1 transcription factor expression and keratinocyte differentiation in wounded fetal skin,” Journal of Investigative Dermatology, vol. 122, no. 3, pp. 791–804, 2004. View at Publisher · View at Google Scholar · View at Scopus
  94. J. P. Brockes, “Amphibian limb regeneration: rebuilding a complex structure,” Science, vol. 276, no. 5309, pp. 81–87, 1997. View at Publisher · View at Google Scholar · View at Scopus
  95. D. M. Gardiner, M. A. Torok, L. M. Mullen, and S. V. Bryant, “Evolution of vertebrate limbs: robust morphology and flexible development,” American Zoologist, vol. 38, no. 4, pp. 659–671, 1998. View at Google Scholar · View at Scopus
  96. E. J. Stelnicki, L. G. Komuves, A. O. Kwong et al., “HOX homeobox genes exhibit spatial and temporal changes in expression during human skin development,” Journal of Investigative Dermatology, vol. 110, no. 2, pp. 110–115, 1998. View at Google Scholar · View at Scopus
  97. L. G. Kömüves, E. Michael, J. M. Arbeit et al., “HOXB4 homeodomain protein is expressed in developing epidermis and skin disorders and modulates keratinocyte proliferation,” Developmental Dynamics, vol. 224, no. 1, pp. 58–68, 2002. View at Publisher · View at Google Scholar · View at Scopus
  98. K. Jain, V. Sykes, T. Kordula, and D. Lanning, “Homeobox genes Hoxd3 and Hoxd8 are differentially expressed in fetal mouse excisional wounds,” Journal of Surgical Research, vol. 148, no. 1, pp. 45–48, 2008. View at Publisher · View at Google Scholar · View at Scopus
  99. E. J. Stelnicki, J. Arbeit, D. L. Cass, C. Saner, M. Harrison, and C. Largman, “Modulation of the human homeobox genes PRX-2 and HOXB13 in scarless fetal wounds,” Journal of Investigative Dermatology, vol. 111, no. 1, pp. 57–63, 1998. View at Publisher · View at Google Scholar · View at Scopus
  100. J. A. Mack, S. R. Abramson, Y. Ben et al., “HOXB13 knockout adult skin exhibits high levels of hyaluronan and enhanced wound healing,” The FASEB Journal, vol. 17, no. 10, pp. 1352–1354, 2003. View at Google Scholar · View at Scopus
  101. K. J. Rolfe, L. M. Irvine, A. O. Grobbelaar, and C. Linge, “Differential gene expression in response to transforming growth factor-β1 by fetal and postnatal dermal fibroblasts,” Wound Repair and Regeneration, vol. 15, no. 6, pp. 897–906, 2007. View at Publisher · View at Google Scholar · View at Scopus
  102. A. S. Colwell, M. T. Longaker, and H. P. Lorenz, “Identification of differentially regulated genes in fetal wounds during regenerative repair,” Wound Repair and Regeneration, vol. 16, no. 3, pp. 450–459, 2008. View at Publisher · View at Google Scholar · View at Scopus
  103. W. Chen, X. Fu, S. Ge et al., “Profiling of genes differentially expressed in a rat of early and later gestational ages with high-density oligonucleotide DNA array,” Wound Repair and Regeneration, vol. 15, no. 1, pp. 147–155, 2007. View at Publisher · View at Google Scholar · View at Scopus
  104. M. R. Khorramizadeh, E. E. Tredget, C. Telasky, Q. Shen, and A. Ghahary, “Aging differentially modulates the expression of collagen and collagenase in dermal fibroblasts,” Molecular and Cellular Biochemistry, vol. 194, no. 1-2, pp. 99–108, 1999. View at Publisher · View at Google Scholar · View at Scopus
  105. W. Gerstein, “Cell proliferation in human fetal epidermis,” Journal of Investigative Dermatology, vol. 57, no. 4, pp. 262–265, 1971. View at Google Scholar · View at Scopus
  106. R. Carter, V. Sykes, and D. Lanning, “Scarless fetal mouse wound healing may initiate apoptosis through caspase 7 and cleavage of PARP,” Journal of Surgical Research, vol. 156, no. 1, pp. 74–79, 2009. View at Publisher · View at Google Scholar · View at Scopus
  107. D. Sopher, “A study of wound healing in the fetal tissues of the cynomolgus monkey,” Laboratory Animal Handbooks, vol. 6, pp. 327–335, 1975. View at Google Scholar
  108. J. D. Burrington, “Wound healing in the fetal lamb,” Journal of Pediatric Surgery, vol. 6, no. 5, pp. 523–528, 1971. View at Google Scholar · View at Scopus
  109. J. Hohlfeld, A. De Buys Roessingh, N. Hirt-Burri et al., “Tissue engineered fetal skin constructs for paediatric burns,” The Lancet, vol. 366, no. 9488, pp. 840–842, 2005. View at Publisher · View at Google Scholar · View at Scopus