The fibroblast‐populated collagen matrix as a model of wound healing: a review of the evidence

The fibroblast‐populated collagen matrix (FPCM) has been utilized as an in vitro model of wound healing for more than 2 decades. It offers a reasonable approximation of the healing wound during the phases of established granulation tissue and early scar. The gross and microscopic morphology of the FPCM and the healing wound are similar at analogous phases. The processes of proliferation, survival/apoptosis, protein synthesis, and contraction act in similar directions in these two models, and the response to exogenous agents also is consistent between them. If its limitations are respected, then the FPCM can be used as a model of the healing wound. (WOUND REP REG 2004;12:–)

[1]  Frederick Grinnell,et al.  Fibroblasts, myofibroblasts, and wound contraction , 1994, The Journal of cell biology.

[2]  L Orci,et al.  Transforming growth factor beta stimulates collagen-matrix contraction by fibroblasts: implications for wound healing. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[3]  M. Carlson,et al.  Release of mechanical tension triggers apoptosis of human fibroblasts in a model of regressing granulation tissue. , 1999, Experimental cell research.

[4]  M J Banda,et al.  Large induction of keratinocyte growth factor expression in the dermis during wound healing. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[5]  B. Coulomb,et al.  Glycosaminoglycans modulate cell-matrix interactions of human fibroblasts and endothelial cells in vitro. , 1996, Journal of cell science.

[6]  L. Dubertret,et al.  Activities of human acidic fibroblast growth factor in an in vitro dermal equivalent model. , 1991, The Journal of investigative dermatology.

[7]  M. Sporn,et al.  Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[8]  H. Mühl,et al.  Counterregulation of interleukin-18 mRNA and protein expression during cutaneous wound repair in mice. , 1999, The Journal of investigative dermatology.

[9]  I. Ono,et al.  Development of a chronic type skin defect model and a study of cytokine secretion using the model , 2000, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[10]  W. Garner,et al.  TNF-alpha stimulates activation of pro-MMP2 in human skin through NF-(kappa)B mediated induction of MT1-MMP. , 2001, Journal of cell science.

[11]  F. Grinnell,et al.  Increased Myosin Light Chain Phosphorylation Is Not Required for Growth Factor Stimulation of Collagen Matrix Contraction* , 1999, The Journal of Biological Chemistry.

[12]  A. Viidik,et al.  The influence of cortisol on wound healing of the skin and distant connective tissue response. , 1979, Surgery, gynecology & obstetrics.

[13]  M. P. Welch,et al.  Collagen matrices attenuate the collagen-synthetic response of cultured fibroblasts to TGF-beta. , 1995, Journal of cell science.

[14]  Robert A. Brown,et al.  Mechanical loading regulates protease production by fibroblasts in three‐dimensional collagen substrates , 2000, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[15]  B. Hirschel,et al.  Contraction of Granulation Tissue in vitro: Similarity to Smooth Muscle , 1971, Science.

[16]  A. Ludlow,et al.  Active transforming growth factor-beta in wound repair: determination using a new assay. , 1999, The American journal of pathology.

[17]  F. Yao,et al.  Age and growth factors in porcine full‐thickness wound healing , 2001, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[18]  D. Foreman,et al.  Neutralisation of TGF-β 1 and TGF-β 2 or exogenous addition of TGF-β 3 to cutaneous rat wounds reduces scarring , 1995 .

[19]  J. V. Vande Berg,et al.  In vitro fibroblast populated collagen lattices are not good models of in vivo clinical wound healing , 2000, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[20]  J. Morgan,et al.  Particle-mediated gene transfer of PDGF isoforms promotes wound repair. , 1999, The Journal of investigative dermatology.

[21]  S. Jimenez,et al.  Growth properties and biochemical characterization of collagens synthesized by adult rat heart fibroblasts in culture. , 1992, Journal of molecular and cellular cardiology.

[22]  Kenneth M. Yamada,et al.  Cell interactions with three-dimensional matrices. , 2002, Current opinion in cell biology.

[23]  A. Ghahary,et al.  The effect of interferon alpha 2b on the expression of cytoskeletal proteins in an in vitro model of wound contraction. , 1995, The Journal of laboratory and clinical medicine.

[24]  M. Abercrombie,et al.  Collagen Formation and Wound Contraction during Repair of Small Excised Wounds in the Skin of Rats , 1954 .

[25]  Peter K. Hayward,et al.  Preclinical Wound‐Healing Studies with Recombinant Human Basic Fibroblast Growth Factor , 1991, Annals of the New York Academy of Sciences.

[26]  R. Holzheimer,et al.  Local and systemic concentrations of pro- and anti-inflammatory cytokines in human wounds. , 2000, European journal of medical research.

[27]  J. Norton,et al.  The Local Effects of Cachectin/Tumor Necrosis Factor on Wound Healing , 1991, Annals of surgery.

[28]  L. Boros,et al.  Interleukin‐1α gene expression during wound healing , 1995, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[29]  C. Munaut,et al.  Distinct pathways in the over-expression of matrix metalloproteinases in human fibroblasts by relaxation of mechanical tension. , 2001, Matrix biology : journal of the International Society for Matrix Biology.

[30]  M. Longaker,et al.  Fetal Fibroblast Contraction of Collagen Matrices In Vitro: The Effects of Epidermal Growth Factor and Transforming Growth Factor-β , 1994, Annals of plastic surgery.

[31]  R. Page,et al.  Development of a three-dimensional extracellular matrix synthesized by human diploid fibroblasts in vitro. , 1986, Journal of cell science.

[32]  H. Murata,et al.  TGF-β3 stimulates and regulates collagen synthesis through TGF-β1- dependent and independent mechanisms , 1997 .

[33]  J. Davidson,et al.  Epidermal growth factor increases granulation tissue formation dose dependently. , 1987, The Journal of surgical research.

[34]  F. Grinnell,et al.  Long-term culture of fibroblasts in contracted collagen gels: effects on cell growth and biosynthetic activity. , 1989, The Journal of investigative dermatology.

[35]  D. Lauffenburger,et al.  Epidermal growth factor induces acute matrix contraction and subsequent calpain‐modulated relaxation , 2002, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[36]  H. Moses,et al.  Spatial and temporal patterns of immunoreactive transforming growth factor beta 1, beta 2, and beta 3 during excisional wound repair. , 1993, The American journal of pathology.

[37]  R. Isseroff,et al.  Inhibition of collagen lattice contraction by pentoxifylline and interferon-alpha, -beta, and -gamma. , 1994, The Journal of investigative dermatology.

[38]  D. Romberger,et al.  Contraction of fibroblast-containing collagen gels: Initial collagen concentration regulates the degree of contraction and cell survival , 2001, In Vitro Cellular & Developmental Biology - Animal.

[39]  E Bell,et al.  The reconstitution of living skin. , 1983, The Journal of investigative dermatology.

[40]  T. Crombleholme,et al.  Diminished interleukin-8 (IL-8) production in the fetal wound healing response. , 1998, The Journal of surgical research.

[41]  J. McPherson,et al.  Platelet isoforms of platelet-derived growth factor stimulate fibroblasts to contract collagen matrices. , 1989, The Journal of clinical investigation.

[42]  J. Davidson,et al.  Transforming growth factor-beta stimulates wound healing and modulates extracellular matrix gene expression in pig skin: incisional wound model. , 1991, The Journal of investigative dermatology.

[43]  S. Rennard,et al.  Phosphodiesterase 4 inhibitor cilomilast inhibits fibroblast-mediated collagen gel degradation induced by tumor necrosis factor-alpha and neutrophil elastase. , 2002, American journal of respiratory cell and molecular biology.

[44]  E. M. Wills.  Studies in Wound Healing , 1999 .

[45]  N. Horiuchi,et al.  Induction of collagenase-2 (matrix metalloproteinase-8) gene expression by interleukin-1beta in human gingival fibroblasts. , 2001, Journal of periodontal research.

[46]  F. Grinnell,et al.  Differences in the Regulation of Fibroblast Contraction of Floating Versus Stressed Collagen Matrices* , 1999, The Journal of Biological Chemistry.

[47]  M. Suzuki,et al.  The life cycle of the myofibroblast. , 1977, Surgery, gynecology & obstetrics.

[48]  A. Bosserhoff,et al.  Effects of Mometasone Furoate on Human Keratinocytes and Fibroblasts in vitro , 1998, Skin Pharmacology and Physiology.

[49]  T. Tuan,et al.  In vitro fibroplasia: matrix contraction, cell growth, and collagen production of fibroblasts cultured in fibrin gels. , 1996, Experimental cell research.

[50]  P. Basset,et al.  Expression of Matrix Metalloproteinases during Rat Skin Wound Healing: Evidence that Membrane Type-1 Matrix Metalloproteinase Is a Stromal Activator of Pro-Gelatinase A , 1997, The Journal of cell biology.

[51]  T. Salo,et al.  Matrix Metalloproteinase-8 Is Expressed in Rheumatoid Synovial Fibroblasts and Endothelial Cells , 1997, The Journal of Biological Chemistry.

[52]  W. Halfter,et al.  Induction of tenascin in healing wounds , 1988, The Journal of cell biology.

[53]  C. McCulloch,et al.  The compliance of collagen gels regulates transforming growth factor-β induction of α-smooth muscle actin in fibroblasts , 1999 .

[54]  E. Eriksson,et al.  Growth Factors in the Repair of Partial Thickness Porcine Skin Wounds , 1997, Plastic and reconstructive surgery.

[55]  S. Jacques,et al.  The systemic administration of gamma interferon inhibits collagen synthesis and acute inflammation in a murine skin wounding model. , 1989, The Journal of investigative dermatology.

[56]  K. Rapala.  The effect of tumor necrosis factor-alpha on wound healing. An experimental study. , 1996, Annales chirurgiae et gynaecologiae. Supplementum.

[57]  A. Desmoulière,et al.  The Role of the Myofibroblast in Wound Healing and Fibrocontractive Diseases , 1988 .

[58]  N. Pejnović,et al.  Aberrant levels of cytokines within the healing wound after burn injury. , 1995, Archives of surgery.

[59]  F. Grinnell,et al.  Transforming growth factor beta stimulates fibroblast-collagen matrix contraction by different mechanisms in mechanically loaded and unloaded matrices. , 2002, Experimental cell research.

[60]  L. Nanney,et al.  Enhancement of wound healing by topical treatment with epidermal growth factor. , 1989, The New England journal of medicine.

[61]  Robert A. Brown,et al.  Duration and orientation of mechanical loads determine fibroblast cyto‐mechanical activation: Monitored by protease release , 2000, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[62]  S. Phan,et al.  Regulation of lung fibroblast alpha-smooth muscle actin expression, contractile phenotype, and apoptosis by IL-1beta. , 1997, Journal of immunology.

[63]  H. Rosenfeldt,et al.  Fibroblast Quiescence and the Disruption of ERK Signaling in Mechanically Unloaded Collagen Matrices* , 2000, The Journal of Biological Chemistry.

[64]  E. Vuorio,et al.  Epidermal growth factor increases collagen production in granulation tissue by stimulation of fibroblast proliferation and not by activation of procollagen genes. , 1987, The Biochemical journal.

[65]  M. Sporn,et al.  Transforming growth factor β levels in rat wound chambers , 1987 .

[66]  J. Fluck,et al.  Normal human primary fibroblasts undergo apoptosis in three-dimensional contractile collagen gels. , 1998, The Journal of investigative dermatology.

[67]  A K Harris,et al.  Connective tissue morphogenesis by fibroblast traction. I. Tissue culture observations. , 1982, Developmental biology.

[68]  A. Ghahary,et al.  Myofibroblasts and apoptosis in human hypertrophic scars: the effect of interferon-alpha2b. , 2001, Surgery.

[69]  A. Desmoulière,et al.  Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts , 1993, The Journal of cell biology.

[70]  G. T. Watts,et al.  The marginal localization of the contraction mechanism in open wounds. , 1957, Surgical forum.

[71]  K. von Boguslawski,et al.  Type V collagen in experimental granulation tissue. , 1998, Connective tissue research.

[72]  F. Grinnell,et al.  Fibronectin and fibrinolysis are not required for fibrin gel contraction by human skin fibroblasts , 1989, Journal of cellular physiology.

[73]  F. Hirche,et al.  Fibroblasts in Mechanically Stressed Collagen Lattices Assume a “Synthetic” Phenotype* , 2001, The Journal of Biological Chemistry.

[74]  T. Fitzgerald,et al.  Fibronectin involvement in granulation tissue and wound healing in rabbits. , 1982, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[75]  Albert K. Harris,et al.  Fibroblast traction as a mechanism for collagen morphogenesis , 1981, Nature.

[76]  Frederick Grinnell,et al.  Modulation of fibroblast morphology and adhesion during collagen matrix remodeling. , 2002, Molecular biology of the cell.

[77]  T. Borg,et al.  Beta 1 integrin-mediated collagen gel contraction is stimulated by PDGF. , 1990, Experimental cell research.

[78]  O. Dirsch,et al.  Modulation of Keratinocyte Growth Factor and Its Receptor in Reepithelializing Human Skin , 2003 .

[79]  Jonathon Howard,et al.  Slow local movements of collagen fibers by fibroblasts drive the rapid global self-organization of collagen gels , 2002, The Journal of cell biology.

[80]  H. Dvorak,et al.  Alterations in proteoglycan synthesis common to healing wounds and tumors. , 1991, The American journal of pathology.

[81]  H. D. Cavanagh,et al.  An in vitro force measurement assay to study the early mechanical interaction between corneal fibroblasts and collagen matrix. , 1997, Experimental cell research.

[82]  T M Krummel,et al.  Regulation of wound healing from a connective tissue perspective , 1996, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[83]  I. K. Cohen,et al.  Onset and Localization of Collagen Synthesis during Wound Healing in Open Rat Skin Wounds 1 , 1979, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[84]  Giulio Gabbiani,et al.  Modulation of α‐smooth muscle actin expression in fibroblasts by transforming growth factor‐β isoforms: an in vivo and in vitro study , 1996, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[85]  T. Mio,et al.  Glucocorticoid-induced contractility and F-actin content of human lung fibroblasts in three-dimensional culture. , 2000, American journal of physiology. Lung cellular and molecular physiology.

[86]  B. Tolley,et al.  Topical application of the phospholipid growth factor lysophosphatidic acid promotes wound healing in vivo. , 2001, American journal of physiology. Regulatory, integrative and comparative physiology.

[87]  E. Howard,et al.  Transforming growth factor-beta1 promotes the morphological and functional differentiation of the myofibroblast. , 2000, Experimental cell research.

[88]  F. Grinnell,et al.  Signal transduction pathways activated during fibroblast contraction of collagen matrices. , 1999, Current topics in pathology. Ergebnisse der Pathologie.

[89]  吉田 佐保.  Neutralization of Hepatocyte Growth Factor Leads to Retarded Cutaneous Wound Healing Associated with Decreased Neovascularization and Granulation Tissue Formation , 2004 .

[90]  D. Romberger,et al.  Cytokine inhibition of fibroblast-induced gel contraction is mediated by PGE(2) and NO acting through separate parallel pathways. , 2001, American journal of respiratory cell and molecular biology.

[91]  D. Foreman,et al.  Neutralisation of TGF-beta 1 and TGF-beta 2 or exogenous addition of TGF-beta 3 to cutaneous rat wounds reduces scarring. , 1995, Journal of cell science.

[92]  L. Chow,et al.  Fine Needle Aspiration May Shed Breast Cells into Peripheral Blood as Determined by RT-PCR , 2000, Oncology.

[93]  G. Gabbiani,et al.  Alpha-smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. , 1990, Laboratory investigation; a journal of technical methods and pathology.

[94]  M. Laregina,et al.  The expression of transforming growth factor type beta in fetal and adult rabbit skin wounds. , 1994, Journal of pediatric surgery.

[95]  R. Straith,et al.  THE INFLUENCE OF CORTISONE ON SKIN AND WOUND HEALING IN EXPERIMENTAL ANIMALS , 1951, Plastic and reconstructive surgery.

[96]  P. Russell,et al.  Studies on Wound Healing, with Special Reference to the Phenomenon of Contracture in Experimental Wounds in Rabbits' Skin* , 1956, Annals of surgery.

[97]  D. Hinshaw,et al.  Effects of cortisone on the healing of disrupted abdominal wounds. , 1961, American journal of surgery.

[98]  F. Grinnell,et al.  Stress relaxation of contracted collagen gels: disruption of actin filament bundles, release of cell surface fibronectin, and down-regulation of DNA and protein synthesis. , 1991, Experimental cell research.

[99]  • Epidermis,et al.  WOUND healing. , 1959, The Medical journal of Australia.

[100]  A. Pandit,et al.  The effect of TGF-beta delivered through a collagen scaffold on wound healing. , 1999, Journal of investigative surgery : the official journal of the Academy of Surgical Research.

[101]  I. Ono,et al.  Effects of a collagen matrix containing basic fibroblast growth factor on wound contraction. , 1999, Journal of biomedical materials research.

[102]  F. Coustry,et al.  Effect of transforming growth factor β on fibroblasts in three‐dimensional lattice cultures , 1990, FEBS letters.

[103]  C. Clavel,et al.  Gamma-interferon inhibits extracellular matrix synthesis and remodeling in collagen lattice cultures of normal and scleroderma skin fibroblasts. , 1992, European journal of cell biology.

[104]  R. Gamelli,et al.  Systemic Administration of Interferon-γ Impairs Wound Healing , 1994 .

[105]  L. Dubertret,et al.  The contractility of fibroblasts in a collagen lattice is reduced by corticosteroids. , 1984, The Journal of investigative dermatology.

[106]  C. Heldin,et al.  Regulation of fibroblast-mediated collagen gel contraction by platelet-derived growth factor, interleukin-1 alpha and transforming growth factor-beta 1. , 1992, Journal of cell science.

[107]  A. Vaheri,et al.  Sequential appearance of fibronectin and collagen in experimental granulation tissue. , 1980, Laboratory investigation; a journal of technical methods and pathology.

[108]  D. Romberger,et al.  Fibronectin production by cultured human lung fibroblasts in three-dimensional collagen gel culture , 1998, In Vitro Cellular & Developmental Biology - Animal.

[109]  Chris Janson.  The Oxford Textbook of Surgery , 1995, The Yale Journal of Biology and Medicine.

[110]  M. James,et al.  Acidic fibroblast growth factor accelerates dermal wound healing. , 1992, Growth factors.

[111]  T. K. Hunt,et al.  Selective effects of tumor necrosis factor-alpha on wound healing in rats. , 1989, Surgery.

[112]  K. Ehrlich.  Proteoglycan synthesis by rat lung cells cultured in vitro. , 1981, The Journal of biological chemistry.

[113]  J M Davidson,et al.  Sustained release of epidermal growth factor accelerates wound repair. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[114]  M. Abercrombie,et al.  Wound Contraction in Relation to Collagen Formation in Scorbutic Guinea-pigs , 1956 .

[115]  H. Ehrlich,et al.  Wound closure: evidence of cooperation between fibroblasts and collagen matrix , 1988, Eye.

[116]  S. Rennard,et al.  Lysophosphatidic acid augments fibroblast-mediated contraction of released collagen gels. , 2002, The Journal of laboratory and clinical medicine.

[117]  S. Werner,et al.  Transforming growth factors beta1, beta2, and beta3 and their receptors are differentially regulated during normal and impaired wound healing. , 1996, The Journal of biological chemistry.

[118]  H. Ehrlich,et al.  Fibroblast contraction of collagen lattices in vitro: Inhibition by chronic inflammatory cell mediators , 1983, Journal of cellular physiology.

[119]  F. Isik,et al.  Tissue dispersion and flow cytometry for the cellular analysis of wound healing. , 2002, BioTechniques.

[120]  Thomas A. Mustoe, MD, FACS,et al.  Transforming growth factor beta3 promotes fascial wound healing in a new animal model. , 2000, Archives of surgery.

[121]  E Bell,et al.  Living tissue formed in vitro and accepted as skin-equivalent tissue of full thickness. , 1981, Science.

[122]  J. Couper,et al.  Hepatocyte growth factor and macrophage-stimulating protein are upregulated during excisional wound repair in rats , 2001, Cell and Tissue Research.

[123]  M Eastwood,et al.  Tensional homeostasis in dermal fibroblasts: Mechanical responses to mechanical loading in three‐dimensional substrates , 1998, Journal of cellular physiology.

[124]  K. Doane,et al.  Collagen fibrillogenesis in vitro: interaction of types I and V collagen regulates fibril diameter. , 1990, Journal of cell science.

[125]  Jonathan Bard,et al.  COLLAGEN SUBSTRATA FOR STUDIES ON CELL BEHAVIOR , 1972, The Journal of cell biology.

[126]  S. Rennard,et al.  Glucocorticoids and TGF-β1 Synergize in Augmenting Fibroblast Mediated Contraction of Collagen Gels , 2001, Inflammation.

[127]  J. Aubin,et al.  Association between tension and orientation of periodontal ligament fibroblasts and exogenous collagen fibres in collagen gels in vitro. , 1982, Journal of cell science.

[128]  C. Irwin,et al.  Regulation of fibroblast-induced collagen gel contraction by interleukin-1beta. , 2007, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[129]  F. Silver,et al.  Effects of fibroblasts and basic fibroblast growth factor on facilitation of dermal wound healing by type I collagen matrices. , 1991, Journal of biomedical materials research.

[130]  Mark Eastwood,et al.  Quantitative analysis of collagen gel contractile forces generated by dermal fibroblasts and the relationship to cell morphology , 1996, Journal of cellular physiology.

[131]  M. P. Welch,et al.  Temporal relationships of F-actin bundle formation, collagen and fibronectin matrix assembly, and fibronectin receptor expression to wound contraction , 1990, The Journal of cell biology.

[132]  F. Biancari,et al.  Increased preoperative c-reactive protein level as a prognostic factor for postoperative amputation after femoropopliteal bypass surgery for CLI. , 2001, Annales chirurgiae et gynaecologiae.

[133]  T. K. Hunt,et al.  Effect of Vitamin A on Reversing the Inhibitory Effect of Cortisone on Healing of Open Wounds in Animals and Man , 1969, Annals of surgery.

[134]  G. T. Watts,et al.  Studies in Wound Healing: II. The Role of Granulation Tissue in Contraction. , 1958 .

[135]  Richard A.F. Clark,et al.  The Molecular and Cellular Biology of Wound Repair , 2012, Springer US.

[136]  A. Sommer,et al.  Recombinant basic fibroblast growth factor accelerates wound healing. , 1988, The Journal of surgical research.

[137]  A. Desmoulière,et al.  Apoptosis during wound healing, fibrocontractive diseases and vascular wall injury. , 1997, The international journal of biochemistry & cell biology.

[138]  M. Klagsbrun,et al.  Appearance of heparin-binding EGF-like growth factor in wound fluid as a response to injury. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[139]  G. T. Watts,et al.  Studies in Wound Healing: I. Contraction and the Wound Contents , 1958, Annals of Surgery.

[140]  I. Ono,et al.  Effects of collagen matrix containing transforming growth factor (TGF)-beta(1) on wound contraction. , 2001, Journal of dermatological science.

[141]  R. Bruns,et al.  On the mechanism of skin wound "contraction": a granulation tissue "knockout" with a normal phenotype. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[142]  T. Fahey,et al.  Cytokine production in a model of wound healing: the appearance of MIP-1, MIP-2, cachectin/TNF and IL-1. , 1990, Cytokine.

[143]  Gary R. Grotendorst,et al.  Stimulation of granulation tissue formation by platelet-derived growth factor in normal and diabetic rats. , 1985, The Journal of clinical investigation.

[144]  A. Ghahary,et al.  Effect of interferon‐α2b on guinea pig wound closure and the expression of cytoskeletal proteins in vivo , 1998, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[145]  I. K. Cohen,et al.  Dynamics of the matrix metalloproteinases MMP‐1 and MMP‐8 in acute open human dermal wounds , 1998, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[146]  D. I. Higton,et al.  The force of contraction of full‐thickness wounds of rabbit skin , 1964, The British journal of surgery.

[147]  M. Buck,et al.  Tumor necrosis factor-alpha inhibits collagen alpha1(I) gene expression and wound healing in a murine model of cachexia. , 1996, The American journal of pathology.

[148]  M. Varedi,et al.  Stress-relaxation and contraction of a collagen matrix induces expression of TGF-β and triggers apoptosis in dermal fibroblasts , 2000 .

[149]  T. Skalak,et al.  Lysophosphatidic acid enhances healing of acute cutaneous wounds in the mouse , 2000, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[150]  M. Longaker,et al.  Granulation tissue regression induced by musculocutaneous advancement flap coverage. , 2002, Surgery.

[151]  R. Ross,et al.  Effects of growth factors in vivo. I. Cell ingrowth into porous subcutaneous chambers. , 1987, The American journal of pathology.

[152]  G. T. Watts,et al.  Studies in wound healing: I. Contraction and the wound contents. , 1958 .

[153]  G. Gabbiani,et al.  Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction , 1971, Experientia.

[154]  Kenneth M. Yamada,et al.  Taking Cell-Matrix Adhesions to the Third Dimension , 2001, Science.

[155]  A. Barbul,et al.  Tumor necrosis factor-alpha inhibits in vivo collagen synthesis. , 1993, Surgery.

[156]  H. Ehrlich,et al.  Cell locomotion forces versus cell contraction forces for collagen lattice contraction: an in vitro model of wound contraction. , 1990, Tissue & cell.

[157]  F. Grinnell,et al.  Distribution of fibronectin during wound healing in vivo. , 1981, The Journal of investigative dermatology.

[158]  B. Hinz,et al.  Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. , 2001, Molecular biology of the cell.

[159]  M. J. Edwards,et al.  Programmed cell death in human acute cutaneous wounds , 2001, Journal of cutaneous pathology.

[160]  J. Fluck,et al.  Contraction-dependent apoptosis of normal dermal fibroblasts. , 2001, The Journal of investigative dermatology.

[161]  I. Ono,et al.  Effect of a collagen matrix containing epidermal growth factor on wound contraction , 1998, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[162]  J. Lévêque,et al.  Measurement of mechanical forces generated by skin fibroblasts embedded in a three-dimensional collagen gel. , 1991, The Journal of investigative dermatology.

[163]  J. Jerdan,et al.  Effects of TGF-beta and TGF-beta neutralizing antibodies on fibroblast-induced collagen gel contraction: implications for proliferative vitreoretinopathy. , 1994, Investigative ophthalmology & visual science.

[164]  M. Lehnhardt,et al.  Determination of Endogenous Growth Factors in Human Wound Fluid: Temporal Presence and Profiles of Secretion , 1998, Plastic and reconstructive surgery.

[165]  H. Murata,et al.  TGF-beta3 stimulates and regulates collagen synthesis through TGF-beta1-dependent and independent mechanisms. , 1997, The Journal of investigative dermatology.

[166]  F. Grinnell,et al.  Fibroblast Quiescence in Floating or Released Collagen Matrices , 2001, The Journal of Biological Chemistry.

[167]  R. Galiano,et al.  Effects of insulin‐like growth factor‐I and insulin‐like growth factor binding protein‐1 on wound healing in a dermal ulcer model , 1995, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[168]  M. Laato,et al.  Tumor necrosis factor alpha inhibits wound healing in the rat. , 1991, European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes.

[169]  J. Heino,et al.  Interleukin 1 modulates collagen accumulation by rat granulation tissue cells both in vivo and in vitro , 1988, Experientia.

[170]  M. Longaker,et al.  Wound splinting regulates granulation tissue survival. , 2003, The Journal of surgical research.

[171]  J. Xu,et al.  Extracellular matrix alters PDGF regulation of fibroblast integrins , 1996, The Journal of cell biology.

[172]  S. Werner,et al.  Glucocorticoid-regulated gene expression during cutaneous wound repair. , 2000, Vitamins and hormones.

[173]  A. Desmoulière,et al.  Effect of gamma-interferon on the clinical and biologic evolution of hypertrophic scars and Dupuytren's disease: an open pilot study. , 1994, Plastic and reconstructive surgery.

[174]  Sathyanarayana,et al.  Normoxic wound fluid contains high levels of vascular endothelial growth factor. , 1998, Annals of surgery.

[175]  Thomas A. Mustoe, MD, FACS,et al.  In vivo incisional wound healing augmented by platelet-derived growth factor and recombinant c-sis gene homodimeric proteins , 1988, The Journal of experimental medicine.

[176]  A. Desmoulière,et al.  Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. , 1995, The American journal of pathology.

[177]  Robert A. Brown,et al.  Enhanced fibroblast contraction of 3D collagen lattices and integrin expression by TGF-beta1 and -beta3: mechanoregulatory growth factors? , 2002, Experimental cell research.

[178]  F. Grinnell,et al.  Extracellular matrix organization modulates fibroblast growth and growth factor responsiveness. , 1989, Experimental cell research.

[179]  F. Maquart,et al.  Insulin‐like growth factor‐I (IGF‐i) stimulates protein synthesis and collagen gene expression in monolayer and lattice cultures of fibroblasts , 1992, Journal of cellular physiology.

[180]  E Bell,et al.  Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[181]  G. Gabbiani,et al.  The myofibroblast in wound healing and fibrocontractive diseases , 2003, The Journal of pathology.

[182]  J. Davidson,et al.  Manipulation of the wound-healing process with basic fibroblast growth factor. , 1991, Annals of the New York Academy of Sciences.

[183]  J. Davidson,et al.  Anipulation of the Wound‐Healing Process with Basic Fibroblast Growth Factor a , 1991 .