Dextran derivatives modulate collagen matrix organization in dermal equivalent.
Dextran derivatives can protect heparin binding growth factor implied in wound healing, such as transforming growth factor-beta1 (TGF-beta1) and fibroblast growth factor-2 (FGF-2). The first aim of this study was to investigate the effect of these compounds on human dermal fibroblasts in culture with or without TGF-beta1. Several dextran derivatives obtained by substitution of methylcarboxylate (MC), benzylamide (B) and sulphate (Su) groups were used to determine the effects of each compound on fibroblast growth in vitro. The data indicate that sulphate groups are essential to act on the fibroblast proliferation. The dextran derivative LS21 DMCBSu has been chosen to investigate its effect on dermal wound healing process. Fibroblasts cultured in collagenous matrices named dermal equivalent were treated with the bioactive polymer alone or associated to TGF-beta1 or FGF-2. Cross-sections of dermal equivalent observed by histology or immunohistochemistry, demonstrated that the bioactive polymer accelerates the collagen matrices organization and stimulates the human type-III collagen expression. This bioactive polymer induces apoptosis of myofibroblast, property which may be beneficial in treatment of hypertrophic scar. Culture media analyzed by zymography and Western blot showed that this polymer significantly increases the secretion of zymogen and active form of matrix metalloproteinase-2 (MMP-2), involved in granulation tissue formation. These data suggest that this bioactive polymer has properties which may be beneficial in the treatment of wound healing.
Frank
Laetitia
L
THERAPOL S.A., 63 rue de Strasbourg, 93200 Saint Denis, France. laetitia_frank@yahoo.fr
Lebreton-Decoster
Corinne
C
Godeau
Gaston
G
Coulomb
Bernard
B
Jozefonvicz
Jacqueline
J
D000199:Actins / Q000032:analysis; D001593:Benzyl Compounds / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002675:Child, Preschool; D003094:Collagen / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism; D020405:Dermis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003911:Dextrans / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D015394:Molecular Structure; D009130:Muscle, Smooth / Q000737:chemistry; D017768:Skin, Artificial; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D000199:Actins; D001593:Benzyl Compounds; D024061:Collagen Type III; D003911:Dextrans; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C438406:dextranmethylcarboxylate benzylamide sulfate; D016222:Fibroblast Growth Factor 2; D003094:Collagen; D020778:Matrix Metalloproteinase 2