Laetitia Frank | PubMed Health

PubMed2006

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.

Actins↗

PubMed2004

Effect of a dextran derivative associated with TGF-beta1 or FGF-2 on dermal fibroblast behaviour in dermal equivalents.

Dextran derivatives that mimic the action of heparin have been shown to protect heparin-binding growth factors, such as Transforming Growth Factor-beta1 (TGF-beta1) and Fibroblast Growth Factor-2 (FGF-2). The aim of this study was to investigate the effect of LS21 DMCBSu, a dextran derivative which contains methylcarboxylate, benzylamide and sulfate groups, both by itself and when combined with TGF-beta1 and FGF-2, on the behaviour of fibroblasts. Two systems were assessed: a monolayer culture and three-dimensional collagenous matrices (dermal equivalent). Polymeric biomaterial LS21 DMCBSu and LS21 DMCBSu associated with either TGF-beta1 or FGF-2, were added to the monolayer culture on day 3. After 7 days of culture the number of cells was determined. Two treatments were carried out on the dermal equivalents: 9 days of treatment from day 0 to day 9 of culture and 9 days of treatment from day 21 to day 30 of culture for the premature and the mature dermal equivalents respectively. In the monolayer culture, the bioactive polymer produced a slight increase in fibroblast growth (10% with 10 microg/ml of LS21 DMCBSu) and promoted the stimulating effect of the growth factors on cell growth. In the premature dermal equivalents growth was stimulated by 20% when 10 microg/ml LS21 DMCBSu was added. The dextran derivative mixed with TGF-beta1 slightly inhibited the growth effect of the growth factor in the dermal equivalents. The functionalized dextran with FGF-2 enhanced the stimulating effect of the growth factor in the premature dermal equivalent. A significant increase in cell growth was observed with the fibroblasts treated with the FGF-2 LS21 DMCBSu mixture and FGF-2 (51% and 40%, respectively). However, none of the described treatments affected the cell growth in the mature dermal equivalent. Furthermore, the dextran derivative had no effect on dermal contraction under these experimental conditions (3D culture).

Cell Differentiation↗