heparitin-sulfate and Cicatrix

Several Heparin-Binding Growth Factors (HBGFs) are known to play an important role in bone repair. When osseous tissue is injured, an important increase of protease activities and a massive release of HBGFs occur. The local increase in HBGFs content at the wounded site, produced by a release of this factors from cells implicated in haemostasis and inflammatory reaction and from extracellular matrix associated heparan sulfate proteoglycans (HSPGs), seems to be a crucial step in bone healing. The proteolysis associated with the tissue injury probably limits the growth factors activities at the wound site. In order to define the bone healing potential of molecules that would be able to protect HBGFs against proteolytic activation, we studied the effect of derived dextrans, named carboxymethyl-benzylamide-sulfonated dextrans (CMDBS), behaving as heparan like molecules, in 5 mm in diameter skull trepaned defects in young adult rats. In this model CMDBS induced an important bone regeneration in a dose dependent manner while controls were not repaired. In CMDBS treated animals the defects were repaired and contained a tissue of normal appearance; in several treated animals the sagittal suture, initially removed by the trephination, was restored. This remarkable bone healing potential of CMDBS may result from the capacity to protect the endogenous HBGFs from proteolysis and to modulate their biological activities, in a similar manner to that observed for fibroblast growth factors and HSPGs. CMDBS represent a new form of bone healing agents, which have the advantage of being produced by a controlled chemical synthesis, and of avoiding the use of exogenous growth factors because of their capacity to enhance the bone healing potential of the endogenous growth factors.

Topics: Animals; Bone and Bones; Cicatrix; Dextrans; Fibroblast Growth Factors; Heparitin Sulfate; Osteogenesis; Rats; Wound Healing

Burn-related skin fibrosis leads to loss of tissue function and hypertrophic scar formation with damaging consequences for the patient. There is therefore a great need for an efficient agent to treat burned skin. We report that ReGeneraTing Agent (RGTA) reduces burn-induced skin alteration. The tissue-regenerating effect of RGTA OTR4120 was evaluated after 1-6 days and after 10 months in a rat skin burn model. This effect was also examined in vitro using fibroblasts isolated from control and 6-day-old burned skins. We measured production of dermal collagen I, III, and V and activities of metalloproteinases 2 and 9 (MMP-2 and MMP-9). Ratio of collagen III over collagen I production increased 6 days after the burn, because of a decrease in collagen I production. After 10 months, ratio of collagen III over collagen I in burn sites was still increased compared with control skin, because of an increase in collagen III production. Both abnormalities were corrected by OTR4120. OTR4120 increased pro- and active MMP-2 and MMP-9, compared with healthy and burned controls and therefore accelerated remodeling. Similar data were obtained with cultured fibroblasts from healthy and burned skins. OTR4120 enhanced healing in short- and long-term after burns, reducing the formation of fibrotic tissue, and then represents a potential agent to improve burned skin healing.

Topics: Animals; Biomimetic Materials; Burns; Cicatrix; Fibrillar Collagens; Heparitin Sulfate; Humans; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Rats; Rats, Nude; Skin; Time Factors; Wound Healing

Heparan sulfate (HS), unlike other glycosaminoglycans, is mainly located on cell surfaces but can be shed into the interstitium by a regulated process. It has been found in interstitial fluid drained from cutaneous wounds, but otherwise the conditions under which the release of HS from the cell surface occurs are unknown. To better characterize this process, we have investigated the presence of interstitial HS in various skin diseases with glycosaminoglycan accumulation.. Histologic routine material was stained immunohistochemically using an antibody recognizing HS.. Heparan sulfate immunoreactivity is present in the interstitium of young cutaneous scars and in the interstitium of the inflammatory infiltrate of granuloma annulare. No reactivity was found in a number of non-inflammatory skin diseases with mucin deposition.. The selective presence of interstitial HS in only two of the investigated skin conditions supports the existence of a regulated mechanism to release HS from the surface of cells into the interstitium. It is suggested that HS modulates the biologic actions of growth factors and cytokines not only during wound repair but possibly also in inflammatory skin diseases such as granuloma annulare.

Topics: Cicatrix; Granuloma Annulare; Heparitin Sulfate; Humans; Immunoenzyme Techniques; Mucins; Skin; Wound Healing

Topics: Adult; Aged; Cicatrix; Dermatan Sulfate; Fascia; Female; Femoral Fractures; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Male; Middle Aged; Water

Synthesis of extracellular matrix by dermal fibroblasts is an important component of cutaneous wound repair. Scar remodeling and maturation is generally seen as the result of a fibroblast-regulated equilibrium between production and degradation of specific matrix constituents. Fibroblasts from normal dermis, reparative granulation tissue and mature scars were compared in vitro in terms of their ability to produce extracellular glycosaminoglycans (GAGs). All cell lines secreted dermatan sulfate (DS) and chondroitin sulfate (CS) into the culture medium. Hyaluronate (HA) was detected in medium from mature granulation tissue and scar cells, but little or none was found in medium from early granulation tissue or skin cells. In medium from normal skin fibroblasts, an unusual GAG was identified as a potential variant of DS on the basis of co-migration with HA but susceptibility to digestion with chondroitinase ABC. Heparan sulfate (HS) was the major pericellular GAG of all cultures except the mature scar cells, which contained a predominance of DS. A second pericellular GAG was identified as CS in mature granulation tissue cells, scar cells and skin cells; while HA was identified in the pericellular matrix of early granulation tissue cells. In addition, fibroblasts from both skin and early granulation tissue contained a GAG believed to be a variant of CS. These differences in GAG synthesis/secretion between cells maintained under identical culturing conditions could indicate either that distinct fibroblastic substrains exist during different stages of healing or that influences present during the healing process induce stable phenotypic alterations that are maintained through explant culturing and subsequent subcultivation.

Topics: Animals; Cells, Cultured; Cicatrix; Fibroblasts; Glycosaminoglycans; Heparitin Sulfate; Rabbits; Skin; Wound Healing