The regulatory influence of the pineal gland on superficial wound healing and collagen content is documented. The aim of the present study was to determine whether the pineal gland and its secretory product melatonin regulate collagen accumulation in the scar of the infarcted heart and to explain the mechanisms of its action. To induce myocardial infarction in rats the left coronary artery was ligated. Metoprolol at the dose of 0.2 mg/100 g body weight (b.w.) was injected intraperitoneally to inhibit melatonin secretion. Pinealectomy was performed on some animals. For the in vitro study, cells were isolated from the heart scar and cultured in Dulbecco's modified Eagle medium with 3% fetal calf serum and antibiotics. Collagen content was evaluated as hydroxyproline content according to the Woessner method. Melatonin subcutaneously injected into the rats at the doses of 30 microg/100 g or 60 microg/100 g b.w. increased collagen accumulation in the heart scar. The doses of 3 microg/100 g b.w. and 300 microg/100 g b.w. were not effective. Surgical and pharmacological pinealectomies had opposite effects and reduced collagen content in the scar. However, melatonin administration (60 microg/100 g b.w.) to pinealectomized rats reversed the effect of pinealectomy and normalized collagen levels in heart after infarction. Cells isolated from the heart scar were identified as myofibroblasts. Melatonin (10(-7)-10(-8) m) increased collagen accumulation in the cultures. Collagen accumulation in the scar of the infarcted heart is regulated by melatonin and it exerts effects directly on the myofibroblasts of the infarcted area. Therefore, melatonin-induced collagen accumulation in the infarcted heart could be considered as the event improving the tensile strength of the scar and retarding the development of complications.

Background. Tissue engineering is a strategy aimed at improving the regeneration of injured tissues.Objectives. The aim of the present study was to determine whether a tri-copolymer composed of crosslinked collagen, chondroitin sulfate and hyaluronic acid (Col + CS + HA) provides a better environment for fibroblast and embryonic nerve cell culture than a collagenous scaffold (Col).Material and methods. The porosity of each of the matrices was characterized with a scanning electron microscope. Fibroblasts were isolated from rat wound granulation tissue (polypropylene net implanted subcutaneously). Embryonic nerve cells were obtained from the brains of rat embryos. The cells were applied to scaffolds and then stained with bisbenzimide to calculate cell entrapment within the material. The metabolic activity of the cells cultured within the scaffolds was tested using the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay.Results. The Col scaffolds had a homogenously porous structure with a pore diameter of 50 μm for 70% of pores. The pore diameter in the tri-copolymer (Col + HA + CS) ranged from 24 to 160 μm (95% of total pore volume). Four times more cells (fibroblasts and embryonic nerve cells) were trapped within the superficial part of the collagenous scaffold than that of the tri-copolymer. On the third day of culture the metabolic activity of the fibroblasts within the 2 tested scaffolds was significantly higher than in the control conditions (cell culture on a laminin-coated surface). Also, the embryonic nerve cells demonstrated increased metabolic activity in Col + CS + HA scaffolds than the Col scaffolds.Conclusions. Both fibroblasts and embryonic nerve cells could be seeded within the 2 tested scaffolds. Both the scaffolds provide good conditions for fibroblast culture. However, the Col + CS + HA tri-copolymer is preferable for embryonic nerve cell engineering.

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Background:We sought to determine the usefulness of electrospun dibutyrylchitin (DBC) or poly-(ε-caprolactone [PCL]), in wound treatment. We investigated the mechanisms of action of these polymers on wound healing. Methods:We synthesized DBC, a newly identified ester derivative of chitin, using a patented method comprising the substitution of butyryl groups at positions C-3 and C-6 in chitin molecules. We confirmed the double substitution by the butyric groups using infrared spectrometry. The fibrous scaffolds were obtained using the electrospinning method. A polypropylene net was implanted subcutaneously in the rat and served as a wound model. Results:Both DBC and PCL increased granulation tissue weight in the wound. In contrast to PCL, DBC did not abolish glycosaminoglycan changes in wounds. The tested samples did not impair total collagen synthesis or induce excessive fibrosis. In both PCL-and DBC-treated wounds, we observed a lower level of soluble collagen (compared with controls). The results show better hydration of the wounds in both the DBC and PCL groups. No induction of large edema formation by the tested materials was observed. These polymers induced almost identical macrophagemediated reactions to foreign-body implantation. The implants increased the blood vessel number in a wound. Conclusion:Both PCL and DBC could be used as scaffolds or dressings for wound treatment. The materials were safe and well tolerated by animals. As DBC did not disturb glycosaminoglycan accumulation in wounds and absorbed twice as much liquid as PCL, it can be considered superior.Contexte : Nous avons cherché à déterminer l'utilité du dibutyryl-chitine (DBC) ou du poly-(ε-caprolactone [PCL]) électrofilés dans le traitement des plaies. Nous avons étudié les mécanismes d'action de ces polymères sur la cicatrisation des plaies.Méthodes : Nous avons synthétisé le DBC, un dérivé ester récemment identifié de la chitine, à l'aide d'une méthode brevetée incluant la substitution des groupes butyryl aux positions C-3 et C-6 des molécules de chitine. Nous avons confirmé la substitution double par les groupes butyriques à l'aide de la spectrométrie infrarouge. Les échafaudages fibreux ont été obtenus grâce à la méthode de filage électrostatique. Un filet en polypropylène a été implanté par voie sous-cutanée dans le rat et a servi de modèle de plaie. Résultats :Le DBC et le PCL ont tous deux augmenté le poids du tissu de granulation dans la plaie. Contrairement au PCL, le DBC n'a pas supprimé les changements des glycosaminoglycanes des plaies. Les échantillons examinés n'ont pas perturbé la synthèse totale de collagène ni entraîné une fibrose excessive. Nous avons observé un niveau inférieur de collagène soluble (par rapport aux témoins) tant dans les plaies traitées par PCL que par DBC. Les résultats montrent une amélioration de l'hydratation des plaies tant pour les groupes DBC que PCL. Les matériaux à l'étude n'induisaient pas d'oedème étendu. Ces polymères ont induit des réactions macrophagiques presque identiques à l'implantation ...

The effects of aminoguanidine (a histamine inhibitor) and 48/80 (a histamine liberator) on the levels of histamine, soluble collagen fraction and total collagen in the chick embryos were studied. Histamine content in bones (tibia and femur) and skin markedly increased in the embryos treated with aminoguanidine. Aminoguanidine treatment was followed by a decrease of total collagen and an increase of soluble collagen fraction both in bones and skin. 48/80 did not change the histamine level in the bones but decreased that in the skin. 48/80 administration resulted in an augmentation of the total collagen content in the skin. Both in the skin and bones soluble collagen fraction was found to be lower in 48/80 treated embryos.

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The studies were undertaken to investigate the influence of compound 48/80 on histamine (Hi) and collagen levels of chick embryos after administration of lathyrogen factor, beta-aminopropionitrile (BAPN). Hi and soluble collagen levels in bones (tibia and femur) and skin were significantly higher in the embryos treated with BAPN. Compound 48/80 administered together with BAPN lowered Hi and soluble collagen in the bones and skin as compared with the embryos treated with BAPN alone. Both, in the skin and bones, 48/80 was found to be a protective factor against the changes in biosynthesis of collagen.