Gml 21 in 2012 byun et al reported that the effective

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g/ml [21]. In 2012, Byun et al. reportedthat the effective dose of tacrolimus for the osteoblastic differ-entiation of rat mesenchymal cells was 0.41μg/ml [48].However, in the in vivo conditions, the effective dose of thedrug is significantly different from the one necessary in thevitro environment. Most of the animal studies investigatingthe effect of administration of tacrolimus on bones repairwere performed by intravenous administration. For example,Zheng et al. showed that systemic prescription of the drug hada negative effect on bone-implant contact and the amount ofbone formation around titanium implant in the rat [49].Different animal studies have shown that systemic administra-tion of tacrolimus can cause a decrease in bone mineral den-sity and trabecular bone loss in rats [5055]. In these studies,the dose of tacrolimus was at least 1 mg/kg per day adminis-trated orally. Folwarczna et al. reported that the oral adminis-tration of 0.3 mg/kg/day tacrolimus for a month did not reducethe mineral density of rats femur and tibia [56]. There are twopossibilities for decreasing bone mineral density and trabecu-lar bone loss: one is that tacrolimus has a direct toxic effect onosteogenic cells, which is less likely due to studies donein vitro that show the positive effect of tacrolimus on thedifferentiation of osteoblastic cells and result of this studyconfirms in vitro studies. And the second possibility is aboutthe indirect effect of tacrolimus on bone formation due to itseffect on suppression of the immune system and indirectlyreduces the number of cytokines that contribute to bone for-mation [49].By using a mechanical barrier, such as the use of mem-branes, it is possible to prevent the entry of fibroblasts andsoft connective tissue into bone defects, so cells that haveosteogenic potential but move slowly can accumulate in de-fect [57]. On the other hand, several studies reported foreignbody reaction when using polymeric membrane alone[5861]. The results of this study indicate that in the controlgroup, the number of fibroblasts is significantly higher than inthe other groups. On the other hand, by adding PCL/gelatinmembrane on the empty defect, a lot of multinuclear giant cellaccumulated around PCL/gelatin membrane. Finally, usingmembrane not only prevented defect site from leakage of hy-drogel but also, because of the positive effect of PCL/gelatinon bone healing, improved the number of fibroblast and en-hanced bone healing.ConclusionIn this study, we prepared collagen-based hydrogel scaffoldscontaining tacrolimus and surrounded by a PCL/gelatin mem-brane and characterized them with regard to their utility forusing in bone tissue engineering application. In vivo studyprovided a preliminary evidence of the efficacy of the devel-oped hydrogel for the treatment of bone defects.

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Term
Fall
Professor
NoProfessor
Tags
Collagen, Tacrolimus, Mesenchymal stem cell

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