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JCR 2016
جستجوی مقالات
یکشنبه 23 آذر 1404
Cell Journal
، جلد ۱۵، شماره Suppl ۱، صفحات ۱۰-۱۰
عنوان فارسی
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کلیدواژههای فارسی مقاله
عنوان انگلیسی
Is-21: Construction of A Novel 3D Living Hyaline Cartilaginous Graft (LhCG) As In Vitro Endochondral Niches for Engineered Osteo/Chondrogenesis
چکیده انگلیسی مقاله
This study is designed and practiced for engineered articular regenerative medicine. The traditional approach is to mimic pre-cartilage condensation during primary development, that is, to first generate chondrocyte isogenic groups (colonies) via suspended pellet culture, then condense these chondrocytic pellets into scattered nodules-like microscopic cartilaginous tissues, and further assemble these pieces of micro-tissues into a single piece of tangible macro-scaled cartilaginous tissue. The disadvantage of this “stack-up” strategy is that the final cartilaginous tissue generated remains too small in size to be practically handled for any applications and in the process of scaling up from micro to macro tissue, it would inevitably cause various degrees of phenotype loss as well as introduction of impurities, typically, due to collagen type I related fibrosis. In this study, we have innovatively developed a continuous methodology to directly set up a macro-scaled three-dimensional (3D) living hyaline cartilage graft (LhCG) with the aid of a biomaterial-based interim scaffolding system - alginate hydrogel in which hyaline chondrocytes are accommodated and guided to grow into scattered micro-tissues and further interconnecting them into an integrated 3D macro-network made of pure tissues, interpenetrating with the biomaterialbased scaffolds. By then, alginate hydrogel as an interim scaffold is no longer necessary and thus is completely and noninvasively removed by simple citric leaching treatment so that a pure cartilaginous tissue and chondrocytes based tangible piece of living cartilage graft is created. Owing to the intrinsic non-cell-adhesive property of hydrogel scaffolds, hyaline chondrocytes’ phenotype is always preserved throughout the whole procedure. Hence, after the removal of alginate scaffold, the resultant porous sponge-like LhCG of high purity and genuineness is guaranteed. Furthermore, good osteochondral defect healing and complete integration with adjacent native cartilage (NC) in in situ implantation of LhCG samples in rabbit model demonstrated the competence of LhCG as a cartilage graft. Since the newly made LhCG is porous and rich in ECM, it can serve as a viable open platform for further cell seeding to either enhance cartilaginous formation or target at other tissue or organ regenerations. Given the established cartilaginous construction, we also explored the possibilities of using LhCG as a ready-made platform to mimic endochondral osteogenesis for bone formation. The results suggest that LhCG not only serves as a good living graft for cartilage regeneration, it is able to achieve significant ossification when directed toward osteogenesis via a simple switch in media composition. The on-going research with LhCG is to introduce angiogenesis by hybridizing endothelial progenitor cells (EPCs) in pursuit of a complete ossification in situ. We believe that with capillary network in place in LhCG platform, the application of LhCG is not restricted to cartilage or bone regeneration; LhCG could be directed to many other tissue and organ regenerations.
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http://celljournal.org/journal/article/abstract/786
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