Semipermeable Capsules Wrapping a Multifunctional and Self-regulated Co-culture Microenvironment for Osteogenic Differentiation.
Semipermeable Capsules Wrapping a Multifunctional and Self-regulated Co-culture Microenvironment for Osteogenic Differentiation.
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DOI：
10.1038/srep21883
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发表时间：
2016-02-24
影响因子：
4.6
通讯作者：
Mano JF
中科院分区：
文献类型：
--
作者：
Correia CR;Pirraco RP;Cerqueira MT;Marques AP;Reis RL;Mano JF
受骨多表型细胞环境的启发，提出了一种含有细胞和支持微粒共培养的半渗透储层的新概念。基于对“干细胞生态位”的解构，开发的胶囊被设计为驱动自我调节的成骨。用I型胶原功能化的PLLA微粒，以及脂肪干细胞（ASCs）和内皮细胞（ECs）的共培养，被固定在球形液体胶囊中。胶囊被多层聚赖氨酸、海藻酸盐和壳聚糖纳米层包裹。单独包封ASCs的胶囊或与ECs共培养的胶囊在有或没有成骨分化因子的内皮培养基中培养。结果表明，即使在没有分化因子的情况下，共包封也能促进成骨。ALP活性和基质矿化、骨桥蛋白检测以及BMP-2、RUNX2和BSP的上调支持了这些发现。液化的共胶囊也作为VEGF和BMP-2细胞因子释放系统。所提出的液体胶囊可能是一种有价值的可注射的自我调节系统，用于骨再生，采用高度翻译的细胞来源。
A new concept of semipermeable reservoirs containing co-cultures of cells and supporting microparticles is presented, inspired by the multi-phenotypic cellular environment of bone. Based on the deconstruction of the “stem cell niche”, the developed capsules are designed to drive a self-regulated osteogenesis. PLLA microparticles functionalized with collagen I, and a co-culture of adipose stem (ASCs) and endothelial (ECs) cells are immobilized in spherical liquified capsules. The capsules are coated with multilayers of poly(L-lysine), alginate, and chitosan nano-assembled through layer-by-layer. Capsules encapsulating ASCs alone or in a co-culture with ECs are cultured in endothelial medium with or without osteogenic differentiation factors. Results show that osteogenesis is enhanced by the co-encapsulation, which occurs even in the absence of differentiation factors. These findings are supported by an increased ALP activity and matrix mineralization, osteopontin detection, and the up regulation of BMP-2, RUNX2 and BSP. The liquified co-capsules also act as a VEGF and BMP-2 cytokines release system. The proposed liquified capsules might be a valuable injectable self-regulated system for bone regeneration employing highly translational cell sources.