Injectable osteogenic microtissues containing mesenchymal stromal cells conformally fill and repair critical-size defects

Injectable osteogenic microtissues containing mesenchymal stromal cells conformally fill and repair critical-size defects
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DOI:
10.1016/j.biomaterials.2019.04.001
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发表时间:
2019-07-01
期刊:
影响因子:
14
通讯作者:
Stegemann, Jan P.
Stegemann, Jan P.
中科院分区:
工程技术1区
文献类型:
--
作者:
Annamalai, Ramkumar T.;Hong, Xiaowei;Stegemann, Jan P.

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骨丢失的复杂骨折的修复需要强有力的。空间填充干预,促进骨再生。我们提出了一种基于生物材料的策略,将间充质基质细胞(MSC)与壳聚糖-胶原蛋白基质相结合,形成模块化微组织,设计用于通过针递送以保形地填充腔体缺损。将微组织植入小鼠的颅骨缺损中表明,成骨预分化的MSC导致腔的完全桥接,而未分化的MSC仅在与天然骨并置中产生矿化组织。减少植入物体积会减少骨再生,而增加MSC浓度也会减弱骨形成,这表明细胞-基质比在实现稳健反应方面很重要。在载体凝胶中用微组织保形填充缺损导致完全愈合。总之,这些结果表明,模块化微组织可用于增强MSC的分化功能,并提供增强骨修复的细胞外环境。
Repair of complex fractures with bone loss reauires a potent. space-filling intervention to promote regeneration of bone. We present a biomaterials-based strategy combining mesenchymal stromal cells (MSC) wan a cnitosan-collagen matrix to form modular microtissues designed for delivery through a needle to conformally fill cavital defects. Implantation of microtissues into a calvarial defect in the mouse showed that osteogenically pre-differentiated MSC resulted in complete bridging of the cavity, while undifferentiated MSC produced mineralized tissue only in apposition to native bone. Decreasing the implant volume reduced bone regeneration, while increasing the MSC concentration also attenuated bone formation, suggesting that the cell-matrix ratio is important in achieving a robust response. Conformal filling of the defect with microtissues in a carrier gel resulted in complete healing. Taken together, these results show that modular microtissues can be used to augment the differentiated function of MSC and provide an extracellular environment that potentiates bone repair.