Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation.
Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation.
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DOI：
10.1038/nmat4407
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发表时间：
2015-12
期刊：
影响因子：
41.2
通讯作者：
Mooney DJ
中科院分区：
文献类型：
--
作者：
Huebsch N;Lippens E;Lee K;Mehta M;Koshy ST;Darnell MC;Desai RM;Madl CM;Xu M;Zhao X;Chaudhuri O;Verbeke C;Kim WS;Alim K;Mammoto A;Ingber DE;Duda GN;Mooney DJ
干细胞疗法的有效性受到细胞死亡和对命运的有限控制的阻碍。这些问题可以通过使用大孔生物材料来部分规避，这些大孔生物材料可以提高移植干细胞的存活率，并提供分子线索来指导细胞表型。干细胞的行为也可以在体外通过操纵多孔和非多孔材料的弹性来控制，但转化为体内治疗过程仍然是难以捉摸的。在这里，通过开发可注射的，形成空隙的水凝胶，从弹性解耦孔形成，我们表明，间充质干细胞（MSC）在体外成骨，细胞部署在体外和体内，可以通过修改，分别控制，水凝胶的弹性模量或其化学。当水凝胶用于移植MSC时，水凝胶的弹性调节骨再生，在60 kPa下骨形成最佳。我们的研究结果表明，生物物理线索可以利用直接原位治疗干细胞的行为。
The effectiveness of stem-cell therapies has been hampered by cell death and limited control over fate. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype. Stem cell behavior can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel's elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel's elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem-cell behaviors in situ.