Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells
Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells
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DOI：
10.1016/j.bone.2004.02.027
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发表时间：
2004-08-01
期刊：
影响因子：
4.1
通讯作者：
Mooney, DJ
中科院分区：
文献类型：
--
作者：
Simmons, CA;Alsberg, E;Mooney, DJ
通常需要超生理浓度的外源性生长因子来获得骨再生，目前还不清楚为什么较低水平无效。我们假设骨祖细胞沿着与生长因子和支架特征的适当组合的递送将允许生理剂量的蛋白质用于治疗性骨再生。我们测试了这一假设，通过测量骨形成的大鼠骨髓基质细胞（BMSCs）异位移植在SCID小鼠使用藻酸盐水凝胶。藻酸盐被γ-辐射以改变降解速率，然后用含有RGD的肽共价修饰以控制细胞行为。在相同的运载工具中，我们将骨形态发生蛋白-2（BMP-2）和转化生长因子-β（TGF-β 3）单独或组合。无论植入物降解率如何，单独递送BMP 2或TGF-β 3导致可忽略的骨组织形成长达22周。相比之下，当生长因子从易降解的水凝胶中一起递送时，移植的BMSCs早在植入后6周就有显著的骨形成。此外，骨形成，这似乎发生的软骨内骨化，实现了与双生长因子条件下的蛋白质浓度比以前报道的骨形成所需的低一个数量级以上。这些数据表明，在基于细胞的组织工程系统中，可溶性和生物材料介导的调节信号的适当组合可以导致更高效和更有效的组织再生。(C)2004年爱思唯尔公司All rights reserved.
Supraphysiological concentrations of exogenous growth factors are typically required to obtain bone regeneration, and it is unclear why lower levels are not effective. We hypothesized that delivery of bone progenitor cells along with appropriate combinations of growth factors and scaffold characteristics would allow physiological doses of proteins to be used for therapeutic bone regeneration. We tested this hypothesis by measuring bone formation by rat bone marrow stromal cells (BMSCs) transplanted ectopically in SCID mice using alginate hydrogels. The alginate was gamma-irradiated to vary the degradation rate and then covalently modified with RGD-containing peptides to control cell behavior. In the same delivery vehicle, we incorporated bone morphogenetic protein-2 (BMP2) and transforming growth factor-beta (TGF-beta3), either individually or in combination. Individual delivery of BMP2 or TGF-beta3 resulted in negligible bone tissue formation up to 22 weeks, regardless of the implant degradation rate. In contrast, when growth factors were delivered together from readily degradable hydrogels, there was significant bone formation by the transplanted BMSCs as early as 6 weeks after implantation. Furthermore, bone formation, which appeared to occur by endochondral ossification, was achieved with the dual growth factor condition at protein concentrations that were more than an order of magnitude less than those reported previously to be necessary for bone formation. These data demonstrate that appropriate combinations of soluble and biomaterial-mediated regulatory signals in cell-based tissue engineering systems can result in both more efficient and more effective tissue regeneration. (C) 2004 Elsevier Inc. All rights reserved.