Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, CA 95616, USA.
Biomaterials. 2012 Sep;33(27):6355-61. doi: 10.1016/j.biomaterials.2012.05.045. Epub 2012 Jun 12.
Growth factors play a central role in the development and remodelling of musculoskeletal tissues. To determine which growth factors optimized in vitro ligament formation and mechanics, a Box-Behnken designed array of varying concentrations of growth factors and ascorbic acid were applied to engineered ligaments and the collagen content and mechanics of the grafts were determined. Increasing the amount of transforming growth factor (TGF) β1 and insulin-like growth factor (IGF)-1 led to an additive effect on ligament collagen and maximal tensile load (MTL). In contrast, epidermal growth factor (EGF) had a negative effect on both collagen content and MTL. The predicted optimal growth media (50 μg/ml TGFβ, IGF-1, and GDF-7 and 200 μM ascorbic acid) was then validated in two separate trials: showing a 5.7-fold greater MTL and 5.2-fold more collagen than a minimal media. Notably, the effect of the maximized growth media was scalable such that larger constructs developed the same material properties, but larger MTL. These results show that optimizing the interactions between growth factors and engineered ligament volume results in an engineered ligament of clinically relevant function.
生长因子在肌肉骨骼组织的发育和重塑中起着核心作用。为了确定哪些生长因子能优化体外韧带形成和力学性能，我们采用 Box-Behnken 设计的不同浓度生长因子和抗坏血酸阵列，应用于工程化韧带，并确定移植物的胶原含量和力学性能。增加转化生长因子 (TGF)β1 和胰岛素样生长因子 (IGF)-1 的含量会对韧带胶原和最大拉伸载荷 (MTL) 产生附加效应。相比之下，表皮生长因子 (EGF) 对胶原含量和 MTL 都有负面影响。然后，在两个单独的试验中验证了预测的最佳生长培养基 (50μg/mlTGFβ、IGF-1 和 GDF-7 以及 200μM 抗坏血酸)：显示出 MTL 增加了 5.7 倍，胶原增加了 5.2 倍，比最小培养基多。值得注意的是，最大生长培养基的效果是可扩展的，因此更大的构建体具有相同的材料特性，但更大的 MTL。这些结果表明，优化生长因子与工程化韧带体积之间的相互作用可得到具有临床相关功能的工程化韧带。
