Wang Yongzhong, Singh Amarjit, Xu Peng, Pindrus Mariya A, Blasioli Dominick J, Kaplan David L
Department of Chemical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
Biomaterials. 2006 Jun;27(17):3265-73. doi: 10.1016/j.biomaterials.2006.01.036. Epub 2006 Feb 21.
In human body ascorbic acid plays an essential role in the synthesis and function of skeletal tissues and immune system factors. Ascorbic acid is also a major physiological antioxidant, repairing oxidatively damaged biomolecules, preventing the formation of excessive reactive oxygen species or scavenging these species. We recently reported the synthesis of ascorbic acid-functionalized polymers in which the antioxidant features of the pendant ascorbic acid groups was preserved. In the present work we demonstrate that ascorbic acid-functionalized poly(methyl methacrylate) (AA-PMMA) can modulate the proliferation and osteogenic differentiation of early and late-passage bone marrow-derived human mesenchymal stem cells (MSCs). The covalently coupled ascorbic acid impacted MSCs differently than when ascorbic acid was presented to the cells in soluble form. At optimal concentration, the covalently coupled ascorbic acid and soluble ascorbic acid synergistically promoted and retained the ability of MSCs to respond to osteogenic stimulation over extensive cell expansions in vitro. In the presence of soluble ascorbic acid, AA-PMMA films prepared at optimal concentrations (0.1 mg/ml in the present study) showed a significant promotive effect over other concentrations and tissue culture plastic (TCP) with respect to osteogenic differentiation of both EP (young) and LP (old) MSCs. These results suggest that the coupled ascorbic acid is acting mainly at the extracellular level and, at optimal concentrations, the immobilized extracellular ascorbic acid and soluble ascorbic acid synergistically promote osteogenic differentiation of MSCs. Importantly, the covalently coupled ascorbic acid on the films of optimal concentration was able to preserve the capacity of MSCs to undergo osteogenic differentiation in vitro. These results suggest an important role for functionalized biomaterials with antioxidant features in control of cell physiology and cell aging phenomena.
在人体中，抗坏血酸在骨骼组织和免疫系统因子的合成及功能中发挥着重要作用。抗坏血酸也是一种主要的生理抗氧化剂，可修复氧化损伤的生物分子，防止过量活性氧物种的形成或清除这些物种。我们最近报道了抗坏血酸功能化聚合物的合成，其中侧链抗坏血酸基团的抗氧化特性得以保留。在本工作中，我们证明抗坏血酸功能化的聚甲基丙烯酸甲酯（AA-PMMA）可以调节早期和晚期传代的人骨髓间充质干细胞（MSC）的增殖和成骨分化。共价偶联的抗坏血酸对MSC的影响与以可溶性形式向细胞提供抗坏血酸时不同。在最佳浓度下，共价偶联的抗坏血酸和可溶性抗坏血酸协同促进并保留了MSC在广泛的体外细胞扩增过程中对成骨刺激作出反应的能力。在存在可溶性抗坏血酸的情况下，以最佳浓度（本研究中为0.1mg/ml）制备的AA-PMMA膜对早期传代（年轻）和晚期传代（年老）MSC的成骨分化均显示出比其他浓度和组织培养塑料（TCP）更显著的促进作用。这些结果表明，偶联的抗坏血酸主要在细胞外水平起作用，并且在最佳浓度下，固定化的细胞外抗坏血酸和可溶性抗坏血酸协同促进MSC的成骨分化。重要的是，最佳浓度膜上共价偶联的抗坏血酸能够保留MSC在体外进行成骨分化的能力。这些结果表明具有抗氧化特性的功能化生物材料在控制细胞生理和细胞衰老现象中具有重要作用。
