Polymers Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8543, USA.
Acta Biomater. 2011 May;7(5):2091-100. doi: 10.1016/j.actbio.2011.01.019. Epub 2011 Jan 25.
Rational design of bioactive tissue engineered scaffolds for directing bone regeneration in vivo requires a comprehensive understanding of cell interactions with the immobilized bioactive molecules. In the current study, substrates possessing gradient concentrations of immobilized peptides were used to measure the concentration-dependent proliferation and osteogenic differentiation of human bone marrow stromal cells. Two bioactive peptides, one derived from extracellular matrix protein (ECM), GRGDS, and one from bone morphogenic protein-2 (BMP-2), KIPKASSVPTELSAISTLYL, were found to synergistically enhance cell proliferation, up-regulate osteogenic mRNA markers bone sialoprotein (BSP) and Runt-related transcription factor 2, and produce mineralization at densities greater than 130 pmol cm(-2) (65 pmol cm(-2) for each peptide). In addition, COOH-terminated self-assembled monolayers alone led to up-regulated BSP mRNA levels at densities above 200 pmol cm(-2) and increased cell proliferation from day 3 to day 14. Taking further advantage of both the synergistic potentials and the concentration-dependent activities of ECM and growth-factor-derived peptides on proliferative activity and osteogenic differentiation, without the need for additional osteogenic supplements, will enable the successful incorporation of the bioactive species into biorelevant tissue engineering scaffolds.
为了在体内引导骨再生，合理设计具有生物活性的组织工程支架需要全面了解细胞与固定化生物活性分子的相互作用。在本研究中，使用具有固定化肽浓度梯度的基底来测量人骨髓基质细胞的浓度依赖性增殖和成骨分化。两种生物活性肽，一种来源于细胞外基质蛋白（ECM），GRGDS，另一种来源于骨形态发生蛋白-2（BMP-2），KIPKASSVPTELSAISTLYL，被发现协同增强细胞增殖，上调成骨 mRNA 标志物骨涎蛋白（BSP）和 Runt 相关转录因子 2，并在密度大于 130 pmol cm(-2)（每个肽 65 pmol cm(-2)）时产生矿化。此外，COOH 端自组装单层本身在密度高于 200 pmol cm(-2)时导致 BSP mRNA 水平上调，并增加细胞增殖从第 3 天到第 14 天。进一步利用 ECM 和生长因子衍生肽在增殖活性和成骨分化方面的协同潜力和浓度依赖性活性，而无需额外的成骨补充剂，将能够成功地将生物活性物质纳入生物相关的组织工程支架中。
