Department of Biomedical Engineering, University of Alabama at Birmingham, Shelby Building 806, 1825 University Boulevard, Birmingham, AL 35294, USA.
Acta Biomater. 2011 Feb;7(2):675-82. doi: 10.1016/j.actbio.2010.08.016. Epub 2010 Aug 20.
An attractive strategy for bone tissue engineering is the use of extracellular matrix (ECM) analogous biomaterials capable of governing biological response based on synthetic cell-ECM interactions. In this study, peptide amphiphiles (PAs) were investigated as an ECM-mimicking biomaterial to provide an instructive microenvironment for human mesenchymal stem cells (hMSCs) in an effort to guide osteogenic differentiation. PAs were biologically functionalized with ECM isolated ligand sequences (i.e. RGDS, DGEA), and the osteoinductive potential was studied with or without conditioned medium, containing the supplemental factors of dexamethasone, β-glycerol phosphate and ascorbic acid. It was hypothesized that the ligand-functionalized PAs would synergistically enhance osteogenic differentiation in combination with conditioned medium. Concurrently, comparative evaluations independent of osteogenic supplements investigated the differentiating potential of the functionalized PA scaffolds as promoted exclusively by the inscribed ligand signals, thus offering the potential for therapeutic effectiveness under physiological conditions. Osteoinductivity was assessed by histochemical staining for alkaline phosphatase (ALP) and quantitative real-time polymerase chain reaction analysis of key osteogenic markers. Both of the ligand-functionalized PAs were found to synergistically enhance the level of visualized ALP activity and osteogenic gene expression compared to the control surfaces lacking biofunctionality. Guided osteoinduction was also observed without supplemental aid on the PA scaffolds, but at a delayed response and not to the same phenotypic levels. Thus, the biomimetic PAs foster a symbiotic enhancement of osteogenic differentiation, demonstrating the potential of ligand-functionalized biomaterials for future bone tissue repair.
一种有吸引力的骨组织工程策略是使用类似细胞外基质 (ECM) 的生物材料，这些材料能够基于合成的细胞-ECM 相互作用来控制生物反应。在这项研究中，肽两亲物 (PAs) 被用作 ECM 模拟生物材料，为人类间充质干细胞 (hMSCs) 提供一个有指导意义的微环境，以引导成骨分化。PA 被生物功能化，具有 ECM 分离的配体序列（即 RGDS、DGEA），并在有无条件培养基的情况下研究了其成骨潜力，该培养基含有补充的地塞米松、β-甘油磷酸和抗坏血酸等因子。假设配体功能化的 PA 会与条件培养基协同增强成骨分化。同时，在没有成骨补充剂的情况下进行的比较评估研究了功能化 PA 支架的分化潜力，这些潜力仅由印刻的配体信号促进，从而为在生理条件下提供治疗效果的潜力。通过碱性磷酸酶 (ALP) 的组织化学染色和关键成骨标志物的定量实时聚合酶链反应分析来评估成骨能力。与缺乏生物功能的对照表面相比，两种配体功能化的 PA 都被发现协同增强了可视化的 ALP 活性和成骨基因表达水平。在没有补充剂的情况下，PA 支架上也观察到了引导性成骨，但反应延迟，且达不到相同的表型水平。因此，仿生 PA 促进了成骨分化的共生增强，证明了配体功能化生物材料在未来骨组织修复中的潜力。
