Osteogenic differentiation of human mesenchymal stem cells synergistically enhanced by biomimetic peptide amphiphiles combined with conditioned medium.

Osteogenic differentiation of human mesenchymal stem cells synergistically enhanced by biomimetic peptide amphiphiles combined with conditioned medium.
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DOI:
10.1016/j.actbio.2010.08.016
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发表时间:
2011-02
期刊:
影响因子:
9.7
通讯作者:
Jun, Ho-Wook
Jun, Ho-Wook
中科院分区:
工程技术1区
文献类型:
--
作者:
Anderson, Joel M.;Vines, Jeremy B.;Patterson, Jessica L.;Chen, Haiyan;Javed, Amjad;Jun, Ho-Wook

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骨组织工程的一个吸引人的策略是使用细胞外基质(ECM)类似的生物材料,能够基于合成的细胞-ECM相互作用来控制生物反应。在本研究中,多肽两亲物(PAS)作为一种模拟细胞外基质的生物材料,为人骨髓间充质干细胞(HMSCs)提供了一个有益的微环境,以引导其向成骨方向分化。用细胞外基质分离的配体序列(RGDS、DGEA)对PA进行生物功能化,并研究在含有地塞米松、β-甘油磷酸和抗坏血酸补充因子的条件培养液中的成骨诱导能力。有人假设,配体功能化的PAS与条件培养液联合使用将协同促进成骨分化。与此同时,独立于成骨补充剂的比较评估研究了仅由内标配体信号促进的功能化PA支架的分化潜力,从而提供了在生理条件下治疗效果的潜力。通过碱性磷酸酶(ALP)组织化学染色和关键成骨标志物的实时定量聚合酶链式反应(RT-PCR)分析来评价成骨活性。与缺乏生物功能的对照表面相比,两种配体功能化的PA都能协同提高ALP活性和成骨基因的表达水平。在PA支架上没有补充辅助的情况下,也观察到引导的成骨诱导,但在延迟反应和不同的表型水平上。因此,仿生PAS促进了成骨分化的共生增强,展示了配体功能化生物材料在未来骨组织修复中的潜力。
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 media, 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 media. 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 PCR 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.
DOI: 10.1021/bm9007452
发表时间: 2009-10-12
期刊: BIOMACROMOLECULES
影响因子: 6.2
作者:
Anderson, Joel M.;Kushwaha, Meenakshi;Tambralli, Ajay;Bellis, Susan L.;Camata, Renato P.;Jun, Ho-Wook
通讯作者: Jun, Ho-Wook
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发表时间: 2004-07-01
期刊: BONE
影响因子: 4.1
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期刊: BIOMATERIALS
影响因子: 14
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DOI: 10.1002/jbm.a.10438
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影响因子: 4.9
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