Biphasic peptide amphiphile nanomatrix embedded with hydroxyapatite nanoparticles for stimulated osteoinductive response.
Biphasic peptide amphiphile nanomatrix embedded with hydroxyapatite nanoparticles for stimulated osteoinductive response.
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DOI：
10.1021/nn203247m
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发表时间：
2011-12-27
期刊：
影响因子：
17.1
通讯作者：
Jun HW
中科院分区：
文献类型：
--
作者：
Anderson JM;Patterson JL;Vines JB;Javed A;Gilbert SR;Jun HW
天然骨细胞外基质(ECM)的形成为骨组织工程提供了一个有吸引力的模板。骨细胞外基质的结构支持和生物复杂性是在由无机羟基磷灰石(HA)纳米颗粒增强的有机纤维网络组成的复合微环境中提供的。重建这种两相组装，研究了一种由自组装多肽两亲性(PA)纳米纤维和散布的HA纳米颗粒组成的骨ECM类似支架。利用人工合成的多肽序列(即RGDS)赋予PAS生物分子配体信号，并与HA纳米颗粒结合形成两相纳米基质水凝胶。推测双相水凝胶可诱导人骨髓间充质干细胞向成骨细胞分化，并通过PA纳米纤维内的RGDS配体信号通路和植入的HA矿化源促进骨愈合。考察了不同质量浓度HA对两相PA水凝胶粘弹稳定性的影响。在初步验证活性的基础上，对包裹的hMSCs在不同的PA水凝胶中的长期细胞性和成骨诱导作用进行了体外研究。通过关键标志物的基因表达来评估成骨成熟的时间进程。一项初步的动物研究证实了双相PA纳米基质在生理条件下的骨愈合能力，该材料使用了临界大小的股骨缺损大鼠模型。在双相PA纳米基质水凝胶中，RGDS配体信号和HA纳米颗粒的组合显示了最有效的骨诱导和比较的骨愈合反应。因此，双相PA纳米基质构建了一种组织良好的支架，与自然骨ECM具有更高的相似性，并有望改善骨组织再生。
Formation of the native bone extracellular matrix (ECM) provides an attractive template for bone tissue engineering. The structural support and biological complexity of bone ECM are provided within a composite microenvironment that consists of an organic fibrous network reinforced by inorganic hydroxyapatite (HA) nanoparticles. Recreating this biphasic assembly, a bone ECM analogous scaffold comprised of self-assembling peptide amphiphile (PA) nanofibers and interspersed HA nanoparticles was investigated. PAs were endowed with biomolecular ligand signaling using a synthetically inscribed peptide sequence (i.e. RGDS) and integrated with HA nanoparticles to form a biphasic nanomatrix hydrogel. It was hypothesized the biphasic hydrogel would induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) and improve bone healing as mediated by RGDS ligand signaling within PA nanofibers and embedded HA mineralization source. Viscoelastic stability of the biphasic PA hydrogels was evaluated with different weight concentrations of HA for improved gelation. After demonstrating initial viability, long-term cellularity and osteoinduction of encapsulated hMSCs in different PA hydrogels were studied in vitro. Temporal progression of osteogenic maturation was assessed by gene expression of key markers. A preliminary animal study demonstrated bone healing capacity of the biphasic PA nanomatrix under physiological conditions using a critical size femoral defect rat model. The combination of RGDS ligand signaling and HA nanoparticles within the biphasic PA nanomatrix hydrogel demonstrated the most effective osteoinduction and comparative bone healing response. Therefore, the biphasic PA nanomatrix establishes a well-organized scaffold with increased similarity to natural bone ECM with the prospect for improved bone tissue regeneration.
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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
影响因子：
9.7
作者：
Andukuri, Adinarayana;Kushwaha, Meenakshi;Tambralli, Ajay;Anderson, Joel M.;Dean, Derrick R.;Berry, Joel L.;Sohn, Young Doug;Yoon, Young-Sup;Brott, Brigitta C.;Jun, Ho-Wook
通讯作者：
Jun, Ho-Wook
影响因子：
14
作者：
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通讯作者：
Tabata, Yasuhiko
影响因子：
--
作者：
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通讯作者：
Katti, Dinesh R.
影响因子：
4.1
作者：
Kim, Jinku;Hefferan, Theresa E.;Lu, Lichun
通讯作者：
Lu, Lichun