Modulation of osteogenic properties of biodegradable polymer/extracellular matrix scaffolds generated with a flow perfusion bioreactor.

Modulation of osteogenic properties of biodegradable polymer/extracellular matrix scaffolds generated with a flow perfusion bioreactor.
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DOI:
10.1016/j.actbio.2010.01.011
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发表时间:
2010-07
期刊:
影响因子:
9.7
通讯作者:
Mikos, Antonios G.
Mikos, Antonios G.
中科院分区:
工程技术1区
文献类型:
--
作者:
Liao, Jiehong;Guo, Xuan;Nelson, Dan;Kasper, F. Kurtis;Mikos, Antonios G.

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在这项研究中,合成和天然成分组成的复合支架具有可控的性能,通过将矿化的细胞外基质(ECM)和静电纺丝聚(ε-己内酯)(PCL)微纤维支架。间充质干细胞(MSCs)培养的PCL支架在流动灌注条件下与培养基中补充地塞米松,以探讨培养时间对矿化的细胞外基质沉积的影响。骨髓间充质干细胞分化成骨谱系,并产生细胞外基质的矿物,胶原蛋白和糖胺聚糖不同的组成与不同的形态,在不同阶段的成骨。为了确定矿化的细胞外基质的存在和成熟是否影响体外成骨分化,将PCL/ECM构建体脱细胞以产生PCL/ECM复合支架,随后用MSC接种并在不存在地塞米松的情况下培养。矿化基质的存在降低了细胞增殖,同时随着时间的推移,随着钙沉积量的增加,刺激碱性磷酸酶活性。与所有其他支架组相比,含有最成熟矿化基质的PCL/ECM复合支架导致碱性磷酸酶活性和钙沉积的最快速增加和最高水平。因此,我们证明了在受控的流动灌注条件下产生的矿化细胞外基质可以赋予骨传导聚合物支架成骨特性,并且即使在没有地塞米松的情况下,这种基质的成熟也会影响体外成骨分化。
In this study, composite scaffolds consisting of both synthetic and natural components with controllable properties were generated by incorporating mineralized extracellular matrix (ECM) and electrospun poly(ε-caprolactone) (PCL) microfiber scaffolds. Mesenchymal stem cells (MSCs) were cultured on PCL scaffolds under flow perfusion conditions with culture medium supplemented with dexamethasone to investigate the effect of culture duration on mineralized extracellular matrix deposition. MSCs differentiated down the osteogenic lineage and produced extracellular matrix with different compositions of mineral, collagen, and glycosaminoglycan with distinct morphologies at various stages of osteogenesis. To determine whether the presence and maturity of mineralized extracellular matrix influences osteogenic differentiation in vitro, PCL/ECM constructs were decellularized to yield PCL/ECM composite scaffolds that were subsequently seeded with MSCs and cultured in the absence of dexamethasone. The presence of mineralized matrix reduced cellular proliferation while stimulating alkaline phosphatase activity with increasing amounts of calcium deposition over time. PCL/ECM composite scaffolds containing the most mature mineralized matrix resulted in the most rapid increase and highest levels of alkaline phosphatase activity and calcium deposition compared to all other scaffold groups. Therefore, we demonstrate that mineralized extracellular matrix generated under controlled flow perfusion conditions can impart osteogenic properties to an osteoconductive polymer scaffold, and that the maturity of this matrix influences osteogenic differentiation in vitro, even in the absence of dexamethasone.
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