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通过超临界流体发泡制备的混合支架中血小板裂解物的控制释放增强人脂肪来源干细胞的成骨分化。

Enhancement of osteogenic differentiation of human adipose derived stem cells by the controlled release of platelet lysates from hybrid scaffolds produced by supercritical fluid foaming.

机构信息

3B's Research Group, Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4806‐909 Taipas, Guimarães, Portugal.

出版信息

J Control Release. 2012 Aug 20;162(1):19-27. doi: 10.1016/j.jconrel.2012.06.001. Epub 2012 Jun 12.

DOI:10.1016/j.jconrel.2012.06.001
PMID:22698936
Abstract

A new generation of scaffolds capable of acting not only as support for cells but also as a source of biological cues to promote tissue regeneration is currently a hot topic of in bone Tissue Engineering (TE) research. The inclusion of growth factor (GF) controlled release functionalities in the scaffolds is a possible strategy to achieve such goal. Platelet Lysate (PL) is an autologous source of GFs, providing several bioactive agents known to act on bone regeneration. In this study, chitosan-chondroitin sulfate nanoparticles loaded with PL were included in a poly(D,L-lactic acid) foam produced by supercritical fluid foaming. The tridimensional (3D) structures were then seeded with human adipose-derived stem cells (hASCs) and cultured in vitro under osteogenic stimulus. The osteogenic differentiation of the seeded hASCs was observed earlier for the PL-loaded constructs, as shown by the earlier alkaline phosphatase peak and calcium detection and stronger Runx2 expression at day 7 of culture, in comparison with the control scaffolds. Osteocalcin gene expression was upregulated in presence of PL during all culture period, which indicates an enhanced osteogenic induction. These results suggest the synergistic effect of PL and hASCs in combinatory TE strategies and support the potential of PL to increase the multifunctionality of the 3D hybrid construct for bone TE applications.

摘要

新一代支架不仅可以作为细胞的支撑物,还可以作为生物信号源,促进组织再生,这是骨组织工程(TE)研究的一个热点话题。在支架中加入生长因子(GF)控制释放功能是实现这一目标的一种可行策略。血小板裂解物(PL)是 GF 的自体来源,提供了几种已知对骨再生有作用的生物活性物质。在这项研究中,载有 PL 的壳聚糖-硫酸软骨素纳米颗粒被包含在由超临界流体发泡制成的聚(D,L-乳酸)泡沫中。然后,将三维(3D)结构用人类脂肪来源的干细胞(hASC)接种,并在体外进行成骨刺激培养。与对照支架相比,负载 PL 的构建体更早地观察到了接种的 hASC 的成骨分化,这表现为碱性磷酸酶峰值和钙检测更早出现,并且在培养的第 7 天 Runx2 表达更强。在整个培养期间,PL 存在时骨钙素基因表达上调,表明成骨诱导增强。这些结果表明 PL 和 hASC 在组合 TE 策略中的协同作用,并支持 PL 增加 3D 杂交构建体用于骨 TE 应用的多功能性的潜力。

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