Relationships between degradability of silk scaffolds and osteogenesis.

Relationships between degradability of silk scaffolds and osteogenesis.
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DOI:
10.1016/j.biomaterials.2010.04.028
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发表时间:
2010-08
期刊:
影响因子:
14
通讯作者:
Kaplan, David L.
Kaplan, David L.
中科院分区:
工程技术1区
文献类型:
--
作者:
Park, Sang-Hyug;Gil, Eun Seok;Shi, Hai;Kim, Hyeon Joo;Lee, Kyongbum;Kaplan, David L.

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骨修复是骨科医学的一个主要关注点,生物材料是再生过程的一个关键方面。然而,如今只有有限的几种生物材料被使用,且很少有研究将生物材料支架设计与降解速率和新骨形成联系起来。就骨再生结果的总体速率和质量而言,使生物材料的重塑速率与新骨形成相匹配是很重要的。我们报道了人骨髓间充质干细胞(hMSCs)在三维丝质支架中的成骨作用和代谢情况。为了研究基质降解、细胞代谢和体外骨组织形成之间的关系,制备了具有两种不同降解速率的支架。通过扫描电子显微镜(SEM)、组织学、化学分析、实时定量聚合酶链反应(real - time PCR)和代谢分析来研究这些关系。根据扫描电子显微镜、冯库萨染色、Ⅰ型胶原染色和钙含量,在设计为降解更快的支架中形成了矿化程度更高的细胞外基质(ECM)。在为期56天的体外研究中,成骨细胞外基质的测量值在降解更快的支架中明显高于降解较慢的支架。代谢分析,包括葡萄糖和乳酸水平,证实了两种支架的降解速率差异,与降解较慢的支架相比,降解更快的支架在成骨过程中支持人骨髓间充质干细胞更高水平的葡萄糖消耗和乳酸合成。结果表明,支架降解速率直接影响人骨髓间充质干细胞的代谢,进而影响成骨速率。了解细胞代谢与支架可降解性之间的相互作用,应该有助于更合理地设计满足体外和体内骨再生需求的支架。
Bone repairs represent a major focus in orthopedic medicine with biomaterials as a critical aspect of the regenerative process. However, only a limited set of biomaterials are utilized today and few studies relate biomaterial scaffold design to degradation rate and new bone formation. Matching biomaterial remodeling rate towards new bone formation is important in terms of the overall rate and quality of bone regeneration outcomes. We report on the osteogenesis and metabolism of human bone marrow derived mesenchymal stem cells (hMSCs) in 3D silk scaffolds. The scaffolds were prepared with two different degradation rates in order to study relationships between matrix degradation, cell metabolism and bone tissue formation in vitro. SEM, histology, chemical assays, real-time PCR and metabolic analyses were assessed to investigate these relationships. More extensively mineralized ECM formed in the scaffolds designed to degrade more rapidly, based on SEM, von Kossa and type I collagen staining and calcium content. Measures of osteogenic ECM were significantly higher in the more rapidly degrading scaffolds than in the more slowly degrading scaffolds over 56 days of study in vitro. Metabolic analysis, including glucose and lactate levels, confirmed the degradation rate differences with the two types of scaffolds, with the more rapidly degrading scaffolds supporting higher levels of glucose consumption and lactate synthesis by the hMSCs upon osteogenesis, in comparison to the more slowly degrading scaffolds. The results demonstrate that scaffold degradation rates directly impact the metabolism of hMSCs, and in turn the rate of osteogenesis. An understanding of the interplay between cellular metabolism and scaffold degradability should aid in the more rational design of scaffolds for bone regeneration needs both in vitro and in vivo.
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