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游离和共聚的γ-环糊精调节用于骨再生的载地塞米松葡聚糖微球的性能。

Free and copolymerized γ-cyclodextrins regulate the performance of dexamethasone-loaded dextran microspheres for bone regeneration.

作者信息

Lima A C, Puga A M, Mano J F, Concheiro A, Alvarez-Lorenzo C

机构信息

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

出版信息

J Mater Chem B. 2014 Aug 14;2(30):4943-4956. doi: 10.1039/c3tb21665a. Epub 2014 Jun 27.

Abstract

Polymeric particles acting as sources of biological cues to promote tissue regeneration are currently an interesting topic in bone tissue engineering research. In this study, microspheres of dextran-methacrylate (dextran-MA) and γ-cyclodextrins (γ-CD) for the delivery of osteogenic agents were prepared by means of photopolymerization on biomimetic superhydrophobic surfaces. The effects of the incorporation of the γ-CD units as free entities or as structural monomers (acrylamidomethyl-γ-cyclodextrin, γ-CD-NMA) on dexamethasone loading and release performance were evaluated in detail in order to achieve osteogenic differentiation of human stem cells. The copolymerization of dextran-MA with γ-CD-NMA improved the loading capacity of the particles and also provided a sustained release of dexamethasone for several days. The biological studies revealed that such microspheres were cytocompatible and capable of inducing the differentiation of human adipose-derived stem cells (hASCs) to osteoblasts, as determined from an increase of alkaline phosphatase (ALP) activity between days 3 and 7. Such results were also confirmed using ALP staining. Therefore, immobilization of γ-CDs onto the dextran-MA network may be particularly useful for the development of cytocompatible implantable spherical biomaterials for bone tissue engineering purposes.

摘要

作为促进组织再生的生物信号源的聚合物颗粒,目前是骨组织工程研究中一个有趣的课题。在本研究中,通过在仿生超疏水表面上进行光聚合制备了用于递送成骨剂的葡聚糖 - 甲基丙烯酸酯(dextran - MA)和γ - 环糊精(γ - CD)微球。为了实现人类干细胞的成骨分化,详细评估了将γ - CD单元作为游离实体或作为结构单体(丙烯酰胺甲基 - γ - 环糊精,γ - CD - NMA)掺入对地塞米松负载和释放性能的影响。葡聚糖 - MA与γ - CD - NMA的共聚提高了颗粒的负载能力,并使地塞米松持续释放数天。生物学研究表明,这种微球具有细胞相容性,并且能够诱导人脂肪来源干细胞(hASCs)分化为成骨细胞,这是通过第3天至第7天碱性磷酸酶(ALP)活性的增加来确定的。使用ALP染色也证实了这些结果。因此,将γ - CD固定在葡聚糖 - MA网络上对于开发用于骨组织工程目的的细胞相容性可植入球形生物材料可能特别有用。

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