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纳米金刚石和骨形态发生蛋白2功能化共聚物支架的体内宿主反应与降解

In Vivo Host Response and Degradation of Copolymer Scaffolds Functionalized with Nanodiamonds and Bone Morphogenetic Protein 2.

作者信息

Suliman Salwa, Sun Yang, Pedersen Torbjorn O, Xue Ying, Nickel Joachim, Waag Thilo, Finne-Wistrand Anna, Steinmüller-Nethl Doris, Krueger Anke, Costea Daniela E, Mustafa Kamal

机构信息

Department of Clinical Dentistry, Center for Clinical Dental Research, University of Bergen, 5009, Bergen, Norway.

Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, 5020, Bergen, Norway.

出版信息

Adv Healthc Mater. 2016 Mar;5(6):730-42. doi: 10.1002/adhm.201500723. Epub 2016 Feb 8.

Abstract

The aim is to evaluate the effect of modifying poly[(l-lactide)-co-(ε-caprolactone)] scaffolds (PLCL) with nanodiamonds (nDP) or with nDP+physisorbed BMP-2 (nDP+BMP-2) on in vivo host tissue response and degradation. The scaffolds are implanted subcutaneously in Balb/c mice and retrieved after 1, 8, and 27 weeks. Molecular weight analysis shows that modified scaffolds degrade faster than the unmodified. Gene analysis at week 1 shows highest expression of proinflammatory markers around nDP scaffolds; although the presence of inflammatory cells and foreign body giant cells is more prominent around the PLCL. Tissue regeneration markers are highly expressed in the nDP+BMP-2 scaffolds at week 8. A fibrous capsule is detectable by week 8, thinnest around nDP scaffolds and at week 27 thickest around PLCL scaffolds. mRNA levels of ALP, COL1α2, and ANGPT1 are significantly upregulating in the nDP+BMP-2 scaffolds at week 1 with ectopic bone seen at week 8. Even when almost 90% of the scaffold is degraded at week 27, nDP are observable at implantation areas without adverse effects. In conclusion, modifying PLCL scaffolds with nDP does not aggravate the host response and physisorbed BMP-2 delivery attenuates inflammation while lowering the dose of BMP-2 to a relatively safe and economical level.

摘要

目的是评估用纳米金刚石(nDP)或nDP+物理吸附的骨形态发生蛋白-2(nDP+BMP-2)修饰聚[(L-丙交酯)-共-(ε-己内酯)]支架(PLCL)对体内宿主组织反应和降解的影响。将支架皮下植入Balb/c小鼠体内,并在1、8和27周后取出。分子量分析表明,修饰后的支架比未修饰的降解得更快。第1周的基因分析显示,nDP支架周围促炎标志物的表达最高;尽管PLCL周围炎症细胞和异物巨细胞的存在更为明显。组织再生标志物在第8周时在nDP+BMP-2支架中高度表达。到第8周可检测到纤维囊,在nDP支架周围最薄,在第27周时在PLCL支架周围最厚。第1周时,nDP+BMP-2支架中碱性磷酸酶(ALP)、I型胶原α2(COL1α2)和血管生成素1(ANGPT1)的mRNA水平显著上调,第8周时可见异位骨。即使在第27周时几乎90%的支架已降解,在植入区域仍可观察到nDP,且无不良反应。总之,用nDP修饰PLCL支架不会加重宿主反应,物理吸附的BMP-2递送可减轻炎症,同时将BMP-2的剂量降低到相对安全和经济的水平。

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