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聚乙二醇水凝胶/RGD肽修饰的不同合成水凝胶的生物降解:大鼠的免疫组织化学研究

Biodegradation of different synthetic hydrogels made of polyethylene glycol hydrogel/RGD-peptide modifications: an immunohistochemical study in rats.

作者信息

Herten Monika, Jung Ronald E, Ferrari Daniel, Rothamel Daniel, Golubovic Vladimir, Molenberg Aart, Hämmerle Christoph H F, Becker Jürgen, Schwarz Frank

机构信息

Department of Oral Surgery, Heinrich Heine University, Düsseldorf, Germany.

出版信息

Clin Oral Implants Res. 2009 Feb;20(2):116-25. doi: 10.1111/j.1600-0501.2008.01622.x. Epub 2008 Dec 1.

Abstract

AIM

The aim of the present study was to investigate the pattern of biodegradation of different polyethylene glycol (PEG) hydrogel/RGD-peptide modifications in rats.

MATERIAL AND METHODS

Two different hydrogels were employed: (i) a combination of four-arm PEG-thiol, M(n)=2.3 kDa, and eight-arm PEG-acrylate, M(n)=2.3 kDa (PEG1); and (ii) a combination of four-arm PEG-thiol, M(n)=2.3 kDa, and four-arm PEG-acrylate, M(n)=15 kDa (PEG2). Both PEG1 and PEG2 were either used alone or combined with a nine amino acid cys-RGD peptide (RGD). A non-cross-linked porcine type I and III collagen membrane [BioGide (BG)] served as control. Specimens were randomly allocated in unconnected subcutaneous pouches separated surgically on the back of 60 wistar rats, which were divided into six groups (1, 2, 4, 8, 16, and 24 weeks). Specimens were prepared for histological (tissue integration, foreign body reactions, biodegradation) and immunohistochemical (angiogenesis) analysis.

RESULTS

All materials investigated revealed unimpeded and comparable tissue integration without any signs of foreign body reactions. While BG exhibited transmembraneous blood vessel formation at 1 week, all PEG specimens were just surrounded by a well-vascularized connective tissue. The hydrolytic disruption of PEG1 and PEG1/RGD specimens was associated with an ingrowth of blood vessels at 4 weeks. Biodegradation times were highest for PEG1 (24 weeks)>PEG1/RGD (16 weeks)>BG (4 weeks)>PEG2=PEG2/RGD (2 weeks).

CONCLUSION

Within the limits of the present study, it was concluded that (i) all materials investigated revealed a high biocompatibility and tissue integration, and (ii) hydrogel biodegradation was dependent on PEG composition.

摘要

目的

本研究旨在调查不同聚乙二醇(PEG)水凝胶/RGD肽修饰在大鼠体内的生物降解模式。

材料与方法

使用了两种不同的水凝胶:(i)四臂PEG-硫醇(M(n)=2.3 kDa)和八臂PEG-丙烯酸酯(M(n)=2.3 kDa)的组合(PEG1);(ii)四臂PEG-硫醇(M(n)=2.3 kDa)和四臂PEG-丙烯酸酯(M(n)=15 kDa)的组合(PEG2)。PEG1和PEG2均单独使用或与九氨基酸半胱氨酸-RGD肽(RGD)组合使用。未交联的猪I型和III型胶原膜[BioGide(BG)]用作对照。将标本随机分配到60只Wistar大鼠背部手术分离的不相连皮下袋中,大鼠分为六组(1、2、4、8、16和24周)。制备标本用于组织学(组织整合、异物反应、生物降解)和免疫组织化学(血管生成)分析。

结果

所有研究材料均显示出不受阻碍且相当的组织整合,没有任何异物反应的迹象。虽然BG在1周时表现出跨膜血管形成,但所有PEG标本仅被血管丰富的结缔组织包围。PEG1和PEG1/RGD标本的水解破坏与4周时血管向内生长有关。生物降解时间以PEG1(24周)>PEG1/RGD(16周)>BG(4周)>PEG2 = PEG2/RGD(2周)最高。

结论

在本研究的范围内,得出以下结论:(i)所有研究材料均显示出高生物相容性和组织整合,(ii)水凝胶生物降解取决于PEG组成。

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