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聚乙二醇二丙烯酸酯/透明质酸矿化水凝胶负载 Exendin4 通过诱导成骨促进骨缺损大鼠模型中的骨再生。

PEGDA/HA mineralized hydrogel loaded with Exendin4 promotes bone regeneration in rat models with bone defects by inducing osteogenesis.

机构信息

The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, China.

出版信息

J Biomater Appl. 2021 May;35(10):1337-1346. doi: 10.1177/0885328220987046. Epub 2021 Jan 20.

Abstract

Scaffolds with osteogenic differentiation function play an important role in the healing process of bone defects. Here, we designed a high strength Poly(ethyleneglycol) diacrylate/Hydroxyapatite (PEGDA/HA) mineralized hydrogel loaded with Exendin4 for inducing osteogenic differentiation. In this study, PEGDA hydrogel was prepared by photo initiating method. PEGDA/HA mineralized hydrogel was prepared by in-situ precipitation method, and Exendin4 was loaded by gel adsorption. The effects of different calcium and phosphorus concentrations on the strength and Exendin4 release of PEGDA/HA hydrogels were investigated. Rat models of bone defect were made and randomly divided into 5 groups. The experimental group was implanted with PEGDA hydrogel, Exendin4-PEGDA hydrogel, PEGDA/HA mineralized hydrogel, Exendin4-PEGDA/HA mineralized hydrogel, and no materials were implanted in the blank control group. Computed tomography (CT) and histology were observed 4 and 8 weeks after operation. Our results revealed that the PEGDA/HA mineralized hydrogel had porous structure, high mechanical strength and good biocompatibility. release test showed that the mineralized hydrogel exhibited good sustained release profile within 20 d. The animal experiments showed that the mineralized hydrogel accelerated the formation of new bone after 4 and 8 weeks, and formed a seamless union on the defected bone area after 8 weeks. In conclusions, The Exendin4-PEGDA/HA mineralized hydrogel can effectively repair bone defects in rats, and it is expected to be used as a biomaterial for human bone tissue repair.

摘要

具有成骨分化功能的支架在骨缺损的愈合过程中起着重要作用。在这里,我们设计了一种具有成骨分化诱导功能的高强度聚乙二醇二丙烯酸酯/羟基磷灰石(PEGDA/HA)矿化水凝胶,负载 Exendin4。本研究采用光引发法制备 PEGDA 水凝胶,采用原位沉淀法制备 PEGDA/HA 矿化水凝胶,并通过凝胶吸附负载 Exendin4。考察了不同钙磷浓度对 PEGDA/HA 水凝胶强度和 Exendin4 释放的影响。建立大鼠骨缺损模型,随机分为 5 组,实验组分别植入 PEGDA 水凝胶、Exendin4-PEGDA 水凝胶、PEGDA/HA 矿化水凝胶、Exendin4-PEGDA/HA 矿化水凝胶,空白对照组不植入任何材料。术后 4 周和 8 周分别进行 CT 和组织学观察。结果表明,PEGDA/HA 矿化水凝胶具有多孔结构、较高的力学强度和良好的生物相容性。释放试验表明,矿化水凝胶在 20 天内具有良好的持续释放特性。动物实验表明,矿化水凝胶在 4 周和 8 周后能加速新骨形成,8 周后在缺损骨区形成无缝结合。总之,Exendin4-PEGDA/HA 矿化水凝胶能有效修复大鼠骨缺损,有望作为一种用于人类骨组织修复的生物材料。

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