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瓜尔胶基可注射热响应水凝胶作为骨细胞生长和药物控释的支架

Guar-Based Injectable Thermoresponsive Hydrogel as a Scaffold for Bone Cell Growth and Controlled Drug Delivery.

作者信息

Parameswaran-Thankam Anil, Parnell Charlette M, Watanabe Fumiya, RanguMagar Ambar B, Chhetri Bijay P, Szwedo Peter K, Biris Alexandru S, Ghosh Anindya

机构信息

Department of Chemistry and Center for Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, 2801 South University Avenue, Little Rock, Arkansas 72204, United States.

出版信息

ACS Omega. 2018 Nov 30;3(11):15158-15167. doi: 10.1021/acsomega.8b01765. Epub 2018 Nov 9.

Abstract

In this study, an injectable thermoresponsive hydroxypropyl guar--poly(-vinylcaprolactam) (HPG--PNVCL) copolymer was synthesized by graft polymerization. The reaction parameters such as temperature, time, monomer, and initiator concentrations were varied. In addition, the HPG--PNVCL copolymer was modified with nano-hydroxyapatite (n-HA) by in situ covalent cross-linking using divinyl sulfone (DVS) cross-linker to obtain HPG--PNVCL/n-HA/DVS composite material. Grafted copolymer and composite materials were characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, proton nuclear magnetic resonance spectroscopy (H NMR), and differential scanning calorimetry. The morphology of the grafted copolymer (HPG--PNVCL) and the composite (HPG--PNVCL/n-HA/DVS) was examined using scanning electron microscopy (SEM), which showed interconnected porous honeycomb-like structures. Using Ultraviolet-visible spectroscopy, low critical solution temperature for HPG--PNVCL was observed at 34 °C, which is close to the rheology gel point at 33.5 °C. The thermoreversibility of HPG--PNVCL was proved by rheological analysis. The HPG--PNVCL hydrogel was employed for slow release of the drug molecule. Ciprofloxacin, a commonly known antibiotic, was used for sustainable release from the HPG--PNVCL hydrogel as a function of time at 37 °C because of viscous nature and thermogelation of the copolymer. In vitro cytotoxicity study reveals that the HPG--PNVCL thermogelling polymer works as a biocompatible scaffold for osteoblastic cell growth. Additionally, in vitro biomineralization study of HPG--PNVCL/n-HA/DVS was conducted using a simulated body fluid, and apatite-like structure formation was observed by SEM.

摘要

在本研究中,通过接枝聚合合成了一种可注射的热响应性羟丙基瓜尔胶 - 聚(乙烯基己内酰胺)(HPG - PNVCL)共聚物。改变了诸如温度、时间、单体和引发剂浓度等反应参数。此外,使用二乙烯基砜(DVS)交联剂通过原位共价交联用纳米羟基磷灰石(n - HA)对HPG - PNVCL共聚物进行改性,以获得HPG - PNVCL/n - HA/DVS复合材料。使用傅里叶变换红外光谱、热重分析、质子核磁共振光谱(H NMR)和差示扫描量热法对接枝共聚物和复合材料进行了表征。使用扫描电子显微镜(SEM)检查了接枝共聚物(HPG - PNVCL)和复合材料(HPG - PNVCL/n - HA/DVS)的形态,其显示出相互连接的多孔蜂窝状结构。使用紫外可见光谱,观察到HPG - PNVCL的低临界溶液温度为34℃,这与33.5℃的流变学凝胶点接近。流变学分析证明了HPG - PNVCL的热可逆性。HPG - PNVCL水凝胶用于药物分子的缓释。由于共聚物的粘性性质和热凝胶化作用,常用抗生素环丙沙星在37℃下从HPG - PNVCL水凝胶中作为时间的函数进行可持续释放。体外细胞毒性研究表明,HPG - PNVCL热凝胶聚合物作为成骨细胞生长的生物相容性支架。此外,使用模拟体液对HPG - PNVCL/n - HA/DVS进行了体外生物矿化研究,并通过SEM观察到类磷灰石结构的形成。

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