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整合在斜锆石支架内的纳米结构结冷胶和黄原胶水凝胶储库可促进骨再生。

Nanostructured gellan and xanthan hydrogel depot integrated within a baghdadite scaffold augments bone regeneration.

作者信息

Sehgal Rekha R, Roohani-Esfahani S I, Zreiqat Hala, Banerjee Rinti

机构信息

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.

Biomaterials and Tissue Engineering Research Unit, School of Aerospace Mechanical and Mechatronic Engineering, University of Sydney, Australia.

出版信息

J Tissue Eng Regen Med. 2017 Apr;11(4):1195-1211. doi: 10.1002/term.2023. Epub 2015 Apr 7.

Abstract

Controlled delivery of biological cues through synthetic scaffolds to enhance the healing capacity of bone defects is yet to be realized clinically. The purpose of this study was development of a bioactive tissue-engineered scaffold providing the sustained delivery of an osteoinductive drug, dexamethasone disodium phosphate (DXP), encapsulated within chitosan nanoparticles (CN). Porous baghdadite (BD; Ca ZrSi O ) scaffolds, a zirconia-modified calcium silicate ceramic, was coated with DXP-encapsulated CN nanoparticles (DXP-CN) using nanostructured gellan and xanthan hydrogel (GX). Crosslinker and GX polymer concentrations were optimized to achieve a homogeneous distribution of hydrogel coating within BD scaffolds. Dynamic laser scattering indicated an average size of 521 ± 21 nm for the DXP-CN nanoparticles. In vitro drug-release studies demonstrated that the developed DXP-CN-GX hydrogel-coated BD scaffolds (DXP-CN-GX-BD) resulted in a sustained delivery of DXP over the 5 days (78 ± 6% of drug release) compared with burst release over 1 h, seen from free DXP loaded in uncoated BD scaffolds (92 ± 8% release in 1 h). To estimate the influence of controlled delivery of DXP from the developed scaffolds, the effect on MG 63 cells was evaluated using various bone differentiation assays. Cell culture within DXP-CN-GX-BD scaffolds demonstrated a significant increase in the expression of early and late osteogenic markers of alkaline phosphatase activity, collagen type 1 and osteocalcin, compared to the uncoated BD scaffold. The results suggest that the DXP-releasing nanostructured hydrogel integrated within the BD scaffold caused sustained release of DXP, improving the potential for osteogenic differentiation. Copyright © 2015 John Wiley & Sons, Ltd.

摘要

通过合成支架实现生物信号的可控递送以增强骨缺损的愈合能力,目前尚未在临床上实现。本研究的目的是开发一种生物活性组织工程支架,该支架能够持续递送包裹在壳聚糖纳米颗粒(CN)中的骨诱导药物地塞米松磷酸二钠(DXP)。多孔的斜锆石(BD;CaZrSiO)支架是一种氧化锆改性的硅酸钙陶瓷,使用纳米结构的结冷胶和黄原胶(GX)水凝胶将包裹有DXP的CN纳米颗粒(DXP-CN)涂覆在该支架上。对交联剂和GX聚合物的浓度进行了优化,以实现水凝胶涂层在BD支架内的均匀分布。动态激光散射表明,DXP-CN纳米颗粒的平均尺寸为521±21nm。体外药物释放研究表明,与未涂覆的BD支架中负载的游离DXP在1小时内的突发释放(1小时内释放92±8%)相比,所开发的DXP-CN-GX水凝胶涂覆的BD支架(DXP-CN-GX-BD)在5天内实现了DXP的持续递送(药物释放78±6%)。为了评估从所开发的支架中可控递送DXP的影响,使用各种骨分化测定法评估了对MG 63细胞的影响。与未涂覆的BD支架相比,在DXP-CN-GX-BD支架内进行细胞培养显示,碱性磷酸酶活性、I型胶原蛋白和骨钙素等早期和晚期成骨标志物的表达显著增加。结果表明,整合在BD支架内的释放DXP的纳米结构水凝胶导致DXP的持续释放,提高了成骨分化的潜力。版权所有©2015约翰威立父子有限公司。

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