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利用埃洛石纳米管构建天然DNA基质以制备用于骨再生的可注射治疗性水凝胶。

Engineering natural DNA matrices with halloysite nanotubes to fabricate injectable therapeutic hydrogels for bone regeneration.

作者信息

Miao Yali, Lu Teliang, Cui Shangbin, Xu Ziyang, Liu Xiao, Zhang Yu

机构信息

Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 510080, China.

Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.

出版信息

J Orthop Translat. 2024 Oct 22;49:218-229. doi: 10.1016/j.jot.2024.09.010. eCollection 2024 Nov.

DOI:10.1016/j.jot.2024.09.010
PMID:39507323
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11538604/
Abstract

BACKGROUND

Injectable hydrogels are widely used in drug delivery and the repair of irregular tissue defects due to their advantages such as convenient and minimally invasive operation. Although the existing injectable hydrogels have excellent biocompatibility and osteoconduction, they still face clinical challenges such as low osteogenic activity. The key requirements for improved injectable hydrogels as repair materials for non-load bearing bone defects are optimal handling properties, the ability to fill irregular defects and provide osteoinductive stimulation.

METHODS

We developed an approach to construct injectable hydrogels through a two-step gelation process. In the first step of gelation, the denaturation and rehybridization mechanism of natural biopolymer DNA was utilized to form interconnected structure through hydrogen bonding between complementary base pairs between the DNA strands. In the second step of gelation, the introduction of halloysite nanotubes (HNTs) loaded with osteogenic model drug dexamethasone (Dex) provided additional crosslinking sites through non-covalent interactions with the DNA backbone, including electrostatic interaction and hydrogen bonding interaction.

RESULTS

The DNA-based nanocomposite hydrogel material developed in our work can be used as an injectable filling material for the repair of non-load bearing bone defect and can be loaded with osteogenic model drug dexamethasone (Dex) for improved osteoinductivity, promoting new bone regeneration .

TRANSLATIONAL POTENTIAL OF THIS ARTICLE

This article highlights the potential of using nanocomposite hydrogels to repair non-load bearing bone defects, which are common injuries in the clinic. This study provides a deeper understanding of how to optimize the properties of hydrogels to regulate cell differentiation and tissue formation.

摘要

背景

可注射水凝胶因其操作方便、微创等优点,在药物递送和不规则组织缺损修复中得到广泛应用。尽管现有的可注射水凝胶具有优异的生物相容性和骨传导性,但它们仍面临着诸如成骨活性低等临床挑战。作为非负重骨缺损修复材料的改良可注射水凝胶的关键要求是具有最佳的操作性能、填充不规则缺损的能力以及提供骨诱导刺激。

方法

我们开发了一种通过两步凝胶化过程构建可注射水凝胶的方法。在凝胶化的第一步,利用天然生物聚合物DNA的变性和重新杂交机制,通过DNA链之间互补碱基对之间的氢键形成互连结构。在凝胶化的第二步,引入负载有成骨模型药物地塞米松(Dex)的埃洛石纳米管(HNTs),通过与DNA主链的非共价相互作用提供额外的交联位点,包括静电相互作用和氢键相互作用。

结果

我们工作中开发的基于DNA的纳米复合水凝胶材料可作为非负重骨缺损修复的可注射填充材料,并可负载成骨模型药物地塞米松(Dex)以提高骨诱导性,促进新骨再生。

本文的转化潜力

本文强调了使用纳米复合水凝胶修复非负重骨缺损的潜力,这是临床上常见的损伤。这项研究为如何优化水凝胶性能以调节细胞分化和组织形成提供了更深入的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/108d6c7f0e40/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/54d504fd25a2/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/9b348c6a1a43/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/34773fd3b964/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/b597b172d0bb/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/0dde54aeccf8/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/04e81044804d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/4fd2b4ff1e3a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/108d6c7f0e40/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/54d504fd25a2/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/9b348c6a1a43/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/34773fd3b964/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/b597b172d0bb/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/0dde54aeccf8/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/04e81044804d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/4fd2b4ff1e3a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a98/11538604/108d6c7f0e40/gr7.jpg

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