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用于有效伤口愈合的坚韧、粘性仿生甲基丙烯酰化透明质酸水凝胶

Tough, adhesive biomimetic hyaluronic acid methacryloyl hydrogels for effective wound healing.

作者信息

Peng Zhiwei, Xue Huai, Liu Xiao, Wang Shuguang, Liu Guodong, Jia Xinghai, Zhu Ziqiang, Orvy Moontarij Jahan, Yang Yin, Wang Yunqing, Zhang Dong, Tong Lei

机构信息

Department of Orthopedics, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Xuzhou Medical University, Xuzhou, China.

出版信息

Front Bioeng Biotechnol. 2023 Jul 19;11:1222088. doi: 10.3389/fbioe.2023.1222088. eCollection 2023.

Abstract

The development of cost-effective, biocompatible soft wound dressings is highly desirable; however, conventional dressings are only designed for flat wounds, which creates difficulty with promising healing efficiency in complex practical conditions. Herein, we developed a tough, adhesive biomimetic hyaluronic acid methacryloyl hydrogels composed of chemically crosslinked hyaluronic acid methacryloyl (HAMA) network and poly(N-hydroxyethyl acrylamide) (PHEAA) network rich in multiple hydrogen bonding. Due to the multiple chemical crosslinking sites (acrylamide groups) of HAMA; the bulk HEMA/PHEAA hydrogels presented significant enhancements in mechanical properties (∼0.45 MPa) than common hyaluronic acid hydrogels (<0.1 MPa). The abundant hydrogen bonding also endowed the resultant hydrogels with extremely high adhesiveness on many nonporous substrates, including glass and biological tissues (e.g., heart, liver, lung, kidney, stomach, and muscle), with a considerable interfacial toughness of ∼1432 J m. Accordingly, since both natural hyaluronic acid derivative polymers and hydrophilic PHEAA networks are highly biocompatible, the hydrogel matrix possesses good blood compatibility (<5% of hemolysis ratio) and satisfies the general dressing requirements (>99% of cell viability). Based on these physicochemical features, we have demonstrated that this adhesive hydrogel, administered in the form of a designed patch, could be applied to wound tissue healing by promoting epithelialization, angiogenesis, and collagen deposition. We believe that our proposed biomimetic hydrogel design holds great potential for wound repair and our developed HAMA/PHEAA hydrogels are extremely promising for the next-generation tissue healings in emergency situations.

摘要

开发具有成本效益且生物相容性良好的软伤口敷料是非常必要的;然而,传统敷料仅针对扁平伤口设计,这在复杂的实际情况下实现理想的愈合效率存在困难。在此,我们开发了一种坚韧、具有粘性的仿生甲基丙烯酰化透明质酸水凝胶,它由化学交联的甲基丙烯酰化透明质酸(HAMA)网络和富含多重氢键的聚(N - 羟乙基丙烯酰胺)(PHEAA)网络组成。由于HAMA的多个化学交联位点(丙烯酰胺基团),块状HEMA/PHEAA水凝胶相比普通透明质酸水凝胶(<0.1MPa),其机械性能有显著提高(约0.45MPa)。丰富的氢键还赋予所得水凝胶在许多无孔基材上极高的粘附性,包括玻璃和生物组织(如心脏、肝脏、肺、肾脏、胃和肌肉),界面韧性约为1432J/m。因此,由于天然透明质酸衍生物聚合物和亲水性PHEAA网络都具有高度生物相容性,水凝胶基质具有良好的血液相容性(溶血率<5%)并满足一般敷料要求(细胞活力>99%)。基于这些物理化学特性,我们证明了这种以设计好的贴片形式给药的粘性水凝胶,可通过促进上皮形成、血管生成和胶原蛋白沉积应用于伤口组织愈合。我们相信,我们提出的仿生水凝胶设计在伤口修复方面具有巨大潜力,并且我们开发的HAMA/PHEAA水凝胶在紧急情况下的下一代组织愈合方面极具前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db16/10395096/5ec8094554ea/fbioe-11-1222088-g001.jpg

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