Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment Process
Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment Process
复制标题
基于原位气泡形成水凝胶捕获工艺的可注射多孔透明质酸水凝胶的制备
DOI：
10.3390/polym12051138
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发表时间：
2020-05-01
期刊：
影响因子：
5
通讯作者：
Yuan, Yuan
中科院分区：
文献类型：
--
作者：
Wang, Lixuan;Dong, Shiyan;Yuan, Yuan
可注射水凝胶在再生医学领域有着广泛的应用。然而，当前用于可注射水凝胶的技术在试图产生公认促进细胞行为的仿生多孔结构时面临挑战。在这项研究中，一个可注射的，互联的，多孔的透明质酸（HA）水凝胶的基础上，在原位气泡自生成和包埋过程。通过由EDC/NHS激活的HA和胱胺二盐酸盐之间的酰胺反应，产生CO2气泡，随后由于快速凝胶诱导的保留效应而被截留在基底内部。制备了不同分子量和浓度的HA水凝胶，研究了水凝胶前体溶液的浓度和粘度对水凝胶性能的影响。结果表明，HA 10 -10（10重量%，MW 100，000 Da）和HA 20 -2.5（2.5重量%，分子量为200，000 Da）具有较好的凝胶性和明显的多孔结构。此外，HA 10 -10表现出高弹性模量（32 kPa）。进一步的体内外研究表明，本研究制备的水凝胶均具有良好的生物相容性，细胞行为良好，宿主反应温和。总的来说，这种具有自形成气泡和包埋策略的原位水凝胶被认为提供了一种稳健和通用的平台，以工程化可注射水凝胶，用于组织工程、再生医学和个性化治疗中的各种应用。
Injectable hydrogels have been widely applied in the field of regenerative medicine. However, current techniques for injectable hydrogels are facing a challenge when trying to generate a biomimetic, porous architecture that is well-acknowledged to facilitate cell behaviors. In this study, an injectable, interconnected, porous hyaluronic acid (HA) hydrogel based on an in-situ bubble self-generation and entrapment process was developed. Through an amide reaction between HA and cystamine dihydrochloride activated by EDC/NHS, CO2 bubbles were generated and were subsequently entrapped inside the substrate due to a rapid gelation-induced retention effect. HA hydrogels with different molecular weights and concentrations were prepared and the effects of the hydrogel precursor solution’s concentration and viscosity on the properties of hydrogels were investigated. The results showed that HA10-10 (10 wt.%, MW 100,000 Da) and HA20-2.5 (2.5 wt.%, MW 200,000 Da) exhibited desirable gelation and obvious porous structure. Moreover, HA10-10 represented a high elastic modulus (32 kPa). According to the further in vitro and in vivo studies, all the hydrogels prepared in this study show favorable biocompatibility for desirable cell behaviors and mild host response. Overall, such an in-situ hydrogel with a self-forming bubble and entrapment strategy is believed to provide a robust and versatile platform to engineer injectable hydrogels for a variety of applications in tissue engineering, regenerative medicine, and personalized therapeutics.