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海藻酸钠二醛与天然和合成共聚物的双自交联效应作为可注射原位形成的可生物降解水凝胶

Dual-Self-Crosslinking Effect of Alginate-Di-Aldehyde with Natural and Synthetic Co-Polymers as Injectable In Situ-Forming Biodegradable Hydrogel.

作者信息

Begum Bushra, Koduru Trideva Sastri, Madni Syeda Noor, Fathima Anjum Noor, Seetharaman Shanmuganathan, Veeranna Balamuralidhara, Gupta Vishal Kumar

机构信息

Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Sri Shivarathreeshwara Nagar, Mysuru 570015, India.

Department of Pharmaceutics, Farooqia College of Pharmacy, Mysuru 570019, India.

出版信息

Gels. 2024 Oct 11;10(10):649. doi: 10.3390/gels10100649.

DOI:10.3390/gels10100649
PMID:39451302
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11507163/
Abstract

Injectable, in situ-forming hydrogels, both biocompatible and biodegradable, have garnered significant attention in tissue engineering due to their potential for creating adaptable scaffolds. The adaptability of these hydrogels, made from natural proteins and polysaccharides, opens up a world of possibilities. In this study, sodium alginate was used to synthesize alginate di-aldehyde (ADA) through periodate oxidation, resulting in a lower molecular weight and reduced viscosity, with different degrees of oxidation (54% and 70%). The dual-crosslinking mechanism produced an injectable in situ hydrogel. Initially, physical crosslinking occurred between ADA and borax via borax complexation, followed by chemical crosslinking with gelatin through a Schiff's base reaction, which takes place between the amino groups of gelatin and the aldehyde groups of ADA, without requiring an external crosslinking agent. The formation of Schiff's base was confirmed by Fourier-transform infrared (FT-IR) spectroscopy. At the same time, the aldehyde groups in ADA were characterized using FT-IR, proton nuclear magnetic resonance (¹H NMR), and gel permeation chromatography (GPC), which determined its molecular weight. Furthermore, borax complexation was validated through boron-11 nuclear magnetic resonance (¹¹B NMR). The hydrogel formulation containing 70% ADA, polyethylene glycol (PEG), and 9% gelatin exhibited a decreased gelation time at physiological temperature, attributed to the increased gelatin content and higher degree of oxidation. Rheological analysis mirrored these findings, showing a correlation with gelation time. The swelling capacity was also enhanced due to the increased oxidation degree of PEG and the system's elevated gelatin content and hydrophilicity. The hydrogel demonstrated an average pore size of 40-60 µm and a compressive strength of 376.80 kPa. The lower molecular weight and varied pH conditions influenced its degradation behavior. Notably, the hydrogel's syringeability was deemed sufficient for practical applications, further enhancing its potential in tissue engineering. Given these properties, the 70% ADA/gelatin/PEG hydrogel is a promising candidate and a potential game-changer for injectable, self-crosslinking applications in tissue engineering. Its potential to revolutionize the field is inspiring and should motivate further exploration.

摘要

可注射的原位形成水凝胶具有生物相容性和可生物降解性,因其具有创建适应性支架的潜力而在组织工程领域备受关注。这些由天然蛋白质和多糖制成的水凝胶的适应性开启了一个充满可能性的世界。在本研究中,海藻酸钠通过高碘酸盐氧化合成了海藻酸二醛(ADA),导致分子量降低和粘度减小,氧化程度不同(54%和70%)。双交联机制产生了一种可注射的原位水凝胶。最初,ADA和硼砂通过硼砂络合发生物理交联,随后通过席夫碱反应与明胶进行化学交联,该反应发生在明胶的氨基和ADA的醛基之间,无需外部交联剂。傅里叶变换红外(FT-IR)光谱证实了席夫碱的形成。同时,使用FT-IR、质子核磁共振(¹H NMR)和凝胶渗透色谱(GPC)对ADA中的醛基进行了表征,确定了其分子量。此外,通过硼-11核磁共振(¹¹B NMR)验证了硼砂络合。含有70% ADA、聚乙二醇(PEG)和9%明胶的水凝胶配方在生理温度下的凝胶化时间缩短,这归因于明胶含量的增加和更高的氧化程度。流变学分析反映了这些发现,显示出与凝胶化时间的相关性。由于PEG氧化程度的增加以及体系中明胶含量和亲水性的提高,溶胀能力也增强了。该水凝胶的平均孔径为40-60 µm,抗压强度为376.80 kPa。较低的分子量和不同的pH条件影响了其降解行为。值得注意的是,该水凝胶的可注射性被认为足以满足实际应用,进一步增强了其在组织工程中的潜力。鉴于这些特性,70% ADA/明胶/PEG水凝胶是一个有前途的候选者,也是组织工程中可注射、自交联应用的潜在变革者。其变革该领域的潜力令人鼓舞,应促使进一步探索。

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