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

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.