Abstract
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•Production methods of chitooligosaccharides (COS) have been compared to determine the most biocompatible ones.•The biological activities of COS have been summarized.•A comprehensive discussion on the influence of MW and DD on the effectiveness and characteristics of COS-based hydrogels.•A summary of recent advances in COS-based hydrogels in regenerative medicine.•COS-based hydrogels have been reported to improve the biological response in regenerative medicine applications.
Chitosan’s lack of solubility in physiological pH and high molecular weight (MW) limits its use in hydrogel scaffolds. Conversion of chitosan to low MW chitooligosaccharides (COS) not only imparts water solubility, it also enhances several other biological properties. When used in hydrogels, the low MW improves the performance of the hydrogels, e.g., the absorptive property, biocompatibility and cell proliferation capability. Most importantly, properties of COS, namely the degree of polymerization (DP) and degree of deacetylation (DD), can be altered to support specific functions in hydrogels used in regenerative medicine. Methods of preparation of COS must therefore be simple and convenient, leading to COS that can be readily used in biomedical applications without requiring extensive post-purification. This review compares these various methods of production of COS and discusses critically the specific advantages that COS can lend to hydrogels, which make COS better alternatives to chitosan in cell-related applications.