The Paradoxical Immunomodulatory Effects of Chitosan in Biomedicine

Chitosan is widely explored in the field of biomedicine due to its abundance and reported properties, including biocompatibility, biodegradability, non-toxicity, mucoadhesion, and anti-microbial activity. Although our understanding of the immune response to chitosan has evolved, confusion remains regarding whether chitosan is a pro- or anti-inflammatory biomaterial. Tackling this knowledge gap is essential for the translation of chitosan-based biomaterials to clinical use. Herein, we provide an overview of the immune responses to chitosan, exploring the roles of endotoxin contamination and physiochemical properties in immunomodulation. Ultimately, this literature review concludes that various physiochemical properties, including molecular weight, degree of deacetylation and polydispersity, endotoxin contamination, and cellular environment, interplay in the complex process of chitosan immunomodulation, which can lead to both pro- and anti-inflammatory effects.