3 - Immunological responses to chitosan for biomedical applications

Abstract

The purpose of this chapter is to provide an overview of immunological responses to chitosan materials, with a particular focus on innate immune responses by blood, polymorphonuclear cells (PMNs), and macrophages. A literature review was carried out, and illustrative data were added along with methods for assaying THP-1 or U937 macrophage-like cell responses to chitosan in vitro. To begin with, it is important to recognize that chitosan is a “catchall” term that describes a family of linear polymers with variable glucosamine and N-acetyl glucosamine content, and heterogeneous molecular weight. When chitosan contains 100% glucosamine, then the polymer has 100% degree of deacetylation (DDA), whereas chitosans with 50–85% DDA are “partly acetylated” Molecular weight and DDA strongly influence innate immune responses, however the physical structure of a chitosan implant can also dramatically alter the immunological response. Chitosans form electrostatic complexes with anionic blood factors and promote platelet activation with a minimal 8kDa molecular weight. Highly deacetylated chitosans have a weak leukocyte infiltration response, while biodegradable partly acetylated chitosans often attract PMNs and stimulate neutrophils to release potent mediators that further amplify the recruitment of neutrophils and macrophages. In vitro, macrophages that phagocytose chitosan were found to secrete higher levels of chemokines; anabolic cytokines; anti-inflammatory factors including IL-10 and interleukin-1 receptor antagonist (IL-1ra), and to undergo inflammasome activation accompanied by IL-beta release. In various in vitro macrophage models, chitin, chitosan, and chitosan oligomers have been reported to have no effect, enhance, or attenuate the release of inflammatory mediators such as TNF-alpha and nitric oxide. Chitosan implants that resist erosion, including nonbiodegradable plastics coated with chitosan, elicit a foreign body response and fibrous capsule formation around the implant. A careful assessment of chitosan structure, purity, dose response, and clearance rate in vivo is required to reveal whether immunological responses to a given chitosan implant are promoting or inhibiting the target performance.