Role of the chito-structural code in controlling inflammatory and tissue regenerative processes in the frame of biomedical applications

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Chitin, one of the most abundant biopolymers on Earth, is part of arthropod shells, cephalopod endoskeleton, and fungal cell walls. It is a water insoluble molecule composed of N-acetyl glucosamine residues. Its partial de-acetylation, a process found e.g. in human pathogenic fungi promotes the solubility of the copolymer in aqueous media, which is called chitosan once it is soluble. Recent studies indicate that the amount and the pattern of the remaining acetyl groups, corresponds to a biochemical code, which is critical for the interaction with the biological environment. The aim of the proposed research is to better understand the structure-functional relationship between this chitin code (codeχ) and the biological response in mammalians. Based on our previous and preliminary studies, we intend to analyze the molecular crosstalk of chitin/chitosan with the complement system, an ancient part of the humoral innate immune system, the chitin-binding protein YKL-40 and heparan sulfate proteoglycans, which we have recently identified as binding partners of chitosans. Chitin was shown to induce the cellular innate immune response such as the activation of macrophages. In contrast, chitosan is postulated as promising biomaterial, which promotes wound healing and tissue regeneration. To understand the underlying codeχ controlling the broad range of biological properties of chitin and chitosan, we will perform interaction studies on the molecular level, in vitro experiments with mammalian cells and in vivo measurements using mouse models. The basis for our research project are chit-polymer physical hydrogels, which are particularly suitable for in vitro experiments and a localized, minimally invasive in vivo application in mice to investigate inflammatory events such as immune cell recruitment or regenerative processes such as angiogenesis.