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

几丁质是地球上最丰富的生物聚合物之一，是节肢动物外壳、头足动物内骨骼和真菌细胞壁的一部分。它是一种不溶于水的分子，由n -乙酰氨基葡萄糖残基组成。它的部分去乙酰化，例如在人类致病真菌中发现的过程，促进共聚物在水介质中的溶解度，一旦它是可溶的，就被称为壳聚糖。最近的研究表明，剩余乙酰基的数量和模式对应于生物化学密码，这对于与生物环境的相互作用至关重要。本研究的目的是为了更好地了解这种几丁质编码（codeχ）与哺乳动物生物反应之间的结构-功能关系。在前期和前期研究的基础上，我们拟分析几丁质/壳聚糖与补体系统（体液先天免疫系统的古老组成部分）、几丁质结合蛋白YKL-40和硫酸肝素蛋白聚糖（我们最近发现的壳聚糖结合伙伴）的分子串音。几丁质可诱导细胞固有免疫反应，如巨噬细胞的活化。相反，壳聚糖被认为是一种有前途的生物材料，可以促进伤口愈合和组织再生。为了了解控制甲壳素和壳聚糖广泛生物学特性的潜在编码χ，我们将在分子水平上进行相互作用研究，在哺乳动物细胞的体外实验和在小鼠模型的体内测量。我们的研究项目的基础是聚合物物理水凝胶，它特别适合于体外实验和局部的、微创的小鼠体内应用，以研究炎症事件，如免疫细胞募集或再生过程，如血管生成。

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.