小分子代谢物功能化材料调控糖尿病创伤免疫代谢微环境研究

糖尿病创伤中免疫细胞功能紊乱导致炎性细胞因子和趋化因子累积是创伤愈合延迟的主要原因，现有材料缺乏免疫细胞群调控能力。本项目基于促炎和抗炎表型免疫细胞代谢差异，拟选用小分子代谢物质（柠檬酸根和琥珀酸根），构建兼具抑制糖酵解代谢和促进氧化磷酸化代谢的小分子代谢物功能化材料，并将其用于调控糖尿病创伤免疫代谢微环境。研究材料组成比例、分子结构等对材料降解行为、力学性能、溶胀性能、热稳定能性及流变性能等性能的影响规律，阐明组成-结构-降解行为之间的机制，实现两种小分子代谢物的可控顺序释放；基于体内外模型，研究材料对T淋巴细胞、嗜中性粒细胞和巨噬细胞活性、增殖、代谢、分化及表型相关蛋白与基因表达的影响规律，揭示小分子代谢物-免疫代谢微环境-创伤愈合过程的适配性规律，阐明小分子代谢物的糖尿病免疫代谢调控与创伤治疗机制，为小分子代谢物功能化材料的免疫代谢调控提供理论依据，并为糖尿病创伤治疗提供新的思路。

The accumulation of inflammatory cytokines and chemokines caused by immune cell dysfunction in diabetic wound is the main reason for delayed wound healing. Many design objectives of the current materials are to regulate the phenotype of macrophages, lacking the ability to regulate immune cell groups. In this project, an innovative small metabolite functionalized-material which can inhibit glycolysis metabolism and promote oxidative phosphorylation metabolism will be synthesized by using small molecules (citric acid and succinic acid) that have the effect of regulating energy metabolism for diabetes immune metabolism regulation and wound healing based on the difference in immune cell metabolism between pro-inflammatory and anti-inflammatory phenotypes. The influences of material monomer composition, molecular weight ratio, and blending ratio on the degradation performance, mechanical properties, swelling performance, thermal stability and rheological properties of bioenergy active materials will be researched, and the relationship between composition-process-physical and chemical properties-degradation performance will be clarified, to achieve the material degradation regulation and two kinds of metabolic small molecules controlled orderly long-term release. Based on in vivo and in vitro models, the effects of materials on T lymphocytes, neutrophils and macrophages activity, proliferation, metabolism, differentiation, and phenotype-related protein and gene expression will be researched, and the adaptability of degradation products-immune metabolism-wound healing process will be revealed, to clarify the mechanism of diabetes immune metabolism regulation and wound treatment of bioenergy active material. This project provides a theoretical basis for the regulation of immune metabolism of bioenergy active materials, and a new perspective for the treatment of diabetic wound.