【作者】 张强；

【导师】 张晓梅；

【作者基本信息】 山东大学 ， 材料与化工（专业学位）， 2024， 硕士

【摘要】 慢性伤口是糖尿病的一种常见并发症,由于持续炎症和慢性高血糖导致伤口难以愈合,给全球医疗和社会资源造成巨大压力。此外,免疫反应受损使糖尿病伤口容易受到细菌污染,从而导致更高的炎症风险,使慢性伤口的治疗更具挑战性。随着耐药细菌的出现,慢性伤口的治疗变得更加困难,而将纳米材料用于抗菌能够避免细菌耐药性的产生。作为新型纳米酶的卟啉基多孔有机聚合物(PPOPs)具有高的比表面积、丰富的孔隙、密集的活性位点以及稳定的整体框架,所形成的有机/无机纳米复合材料不仅延续了PPOPs与无机纳米材料各自固有的优势,而且克服了各自的缺陷与不足,甚至还会协同提升复合材料各方面的性能。结合以上背景,本文报道了一种新型的纳米复合材料协同抗菌剂用于细菌感染伤口的治疗,之后将其与水凝胶相结合,制备了一种新型的水凝胶伤口敷料。以下为具体的研究内容:1.伤口细菌感染是一种严重的健康问题,而抗生素的滥用导致了细菌耐药性的产生,使得治疗变得异常困难,因此迫切需要开发新型抗菌材料用于治疗细菌感染的伤口。本章以中空的Cu2S纳米立方笼为模板,采用原位生长的方式,以四苯基甲烷(TPM)和四苯基卟啉铁(FeTPP)作为单体合成了具有立方体结构的纳米复合材料Cu2S@FePPOPTPM。通过多种表征手段和实验方法,证明了该材料不仅具有比表面积大、孔隙率高、稳定性强等优点,还具有优异的类过氧化物酶活性和Cu+的持续释放能力。基于以上令人满意的特性,Cu2S@FePPOPTPM在H2O2存在条件下被用于体外抗菌实验和小鼠伤口感染模型治疗之中,结果表明Cu2S@FePPOPTPM对于金黄色葡萄球菌(S.aureus)和大肠杆菌(E.coli)的最低抑菌浓度分别为64 μg/mL和32 μg/mL,并且该材料可以有效地清除伤口感染处的细菌,促进伤口愈合。因此,Cu2S@FePPOPTPM是一种可靠的广谱抗菌剂,在医疗领域具有广阔的应用前景。2.伤口敷料在糖尿病慢性伤口的治疗中扮演着至关重要的角色,而水凝胶具有良好的保湿性能、天然载药能力和优越的生物相容性,已成为伤口愈合的理想敷料。本章基于氧化透明质酸(OHA)和掺杂纳米复合材料的N-羧甲基壳聚糖(CMC)之间的席夫碱反应,开发了一种pH响应性水凝胶Cu2S@FePPOPTPM@GOx@Gel(简称Cu2S@FePPOPTPM@GOx@Gel),用于糖尿病伤口愈合。在 Cu2S@FePPOP TPM@GOx@Gel中,合成的外层水凝胶表现出酸响应性分解的特征,并且Cu2S@FePPOPTPM@GOx纳米颗粒可以在感染伤口的微酸性环境中释放,纳米材料表面的葡萄糖氧化酶(GOx)可以消耗伤口的高糖,减少炎症反应,缩短炎症周期。同时,高糖分解产生的葡萄糖酸和H2O2促进了亚铜离子(Cu+)的释放,提高了 FePPOPTPM的酶活性。值得注意的是,在糖尿病伤口愈合过程中,Cu2S@FePPOPTPM@GOx@Gel可以调节免疫反应,促进血管生成和胶原沉积。因此,可以预见,合成的集免疫调节、降血糖能力和抗菌活性于一体的Cu2S@FePPOPTPM@GOx(@Gel在细菌清除和糖尿病伤口修复方面具有巨大潜力。更多还原

【Abstract】 Chronic wound is a common complication of diabetes.Due to persistent inflammation and chronic hyperglycemia,it is difficult for the wound to heal,which puts enormous pressure on global medical and social resources.In addition,impaired immune response makes diabetes wounds vulnerable to bacterial contamination,leading to a higher risk of inflammation,making the treatment of chronic wounds more challenging.With the emergence of drug-resistant bacteria,the treatment of chronic wounds has become more difficult,and using nanomaterials for antibacterial purposes can avoid the development of bacterial resistance.As a new type of nanoenzyme,porphyrin-based porous organic polymers(PPOPs)have high specific surface area,abundant pores,dense active sites,and stable overall framework.The organic/inorganic nanocomposites formed not only continue the inherent advantages of PPOPs and inorganic nanomaterials,but also overcome their respective defects and shortcomings,and even synergistically improve the performance of composite materials in all aspects.In combination with the above background,this paper reported a new type of nanocomposite synergistic antibacterial agent for the treatment of bacterial infected wounds,and then combined it with hydrogel to prepare a new type of hydrogel wound dressing.The main research contents are as follows:1.Wound bacterial infection is a serious health problem.The abuse of antibiotics leads to the development of bacterial resistance,making treatment extremely difficult.Therefore,there is an urgent need to develop new antibacterial materials for treating bacterial infected wounds.In this chapter,hollow Cu2S nanocubes were used as templates,and in situ growth was employed to synthesize nanocomposite material Cu2S@FePPOPTPM with cubic structure using tetraphenylmethane(TPM)and 5,10,15,20-tetraphenyl-21H,23H porphyrin iron chloride(FeTPP)as monomers.Through various characterization methods and experimental methods,it has been proven that this material not only has advantages such as large specific surface area,high porosity,and strong stability,but also excellent peroxidase-like activity and sustained release ability of Cu+.Based on the satisfactory characteristics mentioned above,Cu2S@FePPOPTPM was used in vitro antibacterial experiments and mouse wound infection model treatment in the presence of H2O2.These results showed that the minimum inhibitory concentrations of Cu2S@FePPOPTPM for Staphylococcus aureus(S.aureus)and Escherichia coli(E.coli)are 64 μg/mL and 32 μg/mL,respectively.Furthermore,this material can effectively remove bacteria from wound infections and promote wound healing.Therefore,Cu2S@FePPOPTPM is a reliable broad-spectrum antibacterial agent with broad application prospects in the medical field.2.Wound dressings play a vital role in the treatment of chronic wounds of diabetes.Hydrogels have good moisturizing properties,natural drug carrying capacity and superior biocompatibility,becoming the ideal dressings for wound healing.In this chapter,a pH responsive hydrogel Cu2S@FePPOPTPM@GOx@Gel(abbreviated as Cu2S@FePPOPTPM@GOx@Gel),based on the Schiff base reaction between oxidized hyaluronic acid(OHA)and N-carboxyethyl chitosan(CMC)doped with nanocomposites,is used for wound healing of diabetes.The outer layer hydrogel synthesized of Cu2S@FePPOPTPM@GOx@Gel shows the characteristics of acid responsive decomposition,and Cu2S@FePPOPTPM@GOx nanoparticles can be released in the slightly acidic environment of infected wounds.Glucose Oxidase(GOx)on the surface of nanomaterials can consume high sugar in wounds,reduce inflammatory reaction,and shorten the inflammatory cycle.At the same time,the gluconic acid and H2O2 produced by high sugar decomposition promote the release of copper ions and enhance the enzyme activity of FePPOPTPM.It is worth noting that in the process of diabetes wound healing,Cu2S@FePPOPTPM@GOx@Gel has the ability to regulate immune response,promote angiogenesis and collagen deposition.Therefore,it can be predicted that the synthetic compound Cu2S@FePPOPTPM@GOx@Gel,integrating immunomodulation,hypoglycemic activity,and antibacterial activity,holds great potential in bacterial clearance and diabetic wound repair.更多还原