【作者】 徐磊；

【导师】 程凤；

【作者基本信息】 哈尔滨工业大学 ， 化学工程与技术， 2023， 硕士

【摘要】 日常生活中,外伤、手术和疾病都会不可避免的造成皮肤伤口的产生。在伤口修复过程中通常需要敷料以保护伤口免受二次伤害并促进伤口愈合。相比于纱布,海绵等干性敷料,基于水凝胶的湿性敷料已经被证明可以更有效地促进伤口的愈合。但是传统的水凝胶敷料难以针对不同创面进行个性化设计并且缺乏抗菌性、抗氧化性和止血等利于伤口愈合的功能,难以有效促进创面修复。充分考虑3D打印的优势和伤口愈合复杂影响因素,本课题对水凝胶进行合理设计,使其可通过3D打印成型以实现结构精准调控与个性化设计,并且兼具利于伤口愈合的各种功能,从而更好的促进伤口愈合。本课题通过挤出式3D打印实现了多功能水凝胶支架的成型并对其利于伤口愈合的性能进行探究。首先制备了接枝甲基丙烯酸酐的明胶(Gel MA),接枝多巴胺的Gel MA(Gel MA-DA)和聚多巴胺包覆的还原氧化石墨烯(r GO@PDA),并通过FT-IR、~1H-NMR、UV-vis和SEM对上述材料和纤维素纳米纤维(TOCNF)进行了表征。随后通过上述材料制备了多功能水凝胶并表征了多功能水凝胶的理化性质(包括力学强度,溶胀率,电导率,抗氧化性和粘附强度)。并通过流变学测试和打印参数分析探究了多功能水凝胶的可3D打印性。Gel MA和TOCNF为水凝胶的3D打印提供了适宜的流变特性,Gel MA-DA和r GO@PDA为水凝胶提供了利于伤口愈合的多功能性。在此之后对多功能水凝胶利于伤口愈合的生物学性能(包括生物安全性,抗菌性能,止血性能和促进SD大鼠的细菌感染全皮层缺损模型愈合效果评估)进行测试分析。水凝胶理化性质测试表明:多功能水凝胶具有良好的力学强度,适当的溶胀率和7.03 k Pa的高粘附力,为伤口提供良好的保护并吸收伤口渗出物;此外,多功能水凝胶具有超过80%的活性氧(ROS)吸收能力和良好的导电性,利于促进伤口的愈合。流变学测试和打印参数探究表明多功能水凝胶具有良好的可打印性。溶血测试和细胞毒性测试表明多功能水凝胶具有良好的生物相容性。在抗菌试验中多功能水凝胶在以光热为主的多重抗菌能力下对细菌有着高效的杀灭作用。在止血测试中,多功能水凝胶在SD大鼠肝脏和尾部出血伤口表现出了良好的止血性能。最后在SD大鼠的细菌感染全皮层缺损伤口愈合情况分析表明,多功能水凝胶配合其光热作用治疗下能够显著促进伤口愈合。更多还原

【Abstract】 Trauma,surgery and disease inevitably cause skin wounds to develop in everyday life.Dressings are often required during wound repair to protect the wound from secondary damage and promote wound healing.Hydrogel-based wet dressings have been shown to be more effective in promoting wound healing than dry dressings such as gauze and sponges.However,traditional hydrogel dressings are difficult to personalize for different wounds and lack functions that facilitate wound healing such as antibacterial,antioxidant,hemostatic,making it difficult to effectively promote wound repair.Taking into account the advantages of 3D printing and the complexities of wound healing,this project aims to rationalize the design of hydrogel so that they can be 3D printed to achieve precise structural control and personalization,as well as a variety of functions to facilitate wound healing.In this project,multifunctional hydrogel scaffolds were modelled by extrusion3D printing and their wound healing properties were investigated.Gelatin grafted with methacrylic anhydride(Gel MA),Gel MA grafted with dopamine(Gel MA-DA)and polydopamine-coated reduced graphene oxide(r GO@PDA)were first prepared and characterized by FT-IR,~1H-NMR,UV-vis and SEM for these materials and cellulose nanofiber(TOCNF).The multifunctional hydrogels were then prepared and the physicochemical properties(including mechanical strength,swelling rate,electrical conductivity,oxidation resistance and adhesion strength)of the multifunctional hydrogels were characterized by the above materials.Gel MA and TOCNF provided suitable rheological properties for 3D printing of the hydrogels,and Gel MA-DA and r GO@PDA provided multifunctional properties for wound healing.The biological properties of the multifunctional hydrogels for wound healing(including biosafety,antimicrobial properties,hemostatic properties and assessment of the efficacy of promoting healing in SD rat model of bacterially infected total cortical defect)were then tested and analyzed.Physical and chemical properties test of the hydrogel showed that the multifunctional hydrogel has good mechanical strength,appropriate swelling rate and high adhesion of 7.03 k Pa,providing good protection and absorption of wound exudate;in addition,the multifunctional hydrogel has over 80%reactive oxygen species(ROS)absorption and good conductivity,facilitating wound healing.Rheological tests and printing parameters were explored to demonstrate the good printability of the multifunctional hydrogels.Hemolysis and cytotoxicity tests have shown that the multifunctional hydrogel is biocompatible.In antibacterial test the multifunctional hydrogel was highly effective in killing bacteria with multiple antibacterial capabilities,mainly photothermal.In hemostasis tests,the multifunctional hydrogel showed good hemostatic properties in bleeding wounds on the liver and tail of SD rats.Finally,analysis of wound healing in SD rats with bacterially infected total cortical defects showed that the multifunctional hydrogel significantly promoted wound healing when combined with its photothermal treatment.更多还原