酸酐酰化胶原蛋白的制备与表征及应用

Preparation,characterization,and application of acylated collagen with anhydride

背景:胶原蛋白是一种具有良好生物相容性、低毒性、低免疫活性且高细胞亲和力的生物医药材料,然而亲水性和热稳定性较差等缺陷是其在生物医学、组织工程等应用领域亟需解决的关键技术难题之一。目的:阐述酰化胶原蛋白的制备方法、表征及应用的进展。方法:利用PubMed、X-mol和中国知网数据库,检索有关酰化胶原蛋白制备方法、表征及应用的文献,检索时间为1992年1月至2023年5月,英文检索词为“acylated collagen,modified collagen,water-soluble collagen,acetic anhydride”,中文检索词为“酰化胶原蛋白,改性胶原蛋白,水溶性胶原蛋白”。根据纳入与排除标准对所有文章进行初筛后,保留相关性较高的53篇文章进行综述。结果与结论:①酰化胶原蛋白的制备主要是通过酸酐类进行酰化反应所得,反应的位点主要是胶原蛋白的ε-氨基和N端-氨基,同时酰化反应的反应环境需要在碱性环境下进行;②琥珀酸酐是酰化胶原蛋白的首选反应物,同时近几年挖掘出降冰片烯二酸酐、柠檬酸酐以及具有酰化能力的双官能团改性剂来满足各种要求,但仍局限于实验室中制备,复杂的制备流程难以工业化,还需后续研究不断完善;③酰化胶原蛋白的表征手段与胶原蛋白类同,但针对酰化胶原蛋白的水溶性表征仍缺乏标准;④近年来酰化胶原蛋白逐步被用于镜片、水凝胶和敷料的制备及化妆品原料,但关于酰化胶原蛋白的应用研究仍然较少,缺乏完整的体内实验来验证酰化胶原蛋白的实用性。

BACKGROUND:Collagen is a biomedical material with good biocompatibility,low toxicity,low immunoactivity,and high cellular affinity.However,the defects such as hydrophilicity and poor thermal stability are the key technical problems that need to be solved urgently in biomedical,tissue engineering,and other applications.OBJECTIVE:To elaborate on the preparation method,characterization,and application progress of acylated collagen.METHODS:PubMed,X-mol,and CNKI databases were used to search the literature on acylated collagen preparation methods,characterization,and application.The search time was from January 1992 to May 2023.The English search terms were“acylated collagen,modified collagen,water-soluble collagen,acetic anhydride”.Chinese search terms were“acylated collagen,modified collagen,water-soluble collagen”.After an initial screening of all articles according to inclusion and exclusion criteria,53 articles with high relevance were retained for review.RESULTS AND CONCLUSION:(1)The preparation of acylated collagen is mainly obtained by the acylation reaction of acid anhydride,and the reaction sites are mainlyε-amino and N-terminus-amino of collagen,and the reaction environment of acylation reaction needs to be carried out in an alkaline environment.(2)Succinic anhydride is the preferred reactant of acylated collagen.Carbonic anhydride,citric anhydride,and bifunctional modifiers with acylation ability have been excavated in recent years to meet various requirements,but it is still limited to laboratory preparation;complex preparation process is difficult to industrialize,and follow-up research is needed to continuously improve.(3)The characterization methods of acylated collagen are similar to those of collagen,but there is still a lack of standards for the water-soluble characterization of acylated collagen.(4)In recent years,acylated collagen has been gradually used in the preparation of lenses,hydrogels,and dressings,as well as cosmetic raw materials.However,there is still little research on the application of acylated collagen,and there is a lack of complete in vivo experiments to verify the practicality of acylated collagen.