胶原基生物材料制备与应用研究进展  

Research Progress in Preparation and Application of Advanced Collagen-based Biomaterials

作　　者：何晓棠 但晔 陈一宁[1,4] 王云兵 胡晓兵 李正军[1,2] 但卫华[1,2] HE Xiaotang;DAN Ye;CHEN Yining;WANG Yunbing;HU Xiaobing;LI Zhengjun;DAN Weihua(Key Laboratory of Leather Chemistry and Engineering of Ministry of Education,College of Biomass Science and Engineering,Sichuan University,Chengdu 610065,China;Research Center of Biomedicine Engineering of Sichuan University,Chengdu 610065,China;School of Mechanical Engineering,Sichuan University,Chengdu 610065,China;National Engineering Research Center for Biomaterials,Chengdu 610065,China)

机构地区：[1]四川大学轻工科学与工程学院,皮革化学与工程教育部重点实验室,成都610065 [2]四川大学生物医学工程技术研究中心,成都610065 [3]四川大学机械工程学院,成都610065 [4]国家生物医学材料工程技术研究中心,成都610065

出　　处：《材料导报》2023年第2期206-214,共9页Materials Reports

基　　金：中央高校基本科研业务费资助项目(20826041C4159)。

摘　　要：胶原因具有良好的亲水性、柔韧性和趋化性、生物相容性、生物降解性,被认为是改善组织再生最重要的生物材料之一,并广泛应用于食品、化妆品以及再生医学领域。但是,在提取过程中,胶原的结构和自然交联键会遭到破坏,导致其机械强度、热稳定性和抗酶解能力都低于自然状态。受到天然胶原在组织重塑和修复过程中自然交联的启发,研究人员通过引入外源性交联(化学、物理和生物)来优化胶原基材料的机械强度和稳定性。目前,外源性化学、物理或生物交联已被用于修饰胶原的分子结构,通过这些方法制备的胶原基支架材料的刚度、抗张强度和压缩模量都明显提高,但是材料的延展性降低。这些方法主要是通过限制胶原三螺旋结构分子间α链的自由度,防止胶原微纤维排列的破坏,从而提高胶原的热稳定性和机械强度。另外,通过分子间交联掩盖胶原的酶切割位点,能够提高胶原对酶促降解的抵抗力。但是这些方法仍然有一些缺陷,如存在细胞毒性和降低胶原的活性等。研究者们制备了不同物理结构的胶原基材料(脱细胞基质、海绵、水凝胶、自组装纤维、膜、管和多孔球等),以更好地促进不同组织或器官的再生。因此,了解胶原基材料的交联方法和制备技术进展,对开发新型的胶原基生物支架材料至关重要。本文详细总结了制备胶原基材料的外源性交联方法及其优缺点,归纳了不同物理结构的胶原基材料制备方法以及它们在组织再生方面应用的研究进展,并对胶原基材料在再生领域面临的挑战以及未来的发展前景进行了展望。Collagen is considered as an appealing biomaterial with idealistic hydrophilicity,low antigenicity,flexibility,inherent chemotactic activity,bio-compatibility and biodegradability.Collagens are widely used in the food,cosmetics and biomedical industries.However,the mechanical properties,thermal stability and resistance to enzymatic degradatio are depleted during extraction,resulting in inferiorities compared to its natural state.Inspired by natural cross-linking of collagen during tissue remodeling and repair,researchers have developed exogenous chemical,physical and biological cross-linking methods to optimize the stability of collagen-based biomaterials.The stiffness,tensile strength and compressive modulus of collagen-based scaffolds prepared using cross-linking methods have yielded significant improvements,but the flexibility of these collagen materials is lacking.Current methods aim to prevent the destruction of collagen microfiber arrangement by limiting the degrees of freedom of theα-chain between the molecules of the collagen triple helix,thus promoting thermal stability and mechanical strength.In addition,resistance to enzymatic degradation can be improved by masking the enzymatic cleavage sites of collagen using intermolecular crosslinking.However,deficiencies in these methodologies include increased cytotoxicity and decreased bioactivity.To satisfy the requirements of tissue and organ regeneration,researchers have prepared collagen materials in different physical forms(acellular matrix,sponges,hydrogels,self-assembled fibers,membranes,tubes,porous spheres,etc.).Therefore,it is imperative to understand the cross-linking methods and preparation technology of collagen based materials for developing new collagen based scaffold materials.Here,we introduced exogenous crosslinking methods in the fabrication of collagen-based biomaterials and their associated advantages and disadvantages,the preparation of collagen-based materials with different physical structures,the progress and challenges in utilizing col

关 键 词：胶原 交联 生物材料 组织再生 

分 类 号：R318.08[医药卫生—生物医学工程]