中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (22): 3576-3482.doi: 10.12307/2024.525

• 生物材料综述 biomaterial review • 上一篇    下一篇

甲基丙烯酰明胶水凝胶作为细胞三维培养支架在骨组织工程中的应用

王赛楠1,王晓菲2,张  莉1   

  1. 1滨州医学院,山东省滨州市  256600;2滨州医学院附属医院口腔科,山东省滨州市  256600
  • 收稿日期:2023-09-12 接受日期:2023-10-25 出版日期:2024-08-08 发布日期:2024-01-20
  • 通讯作者: 张莉,医学博士,硕士生导师,滨州医学院,山东省滨州市 256600
  • 作者简介:王赛楠,女,1998年生,山东省聊城市人,滨州医学院在读硕士,主要从事口腔牙体牙髓病学研究。
  • 基金资助:
    滨州医学院“临床+X”科技创新项目(BY2021LCX08),项目负责人:张莉

Application of gelatin methacryloyl as a three-dimensional cell culture scaffold in bone tissue engineering

Wang Sainan1, Wang Xiaofei2, Zhang Li1   

  1. 1Binzhou Medical College, Binzhou 256600, Shandong Province, China; 2Department of Stomatology, Affiliated Hospital of Binzhou Medical College, Binzhou 256600, Shandong Province, China
  • Received:2023-09-12 Accepted:2023-10-25 Online:2024-08-08 Published:2024-01-20
  • Contact: Zhang Li, MD, Master’s supervisor, Binzhou Medical College, Binzhou 256600, Shandong Province, China
  • About author:Wang Sainan, Master candidate, Binzhou Medical College, Binzhou 256600, Shandong Province, China
  • Supported by:
    “Clinical+X” Science and Technology Innovation Project of Binzhou Medical College, No. BY2021LCX08 (to ZL)

摘要:


文题释义:

甲基丙烯酰明胶(gelatin methacrylate,GelMA):是一种以明胶及甲基丙烯酸酐为原料的光交联水凝胶,它具有多孔隙结构及可调节性,生物相容性好,且有可注射性,可以根据骨组织缺损的形状及大小,在注射到缺损部位后形成原位复杂几何结构的凝胶,目前已被广泛应用于骨组织工程研究中。
三维(Three-dimensional,3D)细胞培养:将细胞与具有三维结构的支架材料在体外共培养,使细胞能够在3D的立体空间结构中迁移增殖,构成细胞-载体3D复合体系。


背景:骨缺损的治疗一直是临床医生亟待解决的临床难题,用甲基丙烯酰明胶进行细胞体外3D培养,可以为大面积骨缺损的治疗提供新的方向。

目的:文章综述了甲基丙烯酰明胶作为3D细胞培养支架在骨组织工程中的研究进展,以期为临床骨缺损修复提供进一步的参考。
方法:应用计算机检索中国知网及PubMed数据库1986年1月至2023年8月收录的文献,中英文检索词分别为“骨缺损,骨组织工程,生物支架材料,水凝胶,光交联水凝胶,甲基丙烯酰明胶,三维培养,细胞培养”和“Bone defect,Bone tissue engineering,Biomaterial scaffold,Hydrogel,Methylacrylyl photocrosslinked hydrogel,Three-dimensional culture;Cell culture”,最终纳入68篇文献进行综述分析。

结果与结论:①同二维培养相比,3D培养可以在无菌条件下,构建立体三维空间,更好地模拟体内环境,为细胞提供合适的温度、酸碱度及足够的营养,使细胞能够在体外正常生长增殖并保持其正常结构与功能,具有独特优势。②在骨组织工程生物支架材料的选择中,水凝胶因其良好的生物相容性、可降解性及具有立体三维网络结构等优点,已被广泛应用于骨再生的研究。③甲基丙烯酰明胶的物理及生物性能受到浓度、光照时间及光引发剂种类以及反应体系等因素的影响,而这些性能均能对细胞的黏附、生长及增殖,甚至细胞形态及功能产生一定的影响。④甲基丙烯酰明胶因具有良好的生物相容性、物理可调节性、可注射性及光敏性能,已被广泛应用于3D细胞封装、3D生物打印及基于数字光处理的立体光刻技术等细胞3D培养体系中。⑤应用各类复合甲基丙烯酰明胶进行细胞的3D培养,可以更好地促进血管形成及骨再生,为临床骨缺损的治疗提供更多可能。⑥目前甲基丙烯酰明胶的来源、合成的方法以及安全性尚没有健全的标准,需要进一步加强研究,对甲基丙烯酰明胶在3D细胞培养领域的应用进行更深入的完善。

https://orcid.org/0009-0008-6066-9132(王赛楠);https://orcid.org/0000-0002-7341-1930(张莉)

中国组织工程研究杂志出版内容重点:生物材料;骨生物材料口腔生物材料纳米材料缓释材料材料相容性组织工程

关键词: 骨缺损, 骨组织工程, 生物支架材料, 水凝胶, 光交联水凝胶, 甲基丙烯酰明胶, 二维培养, 三维培养, 细胞培养

Abstract: BACKGROUND: The treatment of bone defects has always been a pressing clinical challenge for medical practitioners. The use of gelatin methacryloyl for three-dimensional extracellular cultivation offers a promising direction for the treatment of extensive bone defects.
OBJECTIVE: To review the research progress of gelatin methacryloyl as a three-dimensional cell culture scaffold in bone tissue engineering, aiming to provide further references for clinical bone defect repair.
METHODS: Computerized searches were conducted on the CNKI and PubMed databases for articles published from January 1986 to August 2023. The search terms in Chinese and English were “bone defect, bone tissue engineering, biomaterial scaffold, hydrogel, photocrosslinked hydrogel, gelatin methacryloyl, three-dimensional culture, cell culture” and “bone defect, bone tissue engineering, biomaterial scaffold, hydrogel, gelatin methacryloyl, three-dimensional culture, cell culture”, respectively. Finally, 68 articles were included for review and analysis.
RESULTS AND CONCLUSION: (1) When compared to two-dimensional culture techniques, three-dimensional culture can construct a three-dimensional space under aseptic conditions, more effectively simulating the in vivo environment. It provides cells with the appropriate temperature, pH, and sufficient nutrients, allowing cells to grow and proliferate normally outside the body while maintaining their regular structure and function, offering unique advantages. (2) In the realm of bone tissue engineering, hydrogels stand out as the preferred choice for biomaterial scaffolds. Their excellent biocompatibility, degradability, and inherent three-dimensional network structure make them invaluable in bone regeneration studies. (3) The physical and biological properties of gelatin methacryloyl are influenced by factors such as concentration, light exposure duration, type of photoinitiator, and the overall reaction system. These properties can affect cell adhesion, growth, and proliferation, and even the morphology and function of cells. (4) Gelatin methacryloyl, recognized for its excellent biocompatibility, tunable physical properties, injectability, and photosensitivity, has been extensively used in three-dimensional cell encapsulation, three-dimensional bioprinting, and stereolithography techniques based on digital light processing in three-dimensional cell culture systems. (5) Utilizing a range of composite gelatin methacryloyl in three-dimensional cell culture can significantly promote vascularization and bone regeneration, paving the way for enhanced clinical solutions to bone defects. (6) At present, there is a noticeable gap in standardized guidelines concerning the sources, synthesis methods, and safety of gelatin methacryloyl. It is crucial to intensify research efforts to optimize gelatin methacryloyl’s application in the three-dimensional cell culture field.

Key words: bone defect, bone tissue engineering, biomaterial scaffold, hydrogel, photocrosslinked hydrogel, gelatin methacryloyl, two-dimensional culture, three-dimensional culture, cell culture

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