中国组织工程研究

中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (17): 2667-2674.doi: 10.12307/2024.480

• 组织工程骨材料 tissue-engineered bone • 上一篇    下一篇

聚己内酯-聚多巴胺-AOPDM1支架在高糖环境下的促成骨性能

刘子杨，劳  安，徐陈词，AiRi Shin，吴嘉晴，刘加强   

  1. 上海交通大学医学院附属第九人民医院口腔颅颌面科，上海交通大学口腔医学院，国家口腔医学中心，国家口腔疾病临床医学研究中心，上海市口腔医学重点实验室，上海市口腔医学研究所，上海市  200011
  • 收稿日期:2023-08-02 接受日期:2023-09-18 出版日期:2024-06-18 发布日期:2023-12-14
  • 通讯作者: 刘加强，主任医师，教授，上海交通大学医学院附属第九人民医院口腔颅颌面科，上海交通大学口腔医学院，国家口腔医学中心，国家口腔疾病临床医学研究中心，上海市口腔医学重点实验室，上海市口腔医学研究所，上海市 200011
  • 作者简介:刘子杨，女，1999年生，山东省泰安市人，汉族，硕士在读，主要从事高糖环境成骨、生物材料研究。 劳安，女，1997年生，浙江省宁波市人，汉族，博士在读，主要从事高糖环境成骨、生物材料研究。
  • 基金资助:
    国家自然科学基金面上项目(82071081)，项目名称：PDGF-BB/PI3K信号轴在高糖引发GSK-3β介导的成骨抑制过程中的调控机理，项目负责人：刘加强；上海市卫生健康委员会卫生行业临床研究专项(卓越项目)(20224Z0010)，项目名称：微创颌骨手术联合正畸治疗改善轻度骨性上颌前突的临床研究，项目负责人：刘加强

Polycaprolactone-polydopamine-AOPDM1 scaffold promotes bone formation in a high-glucose environment

Liu Ziyang, Lao An, Xu Chenci, AiRi Shin, Wu Jiaqing, Liu Jiaqiang   

  1. Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
  • Received:2023-08-02 Accepted:2023-09-18 Online:2024-06-18 Published:2023-12-14
  • Contact: Liu Jiaqiang, Chief physician, Professor, Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
  • About author:Liu Ziyang, Master candidate, Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China Lao An, Doctoral candidate, Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
  • Supported by:
    National Natural Science Foundation of China (General Program), No. 82071081 (to LJQ); Shanghai Municipal Health Commission Health Industry Clinical Research Project (Excellence Project), No. 20224Z0010 (to LJQ)

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摘要：


文题释义：

聚己内酯-聚多巴胺-AOPDM1复合支架：聚己内酯是一种高分子化合物，聚多巴胺是受到贻贝中黏附蛋白启发而合成的一种聚合物，AOPDM1是一种从母乳中发现的多肽。利用静电纺丝技术制备聚己内酯电纺膜，用聚多巴胺作为涂层进行表面改性，进而负载多肽AOPDM1，合成了一种复合支架用于骨缺损修复。
骨髓间充质干细胞：是骨髓中的非造血干细胞，是一类起源于中胚层的多能干细胞，具有干细胞的共性，即有自我更新能力及多向分化潜能，在不同诱导条件下能分化为成骨细胞、成软骨细胞、脂肪细胞、血管内皮细胞等多种成熟细胞。


背景：口腔颌面骨组织缺损会严重影响患者的身心健康，当糖尿病患者发生骨缺损时血糖异常导致的骨代谢紊乱使修复治疗更加困难。

目的：试图将一种具有改善肥胖潜在生物活性的多肽AOPDM1应用于糖尿病患者的骨损伤修复。
方法：在正常或高糖环境下，分别采用不同浓度的AOPDM1干预小鼠骨髓间充质干细胞，检测细胞增殖、碱性磷酸酶活性、矿化结节形成及成骨分化基因的表达。利用静电纺丝技术制备聚己内酯支架，以聚多巴胺对支架进行表面改性，制备聚己内酯-聚多巴胺复合支架；最后将支架置于AOPDM1溶液中，制备聚己内酯-聚多巴胺-AOPDM1支架，检测3组支架的水接触角及力学性能。在正常或高糖环境下，将3组支架分别与小鼠骨髓间充质干细胞共培养，检测细胞黏附、碱性磷酸酶活性及骨桥蛋白的表达。

结果与结论：①与正常环境相比，高糖环境抑制了骨髓间充质干细胞的增殖；相同环境下，AOPDM1可促进小鼠骨髓间充质干细胞的增殖。在AOPDM1浓度相同的情况下，与正常环境相比，高糖环境下骨髓间充质干细胞的碱性磷酸酶活性、矿化能力及Ⅰ型胶原、骨桥蛋白、碱性磷酸酶、Runx2 mRNA表达均降低；相同环境下，AOPDM1可提高骨髓间充质干细胞的碱性磷酸酶活性、矿化能力及Ⅰ型胶原、骨桥蛋白、碱性磷酸酶、Runx2 mRNA表达。②聚己内酯-聚多巴胺支架、聚己内酯-聚多巴胺-AOPDM1支架的亲水性高于聚己内酯支架(P < 0.001)，3组支架的抗拉强度与弹性模量比较差异均无显著性意义(P > 0.05)。与其他两组支架相比，聚己内酯-聚多巴胺-AOPDM1支架上的细胞具有更好的黏附形态。当支架相同时，与正常环境相比，高糖环境抑制了骨髓间充质干细胞的碱性磷酸酶活性及骨桥蛋白表达；当环境相同时，聚己内酯-聚多巴胺-AOPDM1支架上骨髓间充质干细胞的碱性磷酸酶活性及骨桥蛋白表达高于其他两组支架。③结果表明，聚己内酯-聚多巴胺-AOPDM支架可促进高糖环境下骨髓间充质干细胞的成骨性能。

https://orcid.org/0000-0002-0737-0827(刘子杨)

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: 多肽, 聚己内酯, 聚多巴胺, 复合支架, 骨髓间充质干细胞, 高糖微环境, 细胞增殖, 成骨分化

Abstract: BACKGROUND: Oral and maxillofacial bone tissue defects can seriously affect the physical and mental health of patients. When bone defects occur in diabetic patients, bone metabolism disorders caused by abnormal blood sugar make it more difficult to repair and treat. 
OBJECTIVE: To attempt to apply AOPDM1, a polypeptide with potential bioactivity to the osteogenic treatment of diabetic patients. 
METHODS: In normal or high-glucose environment, different concentrations of AOPDM1 were used to interfere with mouse bone marrow mesenchymal stem cells, and cell proliferation, alkaline phosphatase activity, mineralization nodules formation and osteogenic differentiation gene expression were detected. The polycaprolactone scaffold was prepared by electrospinning technology, and the scaffold was modified by polydopamine to prepare the polycaprolactone-polydopamine composite scaffold. Finally, the scaffolds were placed in AOPDM1 solution to prepare polycaprolactone-polydopamine-AOPDM1 scaffolds. The water contact angle and mechanical properties of the scaffolds were tested in the three groups. In normal or high-glucose environment, the three groups of scaffolds were co-cultured with mouse bone marrow mesenchymal stem cells, respectively, and cell adhesion, alkaline phosphatase activity and osteopontin expression were detected. 
RESULTS AND CONCLUSION: (1) Compared with normal environment, high-glucose environment inhibited the proliferation of bone marrow mesenchymal stem cells. In the same environment, AOPDM1 could promote the proliferation of mouse bone marrow mesenchymal stem cells. When AOPDM1 concentration was the same, alkaline phosphatase activity, mineralization ability and mRNA expression of type I collagen, osteopontin, alkaline phosphatase, and Runx2 of bone marrow mesenchymal stem cells were decreased in high-glucose environment compared with normal environment. Under the same environment, AOPDM1 could improve the alkaline phosphatase activity, mineralization ability, and mRNA expression of type I collagen, osteopontin, alkaline phosphatase and Runx2 of bone marrow mesenchymal stem cells. (2) The hydrophilicity of polycaprolactone-polydopamine scaffold and polycaprolactone-polydopamine-AOPDM1 scaffold was higher than that of polycaprolactone scaffold (P < 0.001), and there was no significant difference in tensile strength and elastic modulus among the three groups (P > 0.05). Compared with the other two groups of scaffolds, the cells on the polycaprolactone-polydopamine-AOPDM1 scaffold had better adhesion morphology. When the scaffolds were identical, compared with normal environment, high-glucose environment inhibited alkaline phosphatase activity and osteopontin expression of bone marrow mesenchymal stem cells. When the environment was the same, the alkaline phosphatase activity and osteopontin expression of bone marrow mesenchymal stem cells on the polycaprolactone-polydopamine-AOPDM1 scaffold were higher than those on the other two scaffolds. (3) The above results prove that polycaprolactone-polydopamine-AOPDM composite scaffold can promote the osteogenic properties of bone marrow mesenchymal stem cells in high-glucose environment.

Key words: polypeptide, polycaprolactone, polydopamine, composite scaffold, bone marrow mesenchymal stem cell, high-glucose microenvironment, cell proliferation, osteogenic differentiation

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