合成生物学 ›› 2024, Vol. 5 ›› Issue (4): 867-882.DOI: 10.12211/2096-8280.2024-065
王达庆1, 陶婷婷2, 张旭2, 李洪敬1
收稿日期:
2024-08-22
修回日期:
2024-08-28
出版日期:
2024-08-31
发布日期:
2024-09-19
通讯作者:
张旭,李洪敬
作者简介:
基金资助:
Daqing WANG1, Tingting TAO2, Xu ZHANG2, Hongjing LI1
Received:
2024-08-22
Revised:
2024-08-28
Online:
2024-08-31
Published:
2024-09-19
Contact:
Xu ZHANG, Hongjing LI
摘要:
骨骼肌作为人体最丰富的组织之一,是人体运动功能的主要承担者,并且在能量代谢、免疫调节和衰老过程中发挥重要作用。骨骼肌所处的微环境结构复杂,包括多种细胞类型、独特的三维结构以及力学特征。因此,建立高仿生的骨骼肌模型具有一定的挑战性。器官芯片可以精确地模拟人体组织的关键结构和功能特性,从而为骨骼肌模型的建立提供了一种新的途径。本文综述了目前骨骼肌芯片的构建及其在疾病建模、药物评价与再生医学等生物医学研究中的应用。依据人体骨骼肌组织微环境的特点,重点介绍了构建骨骼肌芯片的关键要素,包括动态培养环境、机械刺激、电刺激、血管化与神经化,以及其他工程策略包括各向异性支架的制备与两端锚定的策略等。目前的骨骼肌芯片在细胞来源及功能等方面仍存在一定的局限性。未来通过与基因编辑、生物传感等技术相结合,骨骼肌芯片有望在生物医学研究领域发挥更重要的作用。
中图分类号:
王达庆, 陶婷婷, 张旭, 李洪敬. 骨骼肌芯片及其在生物医学领域的研究进展[J]. 合成生物学, 2024, 5(4): 867-882.
Daqing WANG, Tingting TAO, Xu ZHANG, Hongjing LI. Advances in skeletal muscle-on-a-chip for biomedical research[J]. Synthetic Biology Journal, 2024, 5(4): 867-882.
细胞来源 | 优势 | 局限性 | 应用 |
---|---|---|---|
原代细胞[ | 生理相关性 能够保留患者特定的疾病病理特征 | 增殖能力有限 获取较困难 存在个体差异 | 研究肌肉发育、疾病机制和评估治疗干预措施的理想材料 个性化医疗 |
细胞系[ | 易于获取 增殖速度快 生理一致性 | 缺乏生理相关性 人源细胞系缺乏 | 初步的机制研究与药物筛选 高通量研究 |
干细胞[ | 无限增殖 易于操控 | 分化效率不确定 | 肌肉发育、遗传性肌肉疾病研究 再生医学 |
表1 用于构建骨骼肌芯片的细胞来源
Table 1 Cell sources for skeletal muscle-on-a-chip
细胞来源 | 优势 | 局限性 | 应用 |
---|---|---|---|
原代细胞[ | 生理相关性 能够保留患者特定的疾病病理特征 | 增殖能力有限 获取较困难 存在个体差异 | 研究肌肉发育、疾病机制和评估治疗干预措施的理想材料 个性化医疗 |
细胞系[ | 易于获取 增殖速度快 生理一致性 | 缺乏生理相关性 人源细胞系缺乏 | 初步的机制研究与药物筛选 高通量研究 |
干细胞[ | 无限增殖 易于操控 | 分化效率不确定 | 肌肉发育、遗传性肌肉疾病研究 再生医学 |
材料 | 优势 | 缺点 |
---|---|---|
甲基丙烯酰化明胶(GelMA)[ | 良好的生物相容性 可调交联密度以控制材料的渗透性和机械性能 可以引入其他丙烯酸系链基团以制成复合系统 | 分子量与成分存在批次间差异 不能与光敏或自由基敏感的酶或因子结合使用 |
胶原蛋白[ | 良好的生物相容性 可促进细胞黏附与增殖 通过调整比例可改变机械性能 | 分子量与成分存在批次间差异 成本相对较高 |
纤维蛋白(fibrin)[ | 良好的生物相容性 可促进细胞黏附与增殖 易将细胞封装在内部 | 由于在凝血级联反应中的作用,不能与血流结合 复合蛋白,因此不容易修饰 |
Matrigel[ | 良好的生物相容性 支持细胞迁移和分化 促血管生成 | 分子量与成分存在批次间差异 成本相对较高 |
聚己内酯(PCL)[ | 良好的生物相容性 易于加工 无免疫原性 | 细胞黏附性较差 缺乏生物活性,通常与其他生物活性材料结合使用 |
聚乳酸-乙醇酸共聚物(PLGA)[ | 易于加工 可降解性 | 生物相容性相对较差,需要额外的涂层或处理来提高细胞黏附性 降解过程中会产生乳酸和乙醇酸,可能影响细胞活性 |
表2 用于骨骼肌芯片的生物材料
Table 2 Biomaterials for skeletal muscle-on-a-chip
材料 | 优势 | 缺点 |
---|---|---|
甲基丙烯酰化明胶(GelMA)[ | 良好的生物相容性 可调交联密度以控制材料的渗透性和机械性能 可以引入其他丙烯酸系链基团以制成复合系统 | 分子量与成分存在批次间差异 不能与光敏或自由基敏感的酶或因子结合使用 |
胶原蛋白[ | 良好的生物相容性 可促进细胞黏附与增殖 通过调整比例可改变机械性能 | 分子量与成分存在批次间差异 成本相对较高 |
纤维蛋白(fibrin)[ | 良好的生物相容性 可促进细胞黏附与增殖 易将细胞封装在内部 | 由于在凝血级联反应中的作用,不能与血流结合 复合蛋白,因此不容易修饰 |
Matrigel[ | 良好的生物相容性 支持细胞迁移和分化 促血管生成 | 分子量与成分存在批次间差异 成本相对较高 |
聚己内酯(PCL)[ | 良好的生物相容性 易于加工 无免疫原性 | 细胞黏附性较差 缺乏生物活性,通常与其他生物活性材料结合使用 |
聚乳酸-乙醇酸共聚物(PLGA)[ | 易于加工 可降解性 | 生物相容性相对较差,需要额外的涂层或处理来提高细胞黏附性 降解过程中会产生乳酸和乙醇酸,可能影响细胞活性 |
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