Lu Hsuan-Heng, Ege Duygu, Salehi Sahar, Boccaccini Aldo R
Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, 91058 Erlangen, Germany.
Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, 91058 Erlangen, Germany; Institute of Biomedical Engineering, Bogazici University, Rasathane St., Kandilli 34684, Istanbul, Turkey.
Acta Biomater. 2024 Dec;190:1-23. doi: 10.1016/j.actbio.2024.10.033. Epub 2024 Oct 23.
The regeneration of healthy and functional skeletal muscle at sites of injuries and defects remains a challenge. Mimicking the natural environment surrounding skeletal muscle cells and the application of electrical and mechanical stimuli are approaches being investigated to promote muscle tissue regeneration. Likewise, chemical stimulation with therapeutic (biologically active) ions is an emerging attractive alternative in the tissue engineering and regenerative medicine fields, specifically to trigger myoblast proliferation, myogenic differentiation, myofiber formation, and ultimately to promote new muscle tissue growth. The present review covers the specialized literature focusing on the biochemical stimulation of muscle tissue repair by applying inorganic ions (bioinorganics). Extracting information from the literature, different ions and their potential influence as chemical cues on skeletal muscle regeneration are discussed. It is revealed that different ions and their varied doses have an individual effect at different stages of muscle cellular development. The dose-dependent effects of ions, as well as applications of ions alone and in combination with biomaterials, are also summarized. Some ions, such as boron, silicon, magnesium, selenium and zinc, are reported to exhibit a beneficial effect on skeletal muscle cells in carefully controlled doses, while the effects of other ions such as iron and copper appear to be contradictory. In addition, calcium is an essential regulatory ion for the differentiation of myoblasts. On the other hand, some ions such as phosphate have been shown to inhibit muscle cell behavior. This review thus provides a complete overview of the application of ionic stimulation for skeletal muscle tissue engineering applications, highlighting the importance of inorganic ions as an attractive alternative to the application of small molecules and growth factors to stimulate muscle tissue repair. STATEMENT OF SIGNIFICANCE: Ionic medicine (IM) is emerging as a promising and attractive approach in the field of tissue engineering, including muscle tissue regeneration. IM is based on the delivery of biologically active ions to injury sites, acting as stimulants for the repair process. This method offers a potentially simpler and more affordable alternative to conventional biomolecule-based regulators such as growth factors. Different biologically active ions, depending on their specific doping concentrations, can have varying effects on cellular development, which could be either beneficial or inhibitory. This literature review covers the field of IM in muscle regeneration with focus on the impact of various ions on skeletal muscle regeneration. The paper is thus a critical summary for guiding future research in ionic-related regenerative medicine, highlighting the potential and challenges of this approach for muscle regeneration.
在损伤和缺损部位实现健康且功能正常的骨骼肌再生仍然是一项挑战。模拟骨骼肌细胞周围的自然环境以及施加电刺激和机械刺激是目前正在研究的促进肌肉组织再生的方法。同样，用治疗性（生物活性）离子进行化学刺激是组织工程和再生医学领域中一种新兴的、有吸引力的替代方法，特别是用于触发成肌细胞增殖、肌源性分化、肌纤维形成，并最终促进新的肌肉组织生长。本综述涵盖了专注于通过应用无机离子（生物无机物）对肌肉组织修复进行生化刺激的专业文献。从文献中提取信息，讨论了不同离子及其作为化学信号对骨骼肌再生的潜在影响。结果表明，不同离子及其不同剂量在肌肉细胞发育的不同阶段具有各自的作用。还总结了离子的剂量依赖性效应以及离子单独使用和与生物材料联合使用的情况。据报道，一些离子，如硼、硅、镁、硒和锌，在精确控制的剂量下对骨骼肌细胞具有有益作用，而其他离子如铁和铜的作用似乎相互矛盾。此外，钙是成肌细胞分化的必需调节离子。另一方面，一些离子如磷酸盐已被证明会抑制肌肉细胞行为。因此，本综述全面概述了离子刺激在骨骼肌组织工程应用中的应用，强调了无机离子作为刺激肌肉组织修复的小分子和生长因子的有吸引力的替代方法的重要性。重要性声明：离子医学（IM）正在成为组织工程领域（包括肌肉组织再生）一种有前景且有吸引力的方法。IM基于将生物活性离子输送到损伤部位，作为修复过程的刺激物。这种方法为传统的基于生物分子的调节剂（如生长因子）提供了一种可能更简单、更经济的替代方案。不同的生物活性离子，取决于其特定的掺杂浓度，对细胞发育可能有不同的影响，可能是有益的或抑制性的。这篇文献综述涵盖了离子医学在肌肉再生领域的内容，重点关注各种离子对骨骼肌再生的影响。因此，本文是指导未来离子相关再生医学研究的重要总结，突出了这种方法在肌肉再生方面的潜力和挑战。
