Lu Hsuan-Heng, Froidevaux Clara, Biermann Isabell, Kaňková Hana, Büchner Margitta, Schubert Dirk W, Salehi Sahar, Boccaccini Aldo R
Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, 91058 Erlangen, Germany.
Department for Functional Materials in Medicine and Dentistry, University of Würzburg, 97070 Würzburg, Germany.
Biomater Adv. 2025 Jul;172:214233. doi: 10.1016/j.bioadv.2025.214233. Epub 2025 Feb 24.
Bioprinting shows significant promise in advancing medical treatments by offering patient-specific solutions for repairing skeletal muscle tissues. Zinc (Zn) is one of the key ions in the human body involved in the development of myogenic cells. This study investigates the integration of Zn-doped bioactive inorganic fillers (BIFs) into alginate-dialdehyde-gelatin (ADA-GEL) as composite ink for bioprinting applications. BIFs were mesoporous calcium-silicate-based bioactive glass nanoparticles with nominal composition: 80% SiO-X% CaO-Y% ZnO (X = 20, 18, 15, or 10; Y = 0, 2, 5, or 10; mol%). Ion release profiles confirmed that the addition of Zn ions prevented the burst release of Si and Ca ions. The incorporation of BIFs, particularly at higher dopant concentrations, significantly affected the hydrogel swelling and mechanical properties. With increasing concentration of Zn ions (to 5 mol%), the hydrogels exhibited greater dimensional swelling after 24 h of incubation in aqueous solutions, while all compositions lost weight over time after the initial swelling phase. Indirect cell studies demonstrated that 0.1 wt% BIFs extracts, obtained after 24 h-incubation in a cell culture medium, were cytocompatible with C2C12 cells. Furthermore, bioprinted C2C12 cells encapsulated in the bioinks showed a clear increase in cell number after seven days of culture. In particular, cells in the composite inks containing Zn-BIFs exhibited higher spreading, elongation, and alignment than those in pure ADA-GEL, indicating the biological activity provided by the Zn-BIF particles. This study introduces therefore an effective formulation of ADA-GEL-based composite bioinks enriched with Zn-containing nanoparticles for skeletal muscle tissue engineering applications.
生物打印通过提供针对修复骨骼肌组织的患者特异性解决方案，在推进医学治疗方面显示出巨大的潜力。锌（Zn）是人体中参与肌原细胞发育的关键离子之一。本研究探讨了将锌掺杂的生物活性无机填料（BIFs）整合到藻酸盐-二醛-明胶（ADA-GEL）中作为生物打印应用的复合墨水。BIFs是基于介孔硅酸钙的生物活性玻璃纳米颗粒，标称组成：80%SiO-X%CaO-Y%ZnO（X = 20、18、15或10；Y = 0、2、5或10；摩尔%）。离子释放曲线证实，锌离子的添加阻止了硅和钙离子的突发释放。BIFs的加入，特别是在较高掺杂浓度下，显著影响了水凝胶的溶胀和力学性能。随着锌离子浓度的增加（至5摩尔%），水凝胶在水溶液中孵育24小时后表现出更大的尺寸溶胀，而所有组合物在初始溶胀阶段后随时间重量减轻。间接细胞研究表明，在细胞培养基中孵育24小时后获得的0.1 wt%BIFs提取物与C2C12细胞具有细胞相容性。此外，封装在生物墨水中的生物打印C2C12细胞在培养七天后细胞数量明显增加。特别是，含有锌-BIFs的复合墨水中的细胞比纯ADA-GEL中的细胞表现出更高的铺展、伸长和排列，表明锌-BIF颗粒具有生物活性。因此，本研究介绍了一种有效的基于ADA-GEL的复合生物墨水配方，该配方富含用于骨骼肌组织工程应用的含锌纳米颗粒。
