生物打印仿生微环境用于视网膜再生方法

Beatrice Belgio, Sara Mantero, Filippo Iervolino, F. Potere, Marinella Levi, Federica Boschetti
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摘要

人们一直在努力推进体外培养功能性光感受器的方法,以实施视网膜再生策略。为支持功能性光感受器的形成,支架应复制原生环境。本研究旨在优化藻酸钠-明胶(SA-G)生物墨水,以模拟视网膜特性,同时确保打印的构建体具有高形状保真度。优化后的生物墨水在物理、机械和流变特性、可印刷性评估以及初步生物相容性方面都有全面的表征。该材料显示出恒定的降解率,这对有效的组织再生至关重要,因为它在为细胞分化和极化提供支持的同时,还能逐渐降解,使细胞增殖和基质沉积。优化后的生物墨水显示出与原生光感受器层相当的硬度,有可能为光感受器的成熟提供适当的机械线索。此外,它还表现出剪切稀化行为、屈服应力和快速恢复动力学,这些都是成功挤出所必需的。三维打印构建体的高形状保真度表明,打印复杂图案来驱动光感受器极化是可行的。初步的细胞研究结果表明,细胞分布均匀,细胞存活率长期保持不变。总之,这些研究结果表明,优化的生物墨水可以提供体外培养光感受器所需的机械和地形线索,从而实现视网膜再生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bioprinting of a Biomimetic Microenvironment for a Retinal Regenerative Approach
There is an ongoing effort to advance methodologies for culturing functional photoreceptors in vitro for retinal regenerative strategies. To support the formation of functional photoreceptors, a scaffold should replicate the native environment. The aim of this study was to optimize a sodium alginate–gelatin (SA-G) bioink to mimic the retinal properties while ensuring the printing of constructs with high shape fidelity. The optimized bioink was thoroughly characterized in terms of its physical, mechanical, and rheological properties, printability assessment, and preliminary biocompatibility. The material showed a constant degradation rate, which is crucial for effective tissue regeneration as it provides support for cell differentiation and polarization while gradually degrading to allow cell proliferation and matrix deposition. The optimized bioink displayed stiffness comparable to the native photoreceptor layer, potentially providing appropriate mechanical cues for photoreceptor maturation. Additionally, it exhibited shear-thinning behavior, the presence of yield stress, and fast recovery kinetics, which are essential for successful extrusion. The high shape fidelity of 3D-printed constructs suggested the feasibility of printing complex patterns to drive photoreceptor polarization. The preliminary cell results demonstrated homogeneous cell distribution and sustained cell viability over time. Overall, these findings indicate that the optimized bioink can provide the mechanical and topographical cues necessary for cultivating photoreceptors in vitro for retinal regeneration.
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