School of Medicine, China Medical University, Taichung City 406040, Taiwan.
Department of Plastic & Reconstruction Surgery, China Medical University Hospital, Taichung City 404332, Taiwan.
Cells. 2022 Jun 29;11(13):2069. doi: 10.3390/cells11132069.
The development of 3D printing technologies has allowed us to fabricate complex novel scaffolds for bone regeneration. In this study, we reported the incorporation of different concentrations of calcium silicate (CS) powder into fish gelatin methacrylate (FGelMa) for the fabrication of CS/FGelMa auxetic bio-scaffolds using 3D printing technology. Our results showed that CS could be successfully incorporated into FGelMa without influencing the original structural components of FGelMa. Furthermore, it conveyed that CS modifications both the mechanical properties and degradation rates of the scaffolds were improved in accordance with the concentrations of CS upon modifications of CS. In addition, the presence of CS enhanced the adhesion and proliferation of human periodontal ligament cells (hPDLs) cultured in the scaffold. Further osteogenic evaluation also confirmed that CS was able to enhance the osteogenic capabilities via activation of downstream intracellular factors such as pFAK/FAK and pERK/ERK. More interestingly, it was noted that the application of extrinsic biomechanical stimulation to the auxetic scaffolds further enhanced the proliferation and differentiation of hPDLs cells and secretion of osteogenic-related markers when compared to CS/FGelMa hydrogels without tensile stimulation. This prompted us to explore the related mechanism behind this interesting phenomenon. Subsequent studies showed that biomechanical stimulation works via YAP, which is a biomechanical cue. Taken together, our results showed that novel auxetic scaffolds could be fabricated by combining different aspects of science and technology, in order to improve the future chances of clinical applications for bone regeneration.
3D 打印技术的发展使我们能够制造用于骨再生的复杂新型支架。在这项研究中，我们报告了将不同浓度的硅酸钙 (CS) 粉末掺入鱼明胶甲基丙烯酸酯 (FGelMa) 中，以使用 3D 打印技术制造 CS/FGelMa 各向异性生物支架。我们的结果表明，CS 可以成功掺入 FGelMa 中，而不会影响 FGelMa 的原始结构成分。此外，它表明 CS 修饰可以改善支架的机械性能和降解速率，这与 CS 修饰时 CS 的浓度有关。此外，CS 的存在增强了在支架中培养的人牙周韧带细胞 (hPDL) 的黏附和增殖。进一步的成骨评估也证实 CS 能够通过激活下游细胞内因子（如 pFAK/FAK 和 pERK/ERK）来增强成骨能力。更有趣的是，值得注意的是，与没有拉伸刺激的 CS/FGelMa 水凝胶相比，对外加生物力学刺激的各向异性支架的应用进一步增强了 hPDL 细胞的增殖和分化以及成骨相关标志物的分泌。这促使我们探索这种有趣现象背后的相关机制。随后的研究表明，生物力学刺激通过 YAP 起作用，YAP 是一种生物力学线索。总之，我们的研究结果表明，可以通过结合科学和技术的不同方面来制造新型各向异性支架，以提高骨再生的临床应用的未来机会。
