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3D 打印多孔钽支架通过整合素-β1 激活的 AKT/MAPK 信号通路改善肌肉附着。

3D-Printed Porous Tantalum Scaffold Improves Muscle Attachment via Integrin-β1-Activated AKT/MAPK Signaling Pathway.

机构信息

Department of Oral Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.

Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai 200011, China.

出版信息

ACS Biomater Sci Eng. 2023 Feb 13;9(2):889-899. doi: 10.1021/acsbiomaterials.2c01155. Epub 2023 Jan 26.

Abstract

3D-printed porous titanium (Ti) alloy scaffolds have been reported for facilitating muscle attachment in our previous study. However, the anti-avulsion ability needs to be improved. In this study, we used 3D-printed porous tantalum (Ta) scaffolds to improve muscle attachment. The differences in chemical and physical characteristics and muscle adhesion between the two scaffolds were tested and compared in the gene and protein level both in vitro and in vivo. The possible molecular mechanism was analyzed and further proved. The results showed that compared with the porous Ti alloy, porous Ta had better cell proliferation, differentiation, migration, and adhesion via the integrin-β1 (Itgb1)-activated AKT/MAPK signaling pathway in L6 rat myoblasts. When artificially down-regulated the expression of Itgb1, cell adhesion and myogenesis differentiation were affected and the phosphorylation of the AKT/MAPK signaling pathway was suppressed. In rat intramuscular implantation, porous Ta had a significantly higher muscle ingrowth rate (85.63% ± 4.97 vs 65.98% ± 4.52, < 0.01) and larger avulsion force (0.972 vs 0.823 N/mm, < 0.05) than the porous Ti alloy. These findings demonstrate that the 3D-printed porous Ta scaffold is beneficial for further clinical application of muscle attachment.

摘要

3D 打印多孔钛(Ti)合金支架在我们之前的研究中被报道可促进肌肉附着。然而,其抗撕裂能力需要提高。在这项研究中,我们使用 3D 打印多孔钽(Ta)支架来提高肌肉附着。我们在体外和体内基因和蛋白质水平上测试并比较了两种支架在化学和物理特性以及肌肉黏附方面的差异。分析并进一步证明了可能的分子机制。结果表明,与多孔 Ti 合金相比,多孔 Ta 通过整合素-β1(Itgb1)激活的 AKT/MAPK 信号通路在 L6 大鼠成肌细胞中具有更好的细胞增殖、分化、迁移和黏附能力。当人工下调 Itgb1 的表达时,细胞黏附和肌生成分化受到影响,AKT/MAPK 信号通路的磷酸化受到抑制。在大鼠肌肉内植入实验中,多孔 Ta 具有更高的肌肉内生长速度(85.63%±4.97 比 65.98%±4.52, < 0.01)和更大的撕裂力(0.972 比 0.823 N/mm, < 0.05)。这些发现表明,3D 打印多孔 Ta 支架有利于进一步将其应用于肌肉附着。

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