Gu Peiyang, Xu Yang, Liu Quanying, Wang Yuxiang, Li Zhulian, Chen Manyu, Mao Ruiqi, Liang Jie, Zhang Xingdong, Fan Yujiang, Sun Yong
National Engineering Research Center for Biomaterials, Sichuan University, 29# Wangjiang Road, Chengdu 610064, China.
College of Biomedical Engineering, Sichuan University, 29# Wangjiang Road, Chengdu 610064, China.
ACS Appl Mater Interfaces. 2022 Jul 13. doi: 10.1021/acsami.2c07649.
Facilitating cell ingrowth and biomineralized deposition inside filaments of 3DP scaffolds are an ideal bone repair strategy. Here, 3D printed PLGA/HA scaffolds with hydroxyapatite content of 50% (P5H5) and 70% (P3H7) were prepared by optimizing 3D printing inks, which exhibited good tailorability and foldability to meet clinical maneuverability. The supercritical CO foaming technology further endowed the filaments of P5H5 with a richer interconnected pore structure (P5H5-C). The finite element and computational fluid dynamics simulation analysis indicated that the porosification could effectively reduce the stress concentration at the filament junction and improved the overall permeability of the scaffold. The results of in vitro experiments confirmed that P5H5-C promoted the adsorption of proteins on the surface and inside of filaments, accelerated the release of Ca and P ions, and significantly upregulated osteogenesis ( I, , and )- and angiogenesis ()-related gene expression. Subcutaneous ectopic osteogenesis experiments in nude mice further verified that P5H5-C facilitated cell growth inside filaments and biomineralized deposition, as well as significantly upregulated the expression of osteogenesis- and angiogenesis-related genes ( I, , , and ) and protein secretion (ALP, RUNX2, and VEGF). The porosification of filaments by supercritical CO foaming provided a new strategy for accelerating osteogenesis of 3DP implants.
促进细胞向内生长以及生物矿化沉积于3D打印支架的细丝内部是一种理想的骨修复策略。在此，通过优化3D打印墨水制备了羟基磷灰石含量为50%（P5H5）和70%（P3H7）的3D打印聚乳酸-羟基乙酸共聚物/羟基磷灰石（PLGA/HA）支架，其展现出良好的可定制性和可折叠性以满足临床操作性。超临界CO₂发泡技术进一步赋予P5H5细丝更丰富的相互连通的孔隙结构（P5H5-C）。有限元及计算流体动力学模拟分析表明，孔隙化可有效降低细丝连接处的应力集中，并提高支架的整体渗透性。体外实验结果证实，P5H5-C促进了细丝表面和内部蛋白质的吸附，加速了钙和磷离子的释放，并显著上调了成骨（I型胶原、骨钙素和骨桥蛋白）和血管生成（血管内皮生长因子）相关基因的表达。裸鼠皮下异位成骨实验进一步验证，P5H5-C促进了细胞在细丝内部的生长和生物矿化沉积，以及显著上调了成骨和血管生成相关基因（I型胶原、骨钙素、骨桥蛋白和血管内皮生长因子）的表达和蛋白质分泌（碱性磷酸酶、RUNX2和血管内皮生长因子）。通过超临界CO₂发泡使细丝孔隙化，为加速3D打印植入物的成骨提供了一种新策略。
