使用3D打印技术制备的有序Bredigite支架通过调节巨噬细胞极化促进关键大小骨缺损的愈合。
The 3D-Printed Ordered Bredigite Scaffold Promotes Pro-Healing of Critical-Sized Bone Defects by Regulating Macrophage Polarization.
发表日期:2023
作者:
Yaowei Xuan, Lin Li, Chenping Zhang, Min Zhang, Junkai Cao, Zhen Zhang
来源:
International Journal of Nanomedicine
摘要:
修复因外伤或肿瘤等造成的大小关键骨缺损在临床实践中是一个复杂的难题;在这种情况下,人工支架表现出了较好的效果。Bredigite (BRT,Ca7MgSi4O16)生物陶瓷作为骨组织工程的有前途的候选材料,具有优异的物理化学特性和生物活性。采用三维(3D)打印技术制备有结构有序的BRT(BRT-O)支架,以随机的BRT(BRT-R)支架和临床可用的β-三钙磷酸(β-TCP)支架作为对照组进行比较。对它们的物理化学特性进行了表征,并利用RAW 264.7细胞、骨髓间充质干细胞(BMSCs)和大鼠颅骨关键大小骨缺损模型评估巨噬细胞极化和骨再生。BRT-O支架呈现出规则的形态和均匀的孔隙度。此外,BRT-O支架在协同生物降解性方面释放出更高浓度的离子产品,而β-TCP支架没有。在体外,BRT-O支架促进了RW A264.7细胞极化为促愈合的M2型巨噬细胞表型,而BRT-R和β-TCP支架则刺激了更多的促炎症的M1型巨噬细胞。用BRT-O支架上播种的巨噬细胞制备的调节培养液明显促进了体外BMSCs的成骨分化。BRT-O引出的免疫微环境显著提高了BMSCs的细胞迁移能力。此外,在大鼠颅骨关键大小骨缺损模型中,BRT-O支架组促进了新骨形成,M2型巨噬细胞浸润比例更高并且表达了成骨相关标志物。因此,在体内,BRT-O支架通过增强M2型巨噬细胞极化在促进关键大小骨缺损方面发挥免疫调节作用。3D打印的BRT-O支架可以成为骨组织工程的有前途的选择,至少在一定程度上通过巨噬细胞极化和骨免疫调节发挥作用。© 2023 Xuan et al.
Repairing critical-sized bone defects secondary to traumatic or tumorous damage is a complex conundrum in clinical practice; in this case, artificial scaffolds exhibited preferable outcomes. Bredigite (BRT, Ca7MgSi4O16) bioceramic possesses excellent physicochemical properties and biological activity as a promising candidate for bone tissue engineering.Structurally ordered BRT (BRT-O) scaffolds were fabricated by a three-dimensional (3D) printing technique, and the random BRT (BRT-R) scaffolds and clinically available β-tricalcium phosphate (β-TCP) scaffolds were compared as control groups. Their physicochemical properties were characterized, and RAW 264.7 cells, bone marrow mesenchymal stem cells (BMSCs), and rat cranial critical-sized bone defect models were utilized for evaluating macrophage polarization and bone regeneration.The BRT-O scaffolds exhibited regular morphology and homogeneous porosity. In addition, the BRT-O scaffolds released higher concentrations of ionic products based on coordinated biodegradability than the β-TCP scaffolds. In vitro, the BRT-O scaffolds facilitated RWA264.7 cells polarization to pro-healing M2 macrophage phenotype, whereas the BRT-R and β-TCP scaffolds stimulated more pro-inflammatory M1-type macrophages. A conditioned medium derived from macrophages seeding on the BRT-O scaffolds notably promoted the osteogenic lineage differentiation of BMSCs in vitro. The cell migration ability of BMSCs was significantly enhanced under the BRT-O-induced immune microenvironment. Moreover, in rat cranial critical-sized bone defect models, the BRT-O scaffolds group promoted new bone formation with a higher proportion of M2-type macrophage infiltration and expression of osteogenesis-related markers. Therefore, in vivo, BRT-O scaffolds play immunomodulatory roles in promoting critical-sized bone defects by enhancing the polarization of M2 macrophages.3D-printed BRT-O scaffolds can be a promising option for bone tissue engineering, at least partly through macrophage polarization and osteoimmunomodulation.© 2023 Xuan et al.