3D-printed TCP-HA scaffolds delivering MicroRNA-302a-3p improve bone regeneration in a mouse calvarial model.

IF 2.5 Q2 DENTISTRY, ORAL SURGERY & MEDICINE BDJ Open Pub Date : 2023-11-24 DOI:10.1038/s41405-023-00177-1

Pirawish Limlawan, Numpon Insin, Laurine Marger, Mélanie Freudenreich, Stéphane Durual, Anjalee Vacharaksa

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Abstract

Objective: To demonstrate hydroxyapatite nanoparticles modified with cationic functional molecules. 3-aminopropyltriethoxysilane (HA-NPs-APTES) carrying microRNA-302a-3p (miR) in the 3D-printed tricalcium phosphate/Hydroxyapatite (TCP/HA) scaffold can increase healing of the critical-sized bone defect.

Materials and methods: 3D-printed TCP/HA were modified with HA-NPs-APTES by two methods (M1, M2). The dispersion of particles was visualized by fluorescent microscopy. Biocompatibility of the scaffolds was tested by alizarin assay. Delivery of miR to the cells and osteogenic gene expression were evaluated by qPCR. After selecting best method (M2), scaffolds, scaffolds+HA-NPs-APTES with or without miR were implanted in 4 mm mouse calvarium defect (n = 4 per group). After 2,4 and 6 weeks, bone regeneration were evaluated by microCT and histology sections.

Results: Both M1 and M2 scaffolds were biocompatible with cell adhesion on its surface. M2 scaffold showed significant increase of miR, suggesting successful delivery, resulted in downregulation of its target mRNA COUP-TFII, and upregulation of RUNX2 mRNA. Calvarium defect with M2 scaffold also showed significantly higher BV/TV and higher number of filled spaces at all time points. Histomorphometry demonstrated new bone formed at the center of the HA-NPs-APTES-miR scaffold earlier than controls.

Conclusion: TCP/HA scaffold modified with HA-NPs-APTES facilitated delivery of miR and enhanced bone regeneration.

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传递MicroRNA-302a-3p的3d打印TCP-HA支架改善小鼠颅骨模型的骨再生。

目的:制备阳离子功能分子修饰的羟基磷灰石纳米粒。在3d打印的磷酸三钙/羟基磷灰石(TCP/HA)支架中携带microRNA-302a-3p (miR)的3-氨基丙基三乙氧基硅烷(HA- nps - aptes)可以促进临界尺寸骨缺损的愈合。材料与方法:采用HA- nps - aptes两种方法(M1, M2)对3d打印的TCP/HA进行修饰。用荧光显微镜观察颗粒的分散情况。采用茜素法检测支架的生物相容性。通过qPCR检测miR在细胞中的表达和成骨基因的表达。选择最佳方法(M2)后，将支架、支架+HA-NPs-APTES(含或不含miR)植入4 mm小鼠颅骨缺损(每组n = 4)。2周、4周和6周后，通过显微ct和组织学切片评估骨再生情况。结果:M1和M2支架表面细胞粘附，具有良好的生物相容性。M2支架miR明显升高，提示递送成功，导致其靶mRNA COUP-TFII下调，RUNX2 mRNA上调。在所有时间点，M2支架的颅骨缺损也显示出更高的BV/TV和更多的填充空间。组织形态学测定显示，HA-NPs-APTES-miR支架中心的新骨形成时间比对照组早。结论:HA- nps - aptes修饰的TCP/HA支架促进miR的传递，增强骨再生。

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