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基于挤压的可生物降解、成骨、顺磁性和多孔铁锰钙镁黄长石骨替代物的3D打印

Extrusion-based 3D printing of biodegradable, osteogenic, paramagnetic, and porous FeMn-akermanite bone substitutes.

作者信息

Putra N E, Leeflang M A, Klimopoulou M, Dong J, Taheri P, Huan Z, Fratila-Apachitei L E, Mol J M C, Chang J, Zhou J, Zadpoor A A

机构信息

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, Mekelweg 2, Delft 2628 CD, The Netherlands.

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology, Mekelweg 2, Delft 2628 CD, The Netherlands.

出版信息

Acta Biomater. 2023 May;162:182-198. doi: 10.1016/j.actbio.2023.03.033. Epub 2023 Mar 25.

Abstract

The development of biodegradable Fe-based bone implants has rapidly progressed in recent years. Most of the challenges encountered in developing such implants have been tackled individually or in combination using additive manufacturing technologies. Yet not all the challenges have been overcome. Herein, we present porous FeMn-akermanite composite scaffolds fabricated by extrusion-based 3D printing to address the unmet clinical needs associated with Fe-based biomaterials for bone regeneration, including low biodegradation rate, MRI-incompatibility, mechanical properties, and limited bioactivity. In this research, we developed inks containing Fe, 35 wt% Mn, and 20 or 30 vol% akermanite powder mixtures. 3D printing was optimized together with the debinding and sintering steps to obtain scaffolds with interconnected porosity of 69%. The Fe-matrix in the composites contained the γ-FeMn phase as well as nesosilicate phases. The former made the composites paramagnetic and, thus, MRI-friendly. The in vitro biodegradation rates of the composites with 20 and 30 vol% akermanite were respectively 0.24 and 0.27 mm/y, falling within the ideal range of biodegradation rates for bone substitution. The yield strengths of the porous composites stayed within the range of the values of the trabecular bone, despite in vitro biodegradation for 28 d. All the composite scaffolds favored the adhesion, proliferation, and osteogenic differentiation of preosteoblasts, as revealed by Runx2 assay. Moreover, osteopontin was detected in the extracellular matrix of cells on the scaffolds. Altogether, these results demonstrate the remarkable potential of these composites in fulfilling the requirements of porous biodegradable bone substitutes, motivating future in vivo research. STATEMENT OF SIGNIFICANCE: We developed FeMn-akermanite composite scaffolds by taking advantage of the multi-material capacity of extrusion-based 3D printing. Our results demonstrated that the FeMn-akermanite scaffolds showed an exceptional performance in fulfilling all the requirements for bone substitution in vitro, i.e., a sufficient biodegradation rate, having mechanical properties in the range of trabecular bone even after 4 weeks biodegradation, paramagnetic, cytocompatible and most importantly osteogenic. Our results encourage further research on Fe-based bone implants in in vivo.

摘要

近年来,可生物降解铁基骨植入物的发展迅速。在开发此类植入物过程中遇到的大多数挑战已通过增材制造技术单独或组合解决。然而,并非所有挑战都已克服。在此,我们展示了通过基于挤压的3D打印制造的多孔FeMn-钙硅石复合支架,以满足与用于骨再生的铁基生物材料相关的未满足的临床需求,包括低生物降解率、MRI不兼容性、机械性能和有限的生物活性。在本研究中,我们开发了含有铁、35 wt%锰和20或30 vol%钙硅石粉末混合物的墨水。3D打印与脱脂和烧结步骤一起进行了优化,以获得具有69%连通孔隙率的支架。复合材料中的铁基体包含γ-FeMn相以及岛状硅酸盐相。前者使复合材料具有顺磁性,因此对MRI友好。含20 vol%和30 vol%钙硅石的复合材料的体外生物降解率分别为0.24和0.27毫米/年,落在骨替代理想生物降解率范围内。尽管进行了28天的体外生物降解,多孔复合材料的屈服强度仍保持在小梁骨值范围内。如Runx2检测所示,所有复合支架都有利于前成骨细胞的粘附、增殖和成骨分化。此外,在支架上细胞的细胞外基质中检测到骨桥蛋白。总之,这些结果证明了这些复合材料在满足多孔可生物降解骨替代物要求方面的巨大潜力,推动了未来的体内研究。重要性声明:我们利用基于挤压的3D打印的多材料能力开发了FeMn-钙硅石复合支架。我们的结果表明,FeMn-钙硅石支架在体外满足骨替代的所有要求方面表现出卓越性能,即足够的生物降解率,即使在4周生物降解后机械性能仍在小梁骨范围内,具有顺磁性、细胞相容性,最重要的是具有成骨性。我们的结果鼓励对铁基骨植入物进行进一步的体内研究。

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