Söhling Nicolas, Neijhoft Jonas, Nienhaus Vinzenz, Acker Valentin, Harbig Jana, Menz Fabian, Ochs Joachim, Verboket René D, Ritz Ulrike, Blaeser Andreas, Dörsam Edgar, Frank Johannes, Marzi Ingo, Henrich Dirk
Department of Trauma, Hand and Reconstructive Surgery, University Hospital, Goethe University Frankfurt am Main, 60590 Frankfurt, Germany.
Department of Mechanical Engineering, Institute of Printing Science and Technology, Technical University of Darmstadt, 64289 Darmstadt, Germany.
Materials (Basel). 2020 Apr 13;13(8):1836. doi: 10.3390/ma13081836.
In Bone Tissue Engineering (BTE), autologous bone-regenerative cells are combined with a scaffold for large bone defect treatment (LBDT). Microporous, polylactic acid (PLA) scaffolds showed good healing results in small animals. However, transfer to large animal models is not easily achieved simply by upscaling the design. Increasing diffusion distances have a negative impact on cell survival and nutrition supply, leading to cell death and ultimately implant failure. Here, a novel scaffold architecture was designed to meet all requirements for an advanced bone substitute. Biofunctional, porous subunits in a load-bearing, compression-resistant frame structure characterize this approach. An open, macro- and microporous internal architecture (100 µm-2 mm pores) optimizes conditions for oxygen and nutrient supply to the implant's inner areas by diffusion. A prototype was 3D-printed applying Fused Filament Fabrication using PLA. After incubation with Saos-2 (Sarcoma osteogenic) cells for 14 days, cell morphology, cell distribution, cell survival (fluorescence microscopy and LDH-based cytotoxicity assay), metabolic activity (MTT test), and osteogenic gene expression were determined. The adherent cells showed colonization properties, proliferation potential, and osteogenic differentiation. The innovative design, with its porous structure, is a promising matrix for cell settlement and proliferation. The modular design allows easy upscaling and offers a solution for LBDT.
在骨组织工程(BTE)中,自体骨再生细胞与支架相结合用于治疗大骨缺损(LBDT)。微孔聚乳酸(PLA)支架在小动物身上显示出良好的愈合效果。然而,简单地扩大设计规模并不能轻易地将其应用于大型动物模型。扩散距离的增加会对细胞存活和营养供应产生负面影响,导致细胞死亡并最终导致植入失败。在此,设计了一种新型支架结构以满足先进骨替代物的所有要求。这种方法的特点是在承重、抗压框架结构中具有生物功能的多孔亚单元。开放的宏观和微孔内部结构(孔径为100 µm - 2 mm)通过扩散优化了向植入物内部区域供应氧气和营养物质的条件。使用PLA通过熔融沉积成型法3D打印出一个原型。与骨肉瘤成骨细胞(Saos - 2)共培养14天后,测定细胞形态、细胞分布、细胞存活情况(荧光显微镜检查和基于乳酸脱氢酶的细胞毒性测定)、代谢活性(MTT试验)和成骨基因表达。贴壁细胞表现出定植特性、增殖潜力和成骨分化能力。这种具有多孔结构的创新设计是细胞沉降和增殖的有前景的基质。模块化设计便于扩大规模,并为大骨缺损治疗提供了一种解决方案。