Dong J, Lin P, Putra N E, Tümer N, Leeflang M A, Huan Z, Fratila-Apachitei L E, Chang J, Zadpoor A A, Zhou J
Department of Biomechanical Engineering, Delft University of Technology, Delft 2628 CD, the Netherlands.
Department of Engineering Structures, Delft University of Technology, Delft 2628 CN, the Netherlands.
Acta Biomater. 2022 Oct 1;151:628-646. doi: 10.1016/j.actbio.2022.08.002. Epub 2022 Aug 5.
The treatment of femoral nonunion with large segmental bone defect is still challenging. Although magnesium alloys have been considered potential materials for such a treatment, their application is limited by their fast degradation. Adding bioceramic particles into magnesium to form Mg-matrix composites is a promising strategy to adjust their biodegradation rates and to improve their mechanical properties and cytocompatibility further. Here, we developed an extrusion-based additive manufacturing technique to fabricate biodegradable Mg-Zn/bioceramic composite scaffolds ex-situ. Inks carrying a Mg-Zn powder and 5, 10 and 15% β-tricalcium phosphate (TCP) powder particles were investigated regarding the dispersion of β-TCP particles in the inks and viscoelastic properties. Optimally formulated inks were then employed for subsequent 3D printing of porous composite scaffolds. The in vitro biodegradation rate of the scaffolds containing 5% β-TCP decreased to 0.5 mm/y, which falls within the range desired for critical-sized bone substitution. As compared to the monolithic Mg-Zn scaffolds, the elastic moduli and yield strengths of the composite scaffolds were much enhanced, which remained in the range of the cancellous bone properties even after 28 d of in vitro degradation. The Mg-Zn/5TCP and Mg-Zn/10TCP scaffolds also exhibited improved biocompatibility when cultured with preosteoblasts, as compared to Mg-Zn scaffolds. In addition, the ALP activity and mineralization level of the composite scaffolds were much enhanced in the extracts of the composite scaffolds. Taken together, this research marks a great breakthrough in fabricating porous Mg-matrix composite scaffolds that meet several design criteria in terms of appropriate biodegradation rate, mechanical properties, and bioactivity. STATEMENT OF SIGNIFICANCE: The treatment of posttraumatic femoral nonunion with large segmental bone defect is still challenging. In this study, we developed a multi-material extrusion-based additive technique to fabricate porous Mg/bioceramic composite scaffolds for such a treatment. The technique allowed for the fine-tuning of printable inks to optimize the dispersion of micro-sized particles. The relative densities of the struts of the fabricated composite scaffolds reached 99%. The added bioceramic particles (β-TCP) exhibited proper interfacial bonding with the Mg alloy matrix. The porous Mg-based composite possessed desired biodegradability, bone-mimicking mechanical properties throughout the in vitro biodegradation period and improved bioactivity to bone cells. These results demonstrated great prospects of extrusion-based 3D printed porous Mg materials to be developed further as ideal biodegradable bone-substituting materials.
治疗伴有大段骨缺损的股骨骨不连仍然具有挑战性。尽管镁合金被认为是用于这种治疗的潜在材料,但其应用受到快速降解的限制。在镁中添加生物陶瓷颗粒以形成镁基复合材料是一种有前景的策略,可调节其生物降解速率,并进一步改善其力学性能和细胞相容性。在此,我们开发了一种基于挤压的增材制造技术,以非原位方式制造可生物降解的Mg-Zn/生物陶瓷复合支架。研究了携带Mg-Zn粉末以及5%、10%和15%β-磷酸三钙(β-TCP)粉末颗粒的油墨中β-TCP颗粒的分散情况和粘弹性。然后将优化配方的油墨用于后续多孔复合支架的3D打印。含有5%β-TCP的支架的体外生物降解速率降至0.5毫米/年,这处于临界尺寸骨替代所需的范围内。与整体式Mg-Zn支架相比,复合支架的弹性模量和屈服强度显著提高,即使在体外降解28天后仍保持在松质骨性能范围内。与Mg-Zn支架相比,Mg-Zn/5TCP和Mg-Zn/10TCP支架在与前成骨细胞共培养时也表现出更好的生物相容性。此外,复合支架提取物中复合支架的碱性磷酸酶活性和矿化水平显著提高。综上所述这项研究在制造多孔镁基复合支架方面取得了重大突破,该支架在适当的生物降解速率、力学性能和生物活性方面符合多项设计标准。意义声明:治疗伴有大段骨缺损的创伤后股骨骨不连仍然具有挑战性。在本研究中,我们开发了一种基于多材料挤压的增材技术,用于制造用于这种治疗的多孔Mg/生物陶瓷复合支架。该技术允许对可打印油墨进行微调,以优化微米级颗粒的分散。制造的复合支架支柱的相对密度达到99%。添加的生物陶瓷颗粒(β-TCP)与镁合金基体表现出良好的界面结合。多孔镁基复合材料在整个体外生物降解期间具有所需的生物降解性、模仿骨的力学性能以及对骨细胞的生物活性改善。这些结果表明,基于挤压的3D打印多孔镁材料作为理想的可生物降解骨替代材料具有进一步开发前景。