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Effective production of multifunctional magnetic-sensitive biomaterial by an extrusion-based additive manufacturing technique
Biomedical Materials ( IF 3.9 ) Pub Date : 2020-12-16 , DOI: 10.1088/1748-605x/abac4c
A F M Rodrigues 1 , P M C Torres 1 , M J S Barros 1, 2, 3 , R Presa 2, 3 , N Ribeiro 1 , J C C Abrantes 1, 4 , J H Belo 5, 6 , J S Amaral 5 , V S Amaral 5 , M Bañobre-López 7 , A Bettencourt 8 , A Sousa 2, 3 , S M Olhero 1
Affiliation  

A calcium phosphate (CaP)-based scaffold used as synthetic bone grafts, which smartly combines precise dimensions, controlled porosity and therapeutic functions, presents benefits beyond those offered by conventional practices, although its fabrication is still a challenge. The sintering step normally required to improve the strength of the ceramic scaffolds precludes the addition of any biomolecules or functional particles before this stage.

This study presents a proof of concept of multifunctional CaP-based scaffolds, fabricated by additive manufacturing from an innovative ink composition, with potential for bone regeneration, cancer treatment by local magnetic hyperthermia and drug delivery platforms. Highly loaded inks comprising iron-doped hydroxyapatite and β-tricalcium phosphate powders suspended in a chitosan-based solution, in the presence of levofloxacin (LEV) as model drug and magnetic nanoparticles (MNP), were developed. The sintering step was removed from the production process, and the integrity of the printed scaffolds was assured by the polymerization capacity of the ink composite, using genipin as a crosslinking agent. The effects of MNP and LEV on the inks’ rheological properties, as well as on the mechanical and structural behaviour of non-doped and iron-doped scaffolds, were evaluated. Magnetic and magneto-thermal response, drug delivery and biological performance, such as cell proliferation in the absence and presence of an applied magnetic field, were also assessed. The addition of a constant amount of MNP in the iron-doped and non-doped CaP-based inks enhances their magnetic response and induction heating, with these effects more pronounced for the iron-doped CaP-based ink. These results suggest a synergistic effect between the iron-doped CaP-based powders and the MNP due to ferro/ferrimagnetic interactions. Furthermore, the iron presence enhances human mesenchymal stem cell metabolic activity and proliferation.



中文翻译:

通过基于挤压的增材制造技术有效生产多功能磁敏生物材料

一种用作合成骨移植物的基于磷酸钙 (CaP) 的支架巧妙地结合了精确的尺寸、可控的孔隙率和治疗功能,虽然其制造仍然是一个挑战,但它提供了超出传统做法的益处。提高陶瓷支架强度通常需要的烧结步骤排除了在此阶段之前添加任何生物分子或功能颗粒。

这项研究展示了多功能基于 CaP 的支架的概念证明,该支架由创新的墨水组合物通过增材制造制造,具有骨再生、局部磁热疗和药物输送平台治疗癌症的潜力。在左氧氟沙星 (LEV) 作为模型药物和磁性纳米粒子 (MNP) 存在的情况下,开发了包含悬浮在壳聚糖基溶液中的铁掺杂羟基磷灰石和 β-磷酸三钙粉末的高负载墨水。从生产过程中去除了烧结步骤,使用京尼平作为交联剂,油墨复合材料的聚合能力确保了印刷支架的完整性。MNP 和 LEV 对油墨流变性能的影响,以及对非掺杂和铁掺杂支架的机械和结构行为进行了评估。还评估了磁和磁热响应、药物递送和生物性能,例如在不存在和存在外加磁场的情况下的细胞增殖。在铁掺杂和非掺杂 CaP 基油墨中添加恒定量的 MNP 可增强它们的磁响应和感应加热,对于铁掺杂的 CaP 基油墨,这些效果更为明显。这些结果表明,由于铁/亚铁磁相互作用,铁掺杂的 CaP 基粉末与 MNP 之间存在协同效应。此外,铁的存在增强了人间充质干细胞的代谢活性和增殖。还评估了在不存在和存在施加磁场的情况下的细胞增殖。在铁掺杂和非掺杂 CaP 基油墨中添加恒定量的 MNP 可增强它们的磁响应和感应加热,对于铁掺杂的 CaP 基油墨,这些效果更为明显。这些结果表明,由于铁/亚铁磁相互作用,铁掺杂的 CaP 基粉末与 MNP 之间存在协同效应。此外,铁的存在增强了人间充质干细胞的代谢活性和增殖。还评估了在不存在和存在施加磁场的情况下的细胞增殖。在铁掺杂和非掺杂 CaP 基油墨中添加恒定量的 MNP 可增强它们的磁响应和感应加热,对于铁掺杂的 CaP 基油墨,这些效果更为明显。这些结果表明,由于铁/亚铁磁相互作用,铁掺杂的 CaP 基粉末与 MNP 之间存在协同效应。此外,铁的存在增强了人间充质干细胞的代谢活性和增殖。对于铁掺杂的 CaP 基油墨,这些影响更为明显。这些结果表明,由于铁/亚铁磁相互作用,铁掺杂的 CaP 基粉末与 MNP 之间存在协同效应。此外,铁的存在增强了人间充质干细胞的代谢活性和增殖。对于铁掺杂的 CaP 基油墨,这些影响更为明显。这些结果表明,由于铁/亚铁磁相互作用,铁掺杂的 CaP 基粉末与 MNP 之间存在协同效应。此外,铁的存在增强了人间充质干细胞的代谢活性和增殖。

更新日期:2020-12-16
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