Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Avenida Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
CQE Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001, Lisboa, Portugal.
Mater Sci Eng C Mater Biol Appl. 2019 Aug;101:15-26. doi: 10.1016/j.msec.2019.03.056. Epub 2019 Mar 19.
3D-printing and additive manufacturing can be powerful techniques to design customized structures and produce synthetic bone grafts with multifunctional effects suitable for bone repair. In our work we aimed the development of novel multifunctionalized 3D printed poly(lactic acid) (PLA) scaffolds with bioinspired surface coatings able to reduce bacterial biofilm formation while favoring human bone marrow-derived mesenchymal stem cells (hMSCs) activity. For that purpose, 3D printing was used to prepare PLA scaffolds that were further multifunctionalized with collagen (Col), minocycline (MH) and bioinspired citrate- hydroxyapatite nanoparticles (cHA). PLA-Col-MH-cHA scaffolds provide a closer structural support approximation to native bone architecture with uniform macroporous, adequate wettability and an excellent compressive strength. The addition of MH resulted in an adequate antibiotic release profile that by being compatible with local drug delivery therapy was translated into antibacterial activities against Staphylococcus aureus, a main pathogen associated to bone-related infections. Subsequently, the hMSCs response to these scaffolds revealed that the incorporation of cHA significantly stimulated the adhesion, proliferation and osteogenesis-related gene expression (RUNX2, OCN and OPN) of hMSCs. Furthermore, the association of a bioinspired material (cHA) with the antibiotic MH resulted in a combined effect of an enhanced osteogenic activity. These findings, together with the antibiofilm activity depicted strengthen the appropriateness of this 3D-printed PLA-Col-MH-cHA scaffold for future use in bone repair. By targeting bone repair while mitigating the typical infections associated to bone implants, our 3D scaffolds deliver an integrated strategy with the combined effects further envisaging an increase in the success rate of bone-implanted devices.
3D 打印和增材制造可以是设计定制结构和生产具有多功能效果的合成骨移植物的有力技术，适合骨修复。在我们的工作中，我们旨在开发新型多功能化 3D 打印聚乳酸（PLA）支架，具有仿生表面涂层，能够减少细菌生物膜的形成，同时促进人骨髓间充质干细胞（hMSCs）的活性。为此，我们使用 3D 打印技术来制备 PLA 支架，然后进一步多功能化，添加胶原蛋白（Col）、米诺环素（MH）和仿生柠檬酸-羟基磷灰石纳米颗粒（cHA）。PLA-Col-MH-cHA 支架提供了更接近天然骨结构的结构支撑近似，具有均匀的大孔、适当的润湿性和优异的抗压强度。添加 MH 导致适当的抗生素释放曲线，使其与局部药物输送疗法兼容，转化为对金黄色葡萄球菌的抗菌活性，金黄色葡萄球菌是与骨相关感染相关的主要病原体。随后，hMSCs 对这些支架的反应表明，cHA 的掺入显著刺激了 hMSCs 的粘附、增殖和骨向相关基因表达（RUNX2、OCN 和 OPN）。此外，将仿生材料（cHA）与抗生素 MH 结合，产生了增强的成骨活性的联合效应。这些发现，加上所描述的抗生物膜活性，加强了这种 3D 打印 PLA-Col-MH-cHA 支架在未来骨修复中的适用性。通过靶向骨修复，同时减轻与骨植入物相关的典型感染，我们的 3D 支架提供了一种综合策略，联合效应进一步设想增加骨植入设备的成功率。
