Physical Materials Science and Composite Materials Center, Research School of Chemistry & Applied Biomedical Sciences, National Research Tomsk Polytechnic University, Tomsk 634050, Russia.
Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1-12, Moscow 119234, Russia.
ACS Appl Bio Mater. 2022 Aug 15;5(8):3999-4019. doi: 10.1021/acsabm.2c00496. Epub 2022 Aug 4.
Magnetically responsive composite polymer scaffolds have good potential for a variety of biomedical applications. In this work, electrospun composite scaffolds made of polyhydroxybutyrate (PHB) and magnetite (FeO) particles (MPs) were studied before and after degradation in either PBS or a lipase solution. MPs of different sizes with high saturation magnetization were synthesized by the coprecipitation method followed by coating with citric acid (CA). Nanosized MPs were prone to magnetite-maghemite phase transformation during scaffold fabrication, as revealed by Raman spectroscopy; however, for CA-functionalized nanoparticles, the main phase was found to be magnetite, with some traces of maghemite. Submicron MPs were resistant to the magnetite-maghemite phase transformation. MPs did not significantly affect the morphology and diameter of PHB fibers. The scaffolds containing CA-coated MPs lost 0.3 or 0.2% of mass in the lipase solution and PBS, respectively, whereas scaffolds doped with unmodified MPs showed no mass changes after 1 month of incubation in either medium. In all electrospun scaffolds, no alterations of the fiber morphology were observed. Possible mechanisms of the crystalline-lamellar-structure changes in hybrid PHB/FeO scaffolds during hydrolytic and enzymatic degradation are proposed. It was revealed that particle size and particle surface functionalization affect the mechanical properties of the hybrid scaffolds. The addition of unmodified MPs increased scaffolds' ultimate strength but reduced elongation at break after the biodegradation, whereas simultaneous increases in both parameters were observed for composite scaffolds doped with CA-coated MPs. The highest saturation magnetization─higher than that published in the literature─was registered for composite PHB scaffolds doped with submicron MPs. All PHB scaffolds proved to be biocompatible, and the ones doped with nanosized MPs yielded faster proliferation of rat mesenchymal stem cells. In addition, all electrospun scaffolds were able to support angiogenesis in vivo at 30 days after implantation in Wistar rats.
磁性响应复合聚合物支架在各种生物医学应用中具有良好的应用潜力。在这项工作中，研究了聚羟基丁酸酯 (PHB) 和磁铁矿 (FeO) 颗粒 (MPs) 的电纺复合支架在 PBS 或脂肪酶溶液中降解前后的情况。采用共沉淀法合成了具有高饱和磁化强度的不同尺寸的 MPs，然后用柠檬酸 (CA) 进行包覆。纳米 MPs 在支架制备过程中容易发生磁铁矿-磁赤铁矿相变，拉曼光谱证实了这一点；然而，对于 CA 功能化的纳米粒子，主要相被发现是磁铁矿，有一些磁赤铁矿的痕迹。亚微米 MPs 则不易发生磁铁矿-磁赤铁矿相变。 MPs 对 PHB 纤维的形态和直径没有显著影响。含 CA 包覆 MPs 的支架在脂肪酶溶液和 PBS 中分别损失了 0.3%或 0.2%的质量，而未经修饰的 MPs 掺杂的支架在两种介质中孵育 1 个月后没有质量变化。在所有电纺支架中，都没有观察到纤维形态的变化。提出了在水解和酶降解过程中，杂化 PHB/FeO 支架的结晶-层状结构变化的可能机制。结果表明，颗粒尺寸和颗粒表面功能化影响杂化支架的力学性能。添加未经修饰的 MPs 会增加支架的极限强度，但会降低生物降解后的断裂伸长率，而对于掺杂 CA 包覆 MPs 的复合支架，则观察到两个参数同时增加。掺杂亚微米 MPs 的复合 PHB 支架的饱和磁化强度最高-高于文献中报道的值。所有 PHB 支架均被证明具有生物相容性，掺杂纳米 MPs 的支架可促进大鼠间充质干细胞的快速增殖。此外，所有电纺支架在植入 Wistar 大鼠 30 天后均能支持体内血管生成。
