中科院长春应化所再生医学材料课题组利用磁性纳米粒子在交变磁场下的磁热效应,成功制备了一种可磁控降解的新型组织工程支架和骨科植入材料。该研究通过合成具有磁响应性的四氧化三铁纳米粒子,与聚乳酸-聚羟基乙酸共聚物(PLGA)复合,得到的磁性复合支架具有在交变磁场下加速降解的独特性质,能够通过调节频率、电流等参数对植入材料的降解行为进行实时调控,解决了以往高分子组织工程植入材料在植入体内后其降解速率无法实时调控的难题。该研究工作最近发表于国际知名杂志Advanced Functional Materials(Adv. Funct. Mater. 2021, DOI:10.1002/adfm.202009661),目前影响因子为16.836。该研究成果已经申请中国发明专利(201911249311.0)。

四氧化三铁纳米粒子因具有良好生物相容性及高饱和磁化率,在磁热疗、核磁显影、药物输送、生物分离等领域已得到广泛应用。其中磁热疗是利用磁性材料的磁热效应来实现治疗效果的,即在交变磁场中,磁性材料通过涡流损耗、磁滞、磁矢量旋转和颗粒本身的物理旋转等效应产生热量进而杀死肿瘤细胞。课题组根据可降解聚酯材料的降解行为大多具有明显的温度依赖性的特性,将四氧化三铁纳米粒子引入可降解组织工程材料以制备磁性复合支架,并研究了其在交变磁场下的降解行为。体外降解实验表明磁性支架的降解速率在交变磁场下可被明显加速,其中与疏水高分子基质有较好界面相容性的油酸修饰的四氧化三铁纳米粒子(IO-OA NPs)在相同交变磁场下加速支架降解的效果更为显著。此外,采用粗粒化的分子动力学模拟研究了高频震动的纳米粒子其性质(尺寸、表面修饰等)对高分子基体升温效率的影响。结果表明具有接枝链的小粒子在受到交变力作用时对体系的升温效果更加明显,这可能是因为磁性纳米粒子与聚合物基质之间的运动相关性增强可加速能量传递。磁性纳米材料的引入,弥补了可降解高分子组织工程支架体内降解行为不可调控的难题,分子动力学模拟则进一步提供了纳米材料的优化策略以获得更高的加热效率。磁控降解有望成为一种人为调控植入物降解行为的新策略,可设计出一种具有非侵入性和时空治疗优势的便携可穿戴设备,以实现临床的精准治疗和个体化治疗。

在取得上述研究成果的基础上,该课题组正在进一步深入研究此项技术的临床应用可行性。

 

详见:https://www.163.com/dy/article/G36MGM3H05329TW8.html

 

Figure 1. Schematic illustration of magneto-controlled degradation in polymer implants. a) The preparation methods of magnetic nanoparticles (NPs) and composite scaffolds. b) The degradation device model of scaffolds under alternating magnetic field (AMF). c) Utilizing the magnetocaloric effect of magnetic NPs to regulate the hydrolysis rate of biodegradable polymers. d) The micro-mechanism of the difference in energy transfer caused by the properties of magnetic NPs (within the hands), and corresponding degradation status of scaffolds (out of the hands). e) An expected apparatus to decide the fate of biodegradable polymer implants with the advantages of portable, wearable, noninvasive and spatiotemporal therapy.

 

Figure 2. a) Temperature changes of the scaffolds and PBS media under AMF+. b). Changes in mass loss of the scaffolds at 0-16 weeks during degradation. c). Micro-CT scanned axial graphs (mapping) of the scaffolds after degradation for 0 and 12 weeks.

Figure 6. Model and results of Molecular dynamics simulation. a) Schematic representation of the simulation models, where the red dots represent PLGA with length N = 120 (the pink and orange beads are two representations). The blue and green beads denote IO nanoparticles and the grafted OA chains, respectively. Bonded and non-bonded interactions between different beads are shown in the right column. An alternating force is applied on the blue beads in the z direction to simulate the application of AMF. b) The temperature of PLGA matrix Tmatrix as a function of simulation time t in different systems.