仿生压电梯度水凝胶的构建及其引导细胞空间选择性分化

Construction of magnetically driven piezoelectric gradient hydrogels for regulating spatially selective cell differentiation

  • 摘要: 关节骨软骨的压电性能沿厚度方向呈连续梯度变化,如何在支架材料中实现压电信号的空间调控并引导干细胞空间选择性分化,是骨软骨一体化修复的关键挑战。针对该问题,提出以无机功能粒子为磁响应核心构建仿生压电活性梯度水凝胶的策略:将生物活性玻璃(BG)包覆于Fe3O4表面形成核壳结构磁化BG(FB),使其兼具生物相容性、磁响应性与成骨活性。将其与压电聚合物左旋聚乳酸复合,经混纺及冷冻切片制得磁化复合短纤维,分散于甲基丙烯酸化明胶水凝胶中,通过磁场驱动形成沿厚度方向的连续梯度分布,经光固化获得一体化支架。实验结果表明,在磁场作用下,FB成功引导复合短纤维沿厚度方向呈梯度分布,该梯度支架可产生由上层约150 mV至底层近300 mV的连续递增压电信号,并可引导细胞沿厚度方向呈现空间选择性分化。上述结果证实,通过磁场诱导构建梯度支架的策略可行,为骨软骨一体化修复提供仿生新思路。

     

    Abstract: Articular osteochondral tissue exhibits a continuously graded piezoelectric property along its thickness direction. A key challenge for integrated osteochondral repair is how to spatially regulate piezoelectric signals within a scaffold and thereby guide region-specific stem cell differentiation. To address this issue, a biomimetic piezoelectric active gradient hydrogel was constructed using inorganic functional particles as the magnetic-responsive core. Specifically, bioactive glass (BG) was coated onto Fe3O4 surfaces to form core-shell structured magnetized BG (FB), which combines bio-compatibility, magnetic responsiveness, and osteogenic activity. This inorganic magnetic component was compounded with piezoelectric poly(L-lactic acid), and the mixture was electrospun and cryosectioned into magnetized composite short fibers. These fibers were dispersed in gelatin methacryloyl hydrogel, where a magnetic field was applied to drive their continuous gradient distribution along the thickness direction, followed by pho-to-crosslinking to obtain an integrated scaffold. Experimental results show that the gradient distribution of composite short fibers was successfully guided by FB under a magnetic field. This gradient scaffold produces a graded piezoelectric signal ranging from about 150 mV in the upper layer to nearly 300 mV in the bottom layer, and directs cells to differentiate selectively along the thickness direction. These findings confirm that the magnetic field-induced gradient strategy is feasible and provides a biomimetic route for integrated osteochondral repair.

     

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