Tandon Biranche, Aguilar Cosme Jose R, Xue Ruikang, Srirussamee Kasama, Aguilar-Tadeo Julio, Ballestrem Christoph, Blaker Jonny J, Cartmell Sarah H
Department of Materials Science, School of Natural Sciences, Faculty of Science and Engineering, The University of Manchester, Manchester, UK.
Department of Materials Science, School of Natural Sciences, Faculty of Science and Engineering, The University of Manchester, Manchester, UK; Henry Royce Institute, The University of Manchester, Manchester, UK.
Biomater Adv. 2025 Aug;173:214283. doi: 10.1016/j.bioadv.2025.214283. Epub 2025 Mar 9.
Bone tissue engineering has emerged as a promising approach to address the challenges of bone fracture repair and regeneration. The application of external stimuli (mechanical and electrical) can drive specific cellular responses and osteogenic differentiation, leading to the development of more effective treatments. Piezoelectric materials modulate cellular proliferation and osteogenic differentiation under both static (without mechanical stimulation) and dynamic (with mechanical stimulation) conditions, activating distinct gene expression pathways. In this work, we investigate the combinatorial effect of poly (vinylidene fluoride) (PVDF) poled and non-poled films, and low-intensity pulsed ultrasound (LIPUS) on early-stage osteogenic differentiation of mouse pre-osteoblasts. Static culture with PVDF poled films enhanced Runx2 and Col1α1 expression without impacting alkaline phosphatase (ALP) activity. Inhibition of ERK phosphorylation using U0126 in PVDF poled films resulted in a ~ 6-8-fold increase in ALP activity, suggesting the involvement of an alternative pathway in osteogenic differentiation. Dynamic culture with LIPUS generated an electric potential of approximately 500 mV across PVDF films and an electrical field of 0-10 mV mm. Co-stimulation led to a ~3-fold increase of ALP activity on stimulated PVDF compared to unstimulated films. This study underscores the potential of piezoelectric materials as non-invasive electrical stimulators to enhance the efficacy of ultrasound-based therapies for bone fracture repair.
骨组织工程已成为一种有前景的方法，用于应对骨折修复和再生的挑战。外部刺激（机械和电刺激）的应用可以驱动特定的细胞反应和成骨分化，从而开发出更有效的治疗方法。压电材料在静态（无机械刺激）和动态（有机械刺激）条件下均能调节细胞增殖和成骨分化，激活不同的基因表达途径。在这项工作中，我们研究了聚偏二氟乙烯（PVDF）极化和未极化薄膜以及低强度脉冲超声（LIPUS）对小鼠前成骨细胞早期成骨分化的联合作用。用PVDF极化薄膜进行静态培养可增强Runx2和Col1α1的表达，而不影响碱性磷酸酶（ALP）活性。在PVDF极化薄膜中使用U0126抑制ERK磷酸化导致ALP活性增加约6 - 8倍，这表明在成骨分化中存在另一条途径。用LIPUS进行动态培养在PVDF薄膜上产生了约500 mV的电势和0 - 10 mV/mm的电场。与未刺激的薄膜相比，联合刺激使受刺激的PVDF上的ALP活性增加了约3倍。本研究强调了压电材料作为非侵入性电刺激器的潜力，可提高基于超声的骨折修复治疗的疗效。
