Guillot-Ferriols Maria, García-Briega María Inmaculada, Tolosa Laia, Costa Carlos M, Lanceros-Méndez Senentxu, Gómez Ribelles José Luis, Gallego Ferrer Gloria
Centre for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, 46022 Valencia, Spain.
Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine, Carlos III Health Institute (CIBER-BBN, ISCIII), 46022 Valencia, Spain.
Gels. 2022 Oct 20;8(10):680. doi: 10.3390/gels8100680.
Mesenchymal stem cells (MSCs) osteogenic commitment before injection enhances bone regeneration therapy results. Piezoelectric stimulation may be an effective cue to promote MSCs pre-differentiation, and poly(vinylidene) fluoride (PVDF) cell culture supports, when combined with CoFeO (CFO), offer a wireless in vitro stimulation strategy. Under an external magnetic field, CFO shift and magnetostriction deform the polymer matrix varying the polymer surface charge due to the piezoelectric effect. To test the effect of piezoelectric stimulation on MSCs, our approach is based on a gelatin hydrogel with embedded MSCs and PVDF-CFO electroactive microspheres. Microspheres were produced by electrospray technique, favouring CFO incorporation, crystallisation in β-phase (85%) and a crystallinity degree of around 55%. The absence of cytotoxicity of the 3D construct was confirmed 24 h after cell encapsulation. Cells were viable, evenly distributed in the hydrogel matrix and surrounded by microspheres, allowing local stimulation. Hydrogels were stimulated using a magnetic bioreactor, and no significant changes were observed in MSCs proliferation in the short or long term. Nevertheless, piezoelectric stimulation upregulated RUNX2 expression after 7 days, indicating the activation of the osteogenic differentiation pathway. These results open the door for optimising a stimulation protocol allowing the application of the magnetically activated 3D electroactive cell culture support for MSCs pre-differentiation before transplantation.
注射前间充质干细胞（MSC）的成骨定向可提高骨再生治疗效果。压电刺激可能是促进MSC预分化的有效线索，聚偏二氟乙烯（PVDF）细胞培养支架与CoFeO（CFO）结合时，可提供一种无线体外刺激策略。在外部磁场作用下，CFO的位移和磁致伸缩会使聚合物基质变形，由于压电效应改变聚合物表面电荷。为了测试压电刺激对MSC的影响，我们的方法基于一种嵌入了MSC和PVDF-CFO电活性微球的明胶水凝胶。微球通过电喷雾技术制备，有利于CFO掺入、β相结晶（85%）和结晶度约为55%。细胞封装24小时后证实3D构建体无细胞毒性。细胞存活，均匀分布在水凝胶基质中并被微球包围，从而实现局部刺激。使用磁生物反应器对水凝胶进行刺激，短期和长期内MSC增殖均未观察到显著变化。然而，压电刺激在7天后上调了RUNX2表达，表明成骨分化途径被激活。这些结果为优化刺激方案打开了大门，该方案允许在移植前将磁激活的3D电活性细胞培养支架应用于MSC预分化。
