Barbosa Frederico, Garrudo Fábio F F, Alberte Paola S, Resina Leonor, Carvalho Marta S, Jain Akhil, Marques Ana C, Estrany Francesc, Rawson Frankie J, Aléman Carlos, Ferreira Frederico Castelo, Silva João C
Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
Associate Laboratory i4HB - Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
Sci Technol Adv Mater. 2023 Aug 24;24(1):2242242. doi: 10.1080/14686996.2023.2242242. eCollection 2023.
Osteoporotic-related fractures are among the leading causes of chronic disease morbidity in Europe and in the US. While a significant percentage of fractures can be repaired naturally, in delayed-union and non-union fractures surgical intervention is necessary for proper bone regeneration. Given the current lack of optimized clinical techniques to adequately address this issue, bone tissue engineering (BTE) strategies focusing on the development of scaffolds for temporarily replacing damaged bone and supporting its regeneration process have been gaining interest. The piezoelectric properties of bone, which have an important role in tissue homeostasis and regeneration, have been frequently neglected in the design of BTE scaffolds. Therefore, in this study, we developed novel hydroxyapatite (HAp)-filled osteoinductive and piezoelectric poly(vinylidene fluoride-co-tetrafluoroethylene) (PVDF-TrFE) nanofibers via electrospinning capable of replicating the tissue's fibrous extracellular matrix (ECM) composition and native piezoelectric properties. The developed PVDF-TrFE/HAp nanofibers had biomimetic collagen fibril-like diameters, as well as enhanced piezoelectric and surface properties, which translated into a better capacity to assist the mineralization process and cell proliferation. The biological cues provided by the HAp nanoparticles enhanced the osteogenic differentiation of seeded human mesenchymal stem/stromal cells (MSCs) as observed by the increased ALP activity, cell-secreted calcium deposition and osteogenic gene expression levels observed for the HAp-containing fibers. Overall, our findings describe the potential of combining PVDF-TrFE and HAp for developing electroactive and osteoinductive nanofibers capable of supporting bone tissue regeneration.
骨质疏松相关骨折是欧美地区慢性疾病发病的主要原因之一。虽然相当一部分骨折能够自然愈合，但对于延迟愈合和不愈合的骨折，手术干预对于实现适当的骨再生是必要的。鉴于目前缺乏优化的临床技术来充分解决这一问题，专注于开发用于暂时替代受损骨骼并支持其再生过程的支架的骨组织工程（BTE）策略越来越受到关注。骨骼的压电特性在组织稳态和再生中起着重要作用，但在BTE支架设计中常常被忽视。因此，在本研究中，我们通过静电纺丝法制备了新型的填充羟基磷灰石（HAp）的具有骨诱导性和压电性的聚（偏二氟乙烯 - 共 - 四氟乙烯）（PVDF-TrFE）纳米纤维，其能够复制组织的纤维状细胞外基质（ECM）组成和天然压电特性。所制备的PVDF-TrFE/HAp纳米纤维具有仿生胶原纤维状直径，以及增强的压电和表面性能，这转化为更好的辅助矿化过程和细胞增殖的能力。如含有HAp的纤维所观察到的碱性磷酸酶活性增加、细胞分泌的钙沉积以及成骨基因表达水平提高所示，HAp纳米颗粒提供的生物信号增强了接种的人间充质干/基质细胞（MSCs）的成骨分化。总体而言，我们的研究结果描述了将PVDF-TrFE和HAp结合用于开发能够支持骨组织再生的电活性和骨诱导性纳米纤维的潜力。
