de Sousa Bárbara M, Correia Clara R, Ferreira Jorge A F, Mano João F, Furlani Edward P, Soares Dos Santos Marco P, Vieira Sandra I
Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, 3810-193, Aveiro, Portugal.
Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, 3810-193, Aveiro, Portugal.
NPJ Regen Med. 2021 Nov 23;6(1):80. doi: 10.1038/s41536-021-00184-6.
Replacement orthopedic surgeries are among the most common surgeries worldwide, but clinically used passive implants cannot prevent failure rates and inherent revision arthroplasties. Optimized non-instrumented implants, resorting to preclinically tested bioactive coatings, improve initial osseointegration but lack long-term personalized actuation on the bone-implant interface. Novel bioelectronic devices comprising biophysical stimulators and sensing systems are thus emerging, aiming for long-term control of peri-implant bone growth through biointerface monitoring. These acting-sensing dual systems require high frequency (HF) operations able to stimulate osteoinduction/osteoconduction, including matrix maturation and mineralization. A sensing-compatible capacitive stimulator of thin interdigitated electrodes and delivering an electrical 60 kHz HF stimulation, 30 min/day, is here shown to promote osteoconduction in pre-osteoblasts and osteoinduction in human adipose-derived mesenchymal stem cells (hASCs). HF stimulation through this capacitive interdigitated system had significant effects on osteoblasts' collagen-I synthesis, matrix, and mineral deposition. A proteomic analysis of microvesicles released from electrically-stimulated osteoblasts revealed regulation of osteodifferentiation and mineralization-related proteins (e.g. Tgfb3, Ttyh3, Itih1, Aldh1a1). Proteomics data are available via ProteomeXchange with the identifier PXD028551. Further, under HF stimulation, hASCs exhibited higher osteogenic commitment and enhanced hydroxyapatite deposition. These promising osteoinductive/conductive capacitive stimulators will integrate novel bioelectronic implants able to monitor the bone-implant interface and deliver personalized stimulation to peri-implant tissues.
置换性骨科手术是全球最常见的手术之一,但临床使用的被动植入物无法预防失败率和固有的翻修关节成形术。采用临床前测试的生物活性涂层的优化非器械植入物可改善初始骨整合,但缺乏对骨-植入物界面的长期个性化驱动。因此,包括生物物理刺激器和传感系统的新型生物电子设备正在兴起,旨在通过生物界面监测对植入物周围骨生长进行长期控制。这些作用-传感双系统需要高频(HF)操作,以刺激骨诱导/骨传导,包括基质成熟和矿化。本文展示了一种由薄叉指电极组成的传感兼容电容式刺激器,每天30分钟施加60kHz的高频电刺激,可促进前成骨细胞的骨传导和人脂肪间充质干细胞(hASC)的骨诱导。通过这种电容式叉指系统进行的高频刺激对成骨细胞的I型胶原蛋白合成、基质和矿物质沉积有显著影响。对电刺激成骨细胞释放的微泡进行的蛋白质组学分析揭示了骨分化和矿化相关蛋白(如Tgfb3、Ttyh3、Itih1、Aldh1a1)的调控。蛋白质组学数据可通过ProteomeXchange获得,标识符为PXD028551。此外,在高频刺激下,hASC表现出更高的成骨倾向和增强的羟基磷灰石沉积。这些有前景的骨诱导/传导电容式刺激器将集成新型生物电子植入物,能够监测骨-植入物界面并向植入物周围组织提供个性化刺激。