Engel Nadja, Dau Michael, Engel Vivien, Franz Denise, Klemmstein Fabian, Thanisch Christiane, Kolb Jürgen F, Frank Marcus, Springer Armin, Köhling Rüdiger, Bader Rainer, Frerich Bernhard, Wiesmann Nadine, Heimes Diana, Kämmerer Peer W
Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, Rostock University Medical Center, Schillingallee 35, 18057 Rostock, Germany.
Oscar Langendorff Institute of Physiology, Rostock University Medical Center, Gertrudenstrasse 9, 18057 Rostock, Germany.
Biomedicines. 2023 Feb 24;11(3):697. doi: 10.3390/biomedicines11030697.
(1) Background: Electrical stimulation is a promising alternative to promote bone fracture healing but with the limitation of tracking the osteogenesis progress in vivo. To overcome this issue, we present an opportunity to combine the electrical stimulation of a commercial titanium implant, which promotes osteogenesis within the fracture, with a real-time readout of the osteogenic progress by impedance sensing. This makes it possible to adjust the electrical stimulation modalities to the individual patient's fracture healing process. (2) Methods: In detail, osteogenic differentiation of several cell types was monitored under continuous or pulsatile electrical stimulation at 0.7 V AC/20 Hz for at least seven days on a titanium implant by electric cell-substrate impedance sensing (ECIS). For control, chemical induction of osteogenic differentiation was induced. (3) Results: The most significant challenge was to discriminate impedance changes caused by proliferation events from those initiated by osteogenic differentiation. This discrimination was achieved by remodeling the impedance parameter Alpha (α), which increases over time for pulsatile electrically stimulated stem cells. Boosted α-values were accompanied by an increased formation of actin stress fibers and a reduced expression of the focal adhesion kinase in the cell periphery; morphological alterations known to occur during osteogenesis. (4) Conclusions: This work provided the basis for developing an effective fracture therapy device, which can induce osteogenesis on the one hand, and would allow us to monitor the induction process on the other hand.
(1) 背景:电刺激是促进骨折愈合的一种有前景的替代方法,但存在无法在体内追踪成骨进程的局限性。为克服这一问题,我们提供了一个机会,将促进骨折部位成骨的商用钛植入物的电刺激与通过阻抗传感实时读取成骨进程相结合。这使得根据个体患者的骨折愈合过程调整电刺激方式成为可能。(2) 方法:具体而言,通过电细胞基质阻抗传感(ECIS)在钛植入物上,于0.7 V交流电/20 Hz的连续或脉冲电刺激下监测几种细胞类型的成骨分化至少七天。作为对照,诱导成骨分化的化学诱导。(3) 结果:最显著的挑战是区分由增殖事件引起的阻抗变化与由成骨分化引发的阻抗变化。通过重塑阻抗参数阿尔法(α)实现了这种区分,对于脉冲电刺激的干细胞,α随时间增加。α值升高伴随着肌动蛋白应力纤维形成增加以及细胞周边粘着斑激酶表达降低;这些是成骨过程中已知会出现的形态学改变。(4) 结论:这项工作为开发一种有效的骨折治疗装置奠定了基础,该装置一方面可以诱导成骨,另一方面能让我们监测诱导过程。