Orthopaedic Biomechanics, Department of Biomedical Engineering and Institute of Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB, Eindhoven, the Netherlands.
Curr Osteoporos Rep. 2021 Feb;19(1):75-87. doi: 10.1007/s11914-020-00649-5. Epub 2021 Jan 11.
Novel therapies for damaged and diseased bone are being developed in a preclinical testing process consisting of in vitro cell experiments followed by in vivo animal studies. The in vitro results are often not representative of the results observed in vivo. This could be caused by the complexity of the natural bone environment that is missing in vitro. Ex vivo bone explant cultures provide a model in which cells are preserved in their native three-dimensional environment. Herein, it is aimed to review the current status of bone explant culture models in relation to their potential in complementing the preclinical evaluation process with specific attention paid to the incorporation of mechanical loading within ex vivo culture systems.
Bone explant cultures are often performed with physiologically less relevant bone, immature bone, and explants derived from rodents, which complicates translatability into clinical practice. Mature bone explants encounter difficulties with maintaining viability, especially in static culture. The integration of mechanical stimuli was able to extend the lifespan of explants and to induce new bone formation. Bone explant cultures provide unique platforms for bone research and mechanical loading was demonstrated to be an important component in achieving osteogenesis ex vivo. However, more research is needed to establish a representative, reliable, and reproducible bone explant culture system that includes both components of bone remodeling, i.e., formation and resorption, in order to bridge the gap between in vitro and in vivo research in preclinical testing.
在体外细胞实验之后进行体内动物研究的临床前测试过程中,正在开发用于受损和患病骨骼的新型治疗方法。体外结果通常与体内观察到的结果不一致。这可能是由于体外缺少天然骨环境的复杂性造成的。骨外植体培养提供了一种模型,其中细胞保留在其天然的三维环境中。本文旨在回顾骨外植体培养模型的现状,及其在补充临床前评估过程中的潜力,特别关注在体外培养系统中纳入机械加载。
骨外植体培养通常使用生理相关性较低的骨、未成熟骨和源自啮齿动物的外植体进行,这使得向临床实践的转化变得复杂。成熟骨外植体在保持活力方面遇到困难,特别是在静态培养中。机械刺激的整合能够延长外植体的寿命并诱导新骨形成。骨外植体培养为骨研究提供了独特的平台,并且已经证明机械加载是体外实现成骨的重要组成部分。然而,需要进一步的研究来建立一个具有代表性、可靠和可重复的骨外植体培养系统,该系统包括骨重塑的两个组成部分,即形成和吸收,以缩小临床前测试中体外和体内研究之间的差距。