Bone is an extremely dynamic tissue, undergoing continuous remodeling for its whole lifetime, but its regeneration or augmentation due to bone loss or defects are not always easy to obtain. Bone tissue engineering (BTE) is a promising approach, and its success often relies on a "smart" scaffold, as a support to host and guide bone formation through bone cell precursors. Bone homeostasis is maintained by osteoblasts (OBs) and osteoclasts (OCs) within the basic multicellular unit, in a consecutive cycle of resorption and formation. Therefore, a functional scaffold should allow the best possible OB/OC cooperation for bone remodeling, as happens within the bone extracellular matrix in the body. In the present work OB/OC co-culture models, with and without scaffolds, are reviewed. These experimental systems are intended for different targets, including bone remodeling simulation, drug testing and the assessment of biomaterials and 3D scaffolds for BTE. As a consequence, several parameters, such as cell type, cell ratio, culture medium and inducers, culture times and setpoints, assay methods, etc. vary greatly. This review identifies and systematically reports the in vitro methods explored up to now, which, as they allow cellular communication, more closely resemble bone remodeling and/or the regeneration process in the framework of BTE. STATEMENT OF SIGNIFICANCE: Bone is a dynamic tissue under continuous remodeling, but spontaneous healing may fail in the case of excessive bone loss which often requires valid alternatives to conventional treatments to restore bone integrity, like bone tissue engineering (BTE). Pre-clinical evaluation of scaffolds for BTE requires in vitro testing where co-cultures combining innovative materials with osteoblasts (OBs) and osteoclasts (OCs) closely mimic the in vivo repair process. This review considers the direct and indirect OB/OC co-cultures relevant to BTE, from the early mouse-cell models to the recent bone regenerative systems. The co-culture modeling of bone microenvironment provides reliable information on bone cell cross-talk. Starting from improved knowledge on bone remodeling, bone disease mechanisms may be understood and new BTE solutions are designed.

中文翻译：

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成骨细胞和破骨细胞的共培养系统：以再生方式模拟体外骨重塑。

骨是一种极富活力的组织，在整个生命周期中都经过不断的重塑，但是由于骨丢失或缺损而导致的再生或增强并不总是很容易获得。骨组织工程学（BTE）是一种有前途的方法，其成功通常取决于“智能”支架，以支持通过骨细胞前体宿主和引导骨形成。基本的多细胞单元内的成骨细胞（OBs）和破骨细胞（OCs）在连续的吸收和形成周期中维持骨稳态。因此，功能性支架应该允许最佳的OB / OC协同进行骨重塑，就像体内的骨细胞外基质一样。在目前的工作中，OB / OC共培养模型（带支架和不带支架）进行了回顾。这些实验系统旨在用于不同的目标，包括骨骼重塑模拟，药物测试以及BTE的生物材料和3D支架评估。结果，诸如细胞类型，细胞比例，培养基和诱导物，培养时间和设定点，测定方法等的几个参数变化很大。这篇综述鉴定并系统地报道了迄今为止探索的体外方法，由于它们允许细胞通讯，因此与BTE框架内的骨重塑和/或再生过程更加相似。意义声明：骨骼是处于不断重塑的动态组织，但是如果骨质流失过多，自发愈合可能会失败，这通常需要有效的替代传统疗法来恢复骨骼完整性，例如骨组织工程学（BTE）。对BTE支架进行临床前评估需要进行体外测试，其中将创新材料与成骨细胞（OBs）和破骨细胞（OCs）结合使用的共培养物非常类似于体内修复过程。这篇综述考虑了与BTE相关的直接和间接OB / OC共培养，从早期的小鼠细胞模型到最近的骨再生系统。骨微环境的共培养模型可提供有关骨细胞串扰的可靠信息。从对骨骼重塑的改进知识开始，可以了解骨骼疾病的机制并设计新的BTE解决方案。从早期的小鼠细胞模型到最近的骨再生系统。骨微环境的共培养模型可提供有关骨细胞串扰的可靠信息。从对骨骼重塑的改进知识开始，可以了解骨骼疾病的机制并设计新的BTE解决方案。从早期的小鼠细胞模型到最近的骨再生系统。骨微环境的共培养模型可提供有关骨细胞串扰的可靠信息。从对骨骼重塑的改进知识开始，可以了解骨骼疾病的机制并设计新的BTE解决方案。