Pharmaceutics and Food Technology Department, School of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Universidad Complutense de Madrid (UCM), Madrid, Spain.
Pharmacol Res. 2021 Jul;169:105626. doi: 10.1016/j.phrs.2021.105626. Epub 2021 Apr 21.
Understanding the in vitro biology and behavior of human osteoblasts is crucial for developing research models that reproduce closely the bone structure, its functions, and the cell-cell and cell-matrix interactions that occurs in vivo. Mimicking bone microenvironment is challenging, but necessary, to ensure the clinical translation of novel medicines to treat more reliable different bone pathologies. Currently, bone tissue engineering is moving from 2D cell culture models such as traditional culture, sandwich culture, micro-patterning, and altered substrate stiffness, towards more complex 3D models including spheroids, scaffolds, cell sheets, hydrogels, bioreactors, and microfluidics chips. There are many different factors, such cell line type, cell culture media, substrate roughness and stiffness that need consideration when developing in vitro models as they affect significantly the microenvironment and hence, the final outcome of the in vitro assay. Advanced technologies, such as 3D bioprinting and microfluidics, have allowed the development of more complex structures, bridging the gap between in vitro and in vivo models. In this review, past and current 2D and 3D in vitro models for human osteoblasts will be described in detail, highlighting the culture conditions and outcomes achieved, as well as the challenges and limitations of each model, offering a widen perspective on how these models can closely mimic the bone microenvironment and for which applications have shown more successful results.
了解人成骨细胞的体外生物学和行为对于开发能够紧密复制骨结构、其功能以及体内发生的细胞-细胞和细胞-基质相互作用的研究模型至关重要。模拟骨微环境具有挑战性，但却是必要的，以确保新型药物的临床转化能够更可靠地治疗不同的骨病理学。目前，骨组织工程正在从 2D 细胞培养模型（如传统培养、夹层培养、微图案化和改变基质硬度）向更复杂的 3D 模型（包括球体、支架、细胞片、水凝胶、生物反应器和微流控芯片）发展。在开发体外模型时，需要考虑许多不同的因素，如细胞系类型、细胞培养基、基质粗糙度和硬度，因为它们会显著影响微环境，从而影响体外测定的最终结果。先进的技术，如 3D 生物打印和微流控技术，已经允许更复杂结构的开发，从而在体外和体内模型之间架起了桥梁。在这篇综述中，将详细描述过去和现在用于人成骨细胞的 2D 和 3D 体外模型，突出显示所获得的培养条件和结果，以及每种模型的挑战和局限性，提供了一个更广泛的视角，了解这些模型如何能够紧密模拟骨微环境，以及哪些应用已经显示出更成功的结果。
