Advantages of Using 3D Spheroid Culture Systems in Toxicological and Pharmacological Assessment for Osteogenesis Research

Abstract

Bone differentiation is crucial for skeletal development and maintenance. Its dysfunction can cause various pathological conditions such as rickets, osteoporosis, osteogenesis imperfecta, or Paget's disease. Although traditional two-dimensional cell culture systems have contributed significantly to our understanding of bone biology, they fail to replicate the intricate biotic environment of bone tissue. Three-dimensional (3D) spheroid cell cultures have gained widespread popularity for addressing bone defects. This review highlights the advantages of employing 3D culture systems to investigate bone differentiation. It highlights their capacity to mimic the complex in vivo environment and crucial cellular interactions pivotal to bone homeostasis. The exploration of 3D culture models in bone research offers enhanced physiological relevance, improved predictive capabilities, and reduced reliance on animal models, which have contributed to the advancement of safer and more effective strategies for drug development. Studies have highlighted the transformative potential of 3D culture systems for expanding our understanding of bone biology and developing targeted therapeutic interventions for bone-related disorders. This review explores how 3D culture systems have demonstrated promise in unraveling the intricate mechanisms governing bone homeostasis and responses to pharmacological agents.

Keywords: 3D culture; bone homeostasis; bone regeneration; osteogenic differentiation; toxicological and pharmacological assessment.

Figure 1

The development of three-dimensional (3D) spheroid bone models for toxicological and pharmacological assessment represents a groundbreaking leap in research. Numerous methodologies have been proposed to craft these 3D spheroid bone models, emphasizing unparalleled advantages. The intricacies of the bone-specific microenvironment within the spheroids are magnified through exhaustive analysis, encompassing critical factors such as cell viability, extracellular matrix (ECM) composition, biomechanical properties, and the integration of osteogenic signaling pathways. This convergence results in an unprecedented enhancement of osteogenic differentiation and the establishment of a fortified osteoblast–osteocyte network. Consequently, the regulation of bone matrix mineralization is significantly refined, while mechanical stimuli exhibit unparalleled efficacy within the bone 3D spheroid system. This perspective can encapsulate the multifaceted essence of bone development and functionality within a meticulously simulated 3D environment, elevating the discernment and applicability of toxicological and pharmacological assessments.