Nanoparticle-Assembled Stem Cell Building Blocks for Enhanced 3D Adipose Tissue Engineering and Drug Screening

Traditional 3D culture systems often face challenges such as internal heterogeneity and limited functional maturation, which hinder their reliability in metabolic research and drug discovery. In this study, we developed a 3D adipose spheroid platform by engineering nanobiohybrids through the stable attachment of mesoporous silica nanoparticles (mSiO₂ NPs) to human adipose-derived mesenchymal stem cells (hADMSCs). These nanoparticle-woven building blocks facilitated the formation of 3D spheroids that exhibited significantly enhanced adipogenic differentiation and reduced internal heterogeneity compared to conventional 3D culture models. To evaluate the platform's potential for pharmacological screening, we treated the spheroids with sodium butyrate and assessed its impact on lipid accumulation and adipogenic gene expression. The results demonstrated consistent outcomes in both in vitro and in vivo environments, validating the high physiological relevance and reliability of the system. Overall, these nanobiohybrid-based spheroids offer a promising strategy to overcome the structural and functional limitations of traditional 3D systems, providing a robust and sophisticated tool for drug screening and therapeutic discovery in metabolic research.