From Spheroids to Bioprinting: A Literature Review on Biomanufacturing Strategies of 3D In Vitro Osteosarcoma Models

Osteosarcoma (OS) is a rare primary malignant bone cancer affecting mainly young individuals. Treatment typically consists of chemotherapy and surgical tumor resection, which has undergone few improvements since the 1970s. This therapeutic approach encounters several limitations attributed to the tumor's inherent chemoresistance, marked heterogeneity and metastatic potential. Therefore, the development of in vitro platforms that closely mimic the OS pathophysiology is crucial to understand tumor progression and discover effective anticancer therapeutics. Contrary to 2D monolayer cultures and animal models, 3D in vitro platforms show promise in replicating the 3D tumor macrostructure, cell-cell and cell-extracellular matrix interactions. This review provides an overview of the biomanufacturing strategies employed in developing 3D in vitro OS models, highlighting their role in replicating different aspects of OS and improving OS anticancer research and drug screening. A variety of 3D in vitro models are explored, including both scaffold-free and scaffold-based models, encompassing cell spheroids, hydrogels, and innovative approaches like electrospun nanofibers, microfluidic devices and bioprinted constructs. By examining the distinctive features of each model type, this review offers insights into their potential transformative impact on the landscape of OS research and therapeutic innovation, addressing the challenges and future directions of 3D in vitro OS modeling.This review explores the diverse range of 3D in vitro models of osteosarcoma (OS), the most common bone cancer, highlighting the bioengineering approaches used to enhance the biomimicry of the OS tumor microenvironment and improve therapeutic discovery. It discusses the use of tumor aggregates and scaffold-based systems, namely those developed using advanced techniques such as electrospinning, microfluidics, and 3D bioprinting. image