3D Bioprinting Models for Glioblastoma: From Scaffold Design to Therapeutic Application

Conventional in vitro models fail to accurately mimic the tumor in vivo characteristics, being appointed as one of the causes of clinical attrition rate. Recent advances in 3D culture techniques, replicating essential physical and biochemical cues such as cell-cell and cell-extracellular matrix interactions, have led to the development of more realistic tumor models. Bioprinting has emerged to advance the creation of 3D in vitro models, providing enhanced flexibility, scalability, and reproducibility. This is crucial for the development of more effective drug treatments, and glioblastoma (GBM) is no exception. GBM, the most common and deadly brain cancer, remains a major challenge, with a median survival of only 15 months post-diagnosis. This review highlights the key components needed for 3D bioprinted GBM models. It encompasses an analysis of natural and synthetic biomaterials, along with crosslinking methods to improve structural integrity. Also, it critically evaluates current 3D bioprinted GBM models and their integration into GBM-on-a-chip platforms, which hold noteworthy potential for drug screening and personalized therapies. A versatile development framework grounded on Quality-by-Design principles is proposed to guide the design of bioprinting models. Future perspectives, including 4D bioprinting and machine learning approaches, are discussed, along with the current gaps to advance the field further.