Effectiveness of Bioinks and the Clinical Value of 3D Bioprinted Glioblastoma Models: A Systematic Review

SIMPLE SUMMARY: Glioblastoma is the most malignant cancer of the glioma series, and it is highly invasive. The progression and recurrence of glioblastoma remain common due to the development of drug resistance. Of the current disease models and strategies used in pre-clinical studies for drug testing, three-dimensional (3D) bioprinting is an emerging technology in constructing a glioblastoma model. In this paper, 19 out of 304 articles yielded from the database search were selected and analysed through a systematic process. The selected studies present the effectiveness of different bioinks, which were used to mimic the tumour microenvironment of glioblastoma in bioprinting. The clinical value of the 3D bioprinted glioblastoma models on the efficacy of treatments or drug response was evaluated. ABSTRACT: Many medical applications have arisen from the technological advancement of three-dimensional (3D) bioprinting, including the printing of cancer models for better therapeutic practice whilst imitating the human system more accurately than animal and conventional in vitro systems. The objective of this systematic review is to comprehensively summarise information from existing studies on the effectiveness of bioinks in mimicking the tumour microenvironment of glioblastoma and their clinical value. Based on predetermined eligibility criteria, relevant studies were identified from PubMed, Medline Ovid, Web of Science, Scopus, and ScienceDirect databases. Nineteen articles fulfilled the inclusion criteria and were included in this study. Alginate hydrogels were the most widely used bioinks in bioprinting. The majority of research found that alginate bioinks had excellent biocompatibility and maintained high cell viability. Advanced structural design, as well as the use of multicomponent bioinks, recapitulated the native in vivo morphology more closely and resulted in bioprinted glioblastoma models with higher drug resistance. In addition, 3D cell cultures were superior to monolayer or two-dimensional (2D) cell cultures for the simulation of an optimal tumour microenvironment. To more precisely mimic the heterogenous niche of tumours, future research should focus on bioprinting multicellular and multicomponent tumour models that are suitable for drug screening.