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

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.

3D bioprinting complex models of cancer

“…Each form of technology has its own set of benefits, and its utilization is determined by how well it matches the demands of the tissue being produced. 84 Although each type of technology has its own feature, a commonality they all tend to share is the platform they have provided which has been crucial for the study of cancer pathology and biology. Moreover, these technologies have permitted the screening of anticancer drugs, have the potential to address a variety of medical research problems and have been used in various areas, including functional organ replacement, regenerative medicine, and drug delivery.…”

“…The biophysical properties of the tissue can also be fine-tuned by adjusting the porosity, stiffness, and biochemical properties of the ECM. 84 Chen et al showed that a 3D porous model promoted the formation of tumor cell spheroids compared to 2D models, and it also immensely increased the invasiveness and chemotherapeutic resistance of tumor cells. 77 Compared to 2D models, 3D cancer models can better mimic the TME which includes metastasis, anti-cancer drug resistance, and angiogenesis.…”

“…77 Compared to 2D models, 3D cancer models can better mimic the TME which includes metastasis, anti-cancer drug resistance, and angiogenesis. 84 This is possible since the 3D constructs can accomplish biophysical characteristics which are like the microenvironment of the native tissue, which allows for the study of tumorigenesis and cancer progression. Also, the 3D construct itself degrades over time as cells secrete the native ECM, which supports the original bioprinted structure.…”

“…82 Although less common, mouse glioblastoma cells (GL261) have been used to study the crosstalk between GBM cells and GBM-associated macrophages which were also derived from mouse. 16,31,79,[83][84][85] In this case, since the macrophages were mouse-derived, it was most ideal to use a mouse-derived GBM cell line rather than a human cell line. Patient-derived GBM cells are the most ideal for the study of patient-specific disease progression and drug testing.…”

“…77 Compared to 2D models, 3D cancer models can better mimic the TME which includes metastasis, anti-cancer drug resistance, and angiogenesis. 84 This is possible since the 3D…”