Scientists at Tel Aviv University in Israel have successfully printed a complete active and viable brain tumor with a three-dimensional (or 3D) printer for the first time. The researchers simulated the flowing blood vessels and surrounding brain tissue.
The study, published in the peer-reviewed journal Science Advances, recapitulated the tumor’s heterogeneous environment by creating fibringlioblastoma bioink made from patient-derived glioblastoma cells, microglia, and astrocytes.
The 3D model contains all components of the malignant tumor. It could be the foundation for replacing cell cultures and animal models as a powerful platform for drug target discovery, personalized therapy, and drug development.
Glioblastoma (GB) is the most common malignant brain tumor, accounting for 47.7 percent of all cases. It is also the most aggressive type of brain tumor, affecting 3.21 per 100,000 people in the United States alone. The incidence has increased in many countries.
Cancer is one of the leading causes of death worldwide. About 30 to 40 percent of cancer patients are treated with ineffective drugs. Therefore, preclinical drug screening platforms aim to meet this challenge. Unfortunately, most of the existing methods of identifying pharmacological targets have been of limited effectiveness. There is a need for a reliable and clinically relevant platform for high throughput drug screening.
The conventional preclinical drug development process relies on the in vitro assessment of drug efficacy and toxicity in two-dimensional (2D) cell cultures, followed by animal studies. Over the years, 2D culture studies have been used in biomedical research and drug screening because they are inexpensive. However, the method has difficulty predicting the multiple effects of the treatment in vivo.
The emergence of 3D models shows promise in overcoming the limitations of previous cancer models and reducing the cost of preclinical drug evaluation. Earlier models have been developed but lack the abundance of stromal cells and functional blood vessels that are essential for disease development and progression, and assessment of response to treatment.
3D bioprinted engineered tumor model
A promising new technology in tissue regeneration is 3-D bioprinting, a technology for the precise 3-D construction of complex tissues and organs. This technology enables the positioning of cells and biocompatible materials in layers. It also enables the use of a wide range of biomaterials with different viscosities and cell densities. The technology can better mimic the tumor microenvironment (TME) and provide insight into the full physiological properties of the tumor, including the blood vessels and multi-scale architecture.
Fig. 7 Bridging the translation gap from bed to bench and back. Schematic representation of the methodical approach using a perfusable, micro-engineered vascular 3D-bioprinted tumor model for drug screening and targeting. MRI, magnetic resonance imaging; μ-CT, micro-computed tomography.
The team developed a 3D bio-printed, engineered tumor model based on two bio-inks, a tumor bio-ink and a vascular bio-ink. They focused on 3D bioprinting of glioblastomas, as intratumoral heterogeneity and TME are the major drivers of therapy resistance of GB cells. The development of models that mimic the complex microenvironment of the UK holds promise to facilitate the development of effective treatment options.
After successfully printing the 3D tumor, the researchers showed that, unlike cancer cells growing on petri dishes, the 3D bioprinted model can provide a strong and rapid prediction of the most appropriate treatment for a given reproductive patient.
The team investigated the mechanical properties and biological functionality of the biocompatible fibrin 3D bio-ink. The models resembled GB cellular heterogeneity, cell-cell interaction, and spatial tomography.
The study results showed similar growth curves, drug responses, and genetic signatures of glioblastoma cells grown in the 3D Bio-Ink platform.
We show here that our 3D bio-ink can serve as an alternative to mouse models as it can mimic key features of tumors grown in vivo … “
The 3D bio-printed GB model could help provide effective treatments as personalized therapy and is important for the management of aggressive tumors with short term survival.