1964P - Biomimetics of three-dimensional (3D) osteosarcoma (OS) models: A scoping review

Background

Three-dimensional (3D) cell culture models can recapitulate the native tumour microenvironment (TME) of cancers. However, data on the biomimicry of 3D osteosarcoma (OS) models is unclear. This scoping review (SR) aims to assess how the biomimicry of 3D OS models changes depending on the engineered features of the model. Biomimicry was determined by studying multiple parameters, including cell behaviour and drug resistance.

Methods

The scoping review followed the PRISMA-ScR guidelines and included studies with 3D culture models using osteosarcoma cells. The systematic search, which involved five databases (January 2012-December 2022), identified 293 studies; 70 studies were selected for final analysis: 40 involved drug screening, and 21 included the addition of stromal cells into the model.

Results

Overall, 64% of 3D OS models were scaffold-based compared to self-generated spheroid models. Native scaffolds (42%) comprising mainly collagen/hydroxyapatite predominated, followed by composite scaffolds (22%). For drug screening, both scaffold-based and scaffold-free models were used equally. Thirteen of 15 studies comparing 3D versus 2D drug sensitivity showed decreased sensitivity in 3D models, with several studies showing upregulated resistance genes in 3D models. Furthermore, the use of ECM-mimetic scaffolds and native biomaterials enhanced resistance by OS cells. These suggest biomimetic 3D OS models better recapitulate in vivo TME for drug screening. Co-cultures of OS/stroma cells enhanced biomimicry of 3D models and contributed towards osteogenic differentiation, ECM remodelling, mineralisation, angiogenesis, and OS-stromal cells’ crosstalk. Seven studies demonstrated selective toxicity of chemotherapeutics towards OS cells while sparing stromal cells, providing helpful evidence for novel therapies development.

Conclusions

This SR highlights the biomimicry of 3D OS models in recapitulating in vivo TME. Future work should explore innovative 3D biomimetic models, biomaterials, and advancements in personalised medicine.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.