Honeycomb-Like Hydrogel Microspheres for 3D Bulk Construction of Tumor Models.

Jiachen He,Jie Sun,Yuan Xue,Sihan Hu,Qin Shi,Jian Lu,Chichi Chen,Wenguo Cui,Huiling Yang,Xingzhi Liu,Can Zhu,Ruoyu Cheng,Liang Chen,Lin Wang

doi:10.34133/2022/9809763

Abstract

A two-dimensional (2D) cell culture-based model is widely applied to study tumorigenic mechanisms and drug screening. However, it cannot authentically simulate the three-dimensional (3D) microenvironment of solid tumors and provide reliable and predictable data in response to in vivo, thus leading to the research illusions and failure of drug screening. In this study, honeycomb-like gelatin methacryloyl (GelMA) hydrogel microspheres are developed by synchronous photocrosslinking microfluidic technique to construct a 3D model of osteosarcoma. The in vitro study shows that osteosarcoma cells (K7M2) cultured in 3D GelMA microspheres have stronger tumorous stemness, proliferation and migration abilities, more osteoclastogenetic ability, and resistance to chemotherapeutic drugs (DOX) than that of cells in 2D cultures. More importantly, the 3D-cultured K7M2 cells show more tumorigenicity in immunologically sound mice, characterized by shorter tumorigenesis time, larger tumor volume, severe bone destruction, and higher mortality. In conclusion, honeycomb-like porous microsphere scaffolds are constructed with uniform structure by microfluidic technology to massively produce tumor cells with original phenotypes. Those microspheres could recapitulate the physiology microenvironment of tumors, maintain cell-cell and cell-extracellular matrix interactions, and thus provide an effective and convenient strategy for tumor pathogenesis and drug screening research.

Highlights

One of the top 10 challenges in current tumor therapy is to create tumor models that are close to natural tumors, which can interpret the finding efficiently and accurately with cancer therapeutics
By simulating the microenvironment of tumorigenesis, we can elucidate the mechanisms related to the progression and metastasis of malignant tumors and find the appropriate treatment from the inherent cause, which is the ultimate goal of establishing tumor models in vitro [8]
Several characteristics should be considered: (1) the ability to mimic cell-cell and extracellular matrix (ECM) interactions as in vivo; (2) the ability to maintain the inherent characteristics of tumor cells, including stemness, invasiveness, and drug resistance; (3) with a particular spatial structure, which can ensure the exchange of nutrients, cell metabolites, gases, and so on; and (4) batch uniformity that can ensure the repeatability of the results

Summary

Introduction

One of the top 10 challenges in current tumor therapy is to create tumor models that are close to natural tumors, which can interpret the finding efficiently and accurately with cancer therapeutics. Research on the tumorigenic mechanism and drug screening mainly rely on the tumor cells cultured on the two-dimensional (2D) plate [2]. By simulating the microenvironment of tumorigenesis, we can elucidate the mechanisms related to the progression and metastasis of malignant tumors and find the appropriate treatment from the inherent cause, which is the ultimate goal of establishing tumor models in vitro [8]. For this purpose, it is crucial to develop tumor models which more closely resemble the physiological characteristics of tumors under natural conditions [9]. Several characteristics should be considered: (1) the ability to mimic cell-cell and ECM interactions as in vivo; (2) the ability to maintain the inherent characteristics of tumor cells, including stemness, invasiveness, and drug resistance; (3) with a particular spatial structure, which can ensure the exchange of nutrients, cell metabolites, gases, and so on; and (4) batch uniformity that can ensure the repeatability of the results

Methods

Results

Conclusion