A Novel 3D in Vitro Tumor Model Based on Silk Fibroin/Chitosan Scaffolds To Mimic the Tumor Microenvironment

Abstract

Drug development involves various evaluation processes to ascertain drug effects and rigorous analysis of biological indicators during in vitro preclinical studies. Twodimensional (2D) cell cultures are commonly used in numerous in vitro studies, which are poor facsimiles of the in vivo conditions. Recently, three-dimensional (3D) tumor models mimicking the tumor microenvironment and reducing the use of experimental animals have been developed generating great interest to appraise tumor response to treatment strategies in cancer therapy. In this study, silk fibroin (SF) protein and chitosan (CS), two natural biomaterials, were chosen to construct the scaffolds of 3D cell models. Human non-small cell lung cancer A549 cells in the SF/CS scaffolds were found to have a great tendency to gather and form tumor spheres. A549 cell spheres in the 3D scaffolds showed biological and morphological characteristics much closer to the in vivo tumors. Besides, the cells in 3D models displayed better invasion ability and drug resistance than 2D models. Additionally, differences in drug-resistant and immune-related protein levels were found, which indicated that 3D models might resemble the real-life situation. These findings suggested that these 3D tumor models composed of SF/CS are promising to provide a valuable biomaterial platform in the evaluation of anticancer drugs.

Comparative Study of Silk-Based Magnetic Materials: Effect of Magnetic Particle Types on the Protein Structure and Biomaterial Properties

“…A high content of β-sheet crystals, which can be stimulated through alcohol solutions or water annealing, also helps to improve cell adhesion and tissue growth [ 25 , 27 , 28 ]. In addition, the hydrophilic functional groups on the network composed of the protein chain and its crosslinked structure can make the material absorb water while still maintaining its shape and structure well, permitting its use for bone reconstruction, bioelectronics, and in vivo tumor models [ 29 , 30 , 31 ].…”

Progressive 3D Printing Technology and Its Application in Medical Materials

“…It is significant to mimic in vivo tumor environment with stroma and micro structures for the accuracy of testing new theories and therapies (Costa et al, 2016). Jizhao Li et al developed a 3D cell model with human lung cancer A549 cells applied in scaffolds fabricated with silk fibroin protein and chitosan (Li et al, 2018). By resembling pathological conditions, the 3D tumor model provide a valuable biomaterial platform for in-vitro test of antitumor drugs for nonsmall cell lung cancer.…”

Hydrogels to engineer tumor microenvironmentsin vitro

“…With the growing consensus that elements of the TME need to be incorporated into in vitro tumor models, some investigators have adopted the approach of generating simple, scaffold-less heterospheroids comprising cancer and stromal cells, [190][191][192][193][194][195][196] while some have also leveraged the use of biomaterials to model cancer-TME interactions. [197][198][199][200] The use of scaffolds, including hydrogels, enables the recapitulation of certain biophysical and biochemical aspects of the tumor ECM to support cancer and stromal cell culture. We direct the reader to several excellent review articles on the use of scaffolds for tumor engineering, [201][202][203][204][205][206][207] and focus specifically on describing the use of hydrogels to model the TME in vitro (Fig.…”