Polymeric Hydrogels for In Vitro 3D Ovarian Cancer Modeling

Abstract

Ovarian cancer (OC) grows and interacts constantly with a complex microenvironment, in which immune cells, fibroblasts, blood vessels, signal molecules and the extracellular matrix (ECM) coexist. This heterogeneous environment provides structural and biochemical support to the surrounding cells and undergoes constant and dynamic remodeling that actively promotes tumor initiation, progression, and metastasis. Despite the fact that traditional 2D cell culture systems have led to relevant medical advances in cancer research, 3D cell culture models could open new possibilities for the development of an in vitro tumor microenvironment more closely reproducing that observed in vivo. The implementation of materials science and technology into cancer research has enabled significant progress in the study of cancer progression and drug screening, through the development of polymeric scaffold-based 3D models closely recapitulating the physiopathological features of native tumor tissue. This article provides an overview of state-of-the-art in vitro tumor models with a particular focus on 3D OC cell culture in pre-clinical studies. The most representative OC models described in the literature are presented with a focus on hydrogel-based scaffolds, which guarantee soft tissue-like physical properties as well as a suitable 3D microenvironment for cell growth. Hydrogel-forming polymers of either natural or synthetic origin investigated in this context are described by highlighting their source of extraction, physical-chemical properties, and application for 3D ovarian cancer cell culture.

Model Parameter identification using 2D vs 3D experimental data: a comparative analysis

“…The extensive cell-cell and cell-environment interactions involved in this process have led to the development of a number of 3D cell culture models in order to research facets of this phenomenon [12,[23][24][25][26][27]. We selected a 3D organotypic model [28,29] used extensively to study the invasion and adhesion capabilities of ovarian cancer cells [30][31][32][33][34] and 3D bio-printed multi-spheroids for the quantification of proliferation.…”

Biophysical cues of in vitro biomaterials-based artificial extracellular matrix guide cancer cell plasticity

“…Hydrogels are 3D hydrophilic polymeric networks that can absorb even more than 90% of water by volume while maintaining their structure, thanks to crosslinks among the macromolecular chains [ 18 ]. Hydrogels are extensively used for 3D cell culture due to their tunable biophysical properties, such as macromolecular architecture, porosity, stiffness and other mechanical cues, for mimicking the ECM of tumor tissues in vitro [ 19 ]. The employment of natural, synthetic or composite biomaterials are described in this section by highlighting their ability to optimize the artificial ECM.…”

“…To overcome these drawbacks, synthetic biomaterials are widely developed with a high reproducibility, consistent composition and controllable physical properties [ 40 ]. However, they lack in biological activity and cell stimulation [ 19 ], thus the addition of ECM components or adhesive peptides is usually necessary.…”

Sericultural By-Products: The Potential for Alternative Therapy in Cancer Drug Design

“…Its production overcomes the limitations of using animal models that cannot mimic numerous human aspects, including the immune system, stromal interactions, and metabolism [ 153 ]. By using these tools, numerous cancer aspects can be studied, such as cancer cell differentiation, proliferation, angiogenesis, drug resistance, immunosurveillance, testing new therapeutics, and so on [ 154 ]. There are numerous biomaterials that are currently being used for developing these bioengineered platforms, including alginate, chitosan, SF, agarose, and fibrinogen [ 155 ].…”