An alginate-cellulose based bioink mimics the viscoelastic features of the melanoma microenvironment and its influence on cell cycle and invasion

Abstract

Melanoma, an aggressive tumor from melanocytes, poses challenges despite recent therapeutic advances. Understanding molecular changes in its progression is crucial. Melanoma cells develop in the epidermis, then start spreading into the dermis– the first step of the invasive, progressive process. The dermis is composed of elastic (proteoglycans) and stabilizing (collagens) molecules. To overcome limitations of 2D-cell culture models, we established a 3D-bio-printed dermis model for the analysis of tumor cell features using a blend of alginate and microfibrillar cellulose. Testing different compositions in extrusion-based bioprinting confirmed good printability with high cell viability for AlgCell ink. Mechanical and optical analyses revealed dermis-like viscoelasticity and a pore size allowing nutrition supply and cell movement. We evaluated survival and proliferation of the cells and printed tumor spheroids and determined different migratory behavior comparing alginate to AlgCell. Interestingly, multiphoton microscopy revealed random cellulose fiber distribution around the spheroids after 7 days of cultivation with individual single cells, which had left the tumor spheroid and invaded into the microenvironment. Traditional 2D-models inadequately capture 3D mechanisms like invasion and migration. Our 3D-tumor model mimics the microenvironment, enabling in-depth analyses akin to in vivo conditions. This promises insights into tumor progression and testing of therapeutic interventions.