A bioprinted 3D gut model with crypt-villus structures to mimic the intestinal epithelial-stromal microenvironment.

The intestine is a complex tissue with a characteristic three-dimensional (3D) crypt-villus architecture, which plays a key role in the intestinal function. This function is also regulated by the intestinal stroma that actively supports the intestinal epithelium, maintaining the homeostasis of the tissue. Efforts to account for the 3D complex structure of the intestinal tissue have been focused mainly in mimicking the epithelial barrier, while solutions to include the stromal compartment are scarce and unpractical to be used in routine experiments. Here we demonstrate that by employing an optimized bioink formulation and the suitable printing parameters it is possible to produce fibroblast-laden crypt-villus structures by means of digital light projection stereolithography (DLP-SLA). This process provides excellent cell viability, accurate spatial resolution, and high printing throughput, resulting in a robust biofabrication approach that yields functional gut mucosa tissues compatible with conventional testing techniques.

Improved microfluidic platform for simultaneous multiple drug screening towards personalized treatment.

Development of new targeted therapies is a challenge in the battle against cancer. Although a variety of treatments is currently available, there is no technique for rapidly evaluating the response of cancer patients to the drug. In this work, a microfluidic platform for the real-time simultaneous analysis of the success rate of different nanoparticle based chemotherapeutic drugs is presented. Based on a previous planar chamber and a reported sensitivity enhancing strategy, linear and cross shape microstructures were integrated into the chamber dome of the microfluidic polydimethylsiloxane and glass platform in order to provide a higher fluid mixing and treatment-cell interaction. Several methotrexate (MTX) based treatments (free MTX, MTX loaded Lecithin-PVA nanoparticles, MTX loaded Lecithin-Tween 80 nanoparticles) as well as their respective controls (cell media and both blank nanoparticles) were recirculated through the microchamber over an osteosarcoma cell monolayer. These nanovehicles reduced cell population to less than 20% (LEC-PVA nanoparticles) and 2.3% (LEC-Tween nanoparticles), demonstrating that nanoparticles are a promising target therapy for cancer treatment. Moreover, microstructured platforms demonstrated a higher efficacy in the drug-screening process: due to the liquid folding a higher amount of nanoparticles was internalized by the cells and, therefore, results were observed faster. In fact, the time required to reduce cell viability to the half was nearly a 75% faster. Furthermore, this microfluidic platform offers the capability to test up to five different drugs simultaneously, making it a powerful tool to evaluate the effect of multiple drugs and determine the most effective and personalized treatment.