3D Microvascularized Tissue Models by Laser‐Based Cavitation Molding of Collagen

Abstract

3D tissue models recapitulating human physiology are important for fundamental biomedical research, and they hold promise to become a new tool in drug development. An integrated and defined microvasculature in 3D tissue models is necessary for optimal cell functions. However, conventional bioprinting only allows the fabrication of hydrogel scaffolds containing vessel‐like structures with large diameters (>100 µm) and simple geometries. Recent developments in laser photoablation enable the generation of this type of structure with higher resolution and complexity, but the photo‐thermal process can compromise cell viability and hydrogel integrity. To address these limitations, the present work reports in situ 3D patterning of collagen hydrogels by femtosecond laser irradiation to create channels and cavities with diameters ranging from 20 to 60 µm. In this process, laser irradiation of the hydrogel generates cavitation gas bubbles that rearrange the collagen fibers, thereby creating stable microchannels. Such 3D channels can be formed in cell‐ and organoid‐laden hydrogel without affecting the viability outside the lumen and can enable the formation of artificial microvasculature by the culture of endothelial cells and cell media perfusion. Thus, this method enables organs‐on‐a‐chip and 3D tissue models featuring complex microvasculature.

Spotlight on Three Rs Progress

“…A recent article reported the development of an organoid-based platform that can be used to test drugs against brain metastases in a cost-and time-effective manner. 1 The approach, referred to as METPlatform, employed organotypic cultures derived from established brain metastases (from lung and breast cancer) and used bioluminescence imaging and immunofluorescence as the viability readouts. The team assessed the anti-tumoral activity of a library of 114 compounds and compared their results with those obtained with a traditional cell-based assay.…”

“…A study by Guénette et al 1 aimed to address some of these challenges by developing a reliable and reproducible system to expose cells to gases at the ALI. They set out to establish a way of verifying and optimising ALI exposure conditionsmore specifically, the temperature, relative humidity, airflow parameters and dose.…”

“…phenotypic high-throughput screening (HTS)) is biased toward lipophilic and poorly water-soluble moleculescharacteristics that are usually associated with unfavourable pharmacokinetic activity and which are more difficult to evaluate in subsequent testing. In an attempt to overcome some of these hurdles, Knudsen Dal et al 1 exploited a zebrafish embryo TB model, which relies on infection with a genetically-close relative of M. tuberculosis (Mycobacterium marinum) that results in a disease that recapitulates many key features of the early stages of M. tuberculosis infection.…”

“…They summarised that: "Thus, our approach for 3D patterning collagen scaffolds by cavitation molding enables design freedom and flexibility for realizing 3D tissue models with unprecedented complexity, which hold great promise for applications in drug development, medical research, and artificial organs, leading to exciting new research." 1…”

Multiscale Hybrid Fabrication: Volumetric Printing Meets Two-Photon Ablation

“…2PA is based on multiphoton ionization induced by high-intensity pulsed lasers, [11][12] and has been explored to form cell-instructive microchannels. [13][14][15][16][17][18] Seeking to reproduce a multiscale vasculature-like construct, we show for the first time a hybrid VP and 2PA printing technology. In order to successfully combine these two techniques, we first developed a strategy to remove the VP-generated microdefects.…”