Dissolvable temporary barrier:a novel paradigm for flexible hydrogel patterning in organ-on-a-chip models

A combination of hydrogels and microfluidics allows the construction of biomimetic three-dimensional(3D)tissue models in vitro,which are also known as organ-on-a-chipmodels.The hydrogel patterningwith awell-controlled spatial distribution is typically achieved by embedding sophisticated microstructures to act as a boundary.However,these physical barriers inevitably expose cells/tissues to a less physiologically relevant microenvironment than in vivo conditions.Herein,we present a novel dissolvable temporary barrier(DTB)strategy that allows robust and flexible hydrogel patterning with great freedom of design and desirable flow stimuli for cellular hydrogels.The key aspect of this approach is the patterning of a water-soluble rigid barrier as a guiding path for the hydrogel using stencil printing technology,followed by a barrier-free medium perfusion after the dissolution of the DTB.Single and multiple tissue compartments with different geometries can be established using either straight or curved DTB structures.The effectiveness of this strategy is further validated by generating a 3D vascular network through vasculogenesis and angiogenesis using a vascularized microtumor model.As a new proof-of-concept in vasculature-on-a-chip,DTB enables seamless contact between the hydrogel and the culture medium in closed microdevices,which is an improved protocol for the fabrication ofmultiorgan chips.Therefore,we expect it to serve as a promising paradigm for organ-on-a-chip devices for the development of tumor vascularization and drug evaluation in the future preclinical studies.

Engineering vascularised organoid-on-a-chip:strategies,advances and future perspectives

In recent years,advances in microfabrication technology and tissue engineering have propelled the development of a novel drug screening and disease modelling platform known as organoid-on-a-chip.This platform integrates organoids and organ-on-a-chip technologies,emerging as a promising approach for in vitro modelling of human organ physiology.Organoid-on-a-chip devices leverage microfluidic systems to simulate the physiological microenvironment of specific organs,offering a more dynamic and flexible setting that can mimic a more comprehensive human biological context.However,the lack of functional vasculature has remained a significant challenge in this technology.Vascularisation is crucial for the long-term culture and in vitro modelling of organoids,holding important implications for drug development and personalised medical approaches.This review provides an overview of research progress in developing vascularised organoid-on-a-chip models,addressing methods for in vitro vascularisation and advancements in vascularised organoids.The aim is to serve as a reference for future endeavors in constructing fully functional vascularised organoid-on-a-chip platforms.