InVADE: Integrated Vasculature for Assessing Dynamic Events

Abstract

Drug screening with simplified 2D cell culture and relevant animal testing fail to predict clinical outcomes. With the rising cost of drug development, predictive 3D tissue models with human cells are in urgent demand. Establishing vascular perfusion of 3D tissues has always been a challenge, but it is necessary to mimic drug transport and to capture complex interorgan crosstalk. Here, a versatile multiwell plate is presented empowered by built-in microfabricated vascular scaffolds that define the vascular space and support self-assembly of various parenchymal tissues. In this configuration, assembly and organ-specific function of a metabolically active liver, a free-contracting cardiac muscle, and a metastatic solid tumor are demonstrated, tracking organ function using noninvasive analysis techniques. By linking the 3D tumor and the liver tissue in series, it is demonstrated that the presence of liver tissue is crucial to correctly reveal the efficacy of a chemotherapeutic drug, Tegafur. Furthermore, the complete cancer metastasis cascade is demonstrated across multiple organs, where cancer cells escaping from the solid tumor can invade a distant liver tissue connected through a continuous vascular interface. This combinatory use of microfabricated scaffold onto a standard cell culturing platform can offer important insights into the mechanics of complex interorgan biological events.

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

“…Hydrogel‐based microvascular networks are desirable for engineering functional 3D vascularized tissues in OOC . Zhang et al developed an AngioChip scaffold with a built‐in perfusable vascular network fabricated using a synthetic polymer POMaC by 3D stamping technique, in which a complex microchannel network can be embedded within a 3D scaffold . POMaC, which is characterized by the properties of elasticity and photopolymerization, can be rapidly assembled under mild conditions and biodegraded by hydrolysis.…”

“…A) Microfabricated POMaC tubular networks to enable the vascularization of cardiac tissue. Reproduced with permission . Copyright 2017, Wiley‐VCH.…”

Recapitulating Pancreatic Tumor Microenvironment through Synergistic Use of Patient Organoids and Organ‐on‐a‐Chip Vasculature

“…This ensures that there is no additional dilution of the tissue compartment, beyond the volume of 300 µL placed there as we demonstrated in a previous publication. [33] Furthermore, when the single patient-derived cells were co-cultured with human fibroblasts, we observed a larger size of organoids, suggesting elevated proliferation. This symbiotic interaction between the patient cells and stromal cells is in-line with landmark research reported previously by Ohlund et al with co-culture of mouse tumor organoids and mouse pancreatic stellate cells.…”

Promoting Cardiac Regeneration and Repair Using Acellular Biomaterials

“…Co-culturing multiple cell types in 3D arrangements can generate more mechanistic insight toward predicting in vivo efficacy than 2D cell cultures (Zhang and Radisic, 2017). Microfluidic vascularization is also possible in these models, enabling assessment of neovascularization (Zhang et al, 2016;Lai et al, 2017). These models are currently being developed to simulate ischemic injury to enable detailed investigation into the mechanisms of ischemic heart damage and the effects of therapeutic biomaterials at a mechanistic level (Chen and Vunjak-Novakovic, 2018).…”