3D Bioprinted In Vitro Metastatic Models via Reconstruction of Tumor Microenvironments

Abstract

The development of 3D in vitro models capable of recapitulating native tumor microenvironments could improve the translatability of potential anticancer drugs and treatments. Here, 3D bioprinting techniques are used to build tumor constructs via precise placement of living cells, functional biomaterials, and programmable release capsules. This enables the spatiotemporal control of signaling molecular gradients, thereby dynamically modulating cellular behaviors at a local level. Vascularized tumor models are created to mimic key steps of cancer dissemination (invasion, intravasation, and angiogenesis), based on guided migration of tumor cells and endothelial cells in the context of stromal cells and growth factors. The utility of the metastatic models for drug screening is demonstrated by evaluating the anticancer efficacy of immunotoxins. These 3D vascularized tumor tissues provide a proof‐of‐concept platform to i) fundamentally explore the molecular mechanisms of tumor progression and metastasis, and ii) preclinically identify therapeutic agents and screen anticancer drugs.

A Biomimetic Tumor Model of Heterogeneous Invasion in Pancreatic Ductal Adenocarcinoma

“…Creating tumor models that mimic this heterogeneity in a reliable manner is extremely challenging. Recent developments of engineered tumor models show a great promise to recapitulate a 3D microenvironment to study the TME. However, many of these in vitro models have used isogenic cancer cells, which significantly hamper the capability of mimicking true heterogeneity found in the disease.…”

3D Printed Neural Regeneration Devices

“…In the past few years, tissue engineering has been evolving from 2D to 3D cell culture, which can better mimic the microenvironment of native tissue. To this end, different kinds of naturally derived hydrogels have been used to support 3D cell culture, such as gelatin, collagen, fibrin, hyaluronic acid (HA), and derivatives of natural materials such as alginate, Matrigel, and decellularized extracellular matrix (dECM) . These hydrogels can be loaded with various cells, printed into 3D constructs, and gelated (solidified) in different ways.…”

“…The development of personalized tissue engineering and regenerative strategies aims to create new opportunities to test therapeutic options via reproducing the detailed structural features and functions of native tissues (possibly contributing to solutions for the organ donor shortage) . A requirement for replicating the cytoarchitecture of functional tissues is a clear understanding of the arrangement and spatial distribution of cellular components.…”

“…However, drugs have been discovered that slow the closure of the neuronal growth cone, and thus, if these drugs were printed within the nerve conduit, it could be possible to print an enclosed environment that was friendlier to the developmental processes necessary for axonal extension . Such a strategy could even be compatible with a 4D printing approach, where drugs could be temporally released within a nerve conduit to favor axonal extension for a defined period to a distant target . In addition, it is suggested that the ideal scaffold should provide support for the regeneration of various axon subtypes at specific sensory‐ and motor‐specific fascicles .…”

“…This could result in broad research implications in fundamental research, drug discovery, and personalized healthcare. Particularly, 3D in vitro platforms have been used to replicate the physiological cell‐cell and cell‐ECM interactions that could accelerate the development of new therapies …”