Microporogen-Structured Collagen Matrices for Embedded Bioprinting of Tumor Models for Immuno-Oncology.

Abstract

Embedded bioprinting enables the rapid design and fabrication of complex tissues that recapitulate in vivo microenvironments. However, few biological matrices enable good print fidelity, while simultaneously facilitate cell viability, proliferation, and migration. Here, we introduce a new microporogen-structured (μPOROS) matrix for embedded bioprinting, in which matrix rheology, printing behavior, and porosity are tailored by adding sacrificial microparticles composed of a gelatin-chitosan complex to a prepolymer collagen solution. To demonstrate its utility, we created a three-dimensional tumor model via embedded printing of a murine melanoma cell ink within the μPOROS collagen matrix at 4°C. The collagen matrix is subsequently crosslinked around the microparticles upon warming to 21°C, followed by their melting and removal at 37°C. This process results in a μPOROS matrix with a fibrillar collagen type-I network akin to that observed in vivo. Printed tumor cells remain viable and proliferate, while antigen-specific cytotoxic T cells incorporated in the matrix migrate to the tumor site, where they induce cell death. The integration of our μPOROS matrix with embedded bioprinting opens new avenues for creating complex tissue microenvironments in vitro that may find widespread use in drug discovery, disease modeling, and tissue engineering for therapeutic use. This article is protected by copyright. All rights reserved.