Constructing 3D In Vitro Models of Heterocellular Solid Tumors and Stromal Tissues Using Extrusion-Based Bioprinting

Abstract

Malignant tumor tissues exhibit inter- and intratumoral heterogeneities, aberrant development, dynamic stromal composition, diverse tissue phenotypes, and cell populations growing within localized mechanical stresses in hypoxic conditions. Experimental tumor models employing engineered systems that isolate and study these complex variables using in vitro techniques are under development as complementary methods to preclinical in vivo models. Here, advances in extrusion bioprinting as an enabling technology to recreate the three-dimensional tumor milieu and its complex heterogeneous characteristics are reviewed. Extrusion bioprinting allows for the deposition of multiple materials, or selected cell types and concentrations, into models based upon physiological features of the tumor. This affords the creation of complex samples with representative extracellular or stromal compositions that replicate the biology of patient tissue. Biomaterial engineering of printable materials that replicate specific features of the tumor microenvironment offer experimental reproducibility, throughput, and physiological relevance compared to animal models. In this review, we describe the potential of extrusion-based bioprinting to recreate the tumor microenvironment within in vitro models.

Biomarkers and experimental models for cancer immunology investigation

“…EBB merges a fluid‐dispensing system with an automated robotic system dedicated to extrusion and bio‐printing 289,290 . Its capability of creating porous constructs facilitates the engineering of vasculature in tumor models and the manipulation of cancer lymphatics 291 …”

Co-axial hydrogel spinning for facile biofabrication of prostate cancer-like 3D models

“…To engineer cancer tissues, just as when attempting to engineer healthy living tissues, important characteristics such as architecture, mechanics, and cellular organization, need to be considered to recapitulate healthy or diseased, physiological outcomes [7]. Thus, there's been significant effort in engineering the 3D environments that support cancer cells [8][9][10][11], to address the need for, among others, 3D mechanics and compartmentalization that can approach those present in solid tumors [12]. Integrating these characteristics in cancer models has great potential to improve in vitro screening by enhancing the physiological relevance of the constructs, and thus reduce in vivo testing timelines to the largest extent possible [13,14].…”

Bioprinted cancer-stromal in-vitro models in a decellularized ECM-based bioink exhibit progressive remodeling and maturation

“…Three-dimensional in-vitro culture models have become popular as an alternative to traditional animal preclinical models to test and better understand disease [5,[15][16][17]. These models intend to recapitulate, in a controlled manner, variables that mimic the conditions found in-vivo [5,16].…”

“…These models intend to recapitulate, in a controlled manner, variables that mimic the conditions found in-vivo [5,16]. The ideal 3D in-vitro model must include a 3D environment with relevant architecture and dimensions, a matrix resembling the ECM of the tissue in question, and relevant cell populations for the disease studied [17]. Several biomaterials have been proposed to mimic the ECM in-vitro [18].…”