Abstract
Human tissues, both in health and disease, are exquisitely organized into complex three-dimensional architectures that inform tissue function. In biomedical research, specifically in drug discovery and personalized medicine, novel human-based three-dimensional (3D) models are needed to provide information with higher predictive value compared to state-of-the-art two-dimensional (2D) preclinical models. However, current in vitro models remain inadequate to recapitulate the complex and heterogenous architectures that underlie biology. Therefore, it would be beneficial to develop novel models that could capture both the 3D heterogeneity of tissue (e.g., through 3D bioprinting) and integrate vascularization that is necessary for tissue viability (e.g., through culture in tissue-on-chips). In this proof-of-concept study, we use elastin-like protein (ELP) engineered hydrogels as bioinks for constructing such tissue models, which can be directly dispensed onto endothelialized on-chip platforms. We show that this bioprinting process is compatible with both single cell suspensions of neural progenitor cells (NPCs) and spheroid aggregates of breast cancer cells. After bioprinting, both cell types remain viable in incubation for up to 14 days. These results demonstrate a first step toward combining ELP engineered hydrogels with 3D bioprinting technologies and on-chip platforms comprising vascular-like channels for establishing functional tissue models.
Highlights
Three-dimensional (3D) cell culture systems that model the microenvironment of tissues and organs are expected to yield results with higher predictive value in drug discovery, preclinical testing, and personalized medicine (Langhans, 2018)
The printability of elastin-like protein (ELP)-RGD bioinks at varying concentrations was tested by DoD (Figure 3A) and microextrusion bioprinting (Figure 3B)
The ELP-RGD engineered protein was solubilized in phosphate-buffered saline (PBS) and pre-mixed with the tetra-functional crosslinker tetrakis(hydroxymethyl)phosphonium chloride (THPC) at a 0.5:1 stoichiometric ratio between THPC functional groups and primary amines in the protein
Summary
Three-dimensional (3D) cell culture systems that model the microenvironment of tissues and organs are expected to yield results with higher predictive value in drug discovery, preclinical testing, and personalized medicine (Langhans, 2018). It is well-accepted that 3D culture systems that mimic key factors of native extracellular matrix (ECM) are more representative of the in vivo microenvironment than comparative two-dimensional (2D) cultures (Petersen et al, 1992; Ravi et al, 2015). Vascular tissue interfaces are important in in vitro models of the neural stem cell
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