Using Sacrificial Cell Spheroids for the Bioprinting of Perfusable 3D Tissue and Organ Constructs: A Computational Study

Abstract

A long-standing problem in tissue engineering is the biofabrication of perfusable tissue constructs that can be readily connected to the patient’s vasculature. It was partially solved by three-dimensional (3D) printing of sacrificial material (e.g., hydrogel) strands: upon incorporation in another cell-laden hydrogel, the strands were removed, leaving behind perfusable channels. Their complexity, however, did not match that of the native vasculature. Here, we propose to use multicellular spheroids as a sacrificial material and investigate their potential benefits in the context of 3D bioprinting of cell aggregates and/or cell-laden hydrogels. Our study is based on computer simulations of postprinting cellular rearrangements. The computational model of the biological system is built on a cubic lattice, whereas its evolution is simulated using the Metropolis Monte Carlo algorithm. The simulations describe structural changes in three types of tissue constructs: a tube made of a single cell type, a tube made of two cell types, and a cell-laden hydrogel slab that incorporates a branching tube. In all three constructs, the lumen is obtained after the elimination of the sacrificial cell population. Our study suggests that sacrificial cell spheroids (sacrospheres) enable one to print tissue constructs outfitted with a finer and more complex network of channels than the ones obtained so far. Moreover, cellular interactions might give rise to a tissue microarchitecture that lies beyond the bioprinter’s resolution. Although more expensive than inert materials, sacrificial cells have the potential to bring further progress towards the biofabrication of fully vascularized tissue substitutes.

Magnetic Patterning of Tissue Spheroids Using Polymer Microcapsules Containing Iron Oxide Nanoparticles

“…Growth and differentiation factors could be incorporated in polymeric capsules, and they could direct the differentiation effect. Enhanced magnetic properties of tissue spheroids could also be used for their patterning, magnetic levitation (movie S2), magnetic bioprinting, and, finally, even for possible directed sacrificial tissue spheroids death through the hyperthermia process induced by the alternating magnetic field (for more details, see the recently proposed concept of so-called “sacrospheres”) …”

Bioink Formulation and Machine Learning-Empowered Bioprinting Optimization

“…The researchers evacuated all gelatin from the 3D printed structure after cellular adherence to the channel walls, resulting in HUVEC-lined vascular mimicry. The same idea has been proposed to use sacrificial cell spheroids ( Robu et al, 2019 ). Sacrificial cell spheroids can grow in the tissue but are connected to a mechanism that could initiate cell death, effectively causing those cells to die off and leave a void space in the bioprint.…”

Effects of Processing Parameters of 3D Bioprinting on the Cellular Activity of Bioinks

“…Similarly, photosensitizers coupled with nanoparticles also used for selective destruction of the sacrificial cellular templates. [ 218 ] In Multicellular spheroids microfluidics with hydrogel support, enhances cell‐to‐cell and cell‐to‐matrix interactions. The cellular structure stability is maintained by the expanded actin filaments (cytoskeleton) that generate the force required for maintaining a prestressed lattice.…”