Engineering Vascular Self‐Assembly by Controlled 3D‐Printed Cell Placement

Abstract

Nutrient supply via a functional vasculature is essential during regenerative processes, tissue growth, and homeostasis. 3D bioprinting offers the opportunity to engineer vascularized constructs by combining cells and biocompatible materials in specifically designed fashions. However, the complexity of microvascular dynamic networks can hardly be recapitulated yet, even by sophisticated 3D manufacturing. Ideally, the natural organizational competences of endothelial cells will be harnessed such that engineered vascular networks self-assemble to form complex, controllable microvascular patterns. Here, a bioengineering approach is presented to control microvascular structure formation and to steer cellular self-assembly of endothelial and supporting cells within a multi-material stereolithographic 3D bioprinting concept. Bioengineered vascularized constructs are generated by controlled cell deposition in an enzymatically degradable or a non-degradable material. In vitro, the microvascular structures are regulated in distribution, network orientation, vessel length and branching behavior and developed lumen, signs of vascular stabilization and an interconnected vascular network including anastomosis. This novel biofabrication approach demonstrates the capability to control microvascular network formation by using cellular and spatial cues allowing the generation of distinctly yet precisely vascularized constructs. Such novel approach of controlled microvascular formation may play a fundamental role in the development of vascularized implants or in vitro screening models.

Vascular microphysiological systems

“…As the field of organoid biology has accelerated along with MPS technology, their intersection has resulted in a diverse array of specialized, organ-on-chip models (see Table 2). Beginning with the circulatory system, a few labs have explored strategies for connecting large and small diameters structures in order to generate hierarchical vessel networks that come closer to representing in vivo vasculature [17][18][19]. Other studies have investigated cardiovascular diseases, including a publication that recapitulated vascular malformations from PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit a) activating mutations, finding enlarged, irregular vessel phenotypes and cyst-like structures [20].…”

Utilizing bioprinting to engineer spatially organized tissues from the bottom-up

“…For example, Orellano et al transformed containers during the printing procedure to fabricate a triple layer tissue through light projection printing, where each layer consists of different cells and bioinks (Fig. 5 A) [ 94 ]. Similarly, rapid exchange of bioinks in container is also an option for multi-material projection bioprinting (Fig.…”

Multimaterial Hydrogel 3D Printing

“…The introduction of cavities in artificial vascular structures was achieved by Thomas et al using multimaterial DLP vatswitching. [125,126] The group 3D-printed sacrificial hydrogel structures based on hyaluronic acid, in combination with nonsacrificial biomaterials. The sacrificial layer could be digested by enzymes, leaving behind microchannels in the finished structure.…”