Cell‐Laden Gradient Hydrogel Scaffolds for Neovascularization of Engineered Tissues

Abstract

Gradients in mechanical properties, physical architecture and biochemical composition exist in a variety of complex tissues, yet 3D in vitro models that enable investigation of these cues on cellular processes, especially those contributing to vascularization of engineered tissues are limited. Here, a photopolymerization approach to create cell‐laden hydrogel biomaterials with decoupled and combined gradients in modulus, immobilized cell adhesive peptide (RGD) concentration, and proteolytic degradation enabling spatial encapsulation of vascular spheroids is reported to elucidate their impact on vascular sprouting in 3D culture. Vascular spheroids encapsulated in these gradient scaffolds exhibit spatial variations in total sprout length. Scaffolds presenting an immobilized RGD gradient promote biased vascular sprouting toward increasing RGD concentration. Importantly, biased sprouting is found to be dependent on immobilized RGD gradient characteristics, including magnitude and slope, with increases in these factors contributing to significant enhancements in biased sprouting responses. Conversely, reduction in biased sprouting responses is observed in combined gradient scaffolds possessing opposing gradients in RGD and modulus. The presented work is the first to demonstrate the use of a cell‐laden biomaterial platform to systematically investigate the role of multiple scaffold gradients as well as gradient slope, magnitude and orientation on vascular sprouting responses in 3D culture.

Synthetic Extracellular Matrices for 3D Culture of Schwann Cells, Hepatocytes, and HUVECs

“…Interestingly, unlike the two types of cells above, HUVEVs in plain PIC could not proliferate, whereas HUVECs in PIC-RGD proliferated approximately 5.4 times in 7 days and were well spread. This is in accordance with the other reports, where ECs were observed to spread more in an RGD-richer environment [ 32 ].…”

High‐Throughput Bioprinting of Geometrically‐Controlled Pre‐Vascularized Injectable Microgels for Accelerated Tissue Regeneration

“…The ability of cells to remodel the hydrogel is critical for vasculature formation, however, large rates of remodeling degrade the scaffold before cells assemble the vasculature, which impedes tissue regeneration. [ 49 ] The DLP bioprinting‐based fabrication method allows the engineering of microgels with size, shape, and mechanical properties tailored for controlled remodeling without extensive degradation.…”

Designing of gradient scaffolds and their applications in tissue regeneration

“…The authors have created five different decoupled and combined gradients of immobilized arginine-glycine-aspartic acid (RGD peptide) concentration, stiffness, and protease-sensitivity within the hydrogel to study the vascular sprouting activity in 3D culture. Their findings have concluded that vascularisation of complex tissues requires gradients of various properties like mechanical, degradation rate and adhesion ligand composition [124].…”