Patterned alginate hydrogel spatially guides collagen fibrillogenesis, viscoelasticity and endothelial cell invasion

Angiogenesis following injury is primarily driven by fibrillar proteins within the extracellular matrix, such as collagen. However, protein-based biomaterials have limitations, including uncontrolled degradation and a lack of tunability. The researchers present a solution in the form of patterned interpenetrating networks (IPNs) composed of covalently crosslinked alginate and physically crosslinked collagen.

These IPNs offer the necessary mechanical properties to support the migration of endothelial cells (ECs) in a spatially controlled manner.

The IPNs are created using low molecular weight alginate functionalized with norbornene or tetrazine, enabling two distinct covalent crosslinking methods: UV-mediated crosslinks and degradable crosslinks with matrix metalloproteinase (MMP) sensitive peptides. Photolithography is employed to generate patterns in degradation, collagen fibrillogenesis, microarchitecture, and matrix viscoelasticity.

The researchers then tested the potential of these 3D patterned alginate-collagen (Alg-Col) IPNs to guide EC invasion and proliferation using a microfluidics platform that mimics the conditions of an early healing environment. The results showed that only regions exhibiting collagen fibrillogenesis, alginate degradability, and viscoelasticity demonstrated EC cell invasion patterns similar to those observed in vivo following injury.

The 3D patterned Alg-Col IPNs are compatible with microfluidics, providing a strategy to expand the applications of protein-based hydrogels and serving as a versatile platform for tissue engineering and disease modeling.