Abstract
Natural biopolymer hydrogels often suffer from relatively low moduli and an inability to maintain structure and mechanics under cyclic loading, limiting their utility in dynamic mechanical environments. Here, a cross-linked collagen cryogel scaffold was fabricated by precompression to densify the network. Following lyophilization, the porous scaffolds sustained >90% axial compressive strain with 200 cycles. Ogden hyperelastic modeling and second harmonic generation (SHG) imaging revealed fiber alignment, densification, and strain-stiffening contributing to resilience under repetitive large-scale loading. After rehydration, cross-linked and densified hydrogels showed network stability and recoverability under cyclic loading, with significantly reduced phase transition strains compared to non-cross-linked controls. The scaffolds supported cell encapsulation and maintained cell viability after 50 cycles of 90% strain. Cyclic loading significantly densified the encapsulated cells in the loading direction, comparable to nonloaded controls. Overall, these results suggest that densified, shape memory collagen scaffolds provide a mechanically robust and biocompatible system for dynamic environments.