Shape Memory Collagen Scaffolds Sustain Large-Scale Cyclic Loading

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.