Cell-Mediated Mechanical Stability Enhancement of Biomimetic Collagen-Alginate Hydrogels: A Mechanistic Study on the Two-Dimensional Extracellular Matrix–Cell Interaction

Cell-matrix interactions are a central topic in the field of biomimetic material mechanics. While the influence of matrix stiffness on cellular adhesion, spreading, and differentiation has been extensively investigated, the reciprocal impact of cells on the mechanical properties of biomimetic matrices remains less explored. In this work, we demonstrate that fibroblasts can remodel the mechanical properties of collagen-alginate hybrid hydrogel (CAH) matrices in a 2D culture. We found that, in the absence of cells, CAHs showed a progressive stiffness decline in the cell culture medium due to calcium ion release. In contrast, when fibroblasts were present, the stiffness of the hydrogels remained stable despite calcium ion release. This stabilization was collectively contributed by fibroblast activity and calcium deposition, with cells serving as mineral nucleation sites and reinforcing the local collagen network. Together, these results highlight the role of cells in reshaping the biomaterials' mechanical properties and advance our understanding of the dynamic, reciprocal nature of cell-extracellular matrix interactions.