Engineering Anisotropic Cell Models: Development of Collagen Hydrogel Scaffolds with Magneto‐Responsive PEG Microgels for Tissue Engineering Applications

Mimicking tissue‐oriented organization in vitro has been extensively studied in recent years, using both natural and synthetic materials in combination with external magnetic fields to establish anisotropic conditions. Here, a new combination between magneto‐responsive anisometric PEG microgels and collagen hydrogels is explored to establish anisotropic in vitro models. Different sizes of PEG microgels are tested to assess the impact of both width and aspect ratio on the formation and alignment of collagen hydrogels. Results show that the key properties of collagen hydrogels, regarding fibrillogenesis, rheological properties, and fiber diameter are kept consistent upon the combination with PEG microgels. Furthermore, partial collagen fiber alignment is observed when larger (width 10 µm) PEG microgels are employed and magnetically aligned. In vitro studies show cell alignment within the anisotropic collagen hydrogels from the first day in culture. Interestingly, PEG microgels with higher width and length tend to induce less hydrogel contraction even after 7 days in culture. The results demonstrate the ability to establish a 3D unidirectional collagen hydrogel by magnetically aligning anisometric microgels during the gelation process, which can be promising for different tissue engineering applications. This study proposes a platform that guides cell orientation by combining a collagen hydrogel with magneto‐responsive PEG rod‐shaped microgels, using the Anisogel technology. Results show consistent cell anisotropy during culture and partial collagen fiber orientation, depending on the microgel dimensions. While the initial fiber and mechanical properties of the hydrogels do not change, the larger microgels reduce shrinking during culture.