Comparative Evaluation of a Nanocellulose Hydrogel and Matrigel® in a Vascularized Intestinal–CAM Model

Hydrogel-based scaffolds are central to three-dimensional (3D) epithelial culture systems, yet commonly used matrices such as Matrigel® suffer from batch variability, undefined composition, and limited translational relevance. Here, we comparatively evaluated an animal-free nanocellulose hydrogel (GrowDex®) and Matrigel® in a hybrid vascularized intestinal–chorioallantoic membrane (CAM) model. Pre-cultured epithelial–immune constructs (Caco-2/HT29-MTX with immune components) were embedded in both matrices and grafted onto the CAM for 72 h. Histological and immunohistochemical analyses revealed that nanocellulose-based constructs maintained more cohesive epithelial coverage, improved scaffold integrity, and yielded a more continuous cytokeratin-positive layer at the scaffold–CAM interface. In contrast, Matrigel® constructs frequently exhibited heterogeneous epithelial distribution and central discontinuities. While both matrices enabled CAM engraftment, the chemically defined nanocellulose hydrogel demonstrated enhanced structural robustness during in vivo exposure and histological processing. These findings highlight the suitability of standardized nanocellulose hydrogels for reproducible scaffold-based epithelial models in vascularized environments.