Tunable Hybrid Hydrogels of Alginate and Cell‐Derived dECM to Study the Impact of Matrix Alterations on Epithelial‐to‐Mesenchymal Transition

• DOI: 10.1002/adhm.202401032
• Publication Date: 2024-09-09T07:40:49Z
• Authors: P. Barros da Silva; Xiaoyu Zhao; Sílvia J. Bidarra; Diana S. Nascimento; Vernon LaLone; Bianca N. Lourenço; Joana Paredes; Molly M. Stevens; C. C. Barrias
• Keywords: Decellularization; Matrix (chemical analysis)

Abstract Epithelial‐to‐mesenchymal transition (EMT) is crucial for tumor progression, being linked to alterations in the extracellular matrix (ECM). Understanding ECM's role EMT can uncover new therapeutic targets, yet replicating these interactions vitro remains challenging. It shown that hybrid hydrogels of alginate (ALG) and cell‐derived decellularized ECM (dECM), with independently tunable composition stiffness, are useful 3D‐models explore impact breast on EMT. Soft RGD‐ALG (200 Pa), used as neutral bulk material, supported mammary epithelial cells morphogenesis without spontaneous EMT, allowing define gene, protein, biochemical profiles at different TGFβ1‐induced states. To mimic composition, dECM from TGFβ1‐activated fibroblasts (adECM) generated, which shows upregulation tumor‐associated proteins compared ndECM normal fibroblasts. Using adECM‐ALG hydrogels, it presence adECM induces partial cells, amplifes TGF‐β1 effects ALG ndECM‐ALG. Increasing hydrogel stiffness tumor‐like levels (2.5 kPa) have a synergistic effect, promoting more evident These findings shed light complex interplay between underscoring utility dECM‐ALG valuable platform cancer research.