Biomimetic elastin-collagen hybrid hydrogels crosslinked by energetic electrons: towards a tunable in vitro extracellular matrix model of the lung

• Electron irradiation-induced crosslinking increased Young’s moduli of elastin-collagen hydrogels & reduced pore diameters. • Lung-related cells showed excellent biocompatibility on elastin-collagen hydrogels. • Primary FDLE cells showed viability variances based on hydrogels’ elastin content. • Cells invade elastin-collagen hydrogels–influenced by cell size relative to pores. The extracellular matrix (ECM) is crucial in lung homeostasis and disease progression, with mechanical and compositional alterations linked to pathologies like lung cancer metastases, fibrosis, and respiratory distress syndrome. To better understand the lung environment-cell interaction in such diseases, this study presents a 3D hydrogel model incorporating elastin and collagen, crosslinked using energetic electrons to mimic native lung tissue. The hydrogel’s structure–property relationships, i.e., Young’s modulus and pore diameter, were characterized in response to electron irradiation and varying elastin-collagen ratios (ECRs). Mechanical tests revealed viscoelastic properties and mechanical disparities across deformation modes. Irradiation-induced crosslinking resulted in decreased pore diameters and increased stiffnesses with higher doses. ECR variations revealed slightly larger pores with increased elastin, but no discernible mechanical influence. Lung-related cells (A549, Calu-3, RLE-6TN) and primary fetal distal lung epithelial (FDLE) cells demonstrated high viability and proliferation across all ECRs. FDLE cells performed optimally on hydrogels with a 3:7 ECR, highlighting elastin’s physiological relevance. FDLE and RLE-6TN cells successfully invaded the hydrogels, influenced by cell size relative to pores. These findings offer insights into the effects of energetic electrons and compositional variations on hydrogel mechanics, laying the groundwork for a future versatile in vitro ECM model to study ECM-driven mechanisms in lung diseases.