Translating Sex- and Disease-Informed Design Criteria from Human Lung into Engineered Biomaterials

Male idiopathic pulmonary fibrosis lungs show the highest disease-associated stiffening and fibrillar collagen remodeling, establishing sex- and disease-specific ECM design targets from human lung tissue.

• Why it matters: Most fibrosis biomaterials model disease state or stiffness without accounting for biological sex, despite IPF’s strong male predominance and sex-linked ECM remodeling.
• What they did: The authors reanalyzed a region-resolved human lung proteomics dataset by matrisome features and characterized female and male control and IPF lung tissue for collagen architecture, proteoglycan/GAG remodeling, and mechanics, then translated tissue-informed criteria into PEGMA–dECM hybrid hydrogels.
• The result: Hybrid hydrogels closely recapitulated sex- and disease-associated mechanical relationships, preserved COL1A1-associated abundance patterns more consistently than fibrillar collagen organization, and retained detectable matricellular proteins and GAG-rich matrix with condition-dependent biochemical fidelity.

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