Biology subjects

Noelle, H.

Publications and source records attributed to Noelle, H..

3 recordsLinked to original sources

bioRxiv2026

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

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by pathological extracellular matrix (ECM) remodeling, and a pronounced sex disparity, with approximately 70% of cases occurring in males. Despite these differences, biomaterials used to model fibrosis are commonly designed to replicate disease state or stiffness alone and rarely account for biological sex. Here, we derived sex- and disease-informed biomaterial design criteria from female and male control and IPF human lungs and translated these criteria into engineered hybrid-hydrogels containing human lung decellularized ECM (dECM) and poly(ethylene glycol) alpha methacrylate (PEGMA). Matrisome-focused reanalysis of our previously published region-resolved human lung proteomic dataset revealed region- and sex-associated differences in fibrillar collagens, matricellular proteins, and structural proteoglycans. Complementary characterization of human lung tissue further identified sex- and disease-associated differences in fibrillar collagen architecture, proteoglycan and glycosaminoglycan (GAG) remodeling, and tissue mechanics. Male IPF lungs exhibited the highest levels of disease-associated stiffening and fibrillar collagen remodeling, while female IPF tissue showed comparatively modest mechanical changes despite biochemical remodeling. These measurements established tissue-informed design criteria spanning matrix composition, architecture, and mechanics. We next evaluated whether tissue-derived properties were reproduced or retained following decellularization, processing, and incorporation of donor-derived dECM into hybrid-hydrogels. Engineered hybrid-hydrogels closely recapitulated sex- and disease-associated mechanical relationships, while COL1A1-associated abundance patterns were more consistently preserved than fibrillar collagen organization. Matricellular proteins and GAG-rich matrix remained detectable, although condition-dependent biochemical fidelity varied. This work establishes a human tissue-informed framework for engineering sex- and disease-specific biomaterials, highlighting the importance of defining sex-associated ECM properties and validating individual features following material fabrication to advance human models of IPF and other diseases with sex-associated differences in susceptibility and progression.

bioengineering↗

bioRxiv2026

Proteomic analysis reveals regional sex differences in healthy and fibrotic human lung

Biological sex has systemic effects on gene expression, cell behavior, and disease etiology. Despite these widespread effects, sex as a biological variable is understudied, particularly in chronic lung diseases. In idiopathic pulmonary fibrosis (IPF), 70% of patients are male, and male patients have overall worse survival post-diagnosis. While behavioral differences between sexes might account for some of the epidemiological differences, the contribution of underlying biology is not known. In this study, we performed regional proteomic analysis via laser-captured microdissection-coupled mass spectrometry and analyzed the data for sex-biased protein expression. We discovered that even in control lung, sex differences existed in both airway and alveolar regions. Sex differences became more pronounced in diseased regions, with sex-biased expression of diverse proteins including those involved in extracellular vesicle secretion, cellular metabolism, and extracellular matrix remodeling. These data suggest that baseline sex differences in lung proteome may contribute to sex-specific susceptibility, progression, and clinical outcomes in IPF, underscoring the need for future mechanistic and clinical studies to account for sex as a biological variable.

bioengineering↗

bioRxiv2026

Hydrogel-Embedded Precision-Cut Lung Slices Recapitulate Fibrotic Gene Expression and Enable Therapeutic Response Evaluation

Precision-cut lung slices (PCLS) retain the native cells and extracellular matrix that contribute to the structural and functional integrity of lung tissue. This technique enables the study of cell-matrix interactions and is particularly useful for pre-clinical pharmacological studies. More specifically, PCLS are widely used to model the complex pathophysiology of pulmonary fibrosis, an uncurable and progressive interstitial lung disease. Current ex vivo pulmonary fibrosis models expose PCLS to pro-fibrotic biochemical cues over a short timeframe (hours to days) and quickly collect samples for analysis due to viability concerns. This condensed timeline is a limitation to understanding chronic disease mechanisms. To extend the utility of ex vivo pulmonary fibrosis models, PCLS were embedded in engineered hydrogels and exposed to pro-fibrotic biochemical and biophysical cues. Hydrogel-embedded PCLS maintained greater than 80% total cell viability over 3 weeks in culture. Gene expression patterns in samples exposed to pro-fibrotic cues matched trends measured in human fibrotic lung tissue. Finally, treatment with Nintedanib, a Food and Drug Administration approved pulmonary fibrosis drug, moderately reduced fibroblast activation and influenced epithelial cell differentiation. Collectively, these results show that hydrogel-embedded PCLS models of pulmonary fibrosis extend our ability to study fibrotic processes ex vivo and, when applied to human tissues, present a new approach methodology for studying lung disease and treatment.

bioengineering↗