Human airway-derived extracellular matrix bioinks for the engineering of proximal airway-like constructs: A proof-of-feasibility study
Three-dimensional bioprinting offers a promising strategy for the fabrication of physiologically relevant airway constructs; however, generating hollow, anatomically accurate proximal airway structures using tissue-specific bioinks with sufficient printability and mechanical stability remains challenging. This study describes the development and characterization of biocompatible, polymer-blended human airway-derived decellularized extracellular matrix (AW-dECM) bioinks for extrusion bioprinting of structurally and mechanically relevant proximal airway-like hollow constructs. A formulation consisting of 30 mg/mL AW-dECM and nanofibrillar cellulose-alginate conjugated to RGD supported the fabrication of simple and complex hollow airway structures with elastic moduli of approximately 8-10 kPa, within the range measured for bulk proximal airway tissue. The bioinks also supported preliminary primary human airway epithelial cell viability and adhesion, as well as gene expression patterns consistent with differentiation toward mucociliary and secretory phenotypes during 28 days of air-liquid interface culture. Following subcutaneous implantation in immunocompetent rats, acellular AW-dECM polymer-blended bioinks maintained structural integrity over 30 days and were tolerated without evidence of infection or tissue necrosis, although a localized foreign body response was observed. Collectively, these findings demonstrate proof of concept for combining tissue-specific AW-dECM with commercially available printable polymers to fabricate mechanically relevant hollow airway-like constructs. This approach provides a basis for further development of advanced ex vivo airway models and regenerative airway engineering strategies.
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