02354nas a2200325   4500000000100000008004100001260001500042653004000057653002400097653002000121653001800141653003300159653002300192100001700215700001400232700001700246700001700263700001500280700001800295700001500313700002300328700001800351700001900369245012500388856007200513300001100585490000800596520141000604022001402014       2026                            d  c2026-08-0110aHuman induced pluripotent stem cell10aIntraluminal access10aLung compliance10aLung organoid10aOptical coherence tomography10aPulmonary Fibrosis1 aSatoshi Ikeo1 aYuta Tani1 aJun Sawayama1 aShogo Nagata1 aHarry Choi1 aToshio Suzuki1 aSaburo Ito1 aTetsuharu Nagamoto1 aYuki Yamamoto1 aShoji Takeuchi00aDynamic <i>in vitro</i> platform for mechanical profiling of human pulmonary aciniform organoids via intraluminal access  uhttps://www.sciencedirect.com/science/article/pii/S0142961226001183  a1240940 v3313 aReproducing the biomechanical complexity of human alveoli in vitro remains a major challenge in respiratory research. Here, we present an integrative platform combining Pulmonary Aciniform Organoids (PAcinOs) with a custom device, Dynamic Exposure and Infusion Response Observer (DENIRO), enabling structural visualization, intraluminal access and dynamic real-time biomechanical assessment. Acinar microanatomy of PAcinOs was generated by fusion of multiple spheroids of human induced pluripotent stem cell-derived lung progenitors, and cultured within DENIRO, enabling optical coherence tomography–based volumetry and microfluidic pressure control. The porous interluminal connectivity supports dynamic measurement of changes in collective volume and organoid compliance. Bleomycin treatment induced fibrotic phenotypes, including reduced volume and compliance, mimicking disease-associated mechanical stiffening. Treatment with the antifibrotic drug nintedanib yielded partial mechanical recovery, reflecting the clinically measured treatment response. This human-relevant system models dynamic three-dimensional respiratory biomechanics in vitro, capable of quantitative mechanical and pharmacological testing. Our findings demonstrate that PAcinOs in DENIRO offer a flexible platform for complex lung disease modeling, drug screening and investigation of mechanobiological tissue behavior in vitro.  a0142-9612