An Advanced Lung Organomimetic to Reproduce Human Airway Pathophysiology

PROJECT SUMMARYThree of top five causes of death in humans globally are lung relatedchronic obstructive pulmonary diseaseCOPDlower respiratory infections and lung cancers collectively account for over eight million deaths annuallyCurrentlyin preclinical settingstatic cell cultures and animal models are the most widely used systems for mechanistic and translational studiesHowevercritical limitations of these systems often hinder the translation of findings to humansAs suchthere is a bottleneck on clinical translationdrug developmentbiomarker discovery and mechanistic studies in pulmonary fieldparticularly COPDdue to lack of reliableand humanand disease relevant preclinical modelsHerewe propose to apply tissue microengineering principles from emergingOrgan on Chiptechnologyto develop and commercializeNext Generation Bioartificial Human Lungas an improved experimental research tool to evaluate human lung airway pathophysiology in vitroThis highly innovative microfluidic cell culture device will contain micrometer sized hollow channels inhabited by humanderivedhealthy and diseasedliving cells that will recreate multicellular architecturetissue tissue interfacesand physicochemical microenvironment of the human lung airwayand will enable reproduction of in vivo observed vascular perfusion that is crucial for providing nutrientsoxygen and growth factors to this organomimetic culture systemOur business hypothesis is that for laboratory investigators who conduct pulmonary researchthe Bioartificial Human Lung provides an experimental research tool that enables them to considerably accelerate clinical translation of their basic sciencebetter than animal modelsstaticD culture systems and even currently available microfluidic systemsby enhanced reproduction of complex human organ pathophysiology in vitroTo test this hypothesisin Phase I of the projectwe will pursue these specific aimsto demonstrate feasible fabrication and assembly of the Bioartificial Human Lungandto provide proof ofprinciple data on establishing a living multi cellular co culture containing extracellular matrix and matrix embedded stromal cells in our proposed microdeviceAt the completion of Phase Iit is our expectation that we will have the capability to consistently and reproducibly manufacture the proposed Bioartificial Human Lung and culture primary cells isolated from the human airway in this device and maintain them viable and functional for weeksThis will allow for transition to Phase II to apply the new chip technology to reproduce various lung pathologiesand refine mass scale production capabilities through reproducibility and cost minimizationUltimatelya commercial productwhich enables enhanced clinical translation in the pulmonary field and facilitates faster paced drug development and biomarker discoverywill be available as end user off the shelf product PROJECT NARRATIVELung diseases impose a significant socioeconomic burden and are a leading cause of morbidity and mortality worldwideMoreoverrespiratory medicineunlike several other therapeutic areasfaces a disappointingly low number of new approved therapieswhich is partly due to lack of reliable model systems that can accurately and disease specifically reproduce organ level complexity and pathophysiological responses of human lungOur proposed project aims to develop Next Generation Bioartificial Human Lung as a novel experimental research tool to advance clinical translation in the pulmonary field and importantlyto enable accelerated drug development pace