Chronic obstructive pulmonary disease (COPD) is the 4th leading cause of death worldwide. Long-term respiratory support increases the life expectancy and the quality of life of COPD patients and decreases the cost of care. Currently available artificial lungs, such as Novalung’s iLA system, fail after ~ one month, mainly due to thrombus formation at the blood/machine interface. The size of current systems restrict patient mobility. We aim to create a wearable bioartificial lung (AmbuLung) for long-term application in an outpatient setting. The goals are to (1) miniaturise the existing iLA system, including the supporting technology and patient monitoring system; (2) cellularise the diffusion membrane with endothelial cells to decrease thrombogenicity and to increase the gas-exchange rate; and (3) evaluate the developed system in pre-clinical and clinical studies.The innovation includes (i) development of a novel alveolo-capillary gas-exchange membrane, functionalised with bioactive molecules and seeded with endothelial cells, ii) miniaturisation of mechanical and electronic device components, and (iii) novel vascular access system. For cellularisation, endothelial cells derived from FDA approved clinical grade human pluripotent stem cells will be used. Cell differentiation, scale-up, seeding, and maintenance will be performed using established automatable and scalable dynamic bioreactor technology. A mathematical model will be developed to predict and refine the function of this complex system in vitro and in vivo.AmbuLung will be evaluated in a pig model, assessing functionality, and non-thrombogenicity. The data will provide information required for potential clinical transfer. If successful, a clinical trial will be carried out on 5 COPD patients after acquisition of necessary regulatory approvals. Evaluation of efficacy of the intervention will be based on multidimensional health status grading.