Enhancement of lung tissue regeneration and functional recovery following an acute pulmonary insult by regenerative therapy based on the use of heparan sulfate mimetics (HSM) is a promising approach for the treatment of diffuse alveolar damage (DAD), observed in acute respiratory distress syndrome (ARDS), acute exacerbations of fibrotic interstitial lung diseases or severe COVID-19 pneumonitis. The beneficial effects of HSM would be mainly related to the regeneration of the injured tissue by restructuring the destroyed matrix, protecting the cellular communicating peptides (growth factors, cytokines, chemokines), and by limiting the fibrosis usually observed during the repair process. Using of innovative approaches and models developed by 4 partners including a private one, the MAT-PL project will explore the ability of a heparan sulphate mimetic agent (OTR4132) to reduce inflammation, dysregulated angiogenesis and fibrosis, and improves the outcome of acute pulmonary injuries characteristic of DAD, thus opening a new approach for the prevention and the treatment of lung fibrosis.