Lost in Granulation - Model of the Respiratory Mucosa for In Vitro Analysis of Tissue Granulation by Mechanical Stimulation

• Applicants: Professor Dr. Christian Taube, since 7/2022; Privatdozentin Dr. Anja Lena Thiebes
• Subject Area: Medical Physics, Biomedical Technology ; Pneumology, Thoracic Surgery
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 496706372

The respiratory mucosa lines the respiratory apparatus and protects the airways and lungs. After implantation of stents for treating airway stenoses and valves for treating pulmonary hyperinflation, granulation tissue can be formed which is caused by excessive cell growth. This granulation is a clinical problem as it can impair the implants’ function or cause bleeding and necessitates other invasive procedures. The development of granulation tissue varies greatly from patient to patient, and the pathomechanisms leading to its formation are not known in detail. Potential causes may be excessive mechanical stimuli or a restriction of the microcirculation by the implants, bacterial infections, patient-specific inflammatory reactions or material properties of the implants.Therefore, an in vitro model of the respiratory mucosa will be developed to investigate the mechanisms of granulation tissue formation in response to stent or valve implantation with respect to mechanical stimuli.Models will be grown from human pulmonary primary cells. A 3D culture of epithelial cells, endothelial cells, fibroblasts and macrophages will be established which resembles the physiological mucosa and allows analysis of the complex cell-cell communication. After differentiation, the samples are subjected to defined forces (pressure and friction) through specially designed bioreactors. The formation of granulation is measured and compared. The dynamically stressed samples and static controls are characterized in detail by means of histological, immunohistochemical and molecular biological evaluation. By using human primary cells, the donor-specific response can be evaluated and compared with clinical observations. In addition, clinically used therapeutics will be investigated for their effect and influence on the molecular biological processes in vitro.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Dr. Hendrik Übner, until 7/2022