In Vitro Model for Tissue Engineering of Diaphragm

• Applicant: Privatdozentin Dr. Sahar Salehi-Müller, Ph.D.
• Subject Area: Biomaterials
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 497840077

The diaphragm is a skeletal muscle structure with a large central tendon that separates the thoracic cavity from the abdomen. The major function of the diaphragm is to change the chest volume allowing the breathing process of air exchange in the lungs. Diaphragmatic hernias such as Acquired Diaphragmatic Hernia (ADH) and Congenital Diaphragmatic Hernia (CDH) are the major injuries in the diaphragm which cause difficulties in breathing due to the formation of a hole. As a musculotendinous tissue, the diaphragm has a composite structure with varying stiffness and elasticity from the muscle to the tendon side. Therefore, the engineering of a diaphragm and its muscle-tendon junction (MTJ) is technically challenging. The main challenge is due to the distinct and transitional biochemical and mechanical properties of each skeletal muscle, tendon, and MTJ in the diaphragm. This interdisciplinary project aims to address this challenge and demonstrate an in vitro model for tissue engineering of the diaphragm in the form of an adhesive patch with a graded structure. A fiber-reinforced composite structure will be made of a 3D printed microfibrous mesh and cell-laden tissue-adhesive hydrogel matrix, which will be bioprinted with various compositions. Our approach is based on the sequential layering of 3D printed mesh with porosity gradient and stiffness compatible with soft tissues and cell-laden hydrogel bioinks with various compositions and cell types. 3D printed microfibrous mesh provides the construct stability, radial variation of the mechanical properties, and contact guidance for the radial alignment of 3D printed cells. Furthermore, the hydrogel-based bioink with various composition i) support cells during the printing, ii) enable us to precisely deposit the tendon and muscle cells in the locations representative of tendon or muscle sections of the diaphragm, and iii) provide adhesiveness to wet tissues for a potential application as an adhesive patch. The project's main output will be the demonstration of an adhesive diaphragm patch for the sutureless application and treatment of diaphragmatic hernia. This approach is expected to be a powerful tool for interfacial tissue engineering and studying the development of other types of muscle-tendon junctions.

• DFG Programme: Research Grants
• International Connection: Austria, Italy
• Cooperation Partners: Professor Dr. Andreas Traweger; Professor Libero Vitiello, Ph.D.
• Co-Investigator: Professorin Dr.-Ing. Silvia Budday