Regeneration of nasal and articular cartilage with collagen scaffolds from decellularised cartilage

• Applicants: Professor Dr. Rolf Erwin Brenner; Professor Dr. Rainer Buchholz; Professorin Dr. Nicole Rotter
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery ; Biological Process Engineering ; Otolaryngology, Phoniatrics and Audiology
• Term: from 2015 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 275046058

The treatment of cartilage defects of the nose and joints is, due to the limited regeneration capacity of cartilage, still a major therapeutic challenge. Current treatment options include the application of autologous cells and tissues for reconstruction. Limited availability, donor site morbidity as well as insufficient integration and quality of the regenerated tissue are major drawbacks of the current techniques. A promising alternative is the use of decellularised matrices of xenogenic origin, which provide cartilage-specific structural components as well as biologically active factors. Within this project we plan to investigate whether decellularised cartilage matrices from porcine nasal septal cartilage (nDECM) with and without growthfactor augmentation can enable in-situ recruitment and chondrogenic differentiation of local chondrogenic progenitor cells in order to regenerate cartilage defects. Recently, we developed a novel process for the production of nDECM. This chemical process maintains the natural collagen network while at the same time removing cellular components reliably. Therefore, the material evokes only minimally irritating reactions in-vivo. Also, we were able to identify migratory active chondrogenic progenitor cells (CPC) in nasal as well as in articular cartilage, which both had the capacity to repopulate nDECM in-vitro. We therefore aim to investigate with the help of biochemical analyses which functionally active components remain after the decellularisation process and which components are modified. Afterwards, a procedure to attach growth factors to the nDECM will be established, distribution, release and adsorption kinetics will be measured. Further, we will investigate whether attachment and migration as well as chondrogenic differentiation of CPC and bone marrow derived mesenchymal stem cells are enhanced by augmentation of the nDECM with growth factors. The influence of nDECM on macrophage-dependent inflammatory reactions and proteolytic matrix degradation will be analysed. Finally, with respect to translation to the clinic, nDECM is tested in models of nasal and joint cartilage repair. For this purpose orthotopic models of nasal cartilage defects and articular cartilage osteochondral defects in the rabbit will be used in which nDECM with and without growthfactor augmentation will be transplanted. In summary, the current project combines expertises from otorhinolaryngology, orthopedics and bioprocess engineering to establish a novel therapeutic approach for cartilage repair based on sound in-vitro and in-vivo analyses.

• DFG Programme: Research Grants