Augmentation strategies for chondrocyte transplants for treating focal early osteoarthritic defects by amelioration of cellular senescence

• Applicant: Professor Dr. Peter Angele
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 543637479

Osteoarthritic (OA) changes within the knee joint lead to an increased failure rate and reduced clinical outcome of chondrocyte-based transplants for focal early OA defects. There are two primary reasons for the high failure rate for chondrocyte-based therapies, 1) the inflammatory environment resulting from early OA and 2) extensive chondrocyte expansion leads to loss chondrocyte phenotype and results in poor clinical outcomes upon implantation. We wish to improve clinical outcomes of matrix assisted chondrocyte transplants (MACT) using two approaches: 1) improving the transplant prior to implantation and 2) reducing inflammation within the joint. This grant seeks to develop augmentation strategies for chondrocyte transplants in the treatment of focal early OA defects. Initially, we will examine for the first time, transcriptomic shifts between focal early OA and traumatic cartilage using RNAseq analysis that will lead to the identification of genes and molecular mechanism at early disease stages. The findings will be used for the development of appropriate augmentation strategies for chondrocyte transplants for treating focal early OA. Our previous experience has demonstrated that physioxia has a beneficial effect of cartilage matrix production for mesenchymal stem cell chondrogenesis. We will investigate the effect of physioxia alone and in combination with appropriate pharmacological drugs on early OA chondrocytes to develop an appropriate strategy for improving chondrocyte transplants prior to implantation. This novel strategy would then be applied in our previously published early OA animal model to determine its efficacy in repairing focal early OA defects. Furthermore, we would also use appropriate drugs to modulate the inflammation within the joint, alongside the chondrocyte transplant. This would lead to the development of a novel approach for the treatment of focal early OA defects. The data would provide the basis for clinical translation studies in the future.

• DFG Programme: Research Grants
• Co-Investigator: Professorin Dr. Denitsa Docheva, Ph.D.