Coupled analysis of active biological processes for meniscus tissue regeneration: Experiments, statistical data processing, and datainformed in-silico modeling

• Applicants: Professorin Dr. Claudia Redenbach; Privatdozent Dr. Andreas Martin Seitz; Professor Dr. Bernd Simeon; Professorin Dr. Christina Surulescu
• Subject Area: Mathematics ; Orthopaedics, Traumatology, Reconstructive Surgery
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 465242756

Meniscal lesions are among the most common injuries of the knee joint. While tears in the vascularized, outer region of the meniscus can be treated by different suture techniques with good clinical outcomes, tears in the inner, avascular zone have only limited regeneration potential and result in partial or even total meniscectomy and a high risk of chondral damage that finally might end up in premature osteoarthritis. There is, thus, a strong need for an alternative treatment. Although artificial tissues such as polyurethane or allogenic collagen implants have been introduced in recent years as replacement materials, an adequate and durable meniscal replacement is still missing. Our overall goal is thus the development of a regenerative approach where an artificial scaffold is seeded with mesenchymal stem cells that differentiate into chondrocytes and build up a stable collagen structure. Patient-specific data of real menisci serve as target parameters for our interdisciplinary investigations. While we have made great strides towards this goal in the still running first project phase, there are several challenging issues ahead that can only be addressed in a long-term study and a corresponding second project phase. More specifically, the proposed second project phase will advance the present mathematical models, mainly diffusion-reaction-advection equations with mechanical coupling terms, their numerical simulation, and the experimental cell culturing framework to a new level. There, improvements of the in-vitro experiment can be identified and derived from exploration of the insilico model , and the experiments as well as quantitative image analysis enable in turn a more detailed and data-informed mathematical description. Control variables in this regard are not only the biological and chemical processes, but also characteristic properties of the scaffold geometry. By expanding the experimental studies and the computational model to patient-specific meniscus tissues, we propose to create a hypothetical ex-vivo framework that can provide insight into the relevant processes after an implantation with artificial replacement tissues. Our proposal combines mathematical modeling on multiple scales for a new problem class, numerical simulation in space and time with emphasis on model order reduction and parameter identification, and advanced in-vitro experiments with artificial scaffolds and native meniscus tissues. Additional expertise from quantitative image analysis strengthens our interdisciplinary approach, yielding important new data and also carrying the potential for scaffold design. Summarizing, the major outcome of this project will set up the rationale for the future design of regenerative meniscus replacement material.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2311: Robust coupling of continuum-biomechanical in silico models to establish active biological system models for later use in clinical applications - Co-design of modeling, numerics and usability
• Co-Investigators: Professor Dr. Martin Faschingbauer; Professorin Dr. Anita Ignatius