Speaker
Description
Traumatic injuries to the osteochondral tissues of diarthrodial joints like the knee result in pain, functional impairment, and increased risk of developing post-traumatic osteoarthritis (PTOA) and its comorbidities. Strikingly, up to 50% of patients suffering from severe trauma to the knee joint develop PTOA within 10 years from the injury. Current treatments, based on allografts, cell-free grafts or cell-based therapies, are expensive and often with limited availability, ultimately leading to total arthroplasty to relieve the pain and restore function. However, the risk of revision of these implants is unacceptably high in young active patients, predicting a looming epidemic of revision surgeries as these implants start to fail. In this context, there is an urgent need for better therapies to treat the original lesion and prevent its progression to OA. The LUMINATE project proposes a personalized, one-stage regenerative approach to target large osteochondral lesions, thus preventing PTOA development and avoiding costly and invasive arthroplasty surgeries.
LUMINATE will develop a next level in situ bioprinting unit, called EndoFLight, which combines three multimaterial and multiscale toolheads (i.e., micro-extrusion, filamented light, jetting) to print bone and cartilage photoresins laden with allogenic and patient-derived cells directly at the site of injury. Composite photoresins will be based on photo-crosslinkable gelatin and their properties will be extensively fine-tuned to match both the processability, mechanical and biological requirements. EndoFLight will use filamented light to bioprint highly architected scaffolds with excellent cell guidance properties in seconds, resembling the natural organization of the native tissues (i.e., Benninghoff arcades) and enhancing the regeneration process. Together with micro-extrusion and jetting, EndoFLight will enable the deposition at different scales of multiple biomaterials, biomolecules (e.g., BMP2, GDF5) and cell types with light-assisted crosslinking of complex structures directly in vivo in a minimally invasive manner. EndoFLight will feature an optical sensor for segmenting the defect and predicting the correct volume of materials to deposit leveraging Artificial Intelligence and will be compatible with commercial arthroscopic instruments (i.e., rigid trocar for insertion), thus enabling a minimally invasive surgical procedure.
The EndoFLight bioprinted construct will be extensively characterized in vitro and through explant testing (in vitro and in a mouse model), while the bioprinting suite (i.e., cell-laden photoresins, EndoFLight) will be validated for usability in phantoms and for biological performance in a human-relevant preclinical large animal model, paving the way for its clinical translation after the end of the project. The exploitation of the results will be ensured through market analysis, the foundation of a spin-off that will commercialize the project results, the analysis of regulatory aspects of all components of the bioprinting suite and the adaptation of the protocols to Good Manufacturing Practices. Overall, LUMINATE will ensure wide-spread health benefits to the patients suffering from these lesions and will pave the way for enormous socioeconomic advantages for our aging society.
Acknowledgments:
This project has received funding by the European Union under the call HORIZON-HLTH-2024-TOOL-11-02 (acronym: LUMINATE, number: 101191804).
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