Periodic Reporting for period 1 - Met4Bone (Metabolites as immunomodulatory additives for biomaterials)
Reporting period: 2020-08-01 to 2022-07-31
Biomaterials are widely used for the surgical remediation of various bone defects. However, there are still several risks associated with this treatment. The project's main goal was to develop novel biomaterials for bone regeneration with incorporated endogenous metabolites with immune regulatory properties. We applied a conceptually new approach for biomaterial development where metabolites are incorporated in biomaterials ensuring local delivery of endogenous small molecules to control cell functions. Our ambition is that fundamental knowledge and novel biomaterials generated during this project will result in new therapeutic strategies to improve the recovery of patients suffering from bone fractures.
Several LC-MS and GC-FID-based methods were established for analyzing metabolites in biological samples. The in vivo experiments were carried out to characterize the systemic alterations in the metabolite profile during bone healing. Based on the obtained results, an amino acid was identified that could be incorporated into biomaterials to promote bone tissue regeneration. Furthermore, we comprehensively characterize calcium phosphate-based biomaterials' influence on cell metabolism. The project's results have been presented at four conferences and contributed to the publication of three manuscripts. Moreover, project aims, goals, results, and MSCA were promoted in more than 20 different dissemination and outreach activities aimed at different target audiences, including researchers, students, policymakers, and school kids.
The results of the MSCA-IF project significantly contributed to the emerging field of immunomodulatory biomaterials development. We have characterized the systemic metabolism changes during bone healing and identified potential endogenous metabolites that could be incorporated into biomaterials to promote bone regeneration. Furthermore, for the first time, we have comprehensively characterized calcium phosphate-based biomaterials' influence on cell metabolism. The gained knowledge can be used for the metabolomics-driven design of biomaterials and to develop a new in vitro screening platform for biomaterials by combining in vitro cell culture models and mass spectrometry-based metabolomics readout. The project's most important socio-economic benefit would be improved bone disease patients' management and quality of life and reduced health care costs. Even though due to the fundamental nature, the project does not result in an immediate benefit for the patients, we anticipate that in a 5-10 year time frame, the result obtained in this project will lead to novel clinical treatment procedures for bone fractures. Based on preliminary and literature data, our conservative estimate is that such therapy will result in at least a 10% reduction in healing time. Considering the average bone fracture healing time of 6-8 weeks, it would result in at least 6 days' faster recovery.