System medical analysis for the personalized treatment of bone defects in patients with diabetes - animal models, biobanks and modeling

The vision of SyMBoD is to enable endogenous regeneration in an area of unsolved clinical need by providing an innovative system medicine-based digital technology towards a theranostic platform. We will use patients with non-union and type 2 diabetes mellitus (T2DM) as a role model to achieve a holistic understanding of system interplay that would impede regeneration and lead to substantial morbidity. Patients with a lack of endogenous bone regeneration capability (diagnostics based on omics and imaging data) will be provided with personalized (3D printed) smart implants that restore the hampered blood supply enabling cellular self-organization to regenerate defects that do not heal otherwise. SyMBoD, a strategic partnership of 5 academics and 1 SME, will embark on such an endeavor by creating synergies between the fields of system medicine and additive manufacturing, breaking boundaries across a multitude of disciplines to innovate solutions. We will focus on de novo mapping of dynamics between non-union and T2DM based on human patient data and use experimental pre-clinical models to reach a mechanistic understanding. Our previous work suggests that additive manufactured scaffolds can be mechano-biologically optimized to enhance bone re-generation. Such scaffolds address biological cascades at different length scales steering cell migration, differentiation and angiogenesis, potentially enabling regeneration of bone that would not heal otherwise, such as non-union in T2DM. In parallel, we will be developing and refining multi-scale computational models and mechano-biological optimization strategies enabling personalized, smart scaffolds for bone defect regeneration. While empowering efficient and effective design processes of personalized scaffolds with GMP level manufacturing using established industry standards, SyMBoD will, for the first time, enable a data and model integration platform for theranostic of personalized bone regenerative therapy.