TP1 - SyMBoD

In vivo: Type 2 diabetes mellitus rat models for bone defect (non-union) regeneration

T2DM is associated with compromised bone healing capacity, mainly due to impaired blood supply to the defect site. Especially for non-unions in T2DM, advanced regenerative therapies are at need to compensate for declined healing capacities. The general possibility of guiding bone regeneration purely by a mechano-biologically optimized scaffold has been demonstrated by our group. However, it is yet unknown if such principles would hold true in T2DM patients, as the underlying mechanisms that are altered bone regeneration mechanism among individuals are only partially known. The overarching goal of this SP is to elucidate the potential of using additive manufactured scaffolds with optimized biophysical and biomechanical properties for driving bone healing of non-union in T2DM population. We hypothesise that the regulation of scaffolds’ internal architecture will allow for an optimized structure encouraging blood vessel in-growth while retaining appropriate biomechanical cue to promote bone regeneration, even in metabolically challenged (i.e. T2DM) group. Initially, scaffold design will be refine based on a periodic architecture as suggested from our previous work with larger pores oriented towards the vasculature bundle to promote in-growth of nutrient artery. Scaffolds will be evaluated in a critical-sized femoral segmental defect rat model (healthy vs. T2DM) with/without soft tissue trauma to recapitulate bone defect in real-world scenario. Leveraging on combination of advanced imaging technology, tissue growth kinetics within the regenerating niche will be evaluated contributing towards validation of models developed in SP4. Based upon outcome of SP3 and 4, iterative designs of scaffolds will be evaluated and validated contributing towards the establishment of a digital platform technology enabling personalization of scaffold-guided bone regenerative therapy.