Masoud Hasany

Project title: 3D Printed Multifunctional Hydrogels: A Glimpse of the “Holy Grail” in Diabetic Bone Regeneration

Host Institution: Technical University of Denmark (DTU)

Host Supervisor: Dr. Mehdi Mehrali

Co-host Institution: Eindhoven University of Technology (TU/e)

Co-host Supervisor: Dr. Sandra Hofmann

Summary project: Diabetes mellitus is one of the major causes of premature mortality worldwide. Diabetes-associated complications lower the patient life quality significantly and impose a major burden on the healthcare system and labour market. Lower bone quality, higher risk of bone fracture (up to 7-fold), and long and very complex healing process (about 87% slower) are of important diabetes complications. In all diabetes complications, there is a causal loop in action in which every pathological factor extensively affects and pronounces the others. In diabetic bone, specific cellular pathways and metabolites disrupt the coupling between osteoblast and osteoclast and shift the balance toward significant bone resorption and longer bone regeneration. Despite the outstanding advances in bone tissue engineering, a handful of therapeutical scaffold-based strategies have been devised for diabetic bone treatment, which is attributed to the difficulty and complexity of the diabetic pathological condition. The grand goal of this project is to impair this loop irreversibly in different sites by offering a multifunctional 3D bioprinted hydrogel system. In this therapeutical scaffold, every constituent component will be designed, synthesized, and tailored specifically for controlling pathological factors dominant in the diabetic bone condition. More specifically, the cell encapsulated hydrogel will decrease ROS, downregulate RANKL and RAGE, increase stem cell migration to the target site, induce anti-inflammation, and provide cues suitable for osteogenesis and vasculogenesis. Finally, the successful combination of this bioink will be evaluated, for the first time, in a novel living ex-vivo diabetic bone model before moving to preclinical in vivo studies.