DNA hydrogels for bone regeneration

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Clinical management of bone loss due to inflammatory and neoplastic diseases requires the development of custom-engineered materials that can reliably recapitulate the fundamental biological processes that enable bone regeneration. These processes involve osteogenic cell recruitment and differentiation, and the provision of molecular templates that promote guided mineralization of hydroxyapatite (HA). Current biomaterials are limited because their molecular properties mediate only a subset of these processes. Nanoengineered DNA have an intrinsic capacity for 3D assembly and have recently been proposed as extracellular matrix (ECM)-mimetic scaffolds. These DNA-based materials have been used for guided mineralization and soft tissue regeneration, but applications in bone regeneration have not been explored.Objective: To optimize DNA-based material, DNA hydrogel, composition to promote full bone defect repair in a rat calvaria model.Hypothesis: Stiffer DNA hydrogels and DNA hydrogels functionalized with mineralization-promoting and/or cell adhesion peptides, will upregulate osteodifferentiation and promote mineralization leading to bone repair.Collaborative team: The team at University of Toronto (Carneiro) will design and synthesize DNA hydrogels with varying composition. The team at UNESP in Brazil (Okamoto) will test the DNA hydrogels in rat calvaria bone models. Animal model results will inform the optimization of the dna hydrogels in an iterative manner, thus informing the development of biomaterials with promising bone regeneration properties. Significance: Development of DNA-based biomaterials for bone repair will lead to new breakthroughs that will improve the quality of life and lower healthcare costs for Canadians, as well as will fuel the creation of new industry and jobs. This work will provide new mechanistic insights and potential innovative therapies for bone regeneration.