A synthetic, three-dimensional bone marrow hydrogel [preprint]

Three-dimensional (3D) synthetic hydrogels have recently emerged as desirable in vitro cell culture platforms capable of representing the extracellular geometry, elasticity, and water content of tissue in a tunable fashion. However, they are critically limited in their biological functionality. Hydrogels are typically decorated with a scant 1-3 peptide moieties to direct cell behavior, which vastly underrepresents the proteins found in the extracellular matrix (ECM) of real tissues. Further, peptides chosen are ubiquitous in ECM, and are not derived from specific proteins. We developed an approach to incorporate the protein complexity of specific tissues into the design of biomaterials, and created a hydrogel with the elasticity of marrow, and 20 marrow-specific cell-instructive peptides. Compared to generic PEG hydrogels, our marrow-inspired hydrogel improves stem cell differentiation and proliferation. We propose this tissue-centric approach as the next generation of 3D hydrogel design for applications in tissue engineering