Healing processes are characterized by dynamic microenvironments, where local and temporal control of physicochemical cues orchestrate tissue self-organization. Alginate hydrogels can mimic such microenvironments and allow spatial control of hydrogel stiffness, degradability and presentation of polymer-bound biomolecules. We hypothesize that matrix spatial patterning of biophysical and biochemical cues modulate cell metabolic activity and proliferation, soft and mineralized tissue organization and crosstalk with immune molecules. We aim to use engineered 3D matrices with tunable biophysical and biochemical, in combination with a minimally invasive in vivo model, to test this hypothesis and thereby improve our understanding of physiological bone regeneration and pathological alterations.