The invention provides novel compositions and methods for three-dimensional mineralization templated by synthetic scaffolds having zwitterionic mediators. The invention enables 3-D mineralization nucleation and growth of minerals in a well-controlled and defined manner. The composite materials prepared by the disclosed methods are cytocompatible and/or biodegradable and are suitable for use as medical implants in a variety of applications in skeletal tissue repair and regeneration. For example, cytocompatible zwitterionic sulfobetaine ligands are employed to facilitate 3-D mineralization of HA across covalently crosslinked hydrogels. The overall charge-neutral zwitterionic hydrogel effectively recruited oppositely charged precursor ions while overcame excessive swelling exhibited by anionic and cationic hydrogels under physiological conditions, resulting in denser and structurally well-integrated mineralized composite materials.
