Despite advances in the development of silk fibroin (SF)-based hydrogels, current methods for SF gelation show significant limitations such as lack of reversible crosslinking, use of nonphysiological conditions, and difficulties in controlling gelation time. In the present study, a strategy based on dynamic metal-ligand coordination chemistry is developed to assemble SF-based hydrogel under physiological conditions between SF microfibers (mSF) and a polysaccharide binder. The presented SF-based hydrogel exhibits shearthinning and autonomous self-healing properties, thereby enabling the filling of irregularly shaped tissue defects without gel fragmentation. A biomineralization approach is used to generate calcium phosphate-coated mSF, which is chelated by bisphosphonate ligands of the binder to form reversible crosslinkages. Robust dually crosslinked (DC) hydrogel is obtained through photopolymerization of acrylamide groups of the binder. DC SF-based hydrogel supports stem cell proliferation in vitro and accelerates bone regeneration in cranial critical size defects without any additional morphogenes delivered. The developed self-healing and photopolymerizable SF-based hydrogel possesses significant potential for bone regeneration application with the advantages of injectability and fit-to-shape molding.

Self‐healing hydrogels based on metal–ligand coordination chemistry provide new and exciting properties that improve injectability, rheological behaviors, and even biological functionalities. The inherent reversibility of coordination bonds improves on the covalent cross‐linking employed previously, allowing for the preparation of completely self‐healing hydrogels. In this article, recent advances in the development of this class of hydrogels are summarized and their applications in biology and medicine are discussed. Various chelating ligands such as bisphosphonate, catechol, histidine, thiolate, carboxylate, pyridines (including bipyridine and terpyridine), and iminodiacetate conjugated onto polymeric backbones, as well as the chelated metal ions and metal ions containing inorganic particles, which are used to form dynamic networks, are highlighted. This article provides general ideas and methods for the design of self‐healing hydrogel biomaterials based on coordination chemistry.

Three-dimensional (3D) printing is a promising technology to develop customized biomaterials in regenerative medicine. However, for the majority of printable biomaterials (bioinks) there is always a compromise between excellent printability of fluids and good mechanical properties of solids. Three-dimensional printing of soft materials based on the transition from a fluid to gel state is challenging because of the difficulties to control such transition as well as to maintain uniform conditions three-dimensionally. To solve these challenges, a facile chemical strategy for the development of a novel hydrogel bioink with shear-thinning and self-healing properties based on dynamic metal–ligand coordination bonds is presented. The noncovalent cross-linking allows easy extrusion of the bioink from a reservoir without changing of its bulk mechanical properties. The soft hydrogel can avoid deformation and collapse using omnidirectional embedding of the printable hydrogel into a support gel bath sharing the same cross-linking chemistry. After combination with photoinitiated covalent cross-linking, it enables manufacturing of hydrogel structures with complex shapes and precise location of chemically attached ligands. Living cells can be entrapped in the new printable hydrogel and survive the following in situ photo-cross-linking. The presented printable hydrogel material expands the existing tool-box of bioinks for generation of in vitro 3D tissue-like structures and direct in vivo 3D printing.