Although gradients play an essential role in guiding the function of tissues, achieving synchronous regeneration of gradient tissue injuries remains a challenge. Here, a gradient bimetallic (Cu and Zn) ion–based hydrogel was first constructed via the one-step coordinative crosslinking of sulfhydryl groups with copper and zinc ions for the microstructure reconstruction of the tendon-to-bone insertion. In this bimetallic hydrogel system, zinc and copper ions could not only act as crosslinkers but also provide strong antibacterial effects and induce regenerative capacity in vitro. The capability of hydrogels in simultaneously promoting tenogenesis and osteogenesis was further verified in a rat rotator cuff tear model. It was found that the Cu/Zn gradient layer could induce considerable collagen and fibrocartilage arrangement and ingrowth at the tendon-to-bone interface. Overall, the gradient bimetallic ion–based hydrogel ensures accessibility and provides opportunities to regenerate inhomogeneous tissue with physiological complexity or interface tissue.

The unique properties of self-healing materials hold great potential in the field of biomedical engineering. Although previous studies have focused on the design and synthesis of self-healing materials, their application in in vivo settings remains limited. Here, we design a series of biodegradable and biocompatible self-healing elastomers (SHEs) with tunable mechanical properties, and apply them to various disease models in vivo, in order to test their reparative potential in multiple tissues and at physiological conditions. We validate the effectiveness of SHEs as promising therapies for aortic aneurysm, nerve coaptation and bone immobilization in three animal models. The data presented here support the translation potential of SHEs in diverse settings, and pave the way for the development of self-healing materials in clinical contexts.

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