We report here an injectable, self-healing coordinative hydrogel with antibacterial and angiogenic properties for diabetic wound regeneration. The hydrogel was prepared by coordinative cross-linking of multi-arm thiolated polyethylene glycol (SH-PEG) with silver nitrate (AgNO3). Due to the dynamic nature of Ag-S coordination bond and bacteria-killing activity of Ag+, the resultant coordinative hydrogel featured self-healing, injectable and antibacterial properties. In this study, we synchronously loaded an angiogenic drug, desferrioxamine (DFO), in the coordinative hydrogel during cross-linking. We finally obtained a multifunctional hydrogel that is manageable, resistant to mechanical irritation, antibacterial and angiogenic in vitro. Our in vivo studies further demonstrated that the injectable self-healing hydrogel could efficiently repair diabetic skin wounds with low bacteria-infection and enhance angiogenic activity. In short, besides diabetic skin wound repair, such dynamic multifunctional hydrogel scaffolds would show great promise in the regeneration of different types of exposed wounds, in particular, in situations with disturbed physiological functions, high risk of bacterial infections, and external mechanical irritation.

Introducing hydration layers to hydrogel microspheres (HMs) by coating the surface with liposomes can effectively reduce friction. However, the lubrication can be inactivated when the surface coatings are damaged. To endow HMs with the ability to form self-renewable hydration layers and maintain cellular homeostasis, rapamycin-liposome–incorporating hyaluronic acid–based HMs (RAPA@Lipo@HMs) were created using microfluidic technology and photopolymerization processes. The RAPA@Lipo@HMs improve joint lubrication by using a smooth rolling mechanism and continuously exposing liposomes on the outer surface to form self-renewable hydration layers via frictional wear. In addition, the released autophagy activator (rapamycin)–loaded cationic liposomes can target negatively charged cartilage through electrostatic interactions and maintain cellular homeostasis by increasing autophagy. Furthermore, the in vivo data showed that the RAPA@Lipo@HMs can alleviate joint wear and delay the progression of osteoarthritis. The RAPA@Lipo@HMs can provide efficient lubrication and potentially alleviate friction-related diseases such as osteoarthritis.