A Logic-Based Diagnostic and Therapeutic Hydrogel with Multistimuli Responsiveness to Orchestrate Diabetic Bone Regeneration

The regeneration of diabetic bone defects remains challenging as the innate healing process is impaired by glucose fluctuation, reactive oxygen species (ROS), and overexpression of proteinases (such as matrix metalloproteinases, MMPs). A diagnostic and therapeutic dual-logic-based hydrogel for diabetic bone regeneration is therefore developed through the design of a double-network hydrogel consisting of phenylboronic-acid-crosslinked poly(vinyl alcohol) and gelatin colloids. It exhibits a diagnostic logic to interpret pathological cues (glucose fluctuation, ROS, MMPs) and determines when to release drug in a diabetic microenvironment and a therapeutic logic to program different cargo release to match immune-osteo cascade for better tissue regeneration. The hydrogel is also shown to be mechanically adaptable to the local complexity at the bone defect. Furthermore, the underlying therapeutic mechanism is elucidated, whereby the logic-based cargo release enables the regulation of macrophage polarization by remodeling the mitochondria-related antioxidative system, resulting in enhanced osteogenesis in diabetic bone defects. This study provides critical insight into the design and biological mechanism of dual-logic-based tissue-engineering strategies for diabetic bone regeneration.

Automated summary

By designing a double-network hydrogel, a diagnostic and therapeutic approach for diabetic bone regeneration has been developed. The hydrogel exhibits logic-based drug release and mechanical adaptability, and enhances osteogenesis in diabetic bone defects by regulating macrophage polarization. This study provides critical insights into the design and biological mechanism of dual-logic-based tissue-engineering strategies for diabetic bone regeneration.