Graded Modulation of Inflammation by Metal Ion-Coordinated Peptide-Based Hydrogel Chemical Regulators Promotes Tendon-Bone Junction Regeneration.

After rotator cuff injuries, uncontrolled inflammation hinders tendon-bone junction regeneration and induces scar formation in situ. Therefore, precisely controlling inflammation could be a solution to accelerate tendon-bone junction regeneration. In this study, we synthesized a peptide-metal ion complex hydrogel with thermosensitive capability that can be used as a hydrogel chemical regulator. By the coordination complex between Mg and BMP-12, the free and coordinated Mg can be programmability released from the hydrogel. The fast release of free Mg can prevent inflammation at the early stage of injuries, according to the results of RT-qPCR and immunofluorescence staining. Then, the coordinated Mg was slowly released from the hydrogel and provided an anti-inflammatory environment for tendon-bone junction regeneration in the long term. Finally, the hydrogel demonstrated enhanced therapeutic effects in a rat rotator cuff tear model. Overall, the Mg/BMP-12 peptide-metal ion complex-based hydrogel effectively addresses the regenerative requirements of the tendon-bone junction across various stages by graded modulating inflammation.