Proanthocyanidin B2-Based Adenosine Supramolecular Hydrogel Promotes Tissue Regeneration in Diabetic Periodontitis

Periodontal tissue regeneration in chronic periodontitis associated with diabetes mellitus (CPDM) remains challenging. Oxidative stress and host immune dysregulation driven by hyperglycemia further exacerbate periodontal tissue destruction. Therefore, strategies that reduce oxidative stress and remodel the periodontal immune microenvironment are critical for promoting periodontal regeneration in CPDM. However, the application of supramolecular hydrogels in CPDM therapy remains largely unexplored. In this study, a novel proanthocyanidin B2-based adenosine supramolecular hydrogel-guanosine-adenosine-proanthocyanidin B2 (GAOPCB2)-was developed to enhance tissue regeneration in CPDM. Proanthocyanidin B2 exhibited potent reactive oxygen species (ROS)-scavenging and anti-inflammatory properties, promoting both HUVEC tube formation and stem cell osteogenic differentiation. The natural nucleoside adenosine further enhanced the osteogenic differentiation of stem cells. These findings indicate that the biomimetic GAOPCB2 supramolecular hydrogel possesses robust ROS-scavenging, anti-inflammatory, and osteogenic properties. Therefore, this multifunctional scaffold represents a promising platform for periodontal tissue regeneration in inflammatory environments. As demonstrated by both the in vitro and in vivo findings, the GAOPCB2 hydrogel is a promising therapeutic candidate for CPDM.