Anti-apoptotic effects of ruthenium nanozyme-augmented adipose stem cells accelerate cutaneous wound healing

The failure of conventional therapies for diabetic wounds, including those relying solely on stem cells or antioxidants, stems from an inability to simultaneously overcome the hostile microenvironment characterized by chronic inflammation, excessive apoptosis, and impaired regeneration.

We developed a novel combinatorial platform, Ru@SVF, by integrating ruthenium nanozymes (RuNC) with a stromal vascular fraction gel (SVF-GEL). This design moves beyond simple material addition, aiming for synergy: RuNC provides potent reactive oxygen species (ROS) scavenging and anti-apoptotic signaling, while SVF-GEL ensures sustained release of pro-regenerative growth factors (VEGF, EGF, bFGF). After thorough physicochemical characterization and biocompatibility assessment, its mechanism and efficacy were evaluated in vitro and in a diabetic rat model.

Ru@SVF exhibited excellent biocompatibility and superior functionality. In vitro, it not only robustly suppressed inflammation and mitochondrial apoptosis (via Bax/Bcl-2/Caspase-3,9 regulation) in HUVECs but also enhanced the secretion of key growth factors. In vivo, Ru@SVF treatment led to significantly accelerated wound closure, which was accompanied by reduced apoptosis, diminished inflammatory infiltration, and promoted angiogenesis, outperforming treatments with either RuNC or SVF-gel alone.

The Ru@SVF composite represents a significant advance by synergistically integrating catalytic nano-therapy with functional cell delivery. Its capacity to concurrently resolve inflammation, prevent apoptosis, and activate reparative signaling within a single platform addresses the multifaceted pathology of diabetic wounds more effectively than single-target strategies, offering a novel and promising therapeutic paradigm.