Mesenchymal Stem Cell Protection and Chondrogenic Differentiation in Tracheal Fistula Therapy via Bioactive Platinum Nanozymes

Stem cells are highly regarded in regenerative medicine for their ability to promote wound healing and tissue regeneration, exhibiting great potential for tracheal fistula (TF) repair. However, excessive reactive oxygen species (ROS) at damaged TF sites compromise stem cell viability, differentiation, and functional capacity. This challenge is particularly pronounced due to the limited intrinsic healing potential of the tracheal cartilage, which further complicates effective TF repair. Herein, we report the use of a sodium hyaluronate-platinum nanoparticle composite (SHA-PtNPs) to promote fistula healing while supporting the protection and chondrogenic differentiation of adipose-derived stem cells (ADSCs). In vitro experiments demonstrated that SHA-PtNPs significantly enhanced ADSCs’ viability, migration, ROS scavenging, and anti-inflammatory activity. Under oxidative stress conditions, SHA-PtNPs promoted chondrogenic differentiation, as evidenced by upregulated expression of SRY-box transcription factor 9 (SOX-9), collagen type II alpha 1 chain (COL2A1), and aggrecan (ACAN). Strikingly, the combination of SHA-PtNPs and ADSCs achieved 100% healing by day 14 and facilitated cartilage regeneration, as confirmed by green fluorescent protein (GFP) labeling, verifying ADSC integration. Additionally, SHA-PtNPs-ADSCs reduced ROS levels and inhibited the NF-κB/IκBα/IL-1β signaling pathway, highlighting their potent antioxidative and anti-inflammatory effects. These findings underscore the potential of bioactive platinum (Pt) nanozymes to enhance mesenchymal stem cell protection and chondrogenic differentiation in TF therapy.