Injectable DAT-ALG Hydrogel Mitigates Senescence of Loaded DPMSCs and Boosts Healing of Perianal Fistulas in Crohn’s Disease

Perianal fistulas (PAFs) are a severe complication of Crohn's disease that significantly impact patient prognosis and quality of life. While stem-cell-based strategies have been widely applied for PAF treatment, their efficacy remains limited. Our study introduces an injectable, temperature-controlled decellularized adipose tissue-alginate hydrogel loaded with dental pulp mesenchymal stem cells (DPMSCs) for in vivo fistula treatment. The experimental group demonstrated higher healing rates compared to surgical and DPMSCs groups, as evidenced by magnetic resonance imaging, multiplex immunohistochemical, and ELISA analyses. KEGG enrichment of differential genes suggested cellular senescence involvement in cell therapy efficacy, further confirmed by β-galactosidase staining and senescence markers (p21 and p53). Collectively, our research provides a novel therapy for PAFs and illuminates underlying mechanisms.