Impact of Combined Hdpsc-Derived Exosomes and Sdf-1 Application on Pulp Regeneration and Inflammation: Insights into Fitness, Mental Health, and Systemic Well-Being

Abstract

Objective: To explore the synergistic effects of exosomes secreted by human dental pulp stem cells (hDPSCs) and stromal cell-derived factor-1 (SDF-1) on dental pulp regeneration under inflammatory conditions, with a focus on implications for fitness, mental health, and overall systemic well-being. Methods: hDPSCs were isolated, cultured, and exposed to lipopolysaccharide (LPS) to mimic an inflammatory periodontal environment. Exosomes from these inflamed hDPSCs (I-EXO) were then isolated using ultracentrifugation with 30% sucrose density gradients. The exosomes' morphology was examined via transmission electron microscopy (TEM), and the presence of the exosomal marker CD63 was confirmed through Western blot analysis. Dental scaffolds, derived from isolated premolar teeth, facilitated semi-in-situ pulp regeneration in a subcutaneous model with nude mice. The mice were divided into three groups: a blank control (no implant), an S group (SDF-1 alone), and an I+S group (SDF-1 + I-EXO). Regenerated pulp tissue was assessed using Hematoxylin and Eosin (H&E) and Masson's trichrome staining, while immunohistochemistry was employed to evaluate the expression of CD31, a marker for neovascularization. Results: H&E staining revealed new dental pulp tissue formation in both treatment groups, with the I+S group displaying significantly more new tissue and cellular organization. Masson's trichrome staining identified blue-stained collagen fibrils across all groups, with the I+S group showing well-structured dentin and pulp-like tissue formation. Immunohistochemical analysis demonstrated a statistically significant increase in CD31-positive microvessel counts in all treated groups (p < 0.05), with the highest counts observed in the I+S group, indicating enhanced vascularization. Conclusion: The combined application of hDPSC-derived exosomes and SDF-1 under inflammatory conditions significantly enhances pulp regeneration, tissue vascularization, and the structural organization of collagen fibers and mineralized tissue. These findings suggest potential benefits for dental health, which could indirectly influence fitness levels, mental health, and systemic well-being through the reduction of chronic inflammation and improvement of oral health.