Treatment of Severe Periodontitis using Exosome-Mediated Combination Therapies: A Retrospective Cohort Study

Objectives: Exosomes are essential mediators/communicators of tissue repair via well-established mechanisms of action that include stimulatory effects on angiogenesis and cellular proliferation, differentiation, and matrix biosynthesis. This pioneering clinical study aimed to evaluate the effectiveness of exosomes specifically designed for periodontal regeneration (Periosomes) mixed with 90% anorganic bovine bone/10% collagen (ABBMC), and horizontal platelet-rich fibrin (H-PRF) for the treatment of advanced periodontal osseous defects at 6 months of healing. Materials and Methods: This retrospective cohort study analyzed the medical records of stage-III (severe) periodontitis patients (from poor to hopeless prognosis) who underwent surgery using Periosomes. Eligible patients received standardized periodontal surgery with an ABBC scaffold, H-PRF, and Periosomes with a six-month follow-up. Complete periodontal charting, including probing depth (PD), gingival margin (GM), bleeding on probing (BOP), clinical attachment loss (CAL), gingival index (GI), plaque index (PI), and tooth mobility, were assessed at baseline and six-month follow-up. Pre and post-surgery radiographs were utilized to assess defect bone fill percentages. All data were statistically analyzed for associations with age, sex, and treatment effects, applying log transformations and correlations where needed. Significance was determined at p < 0.05. Results: The study included 13 patients (8 females and 5 males) aged 29 to 73 years, with one-walled (60.9%) and two-walled (39.1%) periodontal defects. Healing was uneventful in all patients. The sites treated with Periosomes showed significant reductions in PD from baseline to 6 months in one-walled defects (8.50 ± 2.41 mm to 3.14 ± 0.77; p <0.0001) and two-walled defects (7.56 ± 1.13 mm to 3.22 ± 0.44; p <0.0001) as well as in CAL from 9.14 ± 3.01 mm to 4.79 ± 2.17 ( p <0.0001) in one-walled defects and from 7.22 ± 1.56 mm to 3.56 ± 1.01 ( p <0.0001) in and two-walled defects. Radiographic fill averaged 79.5% in one-walled and 86.5% in two-walled defects, with improved BOP values in all but one patient. Conclusions: To our knowledge, this is the first human clinical study assessing the use of exosomes in periodontal regenerative therapy. This study demonstrated that the use of exosomes/ABBMC/H-PRF was a safe and effective treatment for advanced periodontal osseous defects. Clinical relevance: This is the first human study using exosomes for the treatment of intrabony defects with poor to hopeless prognosis with results demonstrating successful radiograph bone fill and improved clinical parameters.