Ultrasonic Modulation of Gingival Stem Cell Mobilization
Abstract: Background: Ultrasonic scalers are routinely used in dental hygiene and periodontal therapy for removing plaque and calculus from the tooth and root surfaces. In medicine, ultrasonic tools are also used to accelerate wound healing and tissue regeneration. Studies showed that ultrasonic stimulation activates both bone and soft tissue regeneration in ligaments, joints, fractured bone, heal... read moreing of wounds, skin rejuvenation, nerve stimulation and improving the strength and elasticity of scar tissue. Stem cells residing in mature tissues, also known as mesenchymal stem cells (MSCs), may play a key role in tissue regeneration and wound healing. In the oral cavity, MSCs have been isolated from bone marrow, dental pulp, dental follicles, periodontal ligaments, mucosa, and gingiva. As the connective tissue underlying the human oral mucosa is derived from the neural crest, identification of neural markers such as nestin may be used to monitor gingival MSC populations. Aim & Hypothesis: We hypothesized that ultrasonic stimulation delivered to gingival tissues during piezoelectric scaling and root planing induces MSC mobilization. The aim of this study was to compare the expression of the MSCs marker nestin in gingival tissue after scaling and root planing (SRP) with or without the use of an ultrasonic scaler. A secondary aim of the study was to compare histological changes in the gingiva following SRP and ultrasonic scaling. Material & Methods: This study was a randomized controlled clinical pilot trial designed to investigate the stem cell mobilization potential of ultrasonic SRP. Twelve subjects diagnosed with severe periodontitis were enrolled, and 10 have completed the study. In each subject two non-adjacent teeth in the same quadrant with severe periodontitis, defined as inflammation with more than 4 mm interproximal attachment loss, were selected as study teeth. One study tooth in each subject was randomly assigned to SRP with hand instruments only, while the other study tooth received piezoelectric scaling in addition to SRP with hand instruments. Two gingival punch biopsies were taken from the interproximal papilla of each study tooth before and 1 week after the SRP. One set of biopsies was used for RNA extraction and nestin gene expression measurements with RT-PCR, while the other set of biopsies was sectioned and stained with hematoxylin and eosin for histological analysis. Results: One biopsy from a Piezo treated tooth did not provide sufficient RNA and this subject was excluded from the nestin analysis, resulting in 9 study subjects with 36 biopsies. Nestin gene expression was detected in all 36 biopsies. The mean nestin signal, expressed as nestin/GAPDH ratio, was increased both after SRP and after SRP plus Piezo compared to before treatment levels. Combination therapy with SRP and Piezo yielded the strongest nestin signal. No statistical inference was performed as this was a pilot study. Descriptive histological analysis revealed heavy mononuclear cell infiltrates that was dominated by plasma cells in the before treatment samples. After SRP a decrease in mononuclear cell infiltrates and in an increase in vascularization, neutrophils, fibroblasts and endothelial cells were seen after SRP. All clinical parameters, including PD, CAL and BOP, markedly improved from the initial visit to the final examination. Conclusion: The MSC marker nestin is readily detectable in gingival biopsies. Our data suggest that SRP with or without Piezo may induce stem cell mobilization. Histological analysis indicated a shift from chronic inflammation to acute inflammation and initiation of wound healing after SRP regardless of the use of Piezo. Thus, it may be concluded that SRP promotes gingival health not only by removing plaque and calculus but also by promoting stem cell mobilization, resolving chronic inflammation and accelerating wound healing.
Thesis (M.S.)--Tufts University, 2017.
Submitted to the Dept. of Periodontology.
Advisor: Robert Gyurko.
Committee: Bjorn Steffensen, Driss Zoukhri, and Matthew Finkelman.
Keyword: Dentistry.read less