IADR Abstract Archives
Local Delivery to Modulate Host Response as Potential Periodontitis Treatment.
Objectives: Periodontitis is characterized by the progressive destruction of tooth-supporting alveolar bone and gingival soft tissues, which are mainly caused by chronic inflammation in response to persistent bacterial insult. Recently it has become clear that the pathogenesis of periodontitis is associated with the high ratio of pro-inflammatory M1 to anti-inflammatory M2 macrophages. The goal of this study was to promote chemotaxis of M0 (immature) or M2 (anti-inflammatory) macrophages to the inflamed site and induce M2 phenotype polarization locally. We used C-C motif chemokine ligand 2 (CCL2) known to recruit M0 macrophages, and induce differentiation of endogenous M2 macrophages.
Methods: We fabricated CCL2 controlled release microparticles (MPs) using poly (lactic-co-glycolic) acid. In vitro assessment for CCL2 release was performed and also the chemotaxis ability of CCL2. In addition, the effect of CCL2 delivery was assessed in vivo in three different ligature induced murine periodontitis models representing different clinical scenarios. We have used microCT analysis to determine alveolar bone loss, qPCR to detect inflammatory and reparative markers, TRAP, cell sorting and FACS analysis.
Results: We have successfully synthesized CCL2-loaded PLGA microparticles (MPs) and quantified its sustained release. Microcomputed tomography showed in mouse ligature models a significant reduction of alveolar bone loss in the CCL2 MP group when compared to a blank MP group and to a no treatment group. Tartrate-resistant acidic phosphatase (TRAP) staining showed significantly fewer osteoclasts in the alveolar bone area of animals in the CCL2 MP group in alveolar bone area. Quantitative polymerase chain reaction (qPCR) in the ligature model, and showed a significant decrease of inflammatory markers as well as nuclear factor kappa-Β ligand (RANKL) mRNA expression in CCL2 MP group.
Conclusions: Manipulation of endogenous M2-phenotype macrophages using CCL2 MPs decreased the M1-phenotype/M2-phenotype ratio and prevented alveolar bone loss in mouse periodontitis models. The delivery of CCL2 MPs provides a novel approach to treat periodontal disease.
Methods: We fabricated CCL2 controlled release microparticles (MPs) using poly (lactic-co-glycolic) acid. In vitro assessment for CCL2 release was performed and also the chemotaxis ability of CCL2. In addition, the effect of CCL2 delivery was assessed in vivo in three different ligature induced murine periodontitis models representing different clinical scenarios. We have used microCT analysis to determine alveolar bone loss, qPCR to detect inflammatory and reparative markers, TRAP, cell sorting and FACS analysis.
Results: We have successfully synthesized CCL2-loaded PLGA microparticles (MPs) and quantified its sustained release. Microcomputed tomography showed in mouse ligature models a significant reduction of alveolar bone loss in the CCL2 MP group when compared to a blank MP group and to a no treatment group. Tartrate-resistant acidic phosphatase (TRAP) staining showed significantly fewer osteoclasts in the alveolar bone area of animals in the CCL2 MP group in alveolar bone area. Quantitative polymerase chain reaction (qPCR) in the ligature model, and showed a significant decrease of inflammatory markers as well as nuclear factor kappa-Β ligand (RANKL) mRNA expression in CCL2 MP group.
Conclusions: Manipulation of endogenous M2-phenotype macrophages using CCL2 MPs decreased the M1-phenotype/M2-phenotype ratio and prevented alveolar bone loss in mouse periodontitis models. The delivery of CCL2 MPs provides a novel approach to treat periodontal disease.