Biomaterials for Periodontal Regeneration.

As a widespread chronical disease, periodontitis progressively destroys tooth-supporting structures (periodontium) and eventually leads to tooth loss. Therefore, regeneration of damaged/lost periodontal tissues has been a major subject in periodontal research. During periodontal tissue regeneration, biomaterials play pivotal roles in improving the outcome of the periodontal therapy. With the advancement of biomaterial science and engineering in recent years, new biomimetic materials and scaffolding fabrication technologies have been proposed for periodontal tissue regeneration. This article summarizes recent progress in periodontal tissue regeneration from a biomaterial perspective. First, various guide tissue regeneration/guide bone regeneration membranes and grafting biomaterials for periodontal tissue regeneration are overviewed. Next, the recent development of multifunctional scaffolding biomaterials for alveolar bone/periodontal ligament/cementum regeneration is summarized. Finally, clinical care points and perspectives on the use of biomimetic scaffolding materials to reconstruct the hierarchical periodontal tissues are provided.

Delivering Multifunctional Peptide-Conjugated Gene Carrier/miRNA-218 Complexes from Monodisperse Microspheres for Bone Regeneration.

MicroRNAs (miRNAs) play a pivotal role in regulating gene expression and are considered new molecular targets in bone tissue engineering. However, effective delivery of miRNAs to the defect areas and transfection of the miRNAs into osteogenic progenitor cells has been an obstacle in the application. In this work, miRNA-218 (miR-218) was used as an osteogenic miRNA regulator, and a multifunctional peptide-conjugated gene carrier poly(lactide-co-glycolide)-g-polyethylenimine-b-polyethylene glycol-R9-G4-IKVAVW (PPP-RGI) was developed to condense with miR-218 to form PPP-RGI/miR-218 complexes that were further encapsulated into monodisperse injectable microspheres for enhanced bone regeneration. The PPP-RGI was synthesized via conjugating R9-G4-IKVAVW (RGI), a multifunctional peptide, onto poly(lactide-co-glycolide)-g-polyethylenimine-b-polyethylene glycol (PPP). A microfluidic and synchronous photo-cross-linking process was further developed to encapsulate the PPP-RGI/miR-218 complexes into monodisperse gelatin methacryloyl microspheres. The monodisperse microspheres controlled the delivery of PPP-RGI/miR-218 to the designated defect site, and PPP-RGI facilitated the transfection of miR-218 into osteogenic progenitor cells. An in vivo calvarial defect model showed that the PPP-RGI/miR-218-loaded microspheres significantly enhanced bone tissue regeneration. This work provides a novel approach to effectively deliver miRNA and transfect targeting cells in vivo for advanced regenerative therapies.

Low-intensity pulsed ultrasound upregulates osteogenesis under inflammatory conditions in periodontal ligament stem cells through unfolded protein response.

BACKGROUND: In periodontal tissue engineering, periodontal ligament stem cells derived from patients with periodontitis (P-PDLSCs) are among the most promising and accessible stem cells for repairing disrupted alveolar bone and other connective tissues around the teeth. However, the inflammatory environment influences the osteogenic differentiation ability of P-PDLSCs. We examined low-intensity pulsed ultrasound (LIPUS) in P-PDLSCs in vitro and in rats with experimental periodontitis to determine whether LIPUS can enhance the osteogenic differentiation of stem cells. MATERIALS AND METHODS: P-PDLSCs were harvested and isolated from the periodontal tissues around the teeth of periodontitis patients, and healthy PDLSCs (H-PDLSCs) were obtained from tissues around healthy teeth. After validation by flow cytometry analysis, the P-PDLSCs were cultured in osteogenic medium either pretreated with the endoplasmic reticulum stress (ERS) inhibitor 4-phenyl butyric acid (4-PBA) or not pretreated and then treated with or without LIPUS (90 mW/cm2, 1.5 MHz) for 30 min per day. Cell viability, ERS marker expression, and osteogenic potential were determined between the different treatment groups. LPS-induced H-PDLSCs were used to mimic the inflammatory environment. In addition, we established a model of experimental periodontitis in rats and used LIPUS and 4-PBA as treatment methods. Then, the maxillary bone was collected, and micro-CT and histology staining methods were used to detect the absorption of alveolar bone. RESULTS: Our data showed that the P-PDLSCs derived from periodontitis tissues were in a more pronounced ERS state than were the H-PDLSCs, which resulted in the former being associated with increased inflammation and decreased osteogenic ability. LIPUS can alleviate ERS and inflammation while increasing the bone formation capacity of P-PDLSCs in vivo and in vitro. CONCLUSIONS: LIPUS may be an effective method to enhance the outcome of periodontal tissue engineering treatments of periodontitis by suppressing inflammation and increasing the osteogenic differentiation of P-PDLSCs through the unfolded protein response pathway, and more detailed studies are needed in the future.

Metformin prevents against oxidative stress-induced senescence in human periodontal ligament cells.

Periodontitis is a chronic infectious disease involving periodontal tissues. Periodontal ligament cells (PDLCs) play an important role in the regeneration of periodontal tissue. However, senescent PDLCs have an impeded regenerative potential. Metformin has been reported to prevent senescence at both the cellular and individual levels. The objectives of the present study were to evaluate the effects of metformin on cellular senescence in human PDLCs (hPDLCs) under oxidative stress. hPDLCs were pretreated with metformin, followed by H2O2 exposure. The cell viability, oxidative damage, cellular senescence and osteogenic potential were detected. To inhibit autophagy, hPDLCs were treated with 3-methyladenine before metformin treatment. The present study revealed that H2O2 exposure inhibits proliferation, increased lysosomal ß-galactosidase activity, augments reactive oxidative species (ROS) accumulation, elevates the oxidative damage, stimulates the expression of senescence-related genes and impedes the activity of the osteogenic differentiation of hPDLCs. Metformin pretreatment could partly reverse the detrimental influences of H2O2 on hPDLCs. Moreover, metformin could stimulate autophagy, whereas the inhibition of autophagy with 3-methyladenine reversed the anti-senescence effects of metformin on hPDLCs under oxidative stress. The present study manifested that metformin could alleviate oxidative stress-induced senescence via stimulating autophagy and could partially recover the osteogenic potential of hPDLCs, possibly providing a reference for the discovery of periodontal treatment from the perspective of antisenescence.

Contribution of Interleukin-10-592 (-590, -597) C>A Polymorphisms to Periodontitis Susceptibility: An Updated Meta-Analysis Based on 18 Case-Control Studies.

INTRODUCTION: The association between interleukin-10- (IL-10-) 592 (-590, -597) C>A polymorphisms and susceptibility to chronic or aggressive periodontitis (CP or AgP) is conflicting. This meta-analysis is aimed at quantitatively estimating the association. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and WANFAN were searched for studies performed prior to January 31, 2018, to collect data for our research. Meta-analysis was performed using RevMan 5.3 or STATA 14.0. RESULTS: In total, 18 studies that met our criteria were included. Overall or HWE subgroup analysis of individuals with this polymorphism revealed that in terms of CP susceptibility, there was a significant difference between case groups and control groups in the A allele versus C allele model (OR = 1.38, 95% CI = 1.17-1.64 or OR = 1.38, 95% CI = 1.12-1.70), in the AA versus CC+CA model (OR = 1.49, 95% CI =1.06-2.10 or OR = 1.42, 95% CI = 1.13-1.78), and in the CC versus CA+AA model (OR = 0.69, 95% CI = 0.51-0.92 or OR = 0.68, 95% CI = 0.49-0.93); subgroup analysis based on a nonsmoking population also displayed significance in the A allele versus C allele model (OR = 1.43, 95% CI = 1.15-1.79) and CC versus CA+AA model (OR = 0.62, 95% CI = 0.44-0.87). For this polymorphisms and AgP susceptibility, our analyses revealed a significant association in both the A allele versus C allele model (OR = 1.29, 95% CI = 1.01-1.63) and the AA versus CC+CA model (OR = 1.93, 95% CI = 1.30-2.89); subgroup analysis based on Caucasian or nonsmoking populations showed significant differences in the AA versus CC+CA model (OR = 6.29, 95% CI = 1.78-22.21 or OR = 3.24, 95% CI = 1.59-6.61). CONCLUSIONS: IL-10-592 (-590, -597) A allele and the associated AA genotype may be risk factors for the onset of CP or AgP-particularly for the AA genotype and the increased risk of AgP in Caucasian or nonsmoking populations. Conversely, the CC genotype may act as a protective factor against the onset of CP.

Effects of Papacarie on children with dental caries in primary teeth: a systematic review and meta-analysis.

BACKGROUND: Caries in primary teeth hinder the child to bite and chew and influence their development. Papacarie has the characteristics of selective removal of decayed tissue and can preserve healthy dentine to the maximum, but its efficiency has not been critically evaluated compared to conventional method. AIM: This review is aiming at comparing the Papacarie and traditional method in caries removal in primary dental caries with children. DESIGN: Comprehensive literature searching at PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science to January 2018. RESULTS: Six randomized controlled trials (RCTs) and four prospective controlled clinical trials (CCTs) were included. The microbiota in caries dentine was significantly reduced using the Papacarie treatment (MD = 0.57, 95% CI 0.04 to 1.09, P = 0.03), and the anxiety feeling declined more in the Papacarie group (MD = -1.01, 95% CI -1.72 to -0.30, P < 0.005). There was a greater 200.79 (MD = 200.79, 95%CI 152.50 to 249.09, P < 0.00001) increase in time taken for the Papacarie treatment compared with the conventional method. CONCLUSION: Papacarie exerts a positive effect in reducing the bacteria and decreases the pain during caries removal in primary teeth although it costed a longer treatment time compared with the conventional method.