Alveolar ridge preservation strategies are indicated to minimize the loss of ridge volume that typically follows tooth extraction. The aim of this systematic review was to determine the effect that socket filling with a bone grafting material has on the prevention of postextraction alveolar ridge volume loss as compared with tooth extraction alone in nonmolar teeth. Five electronic databases were searched to identify randomized clinical trials that fulfilled the eligibility criteria. Literature screening and article selection were conducted by 3 independent reviewers, while data extraction was performed by 2 independent reviewers. Outcome measures were mean horizontal ridge changes (buccolingual) and vertical ridge changes (midbuccal, midlingual, mesial, and distal). The influence of several variables of interest (i.e., flap elevation, membrane usage, and type of bone substitute employed) on the outcomes of ridge preservation therapy was explored via subgroup analyses. We found that alveolar ridge preservation is effective in limiting physiologic ridge reduction as compared with tooth extraction alone. The clinical magnitude of the effect was 1.89 mm (95% confidence interval [CI]: 1.41, 2.36; p < .001) in terms of buccolingual width, 2.07 mm (95% CI: 1.03, 3.12; p < .001) for midbuccal height, 1.18 mm (95% CI: 0.17, 2.19; p = .022) for midlingual height, 0.48 mm (95% CI: 0.18, 0.79; p = .002) for mesial height, and 0.24 mm (95% CI: -0.05, 0.53; p = .102) for distal height changes. Subgroup analyses revealed that flap elevation, the usage of a membrane, and the application of a xenograft or an allograft are associated with superior outcomes, particularly on midbuccal and midlingual height preservation.
Gene therapy using non-viral vectors that are safe and efficient in transfecting target cells is an effective approach to overcome the shortcomings of protein delivery of growth factors. The objective of this study was to develop and test a non-viral gene delivery system for bone regeneration utilizing a collagen scaffold to deliver polyethylenimine (PEI)-plasmid DNA (pDNA) [encoding platelet derived growth factor-B (PDGF-B)] complexes. The PEI-pPDGF-B complexes were fabricated at amine (N) to phosphate (P) ratio of 10 and characterized for size, surface charge, and in vitro cytotoxicity and transfection efficacy in human bone marrow stromal cells (BMSCs). The influence of the complex-loaded collagen scaffold on cellular attachment and recruitment was evaluated in vitro using microscopic techniques. The in vivo regenerative capacity of the gene delivery system was assessed in 5 mm diameter critical-sized calvarial defects in Fisher 344 rats. The complexes were ~100 nm in size with a positive surface charge. Complexes prepared at an N/P ratio of 10 displayed low cytotoxicity as assessed by a cell viability assay. Confocal microscopy revealed significant proliferation of BMSCs on complex-loaded collagen scaffolds compared to empty scaffolds. In vivo studies showed significantly higher new bone volume/total volume (BV/TV) % in calvarial defects treated with the complex-activated scaffolds following 4 weeks of implantation (14- and 44-fold higher) when compared to empty defects or empty scaffolds, respectively. Together, these findings suggest that non-viral PDGF-B gene-activated scaffolds are effective for bone regeneration and are an attractive gene delivery system with significant potential for clinical translation.
Global disruptions caused by coronavirus disease 2019 (COVID-19) affects all walks of life, and dentistry and dental education are no exceptions. Dental education uniquely blends didactic courses and hands-on clinical training seamlessly to prepare oral healthcare providers of the future. Apart from economical and access to care implications, closure of all the dental institutions in the United States affects their educational mission greatly, equally disturbing pre-doctoral and graduate training. Efforts are ongoing to continue the educational mission in dental institutions by delivering scheduled course content remotely using multiple online tools. In spite of those efforts, since clinical experiences cannot be completely replaced by any available alternative method of instruction that is 1270
This review and meta-analysis show that IL1A and IL1B genetic variations are significant contributors to CP in whites.
There exists a dire need for improved therapeutics to achieve predictable bone regeneration. Gene therapy using non-viral vectors that are safe and efficient at transfecting target cells is a promising approach to overcoming the drawbacks of protein delivery of growth factors. Here, we investigated the transfection efficiency, cytotoxicity, osteogenic potential and in vivo bone regenerative capacity of chemically modified ribonucleic acid (cmRNA) (encoding BMP-2) complexed with polyethylenimine (PEI) and made comparisons with PEI complexed with conventional plasmid DNA (encoding BMP-2). The polyplexes were fabricated at an amine (N) to phosphate (P) ratio of 10 and characterized for transfection efficiency using human bone marrow stromal cells (BMSCs). The osteogenic potential of BMSCs treated with these polyplexes was validated by determining the expression of bone-specific genes, osteocalcin and alkaline phosphatase as well as through the detection of bone matrix deposition. Using a calvarial bone defect model in rats it was shown that PEI-cmRNA (encoding BMP-2)-activated matrices promoted significantly enhanced bone regeneration compared to PEI-plasmid DNA (BMP-2)-activated matrices. Our proof of concept study suggests that scaffolds loaded with non-viral vectors harboring cmRNA encoding osteogenic proteins may be a powerful tool for stimulating bone regeneration with significant potential for clinical translation.
Conformational analyses of PRP1, a proline-rich acidic salivary protein and major component of the acquired enamel pellicle, have been carried out in solution and upon binding to two enamel prototypes, hydroxyapatite (HA) and carbonated hydroxyapatite (CHA), using Fourier transform infrared spectroscopy (FTIR) in attenuated total reflection (ATR) mode. We have shown for the first time that, in solution, large portions of PRP1 adopt the hydrated polyproline type II (PPII) helical structure in addition to the random coil structure, with the maximum absorbance of the amide I band around 1620 cm(-1). Upon binding to HA or CHA, the protein undergoes significant conformational changes, loosing a considerable portion of hydrated PPII and random coil domains with a shift in the maximum absorbance to 1666 cm(-1), indicating that a large fraction of the protein is composed of beta turns. A small fraction of PPII in a calcium-bound or anhydrous form (approximately 1642 cm(-1)) was also observed in the HA- and CHA-bound proteins, which could play a role in protein-mineral interactions. The conformational changes in PRP1 adsorbed on CHA and HA were similar in nature; however, these changes were greater in the protein bound to HA. Interestingly, these results are in agreement with protein adsorption data that show that less protein is adsorbed onto CHA than onto HA. Our results demonstrate that binding to apatitic mineral surfaces leads to major conformational changes in PRP1, which might reflect the expulsion of water and the formation of protein-mineral and/or protein-protein interactions in the adsorbed layer.
Employing cost-effective biomaterials to deliver chemically modified ribonucleic acid (cmRNA) in a controlled manner addresses the high cost, safety concerns and lower transfection efficiency that exist with protein and gene therapeutic approaches. By eliminating the need for nuclear entry, cmRNA therapeutics can potentially overcome the lower transfection efficiencies associated with non-viral gene delivery systems. Here, we investigated the osteogenic potential of cmRNA encoding BMP-9, in comparison to cmRNA encoding BMP-2. Polyethylenimine (PEI) was used as a vector to increase in vitro transfection efficacy. Complexes of PEI-cmRNA (encoding BMP-2 or BMP-9) were fabricated at an amine (N) to phosphate (P) ratio of 10 and characterized for transfection efficacy in vitro using human bone marrow stromal cells (BMSCs). The osteogenic potential of BMSCs treated with these complexes was determined by evaluating the expression of bone-specific genes as well as through the detection of bone matrix deposition. It was found that alkaline phosphatase (ALP) expression 3 days post transfection in the group treated with BMP-9-cmRNA was significantly higher than the group that received BMP-2-cmRNA treatment. Alizarin red staining and atomic absorption spectroscopy demonstrated enhanced osteogenic differentiation as evidenced by increased bone matrix production by the BMSCs treated with BMP-9-cmRNA when compared to cells treated with BMP-2-cmRNA. In vivo studies showed increased bone formation in calvarial defects treated with the BMP-9-cmRNA and BMP-2-cmRNA collagen scaffolds when compared to empty defects. The connectivity density of the regenerated bone was higher (2-fold-higher) in the group that received BMP-9-cmRNA compared to BMP-2-cmRNA. Together, these findings suggest that cmRNA activated matrix encoding osteogenic molecules can provide a powerful strategy for bone regeneration with significant clinical translational potential.
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