ß-Tricalcium Phosphate-Loaded Chitosan-Based Thermosensitive Hydrogel for Periodontal Regeneration.

The current treatment for periodontitis is aimed at resolving gingival inflammation, whilst complete periodontal tissue regeneration is not predictable, and it represents a therapeutic challenge. Injectable biomaterials hold tremendous potential in dental tissue regeneration. This study aimed to investigate the ability of an injectable thermosensitive ß-tricalcium phosphate (ß-TCP) and chitosan-based hydrogel to carry cells and promote periodontal tissue regeneration. In this study, different concentrations of ß-TCP-loaded chitosan hydrogels were prepared (0%, 2%, 4%, or 6% ß-TCP, 10% ß-glycerol phosphate, and 1.5% chitosan). The characteristics of the hydrogels were tested using rheology, a scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), degradation, and biological analyses. The new biomaterial showed a sol-gel transformation ability at body temperature and exhibited excellent chemical and physical characteristics, whilst the existence of ß-TCP enhanced the structure and the properties of the hydrogels. The SEM confirmed the three-dimensional networks of the hydrogels, and the typical rheological properties of strong gel were observed. The EDX and XRD validated the successful incorporation of ß-TCP, and similar patterns between different groups were found in terms of the FTIR spectra. The stable structure of the hydrogels under 100 °C was confirmed via DSC. Biological tests such as Alamar Blue assay and Live/Dead staining confirmed the remarkable biocompatibility of the hydrogels with pre-osteoblast MC3T3-E1 and human gingival fibroblast (HGF) cells for 14 days, and the results were validated with confocal imaging. This preliminary study shows great promise for the application of the ß-TCP-loaded thermosensitive chitosan hydrogels as a scaffold in periodontal bone and soft tissue repair.

Regenerative Potential of Granulation Tissue in Periodontitis: A Systematic Review and Meta-analysis.

Methods: Electronic searches were conducted in five databases including CENTRAL, MEDLINE, EMBASE, Web of Science, and Dentistry & Oral Sciences Source using a combination of MeSH terms and keywords up to 21 June 2022. Human studies including patients aged over 18 years with all forms of periodontitis were included. Following the risk of bias assessment, both qualitative and quantitative analyses were performed. Results: A total of twelve studies were included in qualitative analysis and six of them in quantitative analyses. The evidence suggested that cells derived from periodontitis granulation tissue have osteogenic, adipogenic, chondrogenic, neurogenic, and angiogenic differentiation abilities as well as immunoregulatory properties. In particular, CD44+, CD73+, CD90+, CD105+, and CD146+ cells were found widely in granulation tissue whilst the only meta-analysis confirmed that CD90+ cells were present in lower numbers within the granulation tissue when compared with healthy periodontal tissue (WMD = -23.43%, 95% CI -30.43 to -16.44, p < 0.00001). Conclusions: This review provided further evidence that granulation tissue from patients with periodontitis can be a potential stem cell source for regenerative therapy.

Slow magnetic relaxation of mononuclear complexes based on uncommon Kramers lanthanide ions CeIII, SmIII and YbIII.

Based on the uncommon Kramers ions CeIII, SmIII and YbIII, complexes [Ce(dppbO2)2Cl3] (1, dppbO2 = 1,2-bis(diphenylphosphino)benzene dioxide), [Sm(dppbO2)2Cl3] (2) and [Yb(dppbO2)2Cl2]Cl (3) toward single-ion magnets were obtained and fully characterized. Complexes 1 and 2 are isostructural seven-coordinate with distorted geometries between a capped trigonal prism and a capped octahedron, while 3 is six-coordinate with an octahedral geometry. Dynamic magnetic property measurements reveal their field induced slow magnetic relaxation behaviours. Fits to the temperature dependent relaxation time (τ) result in effective barriers of 38(2), 11.7(2) and 20.2(6) cm-1 for 1, 2 and 3, respectively, as well as relatively low Raman exponents (3.4(2) for 1 and 2.1(1) for 3). Ab initio calculations were then performed and they indicated that the first excited Kramers doublets (KDs) for 1, 2 and 3 lie at ca. 291, 63.5 and 137 cm-1, respectively, which are much higher than the fitting results. Combining the significant transverse magnetic moments between the ground state KDs and the first excited KDs, we thus attribute the dominant relaxation pathway of the three compounds to a Raman process, while quantum tunnelling of magnetization and direct relaxation processes may coexist. In this case, the obtained effective barriers in a high temperature region for 1 and 3 are actually the energies of the vibrational modes, which lead to second-order Raman processes with exponential temperature dependence.

Microporous elastomeric membranes fabricated with polyglycerol sebacate improved guided bone regeneration in a rabbit model.

PURPOSE: We aimed to fabricate guided bone regeneration (GBR) membrane using polyglycerol sebacate (PGS) and investigate the impact of scaffold pore size on osteogenesis. MATERIALS AND METHODS: PGS microporous membrane was fabricated by salt-leaching technique with various pore sizes. Twenty-eight male New Zealand rabbits were randomly divided into four groups: 25 µm PGS membrane, 53 µm PGS membrane, collagen membrane, and blank control group. Subsequently, standardized and critical-sized tibia defects were made in rabbits and the defective regions were covered with the specifically prepared membranes. After 4 and 12 weeks of in vivo incubation, bone samples were harvested from tibia. Micro-computed tomography scanning was performed on all bone samples. A three-dimensional visible representation of the constructs was obtained and used to compare the ratios of the ossifying volume to total construct volume (bone volume to tissue volume [BV/TV]) of each sample in different groups; then, bone samples were stained with H&E and Masson's trichrome stain for general histology. RESULTS: At 4 weeks, the BV/TV in the 25 µm PGS group was found higher than that in the 53 µm PGS and collagen groups. At 12 weeks, the bone defect site guided by the 25 µm PGS membrane was almost completely covered by the new bone. However, the site guided by the 53 µm PGS membrane or collagen membrane was covered only most of the defects and the left part of the defect was unoccupied. Histological observation further verified these findings. CONCLUSION: We thus concluded that the 25 µm PGS membrane played an advantageous role during 4-12 weeks as compared with those earlier degraded counterparts.

Delivery of antagomiR204-conjugated gold nanoparticles from PLGA sheets and its implication in promoting osseointegration of titanium implant in type 2 diabetes mellitus.

Impaired osseointegration of the implant remains the big hurdle for dental implant therapy in diabetic patients. In this study, the authors first identified that miR204 was strikingly highly expressed in the bone mesenchymal stem cells (BMSCs) of diabetic rats. Forced expression of miR204 repressed the osteogenic potential of BMSCs, while inhibition of miR204 significantly increased the osteogenic capacity. Moreover, the miR204 inhibitor was conjugated with gold nanoparticles (AuNP-antagomiR204) and dispersed them in the poly(lactic-co-glycolic acid) (PLGA) solution. The AuNP-antagomiR204 containing PLGA solution was applied for coating the surface of titanium implant. Electron microscope revealed that an ultrathin sheet was formed on the surface of the implant, and the AuNPs were evenly dispersed in the coated PLGA sheet. Cellular experiments revealed that these encapsulated AuNP-antagomiR204 were able to be released from the PLGA sheet and uptaken by adherent BMSCs. In vivo animal study further confirmed that the AuNP-antagomiR204 released from PLGA sheet promoted osseointegration, as revealed by microcomputerized tomography (microCT) reconstruction and histological assay. Taken together, this study established that miR204 misexpression accounted for the deficient osseointegation in diabetes mellitus, while PLGA sheets aided the release of AuNP-antagomiR204, which would be a promising strategy for titanium implant surface functionalization toward better osseointegration.

The influence of direct laser metal sintering implants on the early stages of osseointegration in diabetic mini-pigs.

BACKGROUND: High failure rates of oral implants have been reported in diabetic patients due to the disruption of osseointegration. The aim of this study was to investigate whether direct laser metal sintering (DLMS) could improve osseointegration in diabetic animal models. METHODS: Surface characterizations were carried out on two types of implants. Cell morphology and the osteogenic-related gene expression of MG63 cells were observed under conditions of DLMS and microarc oxidation (MAO). A diabetes model in mini-pigs was established by intravenous injection of streptozotocin (150 mg/kg), and a total of 36 implants were inserted into the mandibular region. Micro-computed tomography (micro-CT) and histologic evaluations were performed 3 and 6 months after implantation. RESULTS: The Ra (the average of the absolute height of all points) of MAO surface was 2.3±0.3 µm while the DLMS surface showed the Ra of 27.4±1.1 µm. The cells on DLMS implants spread out more podia than those on MAO implants through cell morphology analysis. Osteogenic-related gene expression was also dramatically increased in the DLMS group. Obvious improvement was observed in the micro-CT and Van Gieson staining analyses of DLMS implants compared with MAO at 3 months, although this difference disappeared by 6 months. DLMS implants showed a higher bone-implant contact percentage (33.2%±11.2%) at 3 months compared with MAO group (18.9%±7.3%) while similar results were showed at 6 months between DLMS group (42.8%±10.1%) and MAO group (38.3%±10.8%). CONCLUSION: The three-dimensional environment of implant surfaces with highly porous and fully interconnected channel and pore architectures can improve cell spreading and accelerate the progress of osseointegration in diabetic mini-pigs.

Semaphorin 3A Shifts Adipose Mesenchymal Stem Cells towards Osteogenic Phenotype and Promotes Bone Regeneration In Vivo.

Adipose mesenchymal stem cells (ASCs) are considered as the promising seed cells for bone regeneration. However, the lower osteogenic differentiation capacity limits its therapeutic efficacy. Identification of the key molecules governing the differences between ASCs and BMSCs would shed light on manipulation of ASCs towards osteogenic phenotype. In this study, we screened semaphorin family members in ASCs and BMSCs and identified Sema3A as an osteogenic semaphorin that was significantly and predominantly expressed in BMSCs. The analyses in vitro showed that the overexpression of Sema3A in ASCs significantly enhanced the expression of bone-related genes and extracellular matrix calcium deposition, while decreasing the expression of adipose-related genes and thus lipid droplet formation, resembling a BMSCs phenotype. Furthermore, Sema3A modified ASCs were then engrafted into poly(lactic-co-glycolic acid) (PLGA) scaffolds to repair the critical-sized calvarial defects in rat model. As expected, Sema3A modified ASCs encapsulation significantly promoted new bone formation with higher bone volume fraction and bone mineral density. Additionally, Sema3A was found to simultaneously increase multiple Wnt related genes and thus activating Wnt pathway. Taken together, our study here identifies Sema3A as a critical gene for osteogenic phenotype and reveals that Sema3A-modified ASCs would serve as a promising candidate for bettering bone defect repair.

Semaphorin 3A-modified adipose-derived stem cell sheet may improve osseointegration in a type 2 diabetes mellitus rat model.

Although titanium (Ti) implants are considered to be an optimal choice for the replacement of missing teeth, it remains difficult to obtain sufficient osseointegration in patients with type 2 diabetes mellitus (T2DM). The present study aimed to investigate whether adipose-derived stem cells (ASCs) may be used to improve Ti implant osseointegration in T2DM conditions with the addition of semaphorin 3A (Sema3A), a recently identified osteoprotective protein. Cell morphology was observed using a scanning electron microscope. Cell proliferation was determined using Cell Counting Kit­8. Osteogenic differentiation was confirmed by the staining of alkaline phosphatase, collagen secretion and calcium deposition. An in vivo evaluation was performed in the T2DM rat model, which was induced by a high­fat diet and a low­dose streptozotocin intraperitoneal injection. A Sema3A­modified ASC sheet was wrapped around the Ti implant, which was subsequently inserted into the tibia. The rats were then exposed to Sema3A stimulation. The morphology and proliferation ability of ASCs remained unchanged; however, their osteogenic differentiation ability was increased. Micro­computed tomography scanning and histological observations confirmed that formation of new bone was improved with the use of the Sema3A-modified ASCs sheet. The present study indicated that the Sema3A­modified ASCs sheet may be used to improve osseointegration under T2DM conditions.