Comparing the clinical effects of local administration of minocycline ointment and doxycycline solution in the treatment of acute periodontal abscesses: a retrospective clinical study.

PURPOSE: The objective of this retrospective clinical study was to provide evidence supporting the adjunctive local application of doxycycline solution or minocycline ointment, in conjunction with drainage, for the treatment of acute periodontal abscesses. METHODS: The study included 63 patients who had received treatment for acute periodontal abscesses through drainage supplemented with 1 of 3 types of adjunctive medications during their initial visit (visit 1; baseline): 1) saline irrigation (the control group), 2) 2% minocycline ointment (the TM group), or 3) 300 mg/mL doxycycline irrigation (the TD group). The same adjunctive medication was administered at visit 2, which took place 1 week after visit 1. Probing depth (PD), bleeding on probing (BOP), plaque index, gingival recession, clinical attachment level, and tooth mobility were clinically evaluated at visits 1, 2, and a third visit (visit 3; 4 weeks after visit 1). Statistical significance was considered to be indicated by P values <0.05. RESULTS: By visit 3, all clinical indices and tooth mobility had significantly decreased in each group. At this visit, PD and BOP on the abscess side were significantly lower in the TM and TD groups compared to the control group. The TD group showed a significantly greater improvement than the TM group, with mean PD reductions of 1.09 mm in the control group, 1.88 mm in the TM group, and 2.88 mm in the TD group. Similarly, mean BOP reductions were 45% in the control group, 73.02% in the TM group, and 95.45% in the TD group. CONCLUSIONS: Local and adjunctive administration of doxycycline and minocycline in combination with drainage exhibited clinical advantages over drainage alone in improving PD and BOP. Notably, a doxycycline solution of 300 mg/mL was more effective than a 2% minocycline ointment.

Injectable contraceptive Depo-Provera induces erratic beating patterns in patient-specific induced pluripotent stem cell-derived cardiomyocytes with long QT syndrome type 2.

BACKGROUND: Long QT syndrome type 2 (LQT2) is caused by pathogenic variants in KCNH2. LQT2 may manifest as QT prolongation on an electrocardiogram and present with arrhythmic syncope/seizures and sudden cardiac arrest/death. Progestin-based oral contraceptives may increase the risk of LQT2-triggered cardiac events in women. We previously reported on a woman with LQT2 and recurrent cardiac events temporally related and attributed to the progestin-based contraceptive medroxyprogesterone acetate ("Depo-Provera" [Depo] MilliporeSigma, Catalog# 1378001, St. Louis, MO). OBJECTIVE: The purpose of this study was to evaluate the arrhythmic risk of Depo in a patient-specific induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model of LQT2. METHODS: An iPSC-CM line was generated from a 40-year-old woman with p.G1006Afs∗49-KCNH2. A CRISPR/Cas9 gene-edited/variant-corrected isogenic control iPSC-CM line was generated. FluoVolt (Invitrogen, F10488, Waltham, MA) was used to measure the action potential duration after treatment with 10 µM Depo. Erratic beating patterns characterized as alternating spike amplitudes, alternans, or early afterdepolarization-like phenomena were assessed using multielectrode array (MEA) after 10 µM Depo, 1 µM isoproterenol (ISO), or combined Depo + ISO treatment. RESULTS: Depo treatment shortened the action potential duration at 90% repolarization of G1006Afs∗49 iPSC-CMs from 394 ± 10 to 303 ± 10 ms (P < .0001). Combined Depo + ISO treatment increased the percentage of electrodes displaying erratic beating in G1006Afs∗49 iPSC-CMs (baseline: 18% ± 5% vs Depo + ISO: 54% ± 5%; P < .0001) but not in isogenic control iPSC-CMs (baseline: 0% ± 0% vs Depo + ISO: 10% ± 3%; P = .9659). CONCLUSION: This cell study provides a potential mechanism for the patient's clinically documented Depo-associated episodes of recurrent ventricular fibrillation. This in vitro data should prompt a large-scale clinical assessment of Depo's potential proarrhythmic effect in women with LQT2.

Periodontal probing on digital images compared to clinical measurements in periodontitis patients.

The aim of the study was to compare the supra-alveolar gingival dimension (GD) and the clinical pocket probing depth (PD) by combining data from an intraoral scanner (IOS) and cone-beam computed tomography (CBCT) and identify the clinical features affecting the clinical PD. 1,071 sites from 11 patients were selected for whom CBCT, IOS images, and periodontal charts were recorded at the same visit. CBCT and IOS data were superimposed. GD was measured on cross-sectional images of the probed sites. The level of agreement and correlation between GD and PD were assessed for the entire population and within groups (treated vs untreated, bleeding on probing [BOP] vs no BOP, and PDs of 0-3 mm vs 4-5 mm vs ≥ 6 mm). The mean [± SD] difference between GD and PD was 0.82 [± 0.69] mm, and they were positively correlated (r = 0.790, p < 0.001). The correlations between GD and PD were stronger for untreated sites, sites with BOP, and sites with a larger PD. Within the limitations of this study, the similarity between GD and PD may suggest a possible tendency of overestimation when recording PD.

Immediate loading protocols increase the risk of failure of implants placed by fully guided surgery in partially edentulous jaws: A randomized clinical trial.

AIM: To compare the 1-year outcomes of immediate loading (IL) and delayed loading (DL) protocols for implants placed by fully guided surgery in partially edentulous jaws. MATERIALS AND METHODS: This study included 72 patients who received implant surgery with either IL (93 implants, 36 patients) or DL (94 implants, 26 patients). A prefabricated provisional prosthesis was delivered immediately for the IL group (86 implants, 32 patients) with the exception of 4 subjects in whom an initial torque of >20 Ncm and an implant stability quotient of >65 were not achieved, while all DL-group implants were loaded after 3 months. The 1-year implant survival rate estimated by intention-to-treat (ITT) and per-protocol (PP) analyses, and the marginal bone loss (MBL) estimated by cone-beam computed tomography were statistically evaluated (p < 0.05). RESULTS: The survival rate in the DL group was 100% at both patient and implant levels. With only 26 subjects with 78 implants surviving in the IL group, the survival rates were 69.4% and 83.4% at the patient and implant levels, respectively, in the ITT analysis, and 78.1% and 90.2% in the PP analysis. All intergroup differences in survival rates were statistically significant (p < 0.01). MBL was less than 0.1 mm in both groups (p > 0.05). CONCLUSIONS: IL for implants placed by fully guided surgery in the partially edentulous jaws increased the probability of failure compared to 3-month DL. Regardless of when loading occurred, marginal bone levels remained stable.

Adjunctive use of metronidazole-minocycline ointment in the nonsurgical treatment of peri-implantitis: A multicenter randomized controlled trial.

BACKGROUND: Clinical benefits of local antibiotics as an adjunct to nonsurgical treatment of peri-implantitis have been widely reported, but most studies evaluated incipient peri-implantitis lesions, and showed incomplete treatment success rates. PURPOSE: To assess the clinical and microbiological outcomes of administering metronidazole in combination with minocycline as a local adjunct to the nonsurgical treatment of peri-implantitis. MATERIALS AND METHODS: One hundred and eighteen subjects with peri-implantitis were recruited in a four-center, three-arm, and 12-week randomized controlled trial. Subjects were randomly assigned to receive one of the following treatments: (a) MM-mechanical debridement + metronidazole-minocycline ointment, (b) MC-mechanical debridement + minocycline ointment, (c) NST-mechanical debridement only. RESULTS: Except for four subjects who was excluded during the trial, a total of 114 patients with 114 implants (one implant per each patient) finally completed the trial and were included in the analyses. Multivariate logistic regression analysis revealed that the treatment success rates (absence of bleeding or suppuration on probing, and sites showing pocket probing depth [PPD] ≥5 mm) on at 12 weeks were higher in MM-group patients (31.6%) and MC-group patients (20.5%) compared to NST-group patients (2.7%; p = 0.011 and 0.040, respectively). Subjects with deepest PPD ≥8 mm showed a significant difference in the PPD reduction between MM and MC groups at week 4 (p = 0.025) and week 12 (p = 0.047). Detection ratio of Tannerella forsythia was significantly lower for MM group than MC group (p = 0.038). CONCLUSIONS: Additive use of either MM or MC results in significantly higher treatment success rates compared to sole mechanical debridement in nonsurgical treatment of peri-implantitis. Moreover, MM contributes to a significantly greater reduction in the PPD compared to MC in deep pockets (cris.nih.go.kr KCT0004557).

Alveolar ridge regeneration in two-wall-damaged extraction sockets of an in vivo experimental model.

AIM: To determine the healing outcome following grafting with deproteinized porcine bone mineral (DPBM) with or without collagen membrane coverage in two-wall (both buccal and lingual)-damaged extraction sockets. MATERIALS AND METHODS: Distal roots of three mandibular premolars in six beagle dogs were extracted, and the whole buccal and lingual bony walls were surgically removed. Three treatment protocols were then applied according to the following group allocation: no graft (None), grafting DPBM (BG), and grafting DPBM with coverage by a collagen membrane (BG + M). Two observational periods (2 and 8 weeks) were used with the split-mouth design, and quantitative and qualitative analyses were performed by microcomputed tomography and histology. RESULTS: The dimensions of the alveolar ridge at both grafted sites (BG and BG + M) remained similar to those of the pristine ridge in the histologic and radiographic analyses, whereas the ungrafted sites (None) collapsed both vertically and horizontally. Both grafting protocols produced substantial bony regeneration, but the addition of a covering membrane enhanced the proportion of mineralized tissue within the augmented area, and the BG + M group also showed a significantly larger area of regenerated ridge than the None group (p < .05). CONCLUSIONS: Bone grafting with collagen membrane can maintain the alveolar ridge dimensions with substantial bone regeneration in a two-wall-damaged extraction socket.

Do periodontal defects affect periodontal inflammation and destruction? Histological/microbiological changes and gene expression profiles of a pilot study in beagle dogs.

BACKGROUND: The present study focused on the inflammatory disease progress after periodontal defect induction and aimed to specifically determine periodontal tissue responses following dental plaque accumulation by ligatures on a site with/without standardized periodontal defect induction. METHODS: After 1 month from extraction of the adjacent teeth, semi-circumferential defects were surgically created in the unilateral second and fourth premolars (test group), whereas no defects were being induced at the contralateral sites (control group). One week later, silk was used to ligate the tooth cervix at both sites to encourage the accumulation of dental plaque. Four weeks later, the tissue samples were collected for histological/histomorphometric and microarray analysis. Microbiological analysis was performed before defect induction and at ligatures, and after 4 weeks of dental plaque accumulation. RESULTS: Remarkable inflammation was clinically and histologically observed in both groups after plaque accumulation, and the intrabony type of periodontal defect exaggerated inflammatory cell infiltration into the connective tissue layer. Expression of genes related to inflammation such as IL-1 was highly up-regulated in test sites. However, these inflammatory infiltrations did not invade to a boundary of periodontal ligament and connective tissue attachment in both groups, and histomorphometric results corresponds to these observational results. Bacterial findings also showed no significant differences in detected microbiome compositions between control and test groups at three-time points. CONCLUSION: Intrabony defect might exaggerate the plaque-induced inflammation in the aspect of inflammatory cell infiltration and the related gene expression, but both dental plaque and the pre-existing periodontal defect negligibly disrupt periodontal attachment and the underlying alveolar bone.

Periodontal healing by periodontal ligament fiber with or without cells: A preclinical study of the decellularized periodontal ligament in a tooth replantation model.

BACKGROUND: The periodontal ligament (PDL) comprises cells embedded in the extracellular matrix (ECM) and is required for periodontal healing upon tooth transplantation. However, the extent to which the ECM contributes to periodontal regeneration remains unknown. This study aimed to evaluate effects of separate PDL matrix without cells on periodontal healing. METHODS: Mandibular premolars extracted from six beagle dogs, were 1) left untreated, 2) decellularized, or 3) surface planed. Cytologic, histologic, scanning electron microscopy, and transmission electron microscopy analyses confirmed that detergents could be used to decellularize the PDL. An additional circumferential osteotomy was performed to replant dental roots into extraction sockets. Radiography and histology were used to evaluate periodontal regeneration 8 weeks later, with the data adjusted for multiple testing. RESULTS: In pristine extraction sites, total root resorption (P = 0.034), recovered PDL space (P = 0.012), and new cementum (P = 0.004) were greater in untreated teeth than in roots that underwent surface planing. There were no significant changes when comparing untreated teeth with teeth having a decellularized PDL (P = 0.081, P = 0.170, and P = 1.000, respectively), and decellularized teeth showed significant increase of new cementum compared to surface planed teeth (P = 0.048). In the defect area, only the recovered PDL space (P = 0.034) was greater in untreated teeth when comparing with denuded roots. CONCLUSION: These results suggest that in addition to untreated PDL, decellularized PDL also partially supports reattachment (particularly cementogenesis) in pristine extraction sites but not in defect areas.

Histologic analysis following grafting of damaged extraction sockets using deproteinized bovine or porcine bone mineral: A randomized clinical trial.

OBJECTIVES: This study histologically analyzed biopsy samples obtained from sites of damaged extraction socket grafting using deproteinized bovine bone mineral (DBBM) or deproteinized porcine bone mineral (DPBM) with coverage by a collagen membrane. MATERIAL AND METHODS: One hundred patients participated in this randomized controlled clinical trial of extraction socket grafts performed in cases of periodontally compromised teeth. All participants were blinded to their group allocations, and each material was grafted with coverage by collagen membranes after extraction of the tooth and removal of granulation tissue. At implant placement at 4 months, a biopsy was harvested at the implant site using a trephine was analyzed histologically. RESULTS: Eighty-five biopsy samples were acquired, of which 81 were finally included in the histologic analysis (42 in DBBM and 39 in DPBM group). Both DBBM and DPBM groups showed comparable proportions of residual biomaterial (12.37 ± 5.67% and 12.21 ± 5.75%, respectively), newly formed bone (15.07 ± 10.52% and 18.47 ± 11.47%, respectively), and nonmineralized tissue (72.56 ± 10.07% and 71.55 ± 15.47%, respectively). There were no significant differences in these histologic parameters between the two groups with different biomaterials. CONCLUSION: Comparable histologic bone formation was found in both socket grafted groups with DBBM or DPBM covered by collagen membranes in periodontally damaged extraction sockets. However, a wide variation in new bone formation was found after 4 months of postsurgical healing and a tendency of higher new bone formation was shown at damaged sockets that had an intact unilateral residual wall regardless of buccal or lingual side.

Periodontal healing using a collagen matrix with periodontal ligament progenitor cells in a dehiscence defect model in beagle dogs.

PURPOSE: To histologically characterize periodontal healing at 8 weeks in surgically created dehiscence defects in beagle dogs that received a collagen matrix with periodontal ligament (PDL) progenitor cells. METHODS: The bilateral maxillary premolars and first molars in 6 animals were used. Standardized experimental dehiscence defects were made on the buccal side of 3 premolars, and primary culturing of PDL progenitor cells was performed on the molars. Collagen matrix was used as a scaffold and a delivery system for PDL progenitor cells. The experimental sites were grafted with collagen matrix (COL), PDL progenitor cells with collagen matrix (COL/CELL), or left without any material (CTL). Histologic and histomorphometric analyses were performed after 8 weeks. RESULTS: The defect height from the cementoenamel junction to the most apical point of cementum removal did not significantly differ across the CTL, COL, and COL/CELL groups, at 4.57±0.28, 4.56±0.41, and 4.64±0.27 mm (mean ± standard deviation), respectively; the corresponding values for epithelial adhesion were 1.41±0.51, 0.85±0.29, and 0.30±0.41 mm (P<0.05), the heights of new bone regeneration were 1.32±0.44, 1.65±0.52, and 1.93±0.61 mm (P<0.05), and the cementum regeneration values were 1.15±0.42, 1.81±0.46, and 2.57±0.56 mm (P<0.05). There was significantly more new bone formation in the COL/CELL group than in the CTL group, and new cementum length was also significantly higher in the COL/CELL group. However, there were no significant differences in the width of new cementum among the groups. CONCLUSIONS: PDL progenitor cells carried by a synthetic collagen matrix may enhance periodontal regeneration, including cementum and new bone formation.

Clinical Factors and Cellular Responses of In Situ Human Alveolar Bone-Derived Mesenchymal Stromal Cells Associated With Early Periimplant Marginal Bone Loss: A Prospective Cohort Pilot Study.

PURPOSE: To investigate clinical factors and cellular responses of in situ human alveolar bone-derived mesenchymal stromal cells involved in early periimplant marginal bone loss. MATERIALS AND METHODS: Thirty-seven completely or partially edentulous patients were enrolled in this study. Periapical radiographs were taken at the time of implant surgery, at 3-month follow-up, and at 1-year follow-up. Univariate analysis and multiple logistic regression were performed to investigate the associations between marginal bone loss and study variables. The mRNA expression levels of 21 bone-remodeling- and tissue-healing-associated genes were analyzed by subgroup. RESULTS: Thirty-one patients with 98 implants were followed. The incidence and mean amount of bone loss were higher for overdentures than for other prosthesis and higher for the maxilla than for the mandible. The bone loss group showed lower mRNA expression levels of runt-related transcription factor-2, bone morphogenetic protein-2, and peroxisome proliferator-activated receptor gamma-2 and higher receptor activator of NKκB ligand/osteoprotegerin (RANKL/OPG) ratio. CONCLUSION: Within the limitations of the study, certain genes involved in bone remodeling (runt-related transcription factor-2 [Runx-2], bone morphogenetic protein-2 [BMP-2], and peroxisome proliferator-activated receptor gamma-2 [PPARγ-2]) and RANKL/OPG are correlated with early periimplant bone loss, with the type of suprastructure and the involved jaw being significant clinical factors.

Resonance Frequency Analysis of Tapered Implants Placed at Maxillary Posterior Sites After Lateral Sinus Augmentation: A 1.5-year Follow-Up Prospective Study.

OBJECTIVES: To use resonance frequency analysis to evaluate tapered implants placed at maxillary posterior sites after lateral sinus augmentation. MATERIALS AND METHODS: Patients who had missing teeth in the maxillary posterior area and required lateral sinus augmentation before implant placement were enrolled in this study. After a 6-month healing period, a tapered implant (Osstem TSIV) was placed. Implant success rate, survival rate, and marginal bone loss of the implants were measured. For resonance frequency analysis, implant stability quotient (ISQ) values were measured at each visit during a 1.5-year follow-up period. RESULTS: Twenty-four patients completed the study procedure. The residual bone height was 2.57 ± 1.10 mm (mean ± SD). Healing of the grafted area was uneventful in all cases, and 55 tapered implants were installed. The implant success rate was 95.56%, and the survival rate was 100% throughout the observation period. The marginal bone loss was limited to 0.22 ± 0.44 mm. ISQ increased gradually from 68.40 ± 11.14 to 82.24 ± 4.75 during the 1.5-year follow-up period. CONCLUSION: The tapered implants showed good initial and final stability after placement in the soft bone of the maxillary posterior area after lateral sinus augmentation.

Analysis of fatty acids in mouse tissue via in situ transmethylation with biochar.

Lipid derivatization technology-mediated fatty acid profiling studies have been suggested to dissect the contents of lipids in white fat and brown fat tissue. The focus of this study is to profile fatty acid lipidomics in brown adipose tissue and white adipose tissue of mice by derivatizing their lipids into fatty acid methyl esters via in situ transmethylation using a rice husk-derived biochar as porous media. The in situ transmethylation using biochar is advantageous in biological analysis because there was no loss of samples inevitably occurring in the loss of lipid in solvent extraction and purification steps.

Characteristics of Local Delivery Agents for Treating Peri-Implantitis on Dental Implant Surfaces: A Preclinical Study.

Local delivery agents (LDAs) are widely used in peri-implantitis treatments. The aim of this study was to identify LDAs remaining on the dental implant surfaces and to analyze the components of these residues after applying various cleaning methods. Implants were prepared with a sand-blasted, large-grit, acid-etched surface. Four kinds of LDAs were applied on the implant surfaces: chlorhexidine gel (group 2), tetracycline solution (group 3), and 2 kinds of minocycline hydrochloride agents (groups 4 and 5). Group 1 received normal saline as a control. Two cleaning methods were applied for different durations as follows: (1) running distilled water for 10 seconds (subgroup A), 5 minutes (subgroup B), and 15 minutes (subgroup C); and (2) water spray of a dental-unit chair for 10 seconds (subgroup D) and 5 minutes (subgroup E). Scanning electron microscopy and energy-dispersive x-ray spectroscopy were used to analyze the surface morphology and residue components for all implants. The amount of LDA removed from the implant surfaces in groups 1, 2, 3, and 5 increased with the cleaning duration and pressure. However, Minocline remained coated on the implant surfaces in group 4 under all cleaning conditions. Minocline could not be cleaned off well by water due to its hydrophobicity. Therefore, directly using this agent on implant surfaces with peri-implantitis should be carefully considered. The presence of LDA residues without drug efficacies on implant surfaces might interfere with reosseointegration and act as a reservoir of microorganisms.

Radiographic and histologic observations of sequential healing processes following ridge augmentation after tooth extraction in buccal-bone-deficient extraction sockets in beagle dogs.

OBJECTIVES: To evaluate dimensional ridge alterations and sequential healing processes following ridge augmentation after tooth extraction in damaged extraction sockets with buccal-bone-deficiency. MATERIAL AND METHODS: Bilateral dental roots of three mandibular premolars were extracted with entire removal of the buccal-bone plate in eight beagle dogs. Unilateral sites were grafted with biomaterials (test group) and contralateral sites were healed without grafting (control group). Observations were made after 1, 2, 4, and 8 weeks, and all sites were distributed evenly (n = 6 for each group and period). Radiographic/histomorphometric analyses were performed. RESULTS: In spontaneous healing of damaged extraction sockets, the dimension of regenerated alveolar ridge gradually increased until 4 weeks and then remained stable, but radiographic/histomorphometric analyses revealed evident dimensional shrinkage compared to the pristine tissue at 8 weeks in the coronal and middle areas. Bone grafting retained the pristine dimension of alveolar ridge, and newly formed bone area within the augmented space continuously expanded during the observational period to the outermost border of the space. CONCLUSIONS: Spontaneous healing of damaged extraction sockets caused substantial dimensional shrinkage. However, ridge augmentation can provide space into which new bone may grow continuously, resulting in the final dimensions comparable to those of the pristine alveolar ridge.

Alveolar ridge regeneration of damaged extraction sockets using deproteinized porcine versus bovine bone minerals: A randomized clinical trial.

BACKGROUNDS: Clinical benefits in bone grafting of intact extraction socket have been widely known, but limited evidence is available for the procedure in damaged extraction sockets due to periodontal disease. PURPOSE: This study aimed to determine the dimensional alteration of alveolar ridge following bone grafting of damaged extraction sockets, and compare the outcomes of using deproteinized bovine (DBBM) versus porcine bone mineral (DPBM) in the damaged sockets. MATERIALS AND METHODS: One hundred patients (n = 50 for each group) with periodontitis-induced damaged extraction socket were included in this randomized, single-blind trial. After removal of tooth and granulation tissue, sites were grafted with either DBBM (DBBM group) or DPBM (DPBM group), and covered with collagen membrane. Linear/volumetric analyses of hard and soft-tissue dimensions were performed on reconstructed/superimposed computed tomography and scanned cast images, taken immediately and 4 months after surgery. RESULTS: The two groups showed comparable hard tissue augmentation with minimal reductions in the grafted volume, as well as in vertical (1.22 ± 2.16 and 1.45 ± 1.92 mm for DPBM and DBBM group, respectively) and horizontal (1.43 ± 3.40 and 1.83 ± 2.85 mm on the central section, respectively) dimensions at 4 months after surgery. However, several cases showed large variations in maintenance of the grafted volume. None of the measured parameters in hard and soft tissue dimensions differed significantly between DBBM and DPBM sites. CONCLUSIONS: DBBM and DPBM can comparably augment damaged extraction sockets with minimal postoperative reduction of the grafted volume. However, the large variations in the results should be further evaluated for application in routine dental clinics.

Enhancing proliferation and optimizing the culture condition for human bone marrow stromal cells using hypoxia and fibroblast growth factor-2.

This study aimed to determine the cellular characteristics and behaviors of human bone marrow stromal cells (hBMSCs) expanded in media in a hypoxic or normoxic condition and with or without fibroblast growth factor-2 (FGF-2) treatment. hBMSCs isolated from the vertebral body and expanded in these four groups were evaluated for cellular proliferation/migration, colony-forming units, cell-surface characterization, in vitro differentiation, in vivo transplantation, and gene expression. Culturing hBMSCs using a particular environmental factor (hypoxia) and with the addition of FGF-2 increased the cellular proliferation rate while enhancing the regenerative potential, modulated the multipotency-related processes (enhanced chondrogenesis-related processes/osteogenesis, but reduced adipogenesis), and increased cellular migration and collagen formation. The gene expression levels in the experimental samples showed activation of the hypoxia-inducible factor-1 pathway and glycolysis in the hypoxic condition, with this not being affected by the addition of FGF-2. The concurrent application of hypoxia and FGF-2 could provide a favorable condition for culturing hBMSCs to be used in clinical applications associated with bone tissue engineering, due to the enhancement of cellular proliferation and regenerative potential.

In vivo differentiation of induced pluripotent stem cells into neural stem cells by chimera formation.

Like embryonic stem cells, induced pluripotent stem cells (iPSCs) can differentiate into all three germ layers in an in vitro system. Here, we developed a new technology for obtaining neural stem cells (NSCs) from iPSCs through chimera formation, in an in vivo environment. iPSCs contributed to the neural lineage in the chimera, which could be efficiently purified and directly cultured as NSCs in vitro. The iPSC-derived, in vivo-differentiated NSCs expressed NSC markers, and their gene-expression pattern more closely resembled that of fetal brain-derived NSCs than in vitro-differentiated NSCs. This system could be applied for differentiating pluripotent stem cells into specialized cell types whose differentiation protocols are not well established.

Chemokine in inflamed periodontal tissues activates healthy periodontal-ligament stem cell migration.

AIM: The present study aimed to characterize the expression pattern of chemokines obtained from inflamed periodontal defects and to determine the characteristics of human periodontal-ligament stem cells (hPDLSCs) migrated by each specific chemokine. MATERIALS AND METHODS: Both inflamed and healthy periodontal tissues were obtained from periodontitis patients (n = 11), and the chemokine expression levels were analyzed. The periodontal-tissue-specific chemokines were applied to healthy hPDLSCs from extracted teeth (n = 3), with FGF-2 acting as a positive control. Cells were separated by selected chemokines using transwell method into migrated/unmigrated hPDLSCs. The characteristics of the hPDLSC subpopulation recruited by each chemokine were assessed, and gene expression pattern was analyzed by microarray. RESULTS: Chemokines were categorized into three groups by specific patterns of "appearing," "increasing," and "decreasing/disappearing" from healthy to inflamed tissues. A representative chemokine from each group enhanced the capacities for colony formation and osteogenic/adipogenic differentiation while maintaining the surface markers of hPDLSCs. RANTES/CCL5 significantly increased the cellular migration of hPDLSCs, via enhancement of signaling pathways, regulation of the actin skeleton, and focal adhesion. CONCLUSION: The present study found a specific chemokine profile induced by inflammation in periodontal tissues, with RANTES/CCL5 appearing to play a role in the migration of hPDLSCs into inflammatory periodontal lesions.

In Vivo Evaluation of Commercially Available Gel-Type Polyethylene Glycol Membrane for Carrier of Recombinant Human Bone Morphogenetic Protein-2.

PURPOSE: This study evaluated a commercially available, 3-dimensional gel-type polyethylene glycol (PEG) membrane as a carrier for recombinant human bone morphogenetic protein-2 (rhBMP-2) using a rat calvarial defect model. Another gel-type carrier, fibrin-fibronectin system (FFS), was used as a positive control. MATERIALS AND METHODS: Critical-size defects were made in the rat calvarium, which were allocated to 1 of 10 groups comprising 2 healing periods and biomaterial conditions: 1) sham control, 2) FFS only, 3) FFS plus BMP-2, 4) PEG only, and 5) PEG plus BMP-2. Radiographic and histologic analyses were performed at 2 and 8 weeks after surgery. RESULTS: After 2 weeks, some parts of the FFS were biodegraded and extensive cellular infiltration was observed at sites that received FFS or FFS plus BMP-2. The PEG membrane retained its augmented volume without cellular infiltration at sites that received PEG or PEG plus BMP-2. After 8 weeks, the FFS was completely degraded and replaced by new bone and connective tissues. In contrast, the volume of residual PEG was similar to that at 2 weeks, with slight cellular infiltration. In particular, there was progressive bone regeneration around micro-cracks and resorbed outer surface in the PEG + BMP-2 group. Although the PEG + BMP-2 group showed increased area and percentage of new bone, there was no statistical relevance after 2 and 8 weeks in histomorphometric analyses. However, the appearance of the healing differed (with new bone formation along micro-cracks in the PEG + BMP-2 group), and further studies with longer healing periods are needed to draw conclusions about clinical applications. CONCLUSION: Evidence of mechanical stability and new bone formation along micro-cracks when using PEG plus BMP-2 might support the PEG membrane as a candidate carrier material for rhBMP-2.