The cumulative survival rate of dental implants with micro-threads: a long-term retrospective study.

PURPOSE: This study aimed to evaluate the long-term cumulative survival rate (CSR) of dental implants with micro-threads in the neck over a 10-year follow-up period and to examine the factors influencing the survival rate of dental implants. METHODS: This retrospective study was based on radiographic and dental records. In total, 151 patients received 490 Oneplant® dental implants with an implant neck micro-thread design during 2006-2010 in the Department of Periodontology of Seoul National University Dental Hospital. Implant survival was evaluated using Kaplan-Meier analysis. Cox proportional hazard regression analysis was used to identify the factors influencing implant failure. RESULTS: Ten out of 490 implants (2.04%) failed due to fixture fracture. The CSR of the implants was 97.9%, and no significant difference was observed in the CSR between external- and internal-implant types (98.2% and 97.6%, respectively, P=0.670). In Cox regression analysis, 2-stage surgery significantly increased the risk of implant failure (hazard ratio: 4.769, P=0.039). There were no significant differences in influencing factors, including sex, age, implant diameter, length, fixture type, location, surgical procedure, bone grafting, and restoration type. CONCLUSIONS: Within the limitations of this retrospective study, the micro-thread design of the implant neck was found to be favorable for implant survival, with stable clinical outcomes.

In ovariectomy-induced osteoporotic rat models, BMP-2 substantially reversed an impaired alveolar bone regeneration whereas PDGF-BB failed.

OBJECTIVES: We previously suggested an ovariectomy (OVX)-induced osteoporotic rat model showing an impaired alveolar bone defect healing. This study aimed to evaluate and compare the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human platelet-derived growth factor-BB (rhPDGF-BB) on alveolar bone defect healing in OVX-induced osteoporotic rats. MATERIALS AND METHODS: A total of forty-one female rats were divided into four groups: a collagen group (n=10), a PDGF-BB group (n=11), a BMP-2 group (n=10), and a control group (n=10). Four months after OVX, alveolar bone drill-hole defects were created and grafted with collagen gel, rhPDGF-BB/collagen gel, or rhBMP-2/collagen gel. The defects in the control group were not grafted with any material. Defect healing was evaluated by histological, histomorphometric, and microcomputed tomographic (micro-CT) analyses at 2 and 4 weeks. RESULTS: According to the micro-CT analysis, the BMP-2 group exhibited the greatest bone volume fraction among all groups, while the PDGF-BB group did not show significant differences compared with the collagen group. The histomorphometric analysis showed a significantly larger amount of new bone area in the BMP-2 group than in the control and collagen groups at 4 weeks; however, the PDGF-BB group did not reach significant superiority compared with the other groups. CONCLUSIONS: Alveolar bone regeneration was significantly enhanced by the local use of rhBMP-2/collagen gel compared with the use of rhPDGF-BB/collagen gel in OVX-induced osteoporotic rats. CLINICAL RELEVANCE: A treatment modality using rhBMP-2 may be a promising approach to promote alveolar bone regeneration in patients suffering from postmenopausal osteoporosis.

The impact of surface treatment in 3-dimensional printed implants for early osseointegration: a comparison study of three different surfaces.

3D printing technology has been gradually applied to various areas. In the present study, 3D-printed implants were fabricated with direct metal laser sintering technique for a dental single root with titanium. The 3D implants were allocated into following groups: not treated (3D-None), sandblasted with a large grit and acid-etched (3D-SLA), and target-ion-induced plasma-sputtered surface (3D-TIPS). Two holes were drilled in each tibia of rabbit, and the three groups of implants were randomly placed with a mallet. Rabbits were sacrificed at two, four, and twelve weeks after the surgery. Histologic and histomorphometric analyses were performed for the evaluation of mineralized bone-to-implant contact (mBIC), osteoid-to-implant contact (OIC), total bone-to-implant contact (tBIC), mineralized bone area fraction occupancy (mBAFO), osteoid area fraction occupancy (OAFO), and total bone area fraction occupancy (tBAFO) in the inner and outer areas of lattice structure. At two weeks, 3D-TIPS showed significantly higher inner and outer tBIC and inner tBAFO compared with other groups. At four weeks, 3D-TIPS showed significantly higher outer OIC than 3D-SLA, but there were no significant differences in other variables. At twelve weeks, there were no significant differences. The surface treatment with TIPS in 3D-printed implants could enhance the osseointegration process in the rabbit tibia model, meaning that earlier osseointegration could be achieved.

Ovariectomy and timing of impaired maxillary alveolar bone regeneration: An experimental study in rats.

BACKGROUND: The aim of this study was to seek the critical time for impairment of alveolar bone regeneration after ovariectomy (OVX) in rats. METHODS: A total of 32 female rats were used. Test group rats were divided into a 2M group (n = 8), a 3M group (n = 8) and a 4M group (n = 8) according to the duration from OVX to defect creation. Bilateral OVX was performed in all test groups, and a sham operation was performed in the control group (n = 8). Drill-hole defects (1.5 mm diameter, 2 mm length) were created on both sides of the maxilla. All rats were euthanized 2 and 4 weeks after the surgery. Microcomputed tomographic (micro-CT), histological, and histomorphometric analyses and in vitro experiments were performed. RESULTS: The 4M group showed significantly less new bone formation and a lower bone mineral density than the other groups in the micro-CT analysis. The histomorphometric analysis also revealed that the 4M group showed significantly less new bone formation than the control and 2M groups. The rats in the 4M group showed significantly higher alkaline phosphatase expression levels and a larger number of calcified nodules than rats in the other groups, whereas osteoclastic activity was significantly lower in the 4M group than in the other groups. CONCLUSIONS: The critical time for impairment of alveolar bone regeneration was 4 months after OVX in rats.

Enhanced Bone Regeneration by Diabetic Cell-Based Adenoviral BMP-2 Gene Therapy in Diabetic Animals.

The application of bone morphogenetic protein 2 (BMP-2) has been extensively investigated to improve diabetes-impaired bone healing; however, the delivery of BMP-2 by gene therapy for bone regeneration has rarely been investigated in diabetic animals. In this study, we aimed to evaluate which cells induce more new bone formation in diabetic animals when cell-based BMP2 gene therapy is applied. For this purpose, we harvested bone marrow stromal cells (BMSCs) twice in the same animal before (non-diabetic BMSCs; nBMSCs) and after diabetes induction (diabetic BMSCs; dBMSCs) using modified bone marrow ablation methods. And then, cells were transduced by adenoviral vectors carrying the BMP2 gene (AdBMP2). In in vitro, AdBMP2-transfected dBMSCs (B2/dBMSCs) produced higher BMP-2 mRNA levels over 48 h, whereas AdBMP2-transfected nBMSCs (B2/nBMSCs) exhibited a transient increase in BMP-2 mRNA followed by a decrease to the baseline level within 48 h. Both B2/dBMSCs and B2/nBMSCs induced secretion of BMP-2 for 3 weeks. However, B2/dBMSC BMP-2 secretion peaked from day 3 to 10, whereas B2/nBMSC BMP-2 secretion peaked from day 1 to 7. The analysis of osteogenic activity revealed that mineralization nodule formation and the expression levels of osteogenic genes were significantly higher in B2/dBMSCs than B2/nBMSCs and were accompanied by upregulation of canonical Wnt/ß-catenin and Smad signaling. AdBMP2-transfected autologous cells were implanted into critical-sized calvarial defects in diabetic animals and induced significantly more bone regeneration than non-AdBMP2-transfected cells. In addition, B2/dBMSCs led to significantly more new bone formation than B2/nBMSCs. Thus, BMP2 gene therapy using diabetic cells effectively supported diabetic bone healing and it was related to the enhanced responses to AdBMP2 of dBMSCs.

Transcriptomics and methylomics in chronic periodontitis with tobacco use: a pilot study.

BACKGROUND: Accumulating evidence suggests that tobacco smoking affects the susceptibility to and severity of chronic periodontitis. Epigenetics may explain the role of smoking in the development and progress of periodontal disease. In this study, we performed transcriptomic and methylomic analyses of non-periodontitis and periodontitis-affected gingival tissues according to smoking status. METHODS: Human gingival tissues were obtained from 20 patients, including non-smokers with and without periodontitis (n = 5 per group) and smokers with and without periodontitis (n = 5 per group). Total RNA and genomic DNA were isolated, and their quality was validated according to strict standards. The Illumina NextSeq500 sequencing system was used to generate transcriptome and methylome datasets. RESULTS: Comprehensive analysis, including between-group correlation, differential gene expression, DNA methylation, gene set enrichment, and protein-protein interaction, indicated that smoking may change the transcription and methylation states of extracellular matrix (ECM) organization-related genes, which exacerbated the periodontal condition. CONCLUSIONS: Our results suggest that smoking-related changes in DNA methylation patterns and subsequent alterations in the expression of genes coding for ECM components may be causally related to the increased susceptibility to periodontitis in smokers as they could influence ECM organization, which in turn may have an effect on disease characteristics.

A randomized controlled clinical study of periodontal tissue regeneration using an extracellular matrix-based resorbable membrane in combination with a collagenated bovine bone graft in intrabony defects.

PURPOSE: The purpose of this study was to investigate the feasibility of regenerative therapy with a collagenated bone graft and resorbable membrane in intrabony defects, and to evaluate the effects of the novel extracellular matrix (ECM)-based membrane clinically and radiologically. METHODS: Periodontal tissue regeneration procedure was performed using an ECM-based resorbable membrane in combination with a collagenated bovine bone graft in intrabony defects around the teeth and implants. A novel extracellular matrix membrane (NEM) and a widely-used membrane (WEM) were randomly applied to the test group and the control group, respectively. Cone-beam computed tomography images were obtained on the day of surgery and 6 months after the procedure. Alginate impressions were taken and plaster models were made 1 week and 6 months postoperatively. RESULTS: The quantity of bone tissue, the dimensional changes of the surgically treated intrabony defects, and the changes in width and height below the grafted bone substitutes showed no significant difference between the test and control groups at the 6-month examination. CONCLUSIONS: The use of NEM for periodontal regeneration with a collagenated bovine bone graft showed similar clinical and radiologic results to those obtained using WEM.

Fibronectin-Derived Oligopeptide Stimulates Osteoblast Differentiation Through a Bone Morphogenic Protein 2-Like Signaling Pathway.

BACKGROUND: In previous studies by the authors, it was demonstrated that a fibronectin (FN)-derived oligopeptide, termed F20, stimulates osteoblast differentiation in vitro and bone formation in vivo. However, the fundamental molecular mechanism by which F20 stimulates osteogenesis remains unknown. Therefore, in this study the molecular mechanism underlying the effect of F20 in osteoblast differentiation is investigated. METHODS: The role of F20 in osteoblast differentiation was examined using mouse bone-marrow-derived ST2 cell line. The effect of Smad1/5 was determined following small interfering RNA knockdown. Runt-related transcription factor (Runx) 2, alkaline phosphatase (Alp), and osteocalcin (Oc) mRNA levels were determined by quantitative real-time polymerase chain reaction, and their transcriptional activation was assessed using luciferase reporter assays. Extracellular signal-regulated kinase (ERK) phosphorylation was visualized via immunoblotting. RESULTS: Synthetic oligopeptide F20 stimulated expression of bone marker genes Runx2, Alp, and Oc in ST2 cells via Smad and ERK or mitogen-activated protein kinase signaling pathways as did bone morphogenic protein 2 (BMP2). Furthermore, Runx2 acted as a transcription factor during F20-induced osteoblast differentiation. CONCLUSIONS: Collectively, these results indicate that F20 induces osteoblast differentiation with a pattern similar to that mediated by BMP2 signaling pathway. The authors' previous data also showed that FN-derived oligopeptide improved wound healing, and it is suggested that F20 might serve as a therapeutic biomolecule to facilitate periodontal tissue regeneration.

Relief of Injection Pain During Delivery of Local Anesthesia by Computer-Controlled Anesthetic Delivery System for Periodontal Surgery: Randomized Clinical Controlled Trial.

BACKGROUND: Pain from local anesthetic injection makes patients anxious when visiting a dental clinic. This study aims to determine differences in pain according to types of local anesthetizing methods and to identify the possible contributing factors (e.g., dental anxiety, stress, and sex). METHODS: Thirty-one patients who underwent open-flap debridement in maxillary premolar and molar areas during treatment for chronic periodontitis were evaluated for this study. A randomized, split-mouth, single-masked clinical trial was implemented. The dental anxiety scale (DAS) and perceived stress scale (PSS) were administered before surgery. Two lidocaine ampules for each patient were used for local infiltration anesthesia (supraperiosteal injection). Injection pain was measured immediately after local infiltration anesthesia using the visual analog pain scale (VAS) questionnaire. Results from the questionnaire were used to assess degree of pain patients feel when a conventional local anesthetic technique (CNV) is used compared with a computer-controlled anesthetic delivery system (CNR). RESULTS: DAS and PSS did not correlate to injection pain. VAS scores were lower for CNR than for CNV regardless of the order in which anesthetic procedures were applied. VAS score did not differ significantly with sex. Pearson coefficient for correlation between VAS scores for the two procedures was 0.80, also indicating a strong correlation. CONCLUSION: Within the limitations of the present study, relief from injection pain is observed using CNR.

Bone reconstruction after surgical treatment of experimental peri-implantitis defects at a sandblasted/acid-etched hydroxyapatite-coated implant: an experimental study in the dog.

OBJECTIVES: The objective of this study was to evaluate bone formation/osseointegration following surgical treatment of experimental peri-implantitis at dental implants with different surface characteristics exposed to ligature-induced breakdown conditions. METHODS: Ten turned (control), 10 sandblasted/acid-etched (SA), and 10 SA/hydroxyapatite nanocoated (HA) implants were installed into the edentulated posterior mandible in five Beagle dogs and allowed to osseointegrate for 12 weeks. Ligature-induced breakdown defects were then induced over 23 weeks using stainless steel wire ligatures. The ligatures were removed and soft tissues were allowed to heal for 3 weeks. Next, exposed implant surfaces were decontaminated followed by guided bone regeneration using a collagen membrane and submerged wound healing. The animals were euthanized for histometric analysis at 12 weeks post-surgery. RESULTS: The radiographic analysis showed vertical bone loss following ligature-induced breakdown without statistically significant differences among implant technologies. The histometric analysis showed significantly enhanced bone formation (height) at SA and SA/HA compared with turned implants (p = 0.028) following reconstructive surgery. Bone formation area was greater at SA/HA compared with turned implants, however the difference did not reach statistical significance. CONCLUSIONS: While ligature-induced defect progression does not appear implant surface dependent in this animal model, bone formation at the decontaminated implant surfaces appears more favourable at SA and SA/HA over turned implants following reconstructive surgery.

Efficacy of sonic-powered toothbrushes for plaque removal in patients with peri-implant mucositis.

PURPOSE: The aim of this study was to evaluate the effectiveness of powered toothbrushes for plaque control in patients with peri-implant mucositis, in comparison with manual toothbrushes. METHODS: This randomized, prospective, controlled, clinical parallel study compared the efficacy of manual and powered toothbrushes for plaque control in implant restorations. Patients with bleeding on probing, no residual pocket depth (as indicated by a pocket probing depth ≥ 5 mm), and no radiological peri-implant bone loss were eligible for this study. Patients were requested to complete a questionnaire describing their oral hygiene habits. The duration and frequency of tooth brushing were recorded by subjects in order to assess their compliance. Clinical parameters, including the modified plaque index (mPI), the modified sulcus bleeding index (mSBI), and clinical photographs (buccal and lingual views) were recorded at baseline and at one-month and two-month follow-up visits. RESULTS: Statistically significant differences between patients who used manual toothbrushes and those who used powered toothbrushes were found regarding the frequency of tooth brushing per day and the duration of brushing at one-month and two-month follow-up visits, while no statistically significant differences were found relating to other oral hygiene habits. A statistically significant difference in patient compliance for tooth brushing was found at one month, while no difference was found at two months. Statistically significant decreases in the mPI and the mSBI were observed in both groups from baseline to the one- and two-month follow-ups. The overall reduction of these parameters was not significantly different between the two groups, except for mPI reduction between baseline and one month of follow-up. CONCLUSIONS: Sonic-powered toothbrushes may be a useful device for plaque control in patients with peri-implant mucositis.

Evaluation of the correlation between insertion torque and primary stability of dental implants using a block bone test.

PURPOSE: Implant stability at the time of surgery is crucial for the long-term success of dental implants. Primary stability is considered of paramount importance to achieve osseointegration. The purpose of the present study was to investigate the correlation between the insertion torque and primary stability of dental implants using artificial bone blocks with different bone densities and compositions to mimic different circumstances that are encountered in routine daily clinical settings. METHODS: In order to validate the objectives, various sized holes were made in bone blocks with different bone densities (#10, #20, #30, #40, and #50) using a surgical drill and insertion torque together with implant stability quotient (ISQ) values that were measured using the Osstell Mentor. The experimental groups under evaluation were subdivided into 5 subgroups according to the circumstances. RESULTS: In group 1, the mean insertion torque and ISQ values increased as the density of the bone blocks increased. For group 2, the mean insertion torque values decreased as the final drill size expanded, but this was not the case for the ISQ values. The mean insertion torque values in group 3 increased with the thickness of the cortical bone, and the same was true for the ISQ values. For group 4, the mean insertion torque values increased as the cancellous bone density increased, but the correlation with the ISQ values was weak. Finally, in group 5, the mean insertion torque decreased as the final drill size increased, but the correlation with the ISQ value was weak. CONCLUSIONS: Within the limitations of the study, it was concluded that primary stability does not simply depend on the insertion torque, but also on the bone quality.

Ex vivo bone morphogenetic protein-2 gene delivery using bone marrow stem cells in rabbit maxillary sinus augmentation in conjunction with implant placement.

BACKGROUND: This study evaluates the potential of bone morphogenetic protein 2 (BMP-2) gene-transduced bone marrow stem cells (BMSCs) to facilitate osseous healing after rabbit maxillary sinus augmentation in conjunction with implant placement. METHODS: Autologous BMSCs derived from New Zealand white rabbits were cultured and transduced with BMP-2 using an adenovirus vector. Transduced BMSCs (BMP-2/BMSCs) were then combined with a deproteinized bovine bone mineral (DBBM) scaffold. Twenty-seven animals were randomly allocated into three groups: 1) control, sinus grafted with DBBM alone; 2) BMSC, sinus grafted with non-transduced BMSCs and DBBM; and 3) BMP-2/BMSC, sinus grafted with BMP-2/BMSCs and DBBM. During these procedures, a mini-implant was placed in the floor of the sinus. Animals were sacrificed at 2, 4, and 8 weeks after surgery. New bone area and bone-to-implant contact (BIC) were evaluated histomorphometrically. RESULTS: At 2 and 4 weeks, the BMP-2/BMSC group showed more new bone area and higher BIC than the other two groups. BMP-2/BMSCs were detected with confocal microscopy for up to 4 weeks, which indicates that transduced cells contributed to new bone formation. However, at 8 weeks, there was no difference in new bone area or BIC among the three groups. CONCLUSIONS: These results suggest that BMP-2 delivery using BMSCs may result in earlier and increased bone formation in the maxillary sinus. This finding may offer more stable bone support to implants and reduce healing times. However, this study also revealed limitations in the stimulatory effect of BMP-2/BMSCs, such as diminished activity over time in later healing stages.

Effects of immunosuppressants, FK506 and cyclosporin A, on the osteogenic differentiation of rat mesenchymal stem cells.

PURPOSE: The purpose of this study was to investigate the effects of the immunosuppressants FK506 and cyclosporin A (CsA) on the osteogenic differentiation of rat mesenchymal stem cells (MSCs). METHODS: The effect of FK506 and CsA on rat MSCs was assessed in vitro. The MTT assay was used to determine the deleterious effect of immunosuppressants on stem cell proliferation at 1, 3, and 7 days. Alkaline phosphatase (ALP) activity was analyzed on days 3, 7, and 14. Alizarin red S staining was done on day 21 to check mineralization nodule formation. Real-time polymerase chain reaction (RT-PCR) was also performed to detect the expressions of bone tissue-specific genes on days 1 and 7. RESULTS: Cell proliferation was promoted more in the FK506 groups than the control or CsA groups on days 3 and 7. The FK506 groups showed increased ALP activity compared to the other groups during the experimental period. The ALP activity of the CsA groups did not differ from the control group in any of the assessments. Mineralization nodule formation was most prominent in the FK506 groups at 21 days. RT-PCR results of the FK506 groups showed that several bone-related genes-osteopontin, osteonectin, and type I collagen (Col-I)-were expressed more than the control in the beginning, but the intensity of expression decreased over time. Runx2 and Dlx5 gene expression were up-regulated on day 7. The effects of 50 nM CsA on osteonectin and Col-I were similar to those of the FK506 groups, but in the 500 nM CsA group, most of the genes were less expressed compared to the control. CONCLUSIONS: These results suggest that FK506 enhances the osteoblastic differentiation of rat MSCs. Therefore, FK506 might have a beneficial effect on bone regeneration when immunosuppressants are needed in xenogenic or allogenic stem cell transplantation to treat bone defects.

Biomimetic surface modification using synthetic oligopeptides for enhanced guided bone regeneration in beagles.

BACKGROUND: In previous studies, oligopeptide corresponding to the cell-binding domains of bone morphogenetic proteins that bind to bone morphogenetic protein receptor enhanced the bone regenerative capacity of bovine bone minerals (BBM). The aim of this study is to evaluate the ability of BBM coated with oligopeptide to promote periodontal regeneration in a 1-wall intrabony defect model in dogs. METHODS: The second and third mandibular premolars and first molars of six adult beagles were extracted bilaterally, and the extraction sites were allowed to heal for 10 weeks. The 1-wall intrabony defects were prepared bilaterally on the mesial and distal side of the fourth mandibular premolars. Twenty-four intrabony defects were assigned to four treatment groups: 1) open flap debridement; 2) guided tissue regeneration (GTR); 3) GTR with a collagen membrane and BBM; and 4) GTR with a collagen membrane and BBM coated with the oligopeptide (Pep-BBM). The animals were sacrificed 10 weeks after surgery. For the histometric analysis, defect height, junctional epithelium migration, new cementum, new bone height, and new bone area were measured. New bone volume was measured using microcomputed tomography. RESULTS: Wound healing was generally uneventful. For junctional epithelium migration, the BBM and Pep-BBM groups exhibited mean (± SE) values of 0.53 ± 0.41 and 0.48 ± 0.30 mm, and for new cementum height, 1.71 ± 0.46 and 2.50 ± 2.00 mm, respectively. For junctional epithelium migration and cementum regeneration, there were no significant differences between the two groups. The mean (± SE) values of new bone height and new bone volume in the Pep-BBM group (3.88 ± 0.31 mm and 32.35% ± 9.60%) were significantly greater than the mean values for the BBM group (2.60 ± 0.41 mm and 20.56% ± 1.89%). For bone regeneration, the Pep-BBM group showed superior results compared to the BBM group with statistically significant differences. CONCLUSIONS: Through various parameters to evaluate periodontal regeneration, this oligopeptide coating influenced only the ability of BBM to promote bone regeneration in 1-wall intrabony defects in beagles. Junctional epithelium migration and cementum regeneration were not affected by this oligopeptide coating, and further investigations with special focus on regeneration of the periodontal ligament are necessary.

Initial adhesion of bone marrow stromal cells to various bone graft substitutes.

PURPOSE: The aim of this study is to determine whether certain biomaterials have the potential to support cell attachment. After seeding bone marrow stromal cells onto the biomaterials, we investigated their responses to each material in vitro. METHODS: Rat bone marrow derived stromal cells were used. The biomaterials were deproteinized bovine bone mineral (DBBM), DBBM coated with fibronectin (FN), synthetic hydroxyapatite (HA), HA coated with FN, HA coated with ß-tricalcium phosphate (TCP), and pure ß-TCP. With confocal laser scanning microscopy, actin filaments and vinculin were observed after 6, 12, and 24 hours of cell seeding. The morphological features of cells on each biomaterial were observed using scanning electron microscopy at day 1 and 7. RESULTS: The cells on HA/FN and HA spread widely and showed better defined actin cytoskeletons than those on the other biomaterials. At the initial phase, FN seemed to have a favorable effect on cell adhesion. In DBBM, very few cells adhered to the surface. CONCLUSIONS: Within the limitations of this study, we can conclude that in contrast with DBBM not supporting cell attachment, HA provided a more favorable environment with respect to cell attachment.

Effects of fibrin-binding oligopeptide on osteopromotion in rabbit calvarial defects.

PURPOSE: Fibronectin (FN) has been shown to stimulate bone regeneration in animal models. The aim of this study was to evaluate the capacity of bovine bone mineral coated with synthetic oligopeptides to enhance bone regeneration in rabbit calvarial defects. METHODS: Oligopeptides including fibrin-binding sequences of FN repeats were synthesized on the basis of primary and tertiary human plasma FN structures. Peptide coated and uncoated bone minerals were implanted into 10 mm calvarial defects in New Zealand white rabbits, and the animals were sacrificed at 4 or 8 weeks after surgery. After specimens were prepared, histologic examination and histomorphometric analysis were performed. RESULTS: At 4 weeks after surgery, the uncoated groups showed a limited amount of osteoid formation at the periphery of the defect and the oligopeptide coated groups showed more osteoid formation and new bone formation in the center of the defect as well as at the periphery. At 8 weeks, both sites showed increased new bone formation. However, the difference between the two sites had reduced. CONCLUSIONS: Fibrin-binding synthetic oligopeptide derived from FN on deproteinized bovine bone enhanced new bone formation in rabbit calvarial defects at the early healing stage. This result suggests that these oligopeptides can be beneficial in reconstructing oral and maxillofacial deformities or in regenerating osseous bone defects.

Biological effects of a porcine-derived collagen membrane on intrabony defects.

PURPOSE: To prolong the degradation time of collagen membranes, various cross-linking techniques have been developed. For cross-linking, chemicals such as formaldehyde and glutaraldehyde are added to collagen membranes, but these chemicals could adversely affect surrounding tissues. The aim of this study is to evaluate the ability of porous non-chemical cross-linking porcine-derived collagen nanofibrous membrane to enhance bone and associated tissue regeneration in one-wall intrabony defects in beagle dogs. METHODS: The second and third mandibular premolars and the first molars of 2 adult beagles were extracted bilaterally and the extraction sites were allowed to heal for 10 weeks. One-wall intrabony defects were prepared bilaterally on the mesial and distal side of the fourth mandibular premolars. Among eight defects, four defects were not covered with membrane as controls and the other four defects were covered with membrane as the experimental group. The animals were sacrificed 10 weeks after surgery. RESULTS: Wound healing was generally uneventful. For all parameters evaluating bone regeneration, the experimental group showed significantly superior results compared to the control. In new bone height (NBh), the experimental group exhibited a greater mean value than the control (3.04 ± 0.23 mm/1.57 ± 0.59, P = 0.003). Also, in new bone area (NBa) and new bone volume (NBv), the experimental group showed superior results compared to the control (NBa, 34.48 ± 10.21% vs. 5.09 ± 5.76%, P = 0.014; and NBv, 28.04 ± 12.96 vs. 1.55 ± 0.57, P = 0.041). On the other hand, for parameters evaluating periodontal tissue regeneration, including junctional epithelium migration and new cementum height, there were no statistically significant differences between two groups. CONCLUSIONS: Within the limitations of this study, this collagen membrane enhanced bone regeneration at one-wall intrabony defects. On the other hand, no influence of this membrane on periodontal tissue regeneration could be ascertained in this study.

Ex vivo bone morphogenetic protein-2 gene delivery using gingival fibroblasts promotes bone regeneration in rats.

AIM: The aim of the present study was to investigate bone regeneration following ex vivo bone morphogenetic protein-2 (BMP-2) gene delivery using human gingival fibroblasts (HGFs) in rat calvarial defects. MATERIALS AND METHODS: An 8 mm craniotomy defect was created in Sprague-Dawley rats. The animals were divided into four groups: (1) non-grafted group, the defect was left empty; (2) collagen matrix group, the defect was filled with collagen matrix only; (3) HGF group, the defect was filled with non-transduced HGFs on collagen matrix; (4) BMP-2/HGF group, the defect was filled with BMP-2 gene-transduced HGFs on collagen matrix. Animals were sacrificed at 2 and 4 weeks after surgery, and micro-computed tomographic and histologic observations were performed. RESULTS: The BMP-2/HGF group showed promoted osseous healing of calvarial defects, as compared with the other groups. At both 2 and 4 weeks, regenerated bone area was significantly greater in the BMP-2/HGF group than the other three groups. Quite a few number of transplanted HGFs were observed within the regenerated bone tissues. CONCLUSIONS: The results of this study suggest that ex vivo BMP-2 gene delivery induces prominent bone regeneration in vivo and HGFs may be useful as target cells for ex vivo gene therapy.

Alveolar bone regeneration by transplantation of periodontal ligament stem cells and bone marrow stem cells in a canine peri-implant defect model: a pilot study.

BACKGROUND: The present study was undertaken to evaluate the potential of periodontal ligament stem cells (PDLSCs) and bone marrow SCs (BMSCs) on alveolar bone regeneration in a canine peri-implant defect model. METHODS: Four adult, male beagle dogs were used in this study. Autologous BMSCs from the iliac crests and PDLSCs from extracted teeth were cultured. Three months after extraction, BMSC- and PDLSC-loaded hydroxyapatite/beta-tricalcium phosphate (HA/TCP) (test groups) and cell-free HA/TCP (control group) were implanted in three rectangular, saddle-like peri-implant defects, respectively. The left side of the mandible was initially prepared, and after 8 weeks, the right side was also prepared. The animals were sacrificed after an 8-week healing period. Undecalcified ground sections were prepared. New bone formation and bone-to-implant contact (BIC) were measured histomorphometrically. BMSCs and PDLSCs were fluorescently labeled and traced. RESULTS: Alveolar bone regeneration in surgically created peri-implant saddle-like defects was more effective in test groups than the control group. The BMSC group had the highest new bone formation (34.99% and 40.17% at healing times of 8 and 16 weeks, respectively) followed by the PDLSC group (31.90% and 36.51%) and control group (23.13% and 28.36%), respectively. Test groups exhibited a significantly higher new bone formation than the control group at 8 weeks, but the same was true for only the BMSC group at 16 weeks (P <0.05). Fluorescently labeled cells were identified adjacent to HA/TCP carriers and, partly, near connective tissues and osteoids. CONCLUSION: This study demonstrated the feasibility of using stem cell-mediated bone regeneration to treat peri-implant defects.