Hadar Zigdon-Giladi

Co-transplantation of endothelial progenitor cells and mesenchymal stem cells promote neovascularization and bone regeneration.

BACKGROUND Bone formation relies on sufficient blood supply and osteoprogenitor cells. PURPOSE The study aims to evaluate the influence of endothelial progenitor cells (EPCs) in combination with mesenchymal stem cells (MSCs) on early vascularization and intramembranous bone regeneration. MATERIALS AND METHODS Vertical bone regeneration was tested in rat calvarium guided bone regeneration model. Gold domes were filled with a mixture of 5 × 10(5) osteogenic transformed MSC and 5 × 10(5) EPC (EPC/MSC) that were mixed with β-tricalcium phosphate (βTCP) scaffold. Domes filled with βTCP alone served as control. Rats were sacrificed after 4 or 12 weeks. Histomorphometry was used to determine blood vessel (Bv) density, vertical bone height, and bone area in the regenerated tissue. RESULTS At both time points, new augmented hard tissue filled the space under the dome, and Bv density was higher in the EPC/MSC transplanted group vs control. However, bone height and bone area were similar among the groups 4 weeks posttransplantation, but were doubled in the EPC/MSC transplanted group 12 weeks posttransplantation. CONCLUSIONS EPC/MSC transplantation increases Bv formation in the early stages of healing that precedes enhancement of extracortical bone regeneration in later stages.

Recent advances in bone regeneration using adult stem cells.

Bone is a highly vascularized tissue reliant on the close spatial and temporal association between blood vessels and bone cells. Therefore, cells that participate in vasculogenesis and osteogenesis play a pivotal role in bone formation during prenatal and postnatal periods. Nevertheless, spontaneous healing of bone fracture is occasionally impaired due to insufficient blood and cellular supply to the site of injury. In these cases, bone regeneration process is interrupted, which might result in delayed union or even nonunion of the fracture. Nonunion fracture is difficult to treat and have a high financial impact. In the last decade, numerous technological advancements in bone tissue engineering and cell-therapy opened new horizon in the field of bone regeneration. This review starts with presentation of the biological processes involved in bone development, bone remodeling, fracture healing process and the microenvironment at bone healing sites. Then, we discuss the rationale for using adult stem cells and listed the characteristics of the available cells for bone regeneration. The mechanism of action and epigenetic regulations for osteogenic differentiation are also described. Finally, we review the literature for translational and clinical trials that investigated the use of adult stem cells (mesenchymal stem cells, endothelial progenitor cells and CD34(+) blood progenitors) for bone regeneration.

Mesenchymal stem cells and endothelial progenitor cells stimulate bone regeneration and mineral density.

BACKGROUND Alveolar bone deficiency is a major clinical problem in maxillofacial reconstructive surgery. The available surgical techniques to enhance extracortical bone augmentation are generally unpredictable and not satisfying. The aim of the present study is to quantify extracortical bone augmentation and tissue mineral density (TMD) after cotransplantation of peripheral blood-derived endothelial progenitor cells (EPCs) and bone marrow-derived mesenchymal stem cells (MSCs) by microcomputed tomography (micro-CT). METHODS Bone regeneration was tested in the guided bone regeneration rat calvaria model. Gold domes filled with beta tricalcium phosphate (β-TCP; control [CNT]) or β-TCP mixed with 5 × 10(5) rat EPCs and 5 × 10(5) rat osteogenic transformed MSCs (EPC/otMSCs) were fixed to the exposed calvaria. Rats were sacrificed after 3 months. Bone volume fraction (BV/TV) and TMD were analyzed using micro-CT. In the middle of the dome, a cylindrical region of interest was defined (it represents the area in which implants are placed) and subdivided into bottom, middle, and top to analyze the effect of the distance from the calvaria on bone formation. RESULTS In the whole cylinder, BV/TV and TMD were higher in the EPC/otMSC group compared with CNT (BV/TV: 22.9% ± 4.4% versus 29.1 ± 2.2%, P = 0.02; TMD: 937.79 ± 18.68 versus 960.78 ± 5.8 mgHA/ccm, P = 0.03; CNT versus EPC/otMSC, respectively). In each of the three subregions, BV/TV was higher in the EPC/otMSC group compared with CNT (top: 20.25% ± 2.4% versus 23.74% ± 1.5%, P = 0.007; middle: 23.2% ± 4.8% versus 28% ± 2.2%, P = 0.05; bottom: 25.3% ± 7.6% versus 35.7% ± 4.9%, P = 0.02; CNT versus EPC/otMSC, respectively). CONCLUSION Three-dimensional quantification by micro-CT demonstrated that cotransplantation of EPC/otMSCs significantly improved bone formation and mineral density.

Peripheral Blood-Derived Endothelial Progenitor Cells Enhance Vertical Bone Formation

BACKGROUND This study presents a novel cell-based approach for extra-cortical bone regeneration. OBJECTIVE To enhance vertical bone formation by combining guided bone regeneration and transplantation of peripheral blood-derived endothelial progenitor cells (EPCs) in a rat calvaria model. MATERIALS AND METHODS EPCs were isolated from peripheral blood of inbred rats. Gold domes (7 mm radius, 5 mm height) were filled with β-tricalcium phosphate (βTCP) mixed with 5 × 10(5) EPC. Domes filled with βTCP served as control (CNT). Rats were sacrificed after 3 months. Vertical bone augmentation was analyzed using histology, histomorphometry, and microcomputed tomography (μCT). RESULTS In all rats, hard tissue filled the space under the dome. Histomorphometric analysis revealed that EPC transplantations doubled vertical bone height (EPC 4.04 ± 0.22 mm vs CNT 2.29 ± 0.22 mm, p ≤ .001). EPC also caused ∼50% increase in bone area fraction (EPC 47.3 ± 3.1% vs CNT 31.1 ± 2.7%, p ≤ .003). μCT results also showed that bone volume fraction (BV/TV) was higher in EPC group (p = .0169). In both groups, BV/TV declined from the bottom to the top of the samples. No differences in tissue mineral density were found between EPC and CNT groups. CONCLUSION EPC transplantation significantly improved bone formation especially in the areas that are remote from the original bone.

Ridge Preservation Using Composite Alloplastic Materials: A Randomized Control Clinical and Histological Study in Humans

AIM To evaluate (clinically, histologically, and histo-morphometrically) the use of composite materials (Biphasic calcium sulphate [BCS] with β Tri-Calcium Phosphate (β-TCP) and Hydroxyapatite [HA]) in extraction socket sites and compare it to un-disturbed natural healing. MATERIAL AND METHODS Prospective clinical trial of 36 patients (40 extraction sockets) were randomly assigned to either test or control group. Alveolar ridge horizontal dimension was measured in the middle of the socket at crest and 3 and 6 mm subcrestally. Crestal vertical height was measured at baseline surgery and at 4 month re-entry, at which time bone core biopsies were harvested from the center of the edentulous ridge. Histo-morphometric evaluation of the samples was performed using hematoxylin & eosin stains and morphometric software. RESULTS The change in horizontal ridge width was higher in the control compared to the experimental group: 2.28 ± 2.36 mm versus 0.03 ± 2.32 mm (p = .007) at -3 mm and 2.28 ± 2.43 versus 0.035 ± 3.05 (p = .02) at -6 mm, for the experimental and control sites, respectively. The vertical distance form bone crest to neighboring horizontal line interconnecting the neighboring teeth was minimal in both groups (0.307 ± 2.01 mm versus 0.14 ± 2.03 mm [p = 0.41]). Residual scaffolds occupied 15.99 ± 11.4% of the volume in the grafted (test) sites while bone area fraction was not statistically different among the groups (47.7 ± 10.6% versus 52.6 ± 11.6%, test versus control, respectively p = .39). The percentage of connective tissue in the control group was significantly higher that test group (36.3 ± 19.4% versus 46.7 ± 10.6% test versus control, respectively, p = .013). CONCLUSION Ridge preservation technique using a combination of two synthetic bone grafts β-TCP and HA with BCS resulted in greater stability in the horizontal dimension after 4 months.Aim To evaluate (clinically, histologically, and histo-morphometrically) the use of composite materials (Biphasic calcium sulphate [BCS] with β Tri-Calcium Phosphate (β-TCP) and Hydroxyapatite [HA]) in extraction socket sites and compare it to un-disturbed natural healing. Material and Methods Prospective clinical trial of 36 patients (40 extraction sockets) were randomly assigned to either test or control group. Alveolar ridge horizontal dimension was measured in the middle of the socket at crest and 3 and 6 mm subcrestally. Crestal vertical height was measured at baseline surgery and at 4 month re-entry, at which time bone core biopsies were harvested from the center of the edentulous ridge. Histo-morphometric evaluation of the samples was performed using hematoxylin & eosin stains and morphometric software. Results The change in horizontal ridge width was higher in the control compared to the experimental group: 2.28 ± 2.36 mm versus 0.03 ± 2.32 mm (p = .007) at −3 mm and 2.28 ± 2.43 versus 0.035 ± 3.05 (p = .02) at −6 mm, for the experimental and control sites, respectively. The vertical distance form bone crest to neighboring horizontal line interconnecting the neighboring teeth was minimal in both groups (0.307 ± 2.01 mm versus 0.14 ± 2.03 mm [p = 0.41]). Residual scaffolds occupied 15.99 ± 11.4% of the volume in the grafted (test) sites while bone area fraction was not statistically different among the groups (47.7 ± 10.6% versus 52.6 ± 11.6%, test versus control, respectively p = .39). The percentage of connective tissue in the control group was significantly higher that test group (36.3 ± 19.4% versus 46.7 ± 10.6% test versus control, respectively, p = .013). Conclusion Ridge preservation technique using a combination of two synthetic bone grafts β-TCP and HA with BCS resulted in greater stability in the horizontal dimension after 4 months.

Dimensional changes of the maxillary sinus following tooth extraction in the posterior maxilla with and without socket preservation

BACKGROUND Sinus pneumatization is commonly observed following tooth extraction in the posterior maxilla, however, the role of this pneumatization in the overall changes in the vertical bone height is not clear. PURPOSE To compare dimensional changes in the alveolar ridge and corresponding maxillary sinus following tooth extraction, with or without socket preservation. MATERIALS AND METHODS 42 patients underwent tooth extraction (control group) and 21 patients underwent tooth extraction with socket preservation using DBBM (study group). Panoramic radiographs, prior to and approximately 1 year post extractions were superimposed and matched using a fixed reference unit. The following measurements were performed in the midline of the tooth site: distance of the bone crest to the sinus floor; distance of the sinus floor to the sinus roof and the sagittal circumference of the maxillary. RESULTS The mean change in the distance from the sinus floor to the sinus roof pre and post operatively was 0.30 mm (±0.10 SE) in the study group and 1.30 mm (±0.27 SE) in the control group (P = .0221). The mean change in the distance from the bone crest to the sinus floor was 0.32 mm (±0.09 SE) in the study group and 1.26 mm (±0.28 SE) in the control group (P = .0019), and the mean change in the sinus sagittal circumference was 37.34 mm (±6.10 SE) and 125.95 mm (±15.60 SE), respectively (P = .0001). CONCLUSIONS Ridge preservation using bovine derived xenograft might reduce sinus pneumatization along with minimizing crestal bone resorption.

Intraoperative Measurement of the Distance from the Bottom of Osteotomy to the Mandibular Canal Using a Novel Ultrasonic Device.

BACKGROUND In our previous study, we found that a novel ultrasound (US) device may serve as a useful intraoperative tool to measure the distance from osteotomy to the inferior alveolar canal (IAC). PURPOSE To validate our previous results in a larger group of osteotomies in the posterior mandible. METHODS During dental implant placement surgery, osteotomies were created using a standardized 2-mm-diameter pilot drill. The distance from the bottom of the osteotome to the IAC was assessed using an ultrasonic device and compared with a standard panoramic radiograph used to measure the same residual distance. The total distance from the crestal bone to the IAC was measured on a preoperative computed tomography (CT) and compared with total US measurements by summing the drill depth with residual depth measurements. RESULTS Mean radiographic and US residual distances were 5.19 ± 1.95 mm, 5.01 ± 1.82 mm, p = 0.79 respectively. These measurements presented strong positive correlations (r = 0.61, p = .01). Mean total CT distance was 13.48 ± 2.66 mm; mean total US calculation was 13.69 ± 2.51 mm. No significant difference was found (p > .05). CONCLUSIONS The results support our previous pilot study and confirm that the tested US device identifies the IAC and measures the distance from the osteotomy to the roof of the mandibular canal.Background In our previous study, we found that a novel ultrasound (US) device may serve as a useful intraoperative tool to measure the distance from osteotomy to the inferior alveolar canal (IAC). Purpose To validate our previous results in a larger group of osteotomies in the posterior mandible. Methods During dental implant placement surgery, osteotomies were created using a standardized 2-mm-diameter pilot drill. The distance from the bottom of the osteotome to the IAC was assessed using an ultrasonic device and compared with a standard panoramic radiograph used to measure the same residual distance. The total distance from the crestal bone to the IAC was measured on a preoperative computed tomography (CT) and compared with total US measurements by summing the drill depth with residual depth measurements. Results Mean radiographic and US residual distances were 5.19 ± 1.95 mm, 5.01 ± 1.82 mm, p = 0.79 respectively. These measurements presented strong positive correlations (r = 0.61, p = .01). Mean total CT distance was 13.48 ± 2.66 mm; mean total US calculation was 13.69 ± 2.51 mm. No significant difference was found (p > .05). Conclusions The results support our previous pilot study and confirm that the tested US device identifies the IAC and measures the distance from the osteotomy to the roof of the mandibular canal.

A comparative study on the use of digital panoramic and periapical radiographs to assess proximal bone height around dental implants.

OBJECTIVE The purpose of this study was to compare periapical radiographs (PA) and panoramic radiographs (PAN) in the measurement of proximal bone height around implants. METHOD AND MATERIALS Patients files that contained digital PAN and PA together with information on implant lengths and diameters were selected for this study. For each radiograph, the implant size served as reference for calibration. Proximal radiographic bone levels and the linear distance between the bone crest and implant shoulder were measured twice by one examiner. Paired t test was used to assess intra-examiner variability and differences between the two radiographic methods. Correlation was then assessed using Pearson correlation coefficient test. Significance level was determined at 5%. RESULTS For the PAN measurements, the median mesial distances from bone crest to implant shoulder were 0.53 and 0.56 mm (first and second sets, P = .53). Likewise, for distal measurements these readings were 0.92 and 0.86 mm respectively (P = .66). For PA measurements, the corresponding measurements were 0.33 and 0.44 mm (P = .48) and 0.99 and 0.99 mm (P = .42), respectively. When PAN and PA measurements were compared, no statistically significant differences were detected between the two radiographic modalities. A very high positive correlation (r > 0.91) was attained for the PAN - PA measurements (P < .0001). CONCLUSION PAN are potentially as reliable and reproducible as PA for the assessment of proximal bone height around dental implants.

The association between shallow vestibular depth and peri‐implant parameters: a retrospective 6 years longitudinal study

AIM The aim of this study was to retrospectively evaluate the association between shallow vestibular depth (VD) and peri-implant parameters. MATERIAL AND METHODS Peri-implant parameters were evaluated in 61 periodontal patients under regular supportive periodontal therapy. Clinical parameters included gingival index (GI), plaque index (PI), bleeding on probing (BOP), peri-implant pocket depths (PPD), mucosal recession (MR), relative attachment level (RAL), width and thickness of keratinized mucosa (KMW, KMT) and VD. Radiographic bone level (RBL) was measured on peri-apical radiographs. RESULTS Sites with shallow VD (≤ 4 mm) were associated with higher MR (0.91 mm versus 0.47 mm, p ≤ 0.009), higher RAL (4.23 mm versus 3.59 mm, p ≤ 0.0001) and higher RBL (2.18 mm versus 1.7 mm, p = 0.05) when compared with adequate vestibular depth sites (VD > 4 mm). Moreover, sites with shallow VD presented lower KMW compared with sites with adequate VD (1.24 mm versus 2.38 mm, respectively, p ≤ 0.0001). Slightly greater BOP, and GI were recorded for the shallow VD compared with adequate sites. According to multivariate analysis, factors that could predict RAL included: VD, GI, age, supporting periodontal therapy, implant type and design. CONCLUSIONS Based on this study, inadequate vestibular depth around dental implants may be associated with increased peri-implant bone loss and mucosal recession. Further prospective and intervention studies will be required to fully understand this phenomenon.

Bone preservation in dehiscence-type defects using composite biphasic calcium sulfate plus biphasic hydroxyapatite/β-tricalcium phosphate graft: a histomorphometric case series in canine mandible.

Objectives: To examine bone formation in dehiscence defects using biphasic hydroxyapatite/&bgr;-tricalcium phosphate plus biphasic calcium sulfate (BCP/BCS). Material: After extractions, 24 mandibular buccal dehiscence defects (3 × 3 mm) were treated with BCP/BCS (E), membrane (MC), or control (NC). Histology and histomorphometric analysis were performed. Results: After 6 weeks, bone formation was noticeable in most sites. In subsequent phases, the woven bone was gradually remodeled into lamellar bone and marrow. Vertical new bone height in the E and MC groups (1.06 and 0.85 mm.) was substantially greater than that in the NC group (−0.28 mm). For all groups, there was an overall increase in the height of the newly formed bone through the observation. At week 12, the vertical bone height was 1.95, 2.07, and 0.29 mm, respectively. The mean new bone area in the E and MC groups was much greater than that in the NC group (2.85, 2.80, and −0.20 mm2, respectively). Percent new bone in all 3 groups was similar (36.25%, 34.84%, and 28.34%, respectively). Conclusions: This study demonstrates the efficacy of BCP/BCS graft for bone augmentation in dehiscence-type extraction socket defect.