In vitro assessment of internal implant-abutment connections with different cone angles under static loading using synchrotron-based radiation.

BACKGROUND: The stability of implant-abutment connection is crucial to minimize mechanical and biological complications. Therefore, an assessment of the microgap behavior and abutment displacement in different implant-abutment designs was performed. METHODS: Four implant systems were tested, three with a conical implant-abutment connection based on friction fit and a cone angle < 12 ° (Medentika, Medentis, NobelActive) and a system with an angulated connection (< 40°) (Semados). In different static loading conditions (30 N - 90º, 100 N - 90º, 200 N - 30º) the microgap and abutment displacement was evaluated using synchrotron-based microtomography and phase-contrast radioscopy with numerical forward simulation of the optical Fresnel propagation yielding an accuracy down to 0.1 µm. RESULTS: Microgaps were present in all implant systems prior to loading (0.15-9 µm). Values increased with mounting force and angle up to 40.5 µm at an off axis loading of 100 N in a 90° angle. CONCLUSIONS: In contrast to the implant-abutment connection with a large cone angle (45°), the conical connections based on a friction fit (small cone angles with < 12°) demonstrated an abutment displacement which resulted in a deformation of the outer implant wall. The design of the implant-abutment connection seems to be crucial for the force distribution on the implant wall which might influence peri-implant bone stability.

Comparison of the 3D-microstructure of human alveolar and fibula bone in microvascular autologous bone transplantation: a synchrotron radiation µ-CT study.

Introduction: Autologous bone transplantation is successfully used in reconstructive surgery of large/critical-sized bone defects, whereby the microvascular free fibula flap is still regarded as the gold standard for the reconstruction of such defects in the head and neck region. Here, we report the morphological and lacunar properties of patient-paired bone samples from eight patients from the jaw (AB; recipient site) and the fibula (FB; donor site) on the micron length-scale using Synchrotron µ-CT. Insights into differences and similarities between these bone structures could offer a better understanding of the underlying mechanism for successful surgical outcomes and might clear the path for optimized, nature-inspired bone scaffold designs. Methods: Spatial vessel-pore arrangements, bone morphology, fluid-simulation derived permeability tensor, osteocyte lacunar density, and lacunar morphology are compared. Results: The orientation of the vessel system indicates a homogenous vessel orientation for AB and FB. The average mineral distance (50%) to the closest vessel boundary is higher in AB than in FB (the mean is 96 µm for AB vs. 76 µm for FB; p = 0.021). Average osteocyte lacunar density is found to be higher in AB than in FB (mean 22,874 mm3 vs. 19,376 mm3 for FB; p = 0.038), which might compensate for the high distance from the mineral to the nearest vessel. No significant differences in lacunar volume are found between paired AB and FB. Discussion: A comparable vessel network and similar distribution of vessel porosity between AB and FB may allow the FB graft to exhibit a high regeneration potential when connected to AB, and this might correlate with a high osteoinductive and osteoconductive potential of FB when connected to AB. Since widely used and potent synthetic bone grafts exist, new insight into the bone structure of well-established autologous bone grafts, such as the free fibula flap, could help to improve the performance of such materials and therefore the design of 3D scaffolds.

Association of sex steroid hormones and new bone formation rate after iliac onlay grafting: a prospective clinical pilot study.

PURPOSE: The present prospective study evaluates the association between new bone formation rate in the iliac onlay graft and sex steroid hormone serum levels. METHODS: A total of 15 partially or completely edentulous postmenopausal females and 9 males with less than 5 mm height of the remaining alveolar bone underwent iliac onlay grafting followed by dental implant placement using a two-stage approach. Sex hormone binding globulin and 17ß-estradiol serum levels were investigated by electrochemiluminescence immunoassay, while total testosterone level was analyzed using radioimmunoassay. At the time of implant placement, 12 weeks after grafting, bone biopsies were obtained and analyzed histomorphometrically. Statistical analysis was performed using linear mixed models. RESULTS: Grafting procedure was successfully performed in all patients. The mean new bone formation rate was 32.5% (116 samples). In men the mean new bone formation rate (38.1%) was significantly higher (p < 0.01) than in women (27.6%). Independent of gender 17ß-estradiol and testosterone were positively associated to overall new bone formation rate, albeit a significant influence was only seen for 17ß-estradiol in men (p = 0.020). Sex hormone binding globulin had no influence on new bone formation rate (p = 0.897). There was no significant association between new bone formation rate and age (p = 0.353) or new bone formation rate and body mass index (p = 0.248). CONCLUSION: Positive association of 17ß-estradiol as well as testosterone with new bone formation rate after iliac onlay grafting indicates a role of sex steroid hormones in alveolar bone regeneration, although the observed influence was only significant for 17ß-estradiol in men.

Comparison of the 3D-Microstructure Between Alveolar and Iliac Bone for Enhanced Bioinspired Bone Graft Substitutes.

In oral- and maxillofacial bone augmentation surgery, non-vascularized grafts from the iliac crest demonstrate better clinical performance than alveolar bone grafts. The underlying mechanisms are not fully understood but are essential for the enhancement of bone regeneration scaffolds. Synchrotron Radiation µ-CT at a pixel size of 2.3 µm was used to characterize the gross morphology and the vascular and osteocyte lacuna porosity of patient-matched iliac crest/alveolar bone samples. The results suggest a difference in the spatial distribution of the vascular pore system. Fluid simulations reveal the permeability tensor to be more homogeneous in the iliac crest, indicating a more unidirectional fluid flow in alveolar bone. The average distance between bone mineral and the closest vessel pore boundary was found to be higher in alveolar bone. At the same time, osteocyte lacunae density is higher in alveolar bone, potentially compensating for the longer average distance between the bone mineral and vessel pores. The present study comprehensively quantified and compared the 3D microarchitecture of intraindividual human alveolar and iliac bone. The identified difference in pore network architecture may allow a bone graft from the iliac crest to exhibit higher regeneration potential due to an increased capacity to connect with the surrounding pore network of the residual bone. The results may contribute to understanding the difference in clinical performance when used as bone grafts and are essential for optimization of future scaffold materials.

Efficacy of alternative or adjunctive measures to conventional non-surgical and surgical treatment of peri-implant mucositis and peri-implantitis: a systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy of alternative or adjunctive measures to conventional non-surgical or surgical treatment of peri-implant mucositis and peri-implantitis. MATERIAL AND METHODS: Prospective randomized and nonrandomized controlled studies comparing alternative or adjunctive measures, and reporting on changes in bleeding scores (i.e., bleed0ing index (BI) or bleeding on probing (BOP)), probing depth (PD) values or suppuration (SUPP) were searched. RESULTS: Peri-implant mucositis: adjunctive use of local antiseptics lead to greater PD reduction (weighted mean difference (WMD) = - 0.23 mm; p = 0.03, respectively), whereas changes in BOP were comparable (WMD = - 5.30%; p = 0.29). Non-surgical treatment of peri-implantitis: alternative measures for biofilm removal and systemic antibiotics yielded higher BOP reduction (WMD = - 28.09%; p = 0.01 and WMD = - 17.35%; p = 0.01, respectively). Surgical non-reconstructive peri-implantitis treatment: WMD in PD amounted to - 1.11 mm favoring adjunctive implantoplasty (p = 0.02). Adjunctive reconstructive measures lead to significantly higher radiographic bone defect fill/reduction (WMD = 56.46%; p = 0.01 and WMD = - 1.47 mm; p = 0.01), PD (- 0.51 mm; p = 0.01) and lower soft-tissue recession (WMD = - 0.63 mm; p = 0.01), while changes in BOP were not significant (WMD = - 11.11%; p = 0.11). CONCLUSIONS: Alternative and adjunctive measures provided no beneficial effect in resolving peri-implant mucositis, while alternative measures were superior in reducing BOP values following non-surgical treatment of peri-implantitis. Adjunctive reconstructive measures were beneficial regarding radiographic bone-defect fill/reduction, PD reduction and lower soft-tissue recession, although they did not improve the resolution of mucosal inflammation.

Influence of Medical and Geriatric Factors on Implant Success: An Overview of Systematic Reviews.

PURPOSE: To provide an overview of the influence of medical and geriatric factors on implant survival in order to form clinical recommendations for the practitioner. MATERIALS AND METHODS: This narrative literature review was performed to address the following questions: (1) Is age (> 75 years) a risk factor for implant survival?; (2) Is diabetes mellitus a risk factor for implant survival?; and (3) Is antiresorptive therapy a risk factor for implant survival? The PubMed, Web of Knowledge (Thomson Reuters), and Google Scholar databases were searched for systematic reviews and research papers of evidence level II and above that were published up to February 2019 for each topic. RESULTS: (1) Age > 75 years does not affect implant survival according to short-term follow up (1 to 5 years). However, polypharmacy should be considered in this patient group. (2) Diabetes mellitus is not a risk factor for implant survival in the short term, but there is no information on appropriate perioperative treatment and wound closure. There is little evidence in the literature on the success of bone grafting and progressive loading protocols in diabetic patients. (3) Implant therapy cannot be recommended in patients under high-dose bisphosphonate and antibody therapy. Bone grafting should be avoided under antiresorptive therapy. There are no treatment regimens available for patients with peri-implantitis receiving antiresorptive medication. CONCLUSION: This review suggests that the risk assessment for an implant patient should not be based on age, but rather on the patient's specific risk factors, such as former and current diseases and medication.

Characterization of macrophages infiltrating peri-implantitis lesions.

OBJECTIVES: The mechanisms involved in the initiation and progression of peri-implantitis lesions are poorly understood. It was the aim to determine the content and activation status of macrophages present in human peri-implantitis lesions and compare the current findings with the macrophage polarization associated with periodontitis lesions. MATERIAL AND METHODS: A total of 14 patients were studied in this investigation. Seven were soft tissue biopsies from dental implants affected by peri-implantitis that required explantation. Seven biopsies were from chronic periodontal disease. Immunofluorescence stains were performed using biomarkers to identify macrophages (CD68+ ) undergoing M1 polarization (iNOS+ ) and M2 polarization (CD206+ ), along with Hoechst 33,342 to identify DNA content. All samples were stained and photographed, and double-positive cells for CD68 and iNOS or CD68 and CD206 were quantified. RESULTS: All peri-implantitis biopsies examined revealed a mixed population of macrophages undergoing M1 polarization and M2 polarization. Further analysis demonstrated the co-expression of iNOS and CD206, which indicates the presence of a heterogenic immune response on peri-implantitis lesions. Macrophage polarization in peri-implantitis lesions presents a distinct pattern than in periodontitis. We observed a significant increase in the population of M1 macrophages on peri-implantitis samples compared to periodontal disease samples. CONCLUSION: Our results demonstrate that peri-implantitis has higher numbers of macrophages displaying a distinct macrophage M1 polarization signature compared to periodontitis lesions. This pattern may explain, in part, the distinct nature of peri-implantitis progression vs. periodontitis in humans.

Characterization of macrophage polarization in periodontal disease.

AIM: To explore the M1/M2 status of macrophage polarization from healthy, gingivitis, and periodontitis patient samples. MATERIALS AND METHODS: Gingival biopsies were collected from 42 individuals (14 gingivitis, 18 periodontitis, and 10 healthy samples) receiving periodontal therapy. Histomorphology analysis was performed with haematoxylin and eosin staining. Immunofluorescence was performed using a combination of CD68 (macrophages), iNOS (M1), and CD206 (M2) in order to acquire changes in macrophage polarization at a single-cell resolution. Macrophages were quantified under microscopy using narrow wavelength filters to detect Alexa 488, Alexa 568, Alexa 633 fluorophores, and Hoechst 33342 to identify cellular DNA content. RESULTS: Gingivitis and periodontitis samples showed higher levels of macrophages compared with healthy samples. Unexpectedly, periodontitis samples displayed lower levels of macrophages dispersed in the stromal tissues compared with gingivitis samples; however, it remained higher than healthy tissues. The polarization of macrophages appears to be reduced in periodontitis and showed similar levels to those observed in healthy tissues. CONCLUSIONS: Our study found that gingivitis and periodontitis differ from each other by the levels of macrophage infiltrate, but not by changes in macrophage polarization.

Sclerostin-Neutralizing Antibody Enhances Bone Regeneration Around Oral Implants.

BACKGROUND: Dental implants are an important option for replacement of missing teeth. A major clinical challenge is how best to accelerate bone regeneration and reduce the healing time for functional restoration after implant placement. A sclerostin-neutralizing antibody (Scl-Ab) has been shown to enhance alveolar bone formation and fracture repair. The aim of this study was to investigate the effects of systemic administration of Scl-Ab on dental implant osseointegration and bone regeneration in an experimental alveolar ridge tooth extraction model. MATERIALS AND METHODS: To investigate the effects of Scl-Ab on bone regeneration and dental implant osseointegration, an experimental alveolar bone osteotomy rat model was adopted. One month after extraction of maxillary right first molars, osteotomy defects were created at the coronal aspect of each of the extraction sites, and 1 × 2-mm custom titanium implants were installed into the osteotomies. Coincident with implant placement, Scl-Ab was administered subcutaneously at a dose of 25 mg/kg twice weekly for 10-28 days and compared with a vehicle control. Animals were sacrificed 10, 14, and 28 days after surgery, and maxillae were harvested and analyzed by microcomputed tomography (microCT), histology, and histomorphometry. RESULTS: microCT analysis demonstrated that the maxillary bone volume fraction was approximately 2- to 2.5-fold greater in Scl-Ab-treated animals compared with vehicle alone at days 14 and 28. Consistent with those findings, two-dimensional bone fill percentages within the coronal osteotomy sites were highest in Scl-Ab treatment groups at 28 days. In addition, bone-implant contact at 28 days was approximately twofold greater in the Scl-Ab group compared with the vehicle control. CONCLUSIONS: These results indicate that systemic Scl-Ab administration enhances osseointegration and bone regeneration around dental implants. This approach offers potential as a treatment modality for patients with low bone mass or bone defects to achieve more predictable bone regeneration at alveolar bone defects and to enhance dental implant osseointegration.

Detection of major histocompatibility complex molecules in processed allogeneic bone blocks for use in alveolar ridge reconstruction.

OBJECTIVES: Because processed allogenic bone blocks contain remnants of cells and other organic material, the present study examined the putative presence of major histocompatibility complex (MHC) molecules in protein extracts derived from processed allogeneic bone blocks. STUDY DESIGN: Protein content and the immunogenic potential of 3 different processed allografts (Osteograft, DIZG, Berlin, Germany; Caput femoris, DIZG, Berlin, Germany; Human Spongiosa, Charité Tissue Bank, Berlin, Germany) were assessed by protein extraction and analysis of the presence of MHC class 1 and 2 molecules prior to grafting. MHC concentration was measured by using enzyme-linked immunosorbent assay. RESULTS: Protein content in the allograft materials varied between 0.87 and 1.61 µg protein/mg. In the allograft Human Spongiosa, no MHC was detected, whereas in the allogeneic bone blocks Osteograft and Caput femoris MHC 1 (0.04-0.037 ng/mg graft material) and in Osteograft MHC class 2 molecules were detectable. CONCLUSIONS: The results of the present study suggest that despite thorough processing, a potential antigenicity of allografts is not eliminated. MHC molecules in allografts may sensitize the immune system.

Periodontal Tissue Bioengineering: Is the Future Now?

Periodontitis affects nearly half of the adult population in the United States and leads to periodontium destruction, tooth loss, and tooth mobility. Novel bioengineering has become an area of interest in dentistry, as various approaches aim to regenerate attachment apparatus around diseased teeth with the use of barriers, scaffolds, bone grafts, or biologics. This article emphasizes recent findings in the fields of stem cell/gene therapy, 3-dimensional printing, and innovative scaffold designs for future applications in clinical care.

Clinical trial and in-vitro study comparing the efficacy of treating bony lesions with allografts versus synthetic or highly-processed xenogeneic bone grafts.

BACKGROUND: Our study aim was to compare allogeneic cancellous bone (ACB) and synthetic or highly-processed xenogeneic bone substitutes (SBS) in the treatment of skeletal defects in orthopedic surgery. METHODS: 232 patients treated for bony lesions with ACB (n = 116) or SBS (n = 116) within a 10-year time period were included in this case-control study. Furthermore, both materials were seeded with human osteoblasts (hOB, n = 10) and analyzed by histology, for viability (AlamarBlue®) and protein expression activity (Luminex®). RESULTS: The complication rate was 14.2 %, proportion of defects without bony healing 3.6 %; neither outcome parameter differed comparing the intervention groups. Failed consolidation correlated with an increase in complications (p < 0.03). The rate of complications was further highly significant in association with the location of use (p < 0.001), but did not depend on age, ASA risk classification, BMI, smoking behavior or type of insurance. However, those factors did significantly influence the bony healing rate (p < 0.02). Complication and consolidation rates were independent of gender and the filling substances employed within the different locations. Histological examination revealed similar bone structures, whereas cell remnants were apparent only in the allografts. Both materials were biocompatible in-vitro, and seeded with human osteoblasts. The cells remained vital over the 3-week culture period and produced microscopically typical bone matrix. We observed initially increased expression of osteocalcin, osteopontin, and osteoprotegerin as well as leptin and adiponectin secretion declining after 1 week, especially in the ACB group. CONCLUSION: Although both investigated materials appeared to be similarly suitable for the treatment of skeletal lesions in-vivo and in-vitro, outcome was decisively influenced by other factors such as the site of use or epidemiological parameters.

Pilot investigation of the molecular discrimination of human osteoblasts from different bone entities.

In oral and maxillofacial surgery, autologous grafts from the iliac crest remain the 'gold standard' for alveolar ridge reconstruction, whereas intraoral bone grafts are considered in smaller defects. To date, a comparison of the osteogenic potential of osteoblasts with regard to their tissue origin is missing. Primary osteoblasts have proven useful for the investigation of the tissue-specific osteogenic properties. The present study compares primary human alveolar (aHOBs) and iliac osteoblasts (iHOBs) derived from three female patients undergoing routine intraoral bone grafting. Proliferation potential of the osteoblasts was evaluated using real-time impedance monitoring. Relative gene expression of bone specific biomarkers was analyzed and quantified using quantitative polymerase chain reactions (qPCR). Immunohistochemistry and phase contrast microscopy were performed, as well as alkaline phosphatase assay and alizarin red staining to visualize morphology and mineralization capacity. A twofold faster proliferation rate of aHOBs compared with iHOBs (130 h vs. 80 h) was observed. Alkaline phosphatase activity and alizarin red staining in both HOBs indicated similar mineralization capacity. Gene expression of seven genes (BMP1, CSF-1, TGFBR1, ICAM1, VCAM1, SPP1 and DLX5) was significantly higher in iHOB than in aHOB samples. These data suggest a higher osteogenic potential of osteoblasts derived from the iliac crest compared with primary osteoblasts from the alveolar bone and may lead to a better understanding of the molecular impact of bone cells from different bone entities on bone regeneration in alveolar ridge reconstructions.

Dentoalveolar reconstruction: modern approaches.

PURPOSE OF REVIEW: A variety of bone grafting materials is available to facilitate the augmentation of defective alveolar ridges. This review evaluates current literature regarding bone grafting materials with emphasis on autologous and allogeneic bone block augmentation. RECENT FINDINGS: Autogenous bone is a reliable grafting material providing predictable long-term results with high implant survival/success rates and low morbidity rates. The resorption properties of the iliac crest are well known and are compared with calvarial grafts more prominent. Recent studies demonstrated surgical techniques to prevent graft resorption after iliac crest grafting. Allogeneic block graft and implant survival rates appear promising in short-term clinical studies. SUMMARY: At this stage, iliac crest remains the gold standard in large alveolar bone defects. Autogenous material is not a panacea; however, none of the available materials can currently surpass it. Rather, each material has its specific advantage for certain indications. Evident long-term studies of allogeneic bone grafting are lacking. Detected cells in allogeneic bone substitute material are positive for major histocompatibility complex classes I and II. Despite the promising clinical results achieved with allogeneic bone grafts, the current literature lacks sufficient data on antigenicity.

Comparison of four different allogeneic bone grafts for alveolar ridge reconstruction: a preliminary histologic and biochemical analysis.

OBJECTIVES: Allograft material for alveolar ridge reconstruction is quite promising and appears to be as equally successful as bone autograft material. The aim of the present study was to compare four different allogeneic bone grafts in terms of their histologic structure and DNA content before grafting. STUDY DESIGN: Four allograft specimens from different suppliers were analyzed histologically, and the DNA content was analyzed before clinical use of the allografts. RESULTS: Organic tissue remnants were detected in all of the evaluated samples. In the present samples adipocytes, fibroblasts, osteocytes, and chondrocytes were identified and DNA isolation and purification was possible. CONCLUSION: Demineralized freeze-dried allogeneic bone transplants can stimulate new bone formation and are a viable alternative to bone autograft material. However, the well-tolerated use of allograft material in regard to our findings should be further investigated.