Risk Factors for Early Dental Implant Failure.

PURPOSE: To report the prevalence of early implant failure and evaluate factors that contribute to the early failure of dental implants placed at a teaching clinic. The study also aims to identify risk indicators for early implant loss to better predict and prevent early implant loss in the future. MATERIALS AND METHODS: This retrospective study included all patients with a dental implant placed by the Section of Oral Surgery and Oral Medicine, Department of Clinical Dentistry, University of Bergen, between January 2011 and December 2018. All information was collected from operation logbooks and from patient records. A failed implant in this study was defined as an implant lost before functional loading. RESULTS: A total of 1,005 dental implants were placed in the studied time period, of which 54 failed early, giving an early failure rate (EFR) of 5.4%, with functional loading obtained for the remaining 94.6%. Analysis showed an increased hazard for early implant failure among smokers, men, and younger patients. With an age increase of 10 years, the risk of implant failure was reduced by 14% (hazard ratio [HRR] = 0.86, P = .037). A higher failure rate was found in anterior maxillary implants than in posterior maxillary implants (7.79% vs 3.29%, respectively; HRR = 0.47; P = .041). The probability for early failure in the posterior mandible was significantly increased compared to the posterior maxilla (HRR = 3.68, P = .005). If the first implant failed, it was more likely that the consecutive implant would also fail (HRR = 1.82). In the study, 53.4% of the placed implants were Straumann (EFR = 5.2%), 30.3% were Nobel Biocare (EFR = 7.2%), and 16.3% were Astra Tech (EFR = 2.5%). CONCLUSIONS: This study found that younger, male, and smoker patients were associated with an increase in early failure of dental implants. Significantly increased failure rates were also seen for implants placed in the mandible, and there were differences with respect to implant system. Although differences were found in early failure both for patient- and implant-related factors, the overall early failure rate (5.4%) in this study was low.

Polycrystalline Diamond Coating on Orthopedic Implants: Realization and Role of Surface Topology and Chemistry in Adsorption of Proteins and Cell Proliferation.

Polycrystalline diamond has the potential to improve the osseointegration of orthopedic implants compared to conventional materials such as titanium. However, despite the excellent biocompatibility and superior mechanical properties, the major challenge of using diamond for implants, such as those used for hip arthroplasty, is the limitation of microwave plasma chemical vapor deposition (CVD) techniques to synthesize diamond on complex-shaped objects. Here, for the first time, we demonstrate diamond growth on titanium acetabular shells using the surface wave plasma CVD method. Polycrystalline diamond coatings were synthesized at low temperatures (∼400 °C) on three types of acetabular shells with different surface structures and porosities. We achieved the growth of diamond on highly porous surfaces designed to mimic the structure of the trabecular bone and improve osseointegration. Biocompatibility was investigated on nanocrystalline diamond (NCD) and ultrananocrystalline diamond (UNCD) coatings terminated either with hydrogen or oxygen. To understand the role of diamond surface topology and chemistry in the attachment and proliferation of mammalian cells, we investigated the adsorption of extracellular matrix proteins and monitored the metabolic activity of fibroblasts, osteoblasts, and bone-marrow-derived mesenchymal stem cells (MSCs). The interaction of bovine serum albumin and type I collagen with the diamond surfaces was investigated by confocal fluorescence lifetime imaging microscopy (FLIM). We found that the proliferation of osteogenic cells was better on hydrogen-terminated UNCD than on the oxygen-terminated counterpart. These findings correlated with the behavior of collagen on diamond substrates observed by FLIM. Hydrogen-terminated UNCD provided better adhesion and proliferation of osteogenic cells, compared to titanium, while the growth of fibroblasts was poorest on hydrogen-terminated NCD and MSCs behaved similarly on all tested surfaces. These results open new opportunities for application of diamond coatings on orthopedic implants to further improve bone fixation and osseointegration.

Safety and Clinical Efficacy of Mesenchymal Stem Cell Treatment in Traumatic Spinal Cord Injury, Multiple Sclerosis and Ischemic Stroke - A Systematic Review and Meta-Analysis.

Background: Mesenchymal stem cells (MSCs) is an attractive candidate in regenerative research and clinical trials have assessed their therapeutic potential in different neurological conditions with disparate etiologies. In this systematic review, we aimed to assess safety and clinical effect of MSC treatment in traumatic spinal cord injury (TSCI), multiple sclerosis (MS) and ischemic stroke (IS). Methods: A systematic search was performed 2021-12-10 in MEDLINE, EMBASE, Web of Science and Cochrane where clinical studies assessing MSC treatment in TSCI, MS or IS were included. Studies without control group were excluded for efficacy analysis, but included in the safety analysis. For efficacy, AIS score, EDSS score and mRS were used as clinical endpoints and assessed in a meta-analysis using the random effects model. Findings: Of 5,548 identified records, 54 studies were included. Twenty-six studies assessed MSC treatment in TSCI, 14 in MS and nine in IS, of which seven, seven and five studies were controlled, respectively. There were seven serious adverse events (SAEs), of which four were related to the surgical procedure and included one death due to complications following the implantation of MSCs. Three SAEs were considered directly related to the MSC treatment and all these had a transient course. In TSCI, a meta-analysis showed no difference in conversion from AIS A to C and a trend toward more patients treated with MSCs improving from AIS A to B as compared to controls (p = 0.05). A subgroup analysis performed per protocol, showed more MSC treated patients improving from AIS A to C in studies including patients within 8 weeks after injury (p = 0.04). In MS and IS, there were no significant differences in clinical outcomes between MSC treated patients and controls as measured by EDSS and mRS, respectively. Interpretation: MSC-treatment is safe in patients with TSCI, MS and IS, although surgical implantation of MSC led to one fatal outcome in TSCI. There was no clear clinical benefit of MSC treatment, but this is not necessarily a proof of inefficacy due to the low number of controlled studies. Future studies assessing efficacy of MSC treatment should aim to do this in randomized, controlled studies.

An 8-10 Year Follow-up of Denture Satisfaction and Oral Health-Related Quality of Life with Implant-Retained Mandibular Overdentures.

PURPOSE: To report changes in denture satisfaction and oral health-related quality of life (OHRQoL) in edentulous patients treated with two-implant mandibular overdentures (IODs) over a follow-up of 8 to 10 years. MATERIALS AND METHODS: This is a follow-up of a previous study carried out between 1997 and 2005. The patients were originally randomly divided into one group receiving IODs and another group who had their conventional mandibular dentures relined (RCD group). The RCD group was offered and received IODs at the 2-year follow-up. The participants completed a self-administered questionnaire containing demographics, 15 variables related to denture satisfaction, and 20 questions from the Oral Health Impact Profile (OHIP-20). Changes over time were analyzed using multilevel linear models for denture satisfaction and multilevel ordinal regression analyses for OHIP-20 variables. Comparisons between groups were analyzed using Mann-Whitney U test for ordinal and t test for metric data. RESULTS: Disregarding patients who passed away during follow-up, the 29 responders represented a response rate of 76%. The degree of denture satisfaction and the OHIP-20 scores remained high and stable in the IOD group over the 10-year observation period for all but one variable. The same factors showed only a modest improvement in the RCD group for the first 2 years; however, during the subsequent 8 years of the observation period (after receiving IODs), denture satisfaction and OHIP-20 scores improved to the same level as the original IOD group. CONCLUSION: The positive effect on denture satisfaction and OHRQoL of edentulous patients treated with two-implant mandibular overdentures remained unchanged 8 to 10 years after treatment.

Transition of a Large Tertiary Heart Failure Program in Response to the COVID-19 Pandemic: Changes That Will Endure.

The coronavirus disease 2019 (COVID-19) pandemic imposed severe restrictions on traditional methods of patient care. During the pandemic, the heart failure program at New York-Presbyterian Hospital in New York, NY rapidly and comprehensively transitioned its care delivery model and administrative organization to conform to a new healthcare environment while still providing high-quality care to a large cohort of patients with heart failure, heart transplantation, and left ventricular assist device. In addition to the widespread adoption of telehealth, our program restructured outpatient care, initiating a shared clinic model and introducing a comprehensive remote monitoring program to manage patients with heart failure and heart transplant. All conferences, including administrative meetings, support groups, and educational seminars were converted to teleconferencing platforms. Following the peak of COVID-19, many of the new changes have been maintained, and the program structure will be permanently altered as a lasting effect of this pandemic. In this article, we review the details of our program's transition in the face of COVID-19 and highlight the programmatic changes that will endure.

Patient experience following iliac crest-derived alveolar bone grafting and implant placement.

BACKGROUND: The objective of this study was to assess patient-reported outcomes such as satisfaction and quality of life after advanced alveolar bone augmentation with anterior iliac crest grafting and implant treatment in orally compromised patients. METHODS: This cross-sectional retrospective cohort study included 59 patients (29 women and 30 men) with major functional problems, who underwent advanced alveolar augmentation with autologous iliac bone grafts during a 100-year period (2002-2012). The self-administered questionnaire included 36 validated questions related to (1) demographics, (2) perceived general and oral health, (3) donor site and hospitalization, (4) status of implants and/or prosthesis, and (5) oral health-related quality of life (OHRQoL). RESULTS: Questionnaires were completed by 44 patients: 24 women and 20 men (response rate, 74.6%). Most patients reported good tolerance of the operative iliac bone harvesting (85%) and implant (90%) procedures. Post-operative pain at the donor site was reported by 38%, lasting 18.1 ± 16.1 days. An average of 4.3 ± 3.5 days of hospitalization and 20.2 ± 18.5 days of sick leave was reported. The overall satisfaction with prosthetic reconstruction was 90.5%. OHRQoL was reported with a mean Oral Health Impact Profile-14 (OHIP-14) score of 8.4. CONCLUSION: Favorable OHRQoL and satisfaction were reported after advanced reconstruction of alveolar ridges with iliac crest-derived grafting and implants in severely compromised patients. However, this treatment requires substantial resources including hospitalization and sick leave.

Translation of a standardized manufacturing protocol for mesenchymal stromal cells: A systematic comparison of validation and manufacturing data.

BACKGROUND: Many data are available on expansion protocols for mesenchymal stromal cells (MSCs) for both experimental settings and manufacturing for clinical trials. However, there is a lack of information on translation of established protocols for Good Manufacturing Practice (GMP) from validation to manufacturing for clinical application. We present the validation and translation of a standardized pre-clinical protocol for isolation and expansion of MSCs for a clinical trial for reconstitution of alveolar bone. METHODS: Key parameters of 22 large-scale expansions of MSCs from bone marrow (BM) for validation were compared with 11 expansions manufactured for the clinical trial "Jaw bone reconstruction using a combination of autologous mesenchymal stromal cells and biomaterial prior to dental implant placement (MAXILLO1)" aimed at reconstruction of alveolar bone. RESULTS: Despite variations of the starting material, the robust protocol led to stable performance characteristics of expanded MSCs. Manufacturing of the autologous advanced therapy medicinal product MAXILLO-1-MSC was possible, requiring 21 days for each product. Transport of BM aspirates and MSCs within 24 h was guaranteed. MSCs fulfilled quality criteria requested by the national competent authority. In one case, the delivered MSCs developed a mosaic in chromosomal finding, showing no abnormality in differentiation capacity, growth behavior or surface marker expression during long-term culture. The proportion of cells with the mosaic decreased in long-term culture and cells stopped growth after 38.4 population doublings. CONCLUSIONS: Clinical use of freshly prepared MSCs, manufactured according to a standardized and validated protocol, is feasible for bone regeneration, even if there was a long local distance between manufacturing center and clinical site. Several parameters, such as colony forming units fibroblasts (CFU-F), percentage of CD34+ cells, cell count of mononuclear cells (MNCs) and white blood cells (WBCs), of the BM may serve as a predictive tool for the yield of MSCs and may help to avoid unnecessary costs for MSC manufacturing due to insufficient cell expansion rates.

Cell therapy induced regeneration of severely atrophied mandibular bone in a clinical trial.

BACKGROUND: Autologous grafting, despite some disadvantages, is still considered the gold standard for reconstruction of maxillofacial bone defects. The aim of this study was to evaluate bone regeneration using bone marrow-derived mesenchymal stromal cells (MSCs) in a clinical trial, a less invasive approach than autologous bone grafting. This comprehensive clinical trial included subjects with severe mandibular ridge resorption. METHODS: The study included 11 subjects aged 52-79 years with severe mandibular ridge resorption. Bone marrow cells were aspirated from the posterior iliac crest and plastic adherent cells were expanded in culture medium containing human platelet lysate. The MSCs and biphasic calcium phosphate granules as scaffolds were inserted subperiosteally onto the resorbed alveolar ridge. After 4-6 months of healing, new bone formation was assessed clinically and radiographically, as were safety and feasibility. Bone at the implant site was biopsied for micro-computed topography and histological analyses and dental implants were placed in the newly regenerated bone. Functional outcomes and patient satisfaction were assessed after 12 months. RESULTS: The bone marrow cells, expanded in vitro and inserted into the defect together with biphasic calcium phosphate granules, induced significant new bone formation. The regenerated bone volume was adequate for dental implant installation. Healing was uneventful, without adverse events. The patients were satisfied with the esthetic and functional outcomes. No side effects were observed. CONCLUSIONS: The results of this comprehensive clinical trial in human subjects confirm that MSCs can successfully induce significant formation of new bone, with no untoward sequelae. Hence, this novel augmentation procedure warrants further investigation and may form the basis of a valid treatment protocol, challenging the current gold standard. TRIAL REGISTRATION: EudraCT, 2012-003139-50. Registered on 21 August 2013. ClinicalTrials.gov, NCT 02751125 . Registered on 26 April 2016.

Bone marrow stromal cell paracrine factors direct osteo/odontogenic differentiation of dental pulp cells.

Growth factors play an important role in osteo/odontogenic differentiation of human dental pulp cells (hDPCs). The aim of this in vitro study was to compare the biological effects of recombinant human growth differentiation factor 5 (rhGDF-5) alone and a cocktail of soluble growth factors (conditioned medium) released from human bone marrow mesenchymal stem cells (hBMMSCs) on the morphology, proliferation and osteo/odontogenic differentiation potential of hDPCs. Passage 4 hDPCs were harvested for culture in four different media: (a) DMEM with 10% FBS, (b) odontogenic induction medium (OM), (c) OM plus 500 ng/mL rhGDF-5, and (d) OM plus conditioned medium (CM). Morphological changes at 48 and 120 h were determined by crystal violet staining. The proliferation rates at 3, 24, 48, and 120 h were assayed by MTT. Using real-time reverse transcription-polymerase chain reaction (RT-PCR), the mRNA levels of dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1), collagen type I (Col 1), Runt-related transcription factor 2 (Cbfa1/Runx2), alkaline phosphatase (ALP), osteocalcin (OC), ß3 tubulin (TUBB3), glial cell-derived neurotrophic factor (GDNF), angiopoietin-1 (Ang1), and vascular endothelial growth factor A (VEGFA), were determined at 2, 5, and 9 days. Protein expression of dental sialoprotein (DSP), DMP1, OC, and TUBB3 was recorded at 5 days, using western blot and immunocytochemistry. The effect of the different culture media on mineralization was determined by ALP staining at day 5 and Alizarin red S staining at days 7 and 14. In response to the different culture media, the shape of the hDPCs varied from spindled to polygonal and cuboidal. CM inhibited the cellular proliferation rate, while rhGDF-5 had no effect at early time points, but promoted cellular proliferation at 120 h of culture. In the CM group, the mRNA levels of Cbfa1/Runx2, Col 1, ALP, VEGFA, Ang1, and TUBB3 decreased and the levels of GDNF and OC increased. The mRNA levels of DSPP and DMP1 were inconsistent at the time points evaluated. The staining assays also demonstrated that compared with the other groups, the CM group exhibited lower expression of ALP and higher mineralization levels. Protein expression of DSP, DMP1, OC, and TUBB3 was pronounced by the CM-treated cells. It is concluded that under these in vitro conditions, CM released from hBMMSCs have a greater osteo/odontogenic inductive effect on hDPCs than rhGDF-5.

Effect of compressive force on human osteoblast-like cells and bone remodelling: an in vitro study.

OBJECTIVE: The aim of this study was to determine the effect of continuous compressive force (CF) on expression by human alveolar bone-derived osteoblasts (HOBs) of some specific molecules involved in bone remodelling. DESIGN: HOBs were cultured with or without CF (control, 2.0, 4.0gcm(-2)) for 1, 3 and 7 days. Expression of alkaline phosphatase (ALP), type I collagen (Col I), osteopontin (OPN), osteocalcin (OCN), transcription factor Runx2, receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG) and prostaglandin E2 (PGE2) was analysed by real-time-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and/or immunostaining. RESULTS: The results revealed that CF upregulated ALP and Col I expression at both messenger RNA (mRNA) and protein levels but did not affect expression of OPN and OCN mRNA. Runx2 mRNA was inhibited by CF, which also altered the expression of molecules involved in osteoclastogenesis, by enhancing RANKL expression and suppressing OPG expression. At 4.0gcm(-2) of CF, the expression of RANKL and PGE2 was significantly upregulated. CONCLUSION: The results suggest that initial application of CF on HOBs can simultaneously affect expression of markers related to both osteogenesis and osteoclastogenesis.