Initial retention force of three attachment systems for implant retained-mandibular overdentures: An in vitro study.

PURPOSE: To evaluate and compare the initial retention force of three resilient unsplinted attachment systems for implant-retained mandibular overdentures: two cylindrical attachment systems (Locator R-Tx® and Novaloc®), and one ball attachment system (Ball System). MATERIALS AND METHODS: For each attachment system, initial retention is measured as the average of the maximal dislodging forces during 10 insertion-removal cycles. For the Ball System, three activation degrees of the matrix are included versus four and six color-coded retention devices for the Locator R-Tx® and the Novaloc®, respectively, to represent the complete regular retention devices panel. For each retention device or activation degree, eight samples are tested. RESULTS: The initial retention range is similar between the Ball System (7.7 ± 3.4 N - 19.9 ± 4.6 N) and the Novaloc® (2.0 ± 0.5 N - 18.9 ± 1.4 N) and broader for the Locator R-Tx® (3.3 ± 5.0 N - 60.2 ± 6.0 N). In each attachment system, the initial retention of each retention device is significantly different from the others, except for the two most retentive Novaloc® ones. Retention devices were also classified according to their initial retention (low, medium, and maximum). In each retention group, the Novaloc® and the Ball System provided similar retention values lower than the Locator R-Tx®. CONCLUSION: Most of the retention devices tested provided an initial retention force of over 5 N for all three attachment systems. The Locator R-Tx® had the most comprehensive range, and the Novaloc® seemed to provide the most reproducible values, unlike the Ball System due to the activation required by the operator.

Retention loss and wear assessment of three attachment systems for implant retained-mandibular overdentures: An in vitro study.

BACKGROUND: The stud-shaped attachment systems (AS) with different shape designs (ball, cylindrical, conical) and materials (metallic, plastic, or a combination of both) are commonly used to provide better retention and stability in implant-retained mandibular overdentures (IRMO). PURPOSE: The purpose of the present study was to evaluate and compare the retention loss and the wear (patterns, location, material loss) of three resilient unsplinted AS: a well-established ball attachment system (BAS) and two more recent cylindrical attachment systems (CAS), Locator R-Tx® and Novaloc®. MATERIALS AND METHODS: The implants, their corresponding abutments, the color-coded or position-coded retention devices (RD), the matrix metal housing were incorporated within CAD/CAM resin blocks and cyclically loaded with 19.6 N along the implant axis in a chewing machine to simulate 10,000 insertion-removal cycles (IRC). At cycle 10, 100, 1,000, 5,000, and 10,000, the retention force was measured using a universal testing machine. The wear was qualitatively examined using a binocular magnifier for both systems, and quantitatively assessed from micro-computed tomography acquisitions for CAS. Material loss exceeding 50 µm was considered significant. RESULTS: The three AS showed different retentive behavior along time. All the Locator R-Tx® RD lost more than 50 % of their retention after 10,000 IRC. The retention of the Ball System slightly varied over time, the final retention loss in Bmed and Bmax groups being lower than 25 % of the initial retention. Wear was located at the tip of their gold RD and at the equator area of their ball abutment. For Locator R-Tx®, the more retentive the plastic RD, the greater its wear and retention loss. Only Novaloc® maintained a stable retention with even a slight tendency to increase and showed a negligible wear. Implant abutments of the CAS showed no significant wear. CONCLUSION: After 10,000 IRC, corresponding to approximately 5-years clinical use, almost all RD provided retention force over 5 N, which could be sufficient to maintain satisfaction in most of the patients. The retention loss observed most prominently for the Locator R-Tx®, then for the Ball System, seemed to correlate with the wear observed on their RD. The practitioner may expect less RD maintenance with the Novaloc® stable retention overtime.

Boron substitution in silicate bioactive glass scaffolds to enhance bone differentiation and regeneration.

Commercially available bioactive glasses (BAGs) are exclusively used in powder form, due to their tendency to crystallize. Silicate BAG 1393 was developed to allow fiber drawing and scaffold sintering, but its slow degradation limits its potential. To enable scaffold manufacturing while maintaining glass dissolution rate close to that of commercially available BAGs, the borosilicate glass 1393B20 was developed. This study investigates the potential of 1393B20 scaffolds to support bone regeneration and mineralization in vitro and in vivo, in comparison to silicate 1393. Both scaffolds supported human adipose stem cells proliferation, either in direct contact for the 1393, or mainly around for the 1393B20. Similarly, both BAGs induced osteogenesis and angiogenesis in vitro, with a better pro-angiogenic influence of the 1393B20. In addition, these scaffolds supported bone regeneration and osteoclast/osteoblast activity in vivo in critical-sized rat calvarial defect. Nevertheless, mineralization and collagen formation were significantly enhanced for the 1393B20, at 3-months post-implantation, assigned to faster and more complete dissolution of the scaffolds. Thus, 1393B20 demonstrates greater promise for bone tissue engineering certainly due to its time-controlled release of boron and silicon. STATEMENT OF SIGNIFICANCE: Bioactive glasses (BAGs) show great promise in bone tissue engineering as they effectively bond with bone tissue, fostering integration and regeneration. Silicate BAG 1393 was developed to allow fiber drawing and scaffold sintering, but its slow degradation limits its potential. To enable scaffold manufacturing while maintaining glass dissolution rate close to that of commercially available BAGs, the borosilicate glass 1393B20 was developed. Both BAGs induced osteogenesis and angiogenesis in vitro, with a better pro-angiogenic influence of the 1393B20. The presence of boron in the 1393B20 enhanced mineralization and collagen formation in vivo compared to 1393, probably due to its faster dissolution rate. Here, 1393B20 demonstrated greater promise for bone tissue engineering compared to the well-known 1393 BAG.

Implantation of engineered human microvasculature to study human infectious diseases in mouse models.

Animal models for studying human pathogens are crucially lacking. We describe the implantation in mice of engineered human mature microvasculature consisting of endothelial and perivascular cells embedded in collagen hydrogel that allows investigation of pathogen interactions with the endothelium, including in vivo functional studies. Using Neisseria meningitidis as a paradigm of human-restricted infection, we demonstrated the strength and opportunities associated with the use of this approach.

Evaluation of Retention, Wear, and Maintenance of Attachment Systems for Single- or Two-Implant-Retained Mandibular Overdentures: A Systematic Review.

Attachment systems (AS) enhance retention and stability by anchoring the overdentures to implants. Since 2002, the McGill consensus statement recommends the 2-implant-retained overdentures as the standard choice for edentulous mandible (2-IRMO). Considering the large number of AS available, it remains difficult for a practitioner to make a reasoned choice. A systematic review was conducted in PubMed/Medline and carried out independently by three authors, on retention, wear, and maintenance of AS used clinically or in vitro specifically for 1- or 2-IRMO. The 45 selected studies include 14 clinical and 31 in vitro studies. The risk of bias was evaluated according to the revised Cochrane risk of bias tool for randomized trials (RoB 2). The initial retention force of the cylindrical system is higher than the ball system. The retention loss, related to the wear of the retention device, is responsible for the most common need of maintenance, requiring activation or replacement. Plastic retention devices wear out faster and more significantly than metal ones, implying a worse time behavior of cylindrical systems, but their maintenance rate is similar. Neither system appears categorically superior. Cylindrical systems provide higher initial retention than ball ones; this advantage reduces over time with wear without affecting their need for maintenance.

Hybrid Mineral/Organic Material Induces Bone Bridging and Bone Volume Augmentation in Rat Calvarial Critical Size Defects.

In craniofacial bone defects, the promotion of bone volume augmentation remains a challenge. Finding strategies for bone regeneration such as combining resorbable minerals with organic polymers would contribute to solving the bone volume roadblock. Here, dicalcium phosphate dihydrate, chitosan and hyaluronic acid were used to functionalize a bone-side collagen membrane. Despite an increase in the release of inflammatory mediators by human circulating monocytes, the in vivo implantation of the functionalized membrane allowed the repair of a critical-sized defect in a calvaria rat model with de novo bone exhibiting physiological matrix composition and structural organization. Microtomography, histological and Raman analysis combined with nanoindentation testing revealed an increase in bone volume in the presence of the functionalized membrane and the formation of woven bone after eight weeks of implantation; these data showed the potential of dicalcium phosphate dihydrate, chitosan and hyaluronic acid to induce an efficient repair of critical-sized bone defects and establish the importance of thorough multi-scale characterization in assessing biomaterial outcomes in animal models.

The Potential of FGF-2 in Craniofacial Bone Tissue Engineering: A Review.

Bone is a hard-vascularized tissue, which renews itself continuously to adapt to the mechanical and metabolic demands of the body. The craniofacial area is prone to trauma and pathologies that often result in large bone damage, these leading to both aesthetic and functional complications for patients. The "gold standard" for treating these large defects is autologous bone grafting, which has some drawbacks including the requirement for a second surgical site with quantity of bone limitations, pain and other surgical complications. Indeed, tissue engineering combining a biomaterial with the appropriate cells and molecules of interest would allow a new therapeutic approach to treat large bone defects while avoiding complications associated with a second surgical site. This review first outlines the current knowledge of bone remodeling and the different signaling pathways involved seeking to improve our understanding of the roles of each to be able to stimulate or inhibit them. Secondly, it highlights the interesting characteristics of one growth factor in particular, FGF-2, and its role in bone homeostasis, before then analyzing its potential usefulness in craniofacial bone tissue engineering because of its proliferative, pro-angiogenic and pro-osteogenic effects depending on its spatial-temporal use, dose and mode of administration.

Microvascular maturation by mesenchymal stem cells in vitro improves blood perfusion in implanted tissue constructs.

Blood perfusion of grafted tissue constructs is a hindrance to the success of stem cell-based therapies by limiting cell survival and tissue regeneration. Implantation of a pre-vascularized network engineered in vitro has thus emerged as a promising strategy for promoting blood supply deep into the construct, relying on inosculation with the host vasculature. We aimed to fabricate in vitro tissue constructs with mature microvascular networks, displaying perivascular recruitment and basement membrane, taking advantage of the angiogenic properties of dental pulp stem cells and self-assembly of endothelial cells into capillaries. Using digital scanned light-sheet microscopy, we characterized the generation of dense microvascular networks in collagen hydrogels and established parameters for quantification of perivascular recruitment. We also performed original time-lapse analysis of stem cell recruitment. These experiments demonstrated that perivascular recruitment of dental pulp stem cells is driven by PDGF-BB. Recruited stem cells participated in deposition of vascular basement membrane and vessel maturation. Mature microvascular networks thus generated were then compared to those lacking perivascular coverage generated using stem cell conditioned medium. Implantation in athymic nude mice demonstrated that in vitro maturation of microvascular networks improved blood perfusion and cell survival within the construct. Taken together, these data demonstrate the strong potential of in vitro production of mature microvasculature for improving cell-based therapies.

Priming Dental Pulp Stem Cells from Human Exfoliated Deciduous Teeth with Fibroblast Growth Factor-2 Enhances Mineralization Within Tissue-Engineered Constructs Implanted in Craniofacial Bone Defects.

The craniofacial area is prone to trauma or pathologies often resulting in large bone damages. One potential treatment option is the grafting of a tissue-engineered construct seeded with adult mesenchymal stem cells (MSCs). The dental pulp appears as a relevant source of MSCs, as dental pulp stem cells display strong osteogenic properties and are efficient at bone formation and repair. Fibroblast growth factor-2 (FGF-2) and/or hypoxia primings were shown to boost the angiogenesis potential of dental pulp stem cells from human exfoliated deciduous teeth (SHED). Based on these findings, we hypothesized here that these primings would also improve bone formation in the context of craniofacial bone repair. We found that both hypoxic and FGF-2 primings enhanced SHED proliferation and osteogenic differentiation into plastically compressed collagen hydrogels, with a much stronger effect observed with the FGF-2 priming. After implantation in immunodeficient mice, the tissue-engineered constructs seeded with FGF-2 primed SHED mediated faster intramembranous bone formation into critical size calvarial defects than the other groups (no priming and hypoxia priming). The results of this study highlight the interest of FGF-2 priming in tissue engineering for craniofacial bone repair. Stem Cells Translational Medicine 2019;8:844&857.

Early angiogenesis detected by PET imaging with 64Cu-NODAGA-RGD is predictive of bone critical defect repair.

Therapies using stem cells may be applicable to all fields of regenerative medicine, including craniomaxillofacial surgery. Dental pulp stem cells (DPSCs) have demonstrated in vitro and in vivo osteogenic and proangiogenic properties. The aim of the study was to evaluate whether early angiogenesis investigated by nuclear imaging can predict bone formation within a mouse critical bone defect. Two symmetrical calvarial critical-sized defects were created. Defects were left empty or filled with i) DPSC-containing dense collagen scaffold, ii) 5% hypoxia-primed DPSC-containing dense collagen scaffold, iii) acellular dense collagen scaffold, or iv) left empty. Early angiogenesis assessed by PET using 64Cu-NODAGA-RGD as a tracer was found to be correlated with bone formation determined by micro-CT within the defects from day 30, and to be correlated to the late calcium apposition observed at day 90 using 18F-Na PET. These results suggest that nuclear imaging of angiogenesis, a technique applicable in clinical practice, is a promising approach for early prediction of bone grafting outcome, thus potentially allowing to anticipate alternative regenerative strategies. STATEMENT OF SIGNIFICANCE: Bone defects are a major concern in medicine. As life expectancy increases, the number of bone lesions grows, and occurring complications lead to a delay or even lack of consolidation. Therefore, to be able to predict healing or the absence of scarring at early times would be very interesting. This would not "waste time" for the patient. We report here that early nuclear imaging of angiogenesis, using 64Cu-NODAGA-RGD as a tracer, associated with nuclear imaging of mineralization, using 18F-Na as a tracer, is correlated to late bone healing objectivized by classical histology and microtomography. This nuclear imaging represents a promising approach for early prediction of bone grafting outcome in clinical practice, thus potentially allowing to anticipate alternative regenerative strategies.

Priming Dental Pulp Stem Cells With Fibroblast Growth Factor-2 Increases Angiogenesis of Implanted Tissue-Engineered Constructs Through Hepatocyte Growth Factor and Vascular Endothelial Growth Factor Secretion.

Tissue engineering strategies based on implanting cellularized biomaterials are promising therapeutic approaches for the reconstruction of large tissue defects. A major hurdle for the reliable establishment of such therapeutic approaches is the lack of rapid blood perfusion of the tissue construct to provide oxygen and nutrients. Numerous sources of mesenchymal stem cells (MSCs) displaying angiogenic potential have been characterized in the past years, including the adult dental pulp. Establishment of efficient strategies for improving angiogenesis in tissue constructs is nevertheless still an important challenge. Hypoxia was proposed as a priming treatment owing to its capacity to enhance the angiogenic potential of stem cells through vascular endothelial growth factor (VEGF) release. The present study aimed to characterize additional key factors regulating the angiogenic capacity of such MSCs, namely, dental pulp stem cells derived from deciduous teeth (SHED). We identified fibroblast growth factor-2 (FGF-2) as a potent inducer of the release of VEGF and hepatocyte growth factor (HGF) by SHED. We found that FGF-2 limited hypoxia-induced downregulation of HGF release. Using three-dimensional culture models of angiogenesis, we demonstrated that VEGF and HGF were both responsible for the high angiogenic potential of SHED through direct targeting of endothelial cells. In addition, FGF-2 treatment increased the fraction of Stro-1+/CD146+ progenitor cells. We then applied in vitro FGF-2 priming to SHED before encapsulation in hydrogels and in vivo subcutaneous implantation. Our results showed that FGF-2 priming is more efficient than hypoxia at increasing SHED-induced vascularization compared with nonprimed controls. Altogether, these data demonstrate that FGF-2 priming enhances the angiogenic potential of SHED through the secretion of both HGF and VEGF.