Xerostomia is the phenomenon of dry mouth and is mostly caused by hypofunction of the salivary glands. This hypofunction can be caused by tumors, head and neck irradiation, hormonal changes, ...inflammation or autoimmune disease such as Sjögren's syndrome. It is associated with a tremendous decrease in health-related quality of life due to impairment of articulation, ingestion and oral immune defenses. Current treatment concepts mainly consist of saliva substitutes and parasympathomimetic drugs, but the outcome of these therapies is deficient. Regenerative medicine is a promising approach for the treatment of compromised tissue. For this purpose, stem cells can be utilized due to their ability to differentiate into various cell types. Dental pulp stem cells are adult stem cells that can be easily harvested from extracted teeth. They can form tissues of all three germ layers and are therefore becoming more and more popular for tissue engineering. Another potential benefit of these cells is their immunomodulatory effect. They suppress proinflammatory pathways of lymphocytes and could therefore probably be used for the treatment of chronic inflammation and autoimmune disease. These attributes make dental pulp stem cells an interesting tool for the regeneration of salivary glands and the treatment of xerostomia. Nevertheless, clinical studies are still missing. This review will highlight the current strategies for using dental pulp stem cells in the regeneration of salivary gland tissue.
Cleft alveolar bone defects can be treated potentially with tissue engineered bone grafts. Herein, we developed novel biphasic bone constructs consisting of two clinically certified materials, a ...calcium phosphate cement (CPC) and a fibrin gel that were biofabricated using 3D plotting. The fibrin gel was loaded with mesenchymal stromal cells (MSC) derived from bone marrow. Firstly, the degradation of fibrin as well as the behavior of cells in the biphasic system were evaluated in vitro. Fibrin degraded quickly in presence of MSC. Our results showed that the plotted CPC structure acted slightly stabilizing for the fibrin gel. However, with passing time and fibrin degradation, MSC migrated to the CPC surface. Thus, the fibrin gel could be identified as cell delivery system. A pilot study in vivo was conducted in artificial craniofacial defects in Lewis rats. Ongoing bone formation could be evidenced over 12 weeks but the biphasic constructs were not completely osseous integrated. Nevertheless, our results show that the combination of 3D plotted CPC constructs and fibrin as suitable cell delivery system enables the fabrication of novel regenerative implants for the treatment of alveolar bone defects.
One of the most common hereditary craniofacial anomalies in humans are cleft lip and cleft alveolar bone with or without cleft palate. Current clinical practice, the augmentation of the persisting ...alveolar bone defect by using autologous bone grafts, has considerable disadvantages motivating to an intensive search for alternatives. We developed a novel therapy concept based on 3D printing of biodegradable calcium phosphate-based materials and integration of osteogenic cells allowing fabrication of patient-specific, tissue-engineered bone grafts. Objective of the present study was the
evaluation of implants in a rat alveolar cleft model. Scaffolds were designed according to the defect's geometry with two different pore designs (60° and 30° rotated layer orientation) and produced by extrusion-based 3D plotting of a pasty calcium phosphate cement. The scaffolds filled into the artificial bone defect in the palate of adult Lewis rats, showing a good support. Half of the scaffolds were colonized with rat mesenchymal stromal cells (rMSC) prior to implantation. After 6 and 12 weeks, remaining defect width and bone formation were quantified histologically and by microCT. The results revealed excellent osteoconductive properties of the scaffolds, a significant influence of the pore geometry (60° > 30°), but no enhanced defect healing by pre-colonization with rMSC.
A promising therapeutic option for the treatment of critical-size mandibular defects is the implantation of biodegradable, porous structures that are produced patient-specifically by using additive ...manufacturing techniques. In this work, degradable poly(DL-lactide) polymer (PDLLA) was blended with different mineral phases with the aim of buffering its acidic degradation products, which can cause inflammation and stimulate bone regeneration. Microparticles of CaCO
, SrCO
, tricalcium phosphates (α-TCP, β-TCP), or strontium-modified hydroxyapatite (SrHAp) were mixed with the polymer powder following processing the blends into scaffolds with the Arburg Plastic Freeforming 3D-printing method. An in vitro degradation study over 24 weeks revealed a buffer effect for all mineral phases, with the buffering capacity of CaCO
and SrCO
being the highest. Analysis of conductivity, swelling, microstructure, viscosity, and glass transition temperature evidenced that the mineral phases influence the degradation behavior of the scaffolds. Cytocompatibility of all polymer blends was proven in cell experiments with SaOS-2 cells. Patient-specific implants consisting of PDLLA + CaCO
, which were tested in a pilot in vivo study in a segmental mandibular defect in minipigs, exhibited strong swelling. Based on these results, an in vitro swelling prediction model was developed that simulates the conditions of anisotropic swelling after implantation.
This study aims to measure the cortical and cancellous bone thickness in the upper and lower jaws, serving as a data template for developing pre-defined calcium phosphate cement primary implant ...forms. These measurements are crucial for creating a biphasic scaffold.
Forty complete jaws were assessed for cortical bone shape and thickness using statistical analysis and specific software tools. Sex and age were considered, and four groups were created.
The cumulative thickness of the cortical layer varied from region to region. In both the upper and lower jaws, the cortical layer in the molar region was significantly thicker than in the frontal region. Within the alveolar process, cortical thickness increases with distance from the alveolar crest on both sides. The oral side of the lower jaw is significantly thicker than the vestibular side. For the upper jaw, no significant differences between the oral and vestibular sides were found in this study. Additionally, it is noteworthy that men have a significantly thicker cortical layer than women. Regarding age, no significant overall differences were found.
Mathematical analysis of anatomical forms using polynomial functions improves understanding of jaw anatomy. This approach facilitates the design of patient-specific scaffold structures, minimizing the need for costly and time-consuming planning and enabling more efficient implementation of optimal therapy.
Bone drill chips that are collected during implant site preparation can be reused as autologous bone-grafting material for alveolar ridge augmentation. This study characterized five market-leading ...implant drill sets regarding their geometric properties and ability to produce vital bone chips. The drill geometry of each tool of five commercial implant drill sets was characterized while using optical profile projector devices and SEM. Bone chips were collected during the in vitro preparation of porcine jaw bone with the various drill sets. Produced bone chip masses were measured. The bone chips were cultured in vitro and the number of outgrown cells was determined and measurand for vitality. Furthermore, the thrust force and cutting torque were recorded to examine the mechanical loads of the manual drilling process. The tool geometry and set configuration of one out of five implant drill sets appears to be superior regarding chip mass, vitality, and thrust force. It could be proven that there is a correlation between vitality and thrust force. The thrust force is influenced by the cutting behavior of the tool, which in turn depends on the geometry of the tool. The tool geometry has an influence on the vitality of the augmentation material due to this relationship.
For sinus grafting, different methods and materials are available. One possible shortcoming of particulate bone grafts is either overfilling or augmenting the planned implant area insufficiently. To ...overcome this risk and to determine the implant position prior augmentation, we present an approach using three-dimensional printed scaffolds. A patient with a remaining anterior dentition and bilateral severely atrophied posterior maxilla was seeking oral rehabilitation. The cone beam computed tomography (CBCT) showed residual bone heights between one and two millimeters. Following the three-dimensional reconstruction of the CBCT data, the positions of the implants were determined in areas 16 and 26. Three-dimensional scaffolds adapted to the topography of the sinus were virtually designed and printed using a calcium phosphate cement paste. Bilateral sinus floor augmentation applying the printed scaffolds with an interconnecting porosity followed. After nine months, a satisfying integration of the scaffolds was obvious. At the re-entry, vital bone with sufficient blood supply was found. One implant could be placed in positions 16 and 26, respectively. After five months, the implants could be uncovered and were provided with a temporary denture. The application of three-dimensionally printed scaffolds from calcium phosphate cement paste seems to be a promising technique to graft the severely atrophied posterior maxilla for the placement of dental implants.
Their excellent mechanical properties, degradability and suitability for processing by 3D printing technologies make the thermoplastic polylactic acid and its derivatives favourable candidates for ...biomaterial-based bone regeneration therapies. In this study, we investigated whether bioactive mineral fillers, which are known to promote bone healing based on their dissolution products, can be integrated into a poly(L-lactic-
-glycolic) acid (PLLA-PGA) matrix and how key characteristics of degradation and cytocompatibility are influenced. The polymer powder was mixed with particles of CaCO
, SrCO
, strontium-modified hydroxyapatite (SrHAp) or tricalcium phosphates (α-TCP, β-TCP) in a mass ratio of 90 : 10; the resulting composite materials have been successfully processed into scaffolds by the additive manufacturing method Arburg Plastic Freeforming (APF). Degradation of the composite scaffolds was investigated in terms of dimensional change, bioactivity, ion (calcium, phosphate, strontium) release/uptake and pH development during long-term (70 days) incubation. The mineral fillers influenced the degradation behavior of the scaffolds to varying degrees, with the calcium phosphate phases showing a clear buffer effect and an acceptable dimensional increase. The amount of 10 wt% SrCO
or SrHAp particles did not appear to be appropriate to release a sufficient amount of strontium ions to exert a biological effect
. Cell culture experiments with the human osteosarcoma cell line SAOS-2 and human dental pulp stem cells (hDPSC) indicated the high cytocompatibility of the composites: For all material groups cell spreading and complete colonization of the scaffolds over the culture period of 14 days as well as an increase of the specific alkaline phosphatase activity, typical for osteogenic differentiation, were observed.
The aim of this study is to develop a test bench, which integrates different complexity levels and enables in that way a flexible and dynamic testing for mid and long term intervals as well as ...testing of maximum loads till implant failure of different osteosynthesis systems on the mandible.
For this purpose, an analysis of the state of the art regarding existing test benches was combined with interviews of clinical experts to acquire a list of requirements. Based on these requirements a design for a modular test bench was developed. During the implementation of the test stand, functional tests were continuously carried out and improvements made. Depending on the level of complexity, the test bench can be used either as an incorporated variant or as a standalone solution. In order to verify the performance and the degree of fulfilment of the requirements of these two variants of the test bench, preliminary studies were carried out for all levels of complexity. In these preliminary studies, commercially available osteosynthesis and reconstruction plates were investigated for their biomechanical behaviour and compared with data from the literature.
In total, fourteen test runs were performed for the different levels of complexity. Firstly, five test runs were executed to test the simplified load scenario in the incorporated variant of the test bench. High forces could be transmitted without failure of the miniplates. Secondly a quasi-static test scenario was examined using the incorporated variant with simplified load insertion. Five experiments with a number of cycles between 40,896 and 100,000 cycles were carried out. In one case the quasi-static testing resulted in a fracture of the tested reconstruction plate with a failure mode similar to the clinical observations of failure. The last four test runs were carried out using the standalone variant of the test bench simulating complex load patterns via the insertion of forces through imitated muscles. During the test runs joint forces were measured and the amplitude and vector of the resulting joint forces were calculated for both temporomandibular joints. Differences in the force transmission depending on the implant system in comparison to the zero sample could be observed.
The presented modular test bench showed to be applicable for examination of the biomechanical behavior of the mandible. It is characterized by the adjustability of the complexity regarding the load patterns and enables the subsequent integration of further sensor technologies. Follow-up studies are necessary to further qualify and optimize the test bench.
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