Evaluation of the Dimensional Accuracy of Robot-Guided Laser Osteotomy in Reconstruction with Patient-Specific Implants-An Accuracy Study of Digital High-Tech Procedures.

Background/Objective: With the rapid advancement in surgical technologies, new workflows for mandibular reconstruction are constantly being evaluated. Cutting guides are extensively employed for defining osteotomy planes but are prone to errors during fabrication and positioning. A virtually defined osteotomy plane and drilling holes in robotic surgery minimize potential sources of error and yield highly accurate outcomes. Methods: Ten mandibular replicas were evaluated after cutting-guided saw osteotomy and robot-guided laser osteotomy following reconstruction with patient-specific implants. The descriptive data analysis summarizes the mean, standard deviation (SD), median, minimum, maximum, and root mean square (RMS) values of the surface comparison for 3D printed models regarding trueness and precision. Results: The saw group had a median trueness RMS value of 2.0 mm (SD ± 1.7) and a precision of 1.6 mm (SD ± 1.4). The laser group had a median trueness RMS value of 1.2 mm (SD ± 1.1) and an equal precision of 1.6 mm (SD ± 1.4). These results indicate that robot-guided laser osteotomies have a comparable accuracy to cutting-guided saw osteotomies, even though there was a lack of statistical significance. Conclusions: Despite the limited sample size, this digital high-tech procedure has been shown to be potentially equivalent to the conventional osteotomy method. Robotic surgery and laser osteotomy offers enormous advantages, as they enable the seamless integration of precise virtual preoperative planning and exact execution in the human body, eliminating the need for surgical guides in the future.

A cross-sectional study of the anatomy of the jaws of a central-European caucasian population using cone beam computer tomography as a prerequisite for designing pre-formed calcium phosphate cement scaffolds.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Treatment of critical bone defects using calcium phosphate cement and mesoporous bioactive glass providing spatiotemporal drug delivery.

Calcium phosphate cements (CPC) are currently widely used bone replacement materials with excellent bioactivity, but have considerable disadvantages like slow degradation. For critical-sized defects, however, an improved degradation is essential to match the tissue regeneration, especially in younger patients who are still growing. We demonstrate that a combination of CPC with mesoporous bioactive glass (MBG) particles led to an enhanced degradation in vitro and in a critical alveolar cleft defect in rats. Additionally, to support new bone formation the MBG was functionalized with hypoxia conditioned medium (HCM) derived from rat bone marrow stromal cells. HCM-functionalized scaffolds showed an improved cell proliferation and the highest formation of new bone volume. This highly flexible material system together with the drug delivery capacity is adaptable to patient specific needs and has great potential for clinical translation.

Comprehensive virtual orthognathic planning concept in surgery-first patients.

The surgery-first concept is becoming increasingly popular in orthognathic surgery since it offers major advantages such as a reduction of treatment duration and an increase in patient satisfaction by eliminating phases of presurgical orthodontic decompensation. Here, we present a novel interdisciplinary pathway of a fully virtual orthodontic-surgical planning concept in a surgery-first setting using a 3D-printed cutting guide and a customised maxillary implant for the Le Fort I osteotomy as well as a CAD/CAM-based stereolithographic final splint. Patient data from cone-beam computed tomography of the skull and a full arch dental scan were processed using the OnyxCeph3TM software (Image Instruments). A mutual computer-aided surgical simulation was conducted by the orthodontist and the oral and maxillofacial surgeon to determine the three-dimensional maxillary and mandibular movements. In a separate virtual planning session, the surgeon designed a customised maxillary guide and implant for precise intraoperative transfer (Geomagic Freeform Plus software, 3DSystems). A 3D-printed CAD/CAM-based final splint was fabricated by the orthodontist and used for accurate mandibular repositioning. We established a comprehensive virtual interdisciplinary orthognathic workflow and successfully applied this concept with a high level of accuracy in a series of surgery-first patients with different types of dentofacial anomalies. This novel fully computer-based pathway offers a high potential to improve the outcomes of orthognathic surgery and reduce total treatment time in the management of the orthognathic patient.

A systematic review on the effect of inorganic surface coatings in large animal models and meta-analysis on tricalcium phosphate and hydroxyapatite on periimplant bone formation.

The aim of the present systematic review was to analyse studies using inorganic implant coatings and, in a meta-analysis, the effect of specifically tricalcium phosphate (TCP) and hydroxyapatite (HA) implant surface coatings on bone formation according to the PRISMA criteria. Inclusion criteria were the comparison to rough surfaced titanium implants in large animal studies at different time points of healing. Forty studies met the inclusion criteria for the systematic review. Fifteen of these analyzed the bone-to-implant contact (BIC) around the most investigated inorganic titanium implant coatings, namely TCP and HA, and were included in the meta-analysis. The results of the TCP group show after 14 days a BIC being 3.48% points lower compared with the reference surface. This difference in BIC decreases to 0.85% points after 21-28 days. After 42-84 days, the difference in BIC of 13.79% points is in favor of the TCP-coatings. However, the results are not statistically significant, in part due to the fact that the variability between the studies increased over time. The results of the HA group show a significant difference in mean BIC of 6.94% points after 14 days in favor of the reference surface. After 21-28 days and 42-84 days the difference in BIC is slightly in favor of the test group with 1.53% points and 1.57% points, respectively, lacking significance. In large animals, there does not seem to be much effect of TCP-coated or HA-coated implants over uncoated rough titanium implants in the short term.

Toward Biofabrication of Resorbable Implants Consisting of a Calcium Phosphate Cement and Fibrin-A Characterization In Vitro and In Vivo.

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.

Stimulation of oral mucosal regeneration by low intensity pulsed ultrasound: an in vivo study in a porcine model.

PURPOSE: Many studies have shown the ability of low intensity pulsed ultrasound (LIPUS) to stimulate the bone, cartilage and tendon regeneration but only a few studied LIPUS interest in the regeneration of the oral mucosa. The purpose of this study is to assess the ability of LIPUS to stimulate the regeneration of the palatal mucosa in a porcine model. METHODS: Ten adults mini-pigs were used. Two mucosal wounds were realised on the left and right side of the palate of each pig. The right side was treated with LIPUS at 1 MHz of frequency and 300 mW/cm2 of acoustic intensity. The left side was not treated. The morphology of the wound was evaluated using a polymer silicone molding. RESULTS: The difference between two sides was significant from day 7 with a p value < 0.0001. At day 21, the wound is completely healed on all pigs with LIPUS. The control soft tissue defect exposed a healing of 80%. CONCLUSIONS: The present study showed that the use of LIPUS on the oral mucosa accelerates the healing of the masticatory mucosa.

CD70 Deficiency Associated With Chronic Epstein-Barr Virus Infection, Recurrent Airway Infections and Severe Gingivitis in a 24-Year-Old Woman.

Most of the few patients with homozygous CD70 deficiency described to date suffered from EBV-related malignancies in early childhood. We present a woman with CD70 deficiency diagnosed in adulthood. She presented in childhood with recurrent airway infections due to encapsulated bacteria, herpes zoster and a fulminant EBV infection followed by chronic EBV infection with mild lymphoproliferation and severe gingivitis/periodontal disease with high EBV viral load in saliva and gingival plaques as an adult. Up to the age of 24 years she developed no malignancy despite constant EBV viremia since primary EBV infection 15 years previously. Immunologic evaluation in childhood showed hypogammaglobulinemia with impaired polysaccharide responsiveness. She has been stable on immunoglobulin substitution with no further severe viral infections and no bacterial airway infections in adulthood. Targeted panel sequencing at the age of 20 years revealed a homozygous CD70 missense mutation (ENST00000245903.3:c.2T>C). CD70 deficiency was confirmed by absent CD70 expression of B cells and activated T cell blasts. The patient finished high school, persues an academic career and has rarely sick days at college. The clinical course of our patient may help to counsel parents of CD70-deficient patients with regard to prognosis and therapeutic options including haematopoetic stem cell transplantation.

3D Printing of Bone Grafts for Cleft Alveolar Osteoplasty - In vivo Evaluation in a Preclinical Model.

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 in vivo 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.

Bioprinting of mineralized constructs utilizing multichannel plotting of a self-setting calcium phosphate cement and a cell-laden bioink.

Due to their characteristic resemblance of the mineral component of bone, calcium phosphates are widely accepted as optimal bone substitute materials. Recent research focused on the development of pasty calcium phosphate cement (CPC) formulations, which can be fabricated into various shapes by low-temperature extrusion-based additive manufacturing, namely 3D plotting. While it could be demonstrated that sensitive substances like growth factors can be integrated in such printed CPC scaffolds without impairment of their biological activity live cells cannot be suspended in CPC as they may not be functional when enclosed in a solid and stiff matrix. In contrast, 3D bioprinting of soft cell-laden hydrogels (bioinks) enables the fabrication of constructs with spatially defined cell distribution, which has the potential to overcome problems of conventional cell seeding techniques-but such objects lack mechanical stability. Herein, we combine 3D plotting of CPC and bioprinting of a cell-laden bioink for the first time. As model bioink, an alginate-methylcellulose blend (alg/mc) was used, previously developed by us. Firstly, a fabrication regime was established, enabling optimal setting of CPC and cell survival inside the bioink. As the cells are exposed to the chemical changes of CPC precursors during setting, we studied the compatibility of the complex system of CPC and cell-laden alg/mc for a combined extrusion process and characterized the cellular behavior of encapsulated human mesenchymal stroma cells within the bioink at the interface and in direct vicinity to the CPC. Furthermore, biphasic scaffolds were mechanically characterized and a model for osteochondral tissue grafts is proposed. The manuscript discusses possible impacts of the CPC setting reaction on cells within the bioink and illustrates the advantages of CPC in bioprinting as alternative to the commonly used thermoplasts for bone tissue engineering.

Assessing agreement between preclinical magnetic resonance imaging and histology: An evaluation of their image qualities and quantitative results.

One consequence of demographic change is the increasing demand for biocompatible materials for use in implants and prostheses. This is accompanied by a growing number of experimental animals because the interactions between new biomaterials and its host tissue have to be investigated. To evaluate novel materials and engineered tissues the use of non-destructive imaging modalities have been identified as a strategic priority. This provides the opportunity for studying interactions repeatedly with individual animals, along with the advantages of reduced biological variability and decreased number of laboratory animals. However, histological techniques are still the golden standard in preclinical biomaterial research. The present article demonstrates a detailed method comparison between histology and magnetic resonance imaging. This includes the presentation of their image qualities as well as the detailed statistical analysis for assessing agreement between quantitative measures. Exemplarily, the bony ingrowth of tissue engineered bone substitutes for treatment of a cleft-like maxillary bone defect has been evaluated. By using a graphical concordance analysis the mean difference between MRI results and histomorphometrical measures has been examined. The analysis revealed a slightly but significant bias in the case of the bone volume [Formula: see text] and a clearly significant deviation for the remaining defect width [Formula: see text] But the study although showed a considerable effect of the analyzed section position to the quantitative result. It could be proven, that the bias of the data sets was less originated due to the imaging modalities, but mainly on the evaluation of different slice positions. The article demonstrated that method comparisons not always need the use of an independent animal study, additionally.

Application of tissue-engineered bone grafts for alveolar cleft osteoplasty in a rodent model.

OBJECTIVES: The clinical standard for alveolar cleft osteoplasty is augmentation with autologous bone being available in limited amounts and might be associated with donor site morbidity. The aim of the present study was the creation of tissue-engineered bone grafts and their in vivo evaluation regarding their potential to promote osteogenesis in an alveolar cleft model. MATERIALS AND METHODS: Artificial bone defects with a diameter of 3.3 mm were created surgically in the palate of 84 adult Lewis rats. Four experimental groups (n = 21) were examined: bovine hydroxyl apatite/collagen (bHA) without cells, bHA with undifferentiated mesenchymal stromal cells (MSC), bHA with osteogenically differentiated MSC. In a control group, the defect remained empty. After 6, 9 and 12 weeks, the remaining defect volume was assessed by cone beam computed tomography. Histologically, the remaining defect width and percentage of bone formation was quantified. RESULTS: After 12 weeks, the remaining defect width was 60.1% for bHA, 74.7% for bHA with undifferentiated MSC and 81.8% for bHA with osteogenically differentiated MSC. For the control group, the remaining defect width measured 46.2% which was a statistically significant difference (p < 0.001). CONCLUSIONS: The study design was suitable to evaluate tissue-engineered bone grafts prior to a clinical application. In this experimental set-up with the described maxillary defect, no promoting influence on bone formation of bone grafts containing bHA could be confirmed. CLINICAL RELEVANCE: The creation of a sufficient tissue-engineered bone graft for alveolar cleft osteoplasty could preserve patients from donor site morbidity.

Bone Formation in a Local Defect around Dental Implants Coated with Extracellular Matrix Components.

PURPOSE: The coating of implant surfaces with components of the extracellular matrix offers an approach to influence peri-implant bone healing. In this study, bone healing around coated implants is analyzed in a peri-implant defect model. MATERIALS AND METHODS: Eight months after extraction of the premolar teeth, six dogs received 48 implants (eight per animal) in the mandible. Implant surfaces were sandblasted and acid-etched, and some were additionally coated with collagen type II and chondroitin sulfate (collagen/CS). On each side of the mandible, implants either had no peri-implant defect (control side) or a vertical defect of 5 mm in depth and 0.5, 1.0, or 2.0 mm in width. Implants healed submerged for 8 weeks. Fluorochrome staining, histology, and histomorphometry were used to analyze implant osseointegration. RESULTS: Fluorochrome labels showed an increased mineralization around collagen/CS-coated surfaces at 4 weeks (p = .031). Histomorphometry generally showed lower vertical and horizontal bone apposition with increasing gap size for both surface types. In gapless sites and 0.5-mm gaps, collagen/CS coated implants showed increased bone volume in areas directly adjacent to the implant, in comparison with uncoated implants (p < .05). CONCLUSION: The width of the peri-implant gap influences peri-implant bone formation. Complete filling of all gaps by newly formed bone could not be observed around either surface. In proximity to the surface, implant surface coating by collagen/CS positively influenced bone formation.

Coating with artificial matrices from collagen and sulfated hyaluronan influences the osseointegration of dental implants.

Dental implants are an established therapy for oral rehabilitation. High success rates are achieved in healthy bone, however, these rates decrease in compromised host bone. Coating of dental implants with components of the extracellular matrix is a promising approach to enhance osseointegration in compromised peri-implant bone. Dental titanium implants were coated with an artificial extracellular matrix (aECM) consisting of collagen type I and either one of two regioselectively low sulfated hyaluronan (sHA) derivatives (coll/sHA1Δ6s and coll/sHA1) and compared to commercial pure titanium implants (control). After extraction of the premolar teeth, 36 implants were inserted into the maxilla of 6 miniature pigs (6 implants per maxilla). The healing periods were 4 and 8 weeks, respectively. After animal sacrifice, the samples were evaluated histomorphologically and histomorphometrically. All surface states led to a sufficient implant osseointegration after 4 and 8 weeks. Inflammatory or foreign body reactions could not be observed. After 4 weeks of healing, implants coated with coll/sHA1Δ6s showed the highest bone implant contact (BIC; coll/sHA1Δ6s: 45.4%; coll/sHA1: 42.2%; control: 42.3%). After 8 weeks, a decrease of BIC could be observed for coll/sHA1Δ6s and controls (coll/sHA1Δ6s: 37.3%; control: 31.7 %). For implants coated with coll/sHA1, the bone implant contact increased (coll/sHA1: 50.8%). Statistically significant differences could not be observed. Within the limits of the current study, aECM coatings containing low sHA increase peri-implant bone formation around dental implants in maxillary bone compared to controls in the early healing period.