Accuracy and Sterilizability of In-House Printed Patient-Specific Aortic Model for Surgeon-Modified Stent Grafts-A Workflow Description for Emergency Aortic Endovascular Procedures.

Introduction: The use of 3D-printed aortic models for the creation of surgeon-modified endoprostheses represents a promising avenue in aortic surgery. By focusing on the potential impact of sterilization on model integrity and geometry, this report sheds light on the suitability of these models for creating customized endoprostheses. The study presented here aimed to investigate the safety and viability of 3D-printed aortic models in the context of sterilization processes and subsequent remodeling. Methods: The study involved the fabrication of 3D-printed aortic models using patient-specific imaging data and established additive manufacturing techniques. Five identical aortic models of the same patient were printed. Two models were subjected to sterilization and two to disinfection using commonly employed methods, and one model remained untreated. The models were checked by in-house quality control for deformation (heat map analyses) after the sterilization and disinfection processes. Three models (sterilized, disinfected, and untreated) were sent for ex-house (Lufthansa Technik, AG, Materials Technologies and Central Laboratory Services, Hamburg, Germany) evaluation and subsequent quantification of possible structural changes using advanced imaging and measurement technologies (macroscopic and SEM/EDX examinations). After sterilization and disinfection, each aortic model underwent sterility checks. Results: Based on macroscopic and SEM/EDX examinations, distinct evidence of material alterations attributed to a treatment process, such as a cleaning procedure, was not identified on the three implants. Comparative material analyses conducted via the EDX technique yield consistent results for all three implants. Disinfected and sterilized models tested negative for common pathogens. Conclusions: The evaluation of 3D-printed aortic models' safety after sterilization as well as their suitability for surgeon-modified endoprostheses is a critical step toward their clinical integration. By comprehensively assessing changes in model integrity and geometry after sterilization, this research has contributed to the broader understanding of the use of 3D-printed models for tailor-made endovascular solutions. As medical technologies continue to evolve, research endeavors such as this one can serve as a foundation for harnessing the full potential of 3D printing to advance patient-centered care in aortic surgery.

Mixed Reality as a Digital Visualisation Solution for the Head and Neck Tumour Board: Application Creation and Implementation Study.

The preparation and implementation of interdisciplinary oncological case reviews are time-consuming and complex. The variety of clinical and radiological information must be presented in a clear and comprehensible manner. Only if all relevant patient-specific information is demonstrated in a short time frame can well-founded treatment decisions be made on this basis. Mixed reality (MR) technology as a multimodal interactive user interface could enhance understanding in multidisciplinary collaboration by visualising radiological or clinical data. The aim of the work was to develop an MR-based software prototype for a head and neck tumour board (HNTB) to support clinical decision-making. The article describes the development phases and workflows in the planning and creation of a MR-based software prototype that were required to meet the multidisciplinary characteristics of a HNTB.

A New Approach to Virtual Occlusion in Orthognathic Surgery Planning Using Mixed Reality-A Technical Note and Review of the Literature.

Orthognathic surgery plays a vital role in correcting various skeletal discrepancies of the maxillofacial region. Achieving optimal occlusion is a fundamental aspect of orthognathic surgery planning, as it directly influences postoperative outcomes and patient satisfaction. Traditional methods for setting final occlusion involve the use of dental casts which are time-consuming, prone to errors and cannot be easily shared among collaborating specialties. In recent years, advancements in digital technology have introduced innovative approaches, such as virtual occlusion, which may offer enhanced accuracy and efficiency in orthognathic surgery planning. Furthermore, the emergence of mixed reality devices and their 3D visualization capabilities have brought about novel benefits in the medical field, particularly in computer-assisted planning. This paper presents for the first time a prototype tool for setting virtual occlusion during orthognathic surgery planning using mixed reality technology. A complete walkthrough of the workflow is presented including an explanation of the implicit advantages of this novel tool. The new approach to defining virtual occlusion is set into context with other published methods of virtual occlusion setting, discussing advantages and limitations as well as concepts of surgical occlusion for orthognathic surgery.

Usage of Object Matching Algorithms Combined with Mixed Reality for Enhanced Decision Making in Orbital Reconstruction-A Technical Note.

This technical note describes the usage of object matching to virtually compare different modes of reconstruction in orbital trauma and display the results to the surgeon and the patient pre-operatively via mixed reality devices for enhanced surgical decision making and immersive patient education. A case of an orbital floor fracture is presented for which surface and volume matching were implemented to compare orbital reconstruction utilizing pre-fabricated titanium meshes versus patient-specific implants. The results could be visualized by mixed reality devices to further enhance surgical decision-making. The data sets were demonstrated to the patient in mixed reality for immersive patient education and enhanced shared decision making. The advantages of the new technologies are discussed in view of the new possibilities of improved patient education and informed consent processes, as well as new ways of teaching medical trainees.

Plasma Electrolytic Polished Patient-Specific Orbital Implants in Clinical Use-A Technical Note.

This technical note describes the technique of plasma electrolytic polishing on orbital patient-specific implants and demonstrates clinical handling and use by the insertion of a plasma electrolytic polished orbital implant into a patient.

Simultaneous PSI-Based Orthognathic and PEEK Bone Augmentation Surgery Leads to Improved Symmetric Facial Appearance in Craniofacial Malformations.

(1) The aim of the present study was to compare the outcome of facial symmetry after simultaneous digitally planned patient-specific implant (PSI-) based orthognathic surgery and polyether ether ketone (PEEK) bone augmentation in patients with craniofacial malformations. (2) To evaluate the outcome of the two different surgical approaches (conventional PSI-based orthognathic surgery versus simultaneous PSI-based orthognathic surgery with PEEK bone augmentation), a comparison of five different groups with a combination of the parameters (A) with vs. without laterognathia, (B) syndromic vs. non-syndromic, and (C) surgery with vs. without PEEK bone augmentation was conducted. The digital workflow comprised cone beam CT (CBCT) scans and virtual surgery planning for all patients in order to produce patient specific cutting guides and osteosynthesis plates. Additionally, deformed skulls were superimposed by a non-deformed skull and/or the healthy side was mirrored to produce PSI PEEK implants for augmentation. Retrospective analyses included posterior-anterior conventional radiographs as well as en face photographs taken before and nine months after surgery. (3) Simultaneous orthognathic surgery with PEEK bone augmentation significantly improves facial symmetry compared to conventional orthognathic surgery (6.5%P (3.2-9.8%P) (p = 0.001). (4) PSI-based orthognathic surgery led to improved horizontal bone alignment in all patients. Simultaneous PEEK bone augmentation enhanced facial symmetry even in patients with syndrome-related underdevelopment of both soft and hard tissues.

Prospective Evaluation of Two Wall Orbital Fractures Involving the Medial Orbital Wall: PSI Reconstruction versus PDS Repair-Worth the Effort?

Proper treatment of the two-wall fractured orbit is still controversial. Specifically, there is no consensus on the issue of the necessity of medial orbital wall repair. With anatomically critical structures at risk during the surgical approach, surgeons' view on the necessity of medial orbital wall repair often is restricted and an aesthetically disturbing enophthalmos is more likely to be accepted. Therefore, treatment options range from leaving the medial wall without repair to reconstruction with autogenous tissue or alloplastic materials, which can lead to moderate to severe side effects. However, emerging technologies such as patient-specific implants (PSI) offer a reliable and anatomically correct reconstruction of the bony orbit. This study aimed to evaluate the outcome of full orbital reconstruction using PSIs compared to only orbital floor repair using PDS (bioresorbable polydioxanone) foils leaving the medial orbital wall untouched in traumatic two-wall orbital fractures. Of all patients treated at the University Hospital of Düsseldorf between 2017 and 2019 who suffered from traumatic orbital fracture, only patients with a two-wall orbital fracture involving both the orbital floor and the medial wall (n = 68) were included. Patients were treated either with a PSI (n = 35) or a PDS foil (n = 33). Primary outcome parameters were ophthalmological disturbances analyzed via clinical investigation and intra-orbital angles, volumes and implant position analyzed with radiological 3D-datasets. While a two-wall reconstruction using PSIs led to a significant improvement of the enophthalmos, the rate of postoperative enophthalmos was significantly increased in cases of only orbital floor repair with PDS foils. Radiologically, a significant reconstruction of the three-dimensional bony orbit succeeded with the simple use of PSIs leading to a significant reduction in the traumatically enlarged orbital volume. PSI also led to a significant reduction in the traumatically enlarged medial angle of the orbit. This was not the case for single-floor repair with PDS foil. The results of this study suggest that complex orbital fractures can be reconstructed at an even higher degree of accuracy with selective laser-melted PSIs than PDS foils. In order to achieve a true to original reconstruction of the bony orbit, surgical treatment of the medial orbital wall can be advocated for in the long term depending on the indication.

Advances and Innovations in Ablative Head and Neck Oncologic Surgery Using Mixed Reality Technologies in Personalized Medicine.

The benefit of computer-assisted planning in head and neck ablative and reconstructive surgery has been extensively documented over the last decade. This approach has been proven to offer a more secure surgical procedure. In the treatment of cancer of the head and neck, computer-assisted surgery can be used to visualize and estimate the location and extent of the tumor mass. Nowadays, some software tools even allow the visualization of the structures of interest in a mixed reality environment. However, the precise integration of mixed reality systems into a daily clinical routine is still a challenge. To date, this technology is not yet fully integrated into clinical settings such as the tumor board, surgical planning for head and neck tumors, or medical and surgical education. As a consequence, the handling of these systems is still of an experimental nature, and decision-making based on the presented data is not yet widely used. The aim of this paper is to present a novel, user-friendly 3D planning and mixed reality software and its potential application for ablative and reconstructive head and neck surgery.

Primary Orbital Reconstruction with Selective Laser Melting (SLM) of Patient-Specific Implants (PSIs): An Overview of 96 Surgically Treated Patients.

Contemporary advances in technology have allowed the transfer of knowledge from industrial laser melting systems to surgery; such an approach could increase the degree of accuracy in orbital restoration. The aim of this study was to examine the accuracy of selective laser melted PSIs (patient-specific implants) and navigation in primary orbital reconstruction. Ninety-six patients with orbital fractures were included in this study. Planned vs. achieved orbital volumes (a) and angles (b) were compared to the unaffected side (n = 96). The analysis included the overlay of post-treatment on planned images (iPlan 3.0.5, Brainlab®, Feldkirchen, Germany). The mean difference in orbital volume between the digitally planned orbit and the postoperative orbit was 29.16 cm3 (SD 3.54, presurgical) to 28.33 cm3 (SD 3.64, postsurgical, t = 5.00, df = 95.00; p < 0.001), resulting in a mean volume difference (planned vs. postop) of less than 1 cm3. A 3D analysis of the color mapping showed minor deviations compared to the mirrored unaffected side. The results suggested that primary reconstruction in complex orbital wall fractures can be routinely achieved with a high degree of accuracy by using selective laser melted orbital PSIs.

Analysis of Spontaneous and Induced Osteogenic Differentiation in 3D-micromasses of Human Multipotent Stem Cells.

BACKGROUND/AIM: Craniofacial reconstruction of extensive bone defects causes high morbidity to patients. Contemporary reconstructive surgery aims at restoring lost bone with either autogenous bone or substitutes. Multipotent unrestricted somatic stem cells (USSC) show a potential for osteoblast differentiation and are increasingly used in tissue engineering. The osteogenic potential of USSC micromasses influenced by dexamethasone, ascorbic acid and ß-glycerophosphate (DAG) seems promising. The present study evaluated the effects of DAG and MAPK, ERK and PI3K/Akt-pathway inhibitors on growth and mineralization of USSC micromasses. MATERIALS AND METHODS: Cells: i) USSC-18 (female, Passage 8), ii) USSC-8 (female Passage 9), and iii) USSC-8/17 (male, Passage 8), all cultured in 350 ml DMEM, with 150 ml fetal bovine serum, 5 ml penicillin/streptomycin and 5 ml L-glutamine. Differentiation was induced using 50 µM dexamethasone in DMEM, 50 mM ascorbic acid in PBS and 1 M ß-glycerolphosphate in PBS. Microtome slices were dyed with OsteoImage™ and analyzed under fluorescence microscopy. RESULTS: Significant increase in size and mineralization of DAG-treated micromasses was found on days 3 (p<0.001), 6 (p<0.001) and 7 (p<0.001). The ERK-pathway inhibitor, FR180204, significantly reduced micromass growth and mineralization in non-DAG treated cells (p<0.001) but showed increased mineralization in DAG-treated cells (p=0.014). The PI3K/Akt-pathway inhibitor, LY294002, did not significantly affect micromass growth but significantly decreased mineralization (p<0.001). The MAP-kinase inhibitor, U0126, significantly reduced micromass growth (p=0.001) and mineralization (p=0.001) of DAG-treated cells. CONCLUSION: DAG is a strong initiator of osteogenic differentiation. The PI3K/Akt-pathway inhibitor and the ERK-pathway inhibitor, FR180204, control osteogenic differentiation of 3D-micromasses. These results may facilitate preconditioning of cell cultures in guided tissue regeneration.

Evaluation of the Fitting Accuracy of CAD/CAM-Manufactured Patient-Specific Implants for the Reconstruction of Cranial Defects-A Retrospective Study.

Cranioplasties show overall high complication rates of up to 45.3%. Risk factors potentially associated with the occurrence of postoperative complications are frequently discussed in existing research. The present study examines the positioning of 39 patient-specific implants (PSI) made from polyetheretherketone (PEEK) and retrospectively investigates the relationship between the fitting accuracy and incidence of postoperative complications. To analyze the fitting accuracy of the implants pre- and post-operatively, STL files were created and superimposed in a 3D coordinate system, and the deviations were graphically displayed and evaluated along with the postoperative complications. On average, 95.17% (SD = 9.42) of the measurements between planned and surgically achieved implant position were within the defined tolerance range. In cases with lower accordance, an increased occurrence of complications could not be demonstrated. The overall postoperative complication rate was 64.1%. The fitting of the PEEK-PSI was highly satisfactory. There were predominantly minor deviations of the achieved compared to the planned implant positions; however, estimations were within the defined tolerance range. Despite the overall high accuracy of fitting, a considerable complication rate was found. To optimize the surgical outcome, the focus should instead be directed towards the investigation of other risk factors.

Comparison of the Accuracy and Clinical Parameters of Patient-Specific and Conventionally Bended Plates for Mandibular Reconstruction.

OBJECTIVES: This retrospective study compared two mandibular reconstruction procedures-conventional reconstruction plates (CR) and patient-specific implants (PSI)-and evaluated their accuracy of reconstruction and clinical outcome. METHODS: Overall, 94 patients had undergone mandibular reconstruction with CR (n = 48) and PSI (n = 46). Six detectable and replicable anatomical reference points, identified via computer tomography, were used for defining the mandibular dimensions. The accuracy of reconstruction was assessed using pre- and postoperative differences. RESULTS: In the CR group, the largest difference was at the lateral point of the condyle mandibulae (D2) -1.56 mm (SD = 3.8). In the PSI group, the largest difference between preoperative and postoperative measurement was shown at the processus coronoid (D5) with +1.86 mm (SD = 6.0). Significant differences within the groups in pre- and postoperative measurements were identified at the gonion (D6) [t(56) = -2.217; p = .031 <.05]. In the CR group, the difference was 1.5 (SD = 3.9) and in the PSI group -1.04 (SD = 4.9). CR did not demonstrate a higher risk of plate fractures and post-operative complications compared to PSI. CONCLUSION: For reconstructing mandibular defects, CR and PSI are eligible. In each case, the advantages and disadvantages of these approaches must be assessed. The functional and esthetic outcome of mandibular reconstruction significantly improves with the experience of the surgeon in conducting microvascular grafts and familiarity with computer-assisted surgery. Interoperator variability can be reduced, and training of younger surgeons involved in planning can be reaching better outcomes in the future.

Advances in the Resection and Reconstruction of Midfacial Tumors Through Computer Assisted Surgery.

Curatively intended oncologic surgery is based on a residual-free tumor excision. Since decades, the surgeon's goal of R0-resection has led to radical resections in the anatomical region of the midface because of the three-dimensionally complex anatomy where aesthetically and functionally crucial structures are in close relation. In some cases, this implied aggressive overtreatment with loss of the eye globe. In contrast, undertreatment followed by repeated re-resections can also not be an option. Therefore, the evaluation of the true three-dimensional tumor extent and the intraoperative availability of this information seem critical for a precise, yet substance-sparing tumor removal. Computer assisted surgery (CAS) can provide the framework in this context. The present study evaluated the beneficial use of CAS in the treatment of midfacial tumors with special regard to tumor resection and reconstruction. Therefore, 60 patients diagnosed with a malignancy of the upper jaw has been treated, 31 with the use of CAS and 29 conventionally. Comparison of the two groups showed a higher rate of residual-free resections in cases of CAS application. Furthermore, we demonstrate the use of navigated specimen taking called tumor mapping. This procedure enables the transparent, yet precise documentation of three-dimensional tumor borders which paves the way to a more feasible interdisciplinary exchange leading e.g. to a much more focused radiation therapy. Moreover, we evaluated the possibilities of primary midface reconstructions seizing CAS, especially in cases of infiltrated orbital floors. These cases needed reduction of intra-orbital volume due to the tissue loss after resection which could be precisely achieved by CAS. These benefits of CAS in midface reconstruction found expression in positive changes in quality of life. The present work was able to demonstrate that the area of oncological surgery of the midface is a prime example of interface optimization based on the sensible use of computer assistance. The fact that the system makes the patient transparent for the surgeon and the procedure controllable facilitates a more precise and safer treatment oriented to a better outcome.

Use and Evaluation of a Computer-Assisted Examination Method for the Diagnosis and Analysis of Medication-Related Osteonecrosis of the Jaw.

The aim of the present study was to analyze the size of the preoperatively calculated defect volume of MRONJ patients (medication-related osteonecrosis of the jaw) and to develop a computer-aided tool based on techniques of AI (artificial intelligence) that facilitates diagnostics of MRONJ. For this purpose, on the basis of 3D (three-dimensional) data sets of 175 MRONJ patients, the outline of the necrosis was marked with the software iPlan 3.0.5 (BrainLAB AG) thus determining the respective volume. The correlation of this volume with other 31 collected parameters was analyzed retrospectively. There was a significant correlation between the defect volume on the one hand, and the MRONJ stage, the number of performed operations, and the therapy invasiveness on the other hand. Furthermore, it could be shown that in one third of the cases no defects could be recognized in the 2D imaging by panoramic radiograph, while in the 3D data sets defects already had been demarcated. On the basis of these data, a computer-aided tool based on the principles of AI was developed and validated, which might allow the automated calculation of the 3D defect extension and classification of the MRONJ cases into a ranking system. In conclusion, preparation of a 3D image can be recommended for reliably making the diagnosis "MRONJ." Moreover, knowledge of the exact defect volume serves as a decision-making aid with regard to the choice of therapy, ensures intraoperative certitude, and allows an assessment of the prognosis.

Adenosine receptor 2B activity promotes autonomous growth, migration as well as vascularization of head and neck squamous cell carcinoma cells.

Adenosine is a signaling molecule that exerts dual effects on tumor growth: while it inhibits immune cell function and thereby prevents surveillance by the immune system, it influences tumorigenesis directly via activation of adenosine receptors on tumor cells at the same time. However, the adenosine-mediated mechanisms affecting oncogenic processes particularly in head and neck squamous cell carcinomas (HNSCC) are not fully understood. Here, we investigated the role of adenosine receptor activity on HNSCC-derived cell lines. Targeting the adenosine receptor A2B (ADORA2B) on these cells with the inverse agonist/antagonist PSB-603 leads to inhibition of cell proliferation, transmigration as well as VEGFA secretion in vitro. At the molecular level, these effects were associated with cell cycle arrest as well as the induction of the apoptotic pathway. In addition, shRNA-mediated downmodulation of ADORA2B expression caused decreased proliferation. Moreover, in in vivo xenograft experiments, chemical and genetic abrogation of ADORA2B activity impaired tumor growth associated with decreased tumor vascularization. Together, our findings characterize ADORA2B as a crucial player in the maintenance of HNSCC and, therefore, as a potential therapeutic target for HNSCC treatment.

Profiling antibody responses to infections by Chlamydia abortus enables identification of potential virulence factors and candidates for serodiagnosis.

Enzootic abortion of ewes (EAE) due to infection with the obligate intracellular pathogen Chlamydia (C.) abortus is an important zoonosis leading to considerable economic loss to agriculture worldwide. The pathogen can be transmitted to humans and may lead to serious infection in pregnant women. Knowledge about epidemiology, clinical course and transmission to humans is hampered by the lack of reliable diagnostic tools. Immunoreactive proteins, which are expressed in infected animals and humans, may serve as novel candidates for diagnostic marker proteins and represent putative virulence factors. In order to broaden the spectrum of immunogenic C. abortus proteins we applied 2D immunoblot analysis and screening of an expression library using human and animal sera. We have identified 48 immunoreactive proteins representing potential diagnostic markers and also putative virulence factors, such as CAB080 (homologue of the "macrophage infectivity potentiator", MIP), CAB167 (homologue of the "translocated actin recruitment protein", TARP), CAB712 (homologue of the "chlamydial protease-like activity factor", CPAF), CAB776 (homologue of the "Polymorphic membrane protein D", PmpD), and the "hypothetical proteins" CAB063, CAB408 and CAB821, which are predicted to be type III secreted. We selected two putative virulence factors for further characterization, i.e. CAB080 (cMIP) and CAB063, and studied their expression profiles at transcript and protein levels. Analysis of the subcellular localization of both proteins throughout the developmental cycle revealed CAB063 being the first C. abortus protein shown to be translocated to the host cell nucleus.