Application of three-dimensional printed biomodels in endoscopic spinal surgery.

Background: Three-dimensional printing (3DP) is increasingly used to individualise surgery and may be an effective tool for representing patient anatomy. Current literature on patient-specific anatomical models (biomodels) for minimally invasive spinal surgery is a limited number of case series and cohort studies. However, studies investigating 3DP in other specialties have reported multiple benefits. Methods: This prospective study considered a series of patients (n=33) undergoing elective endoscopic spinal surgery, including combinations of microdiscectomy (n=27), foraminotomy (n=7), and laminectomy (n=3). These surgeries were conducted at vertebral levels ranging from L2/3 to L5/S1. The surgeon then recorded the impact on preoperational planning, intraoperative decision-making and accelerating the learning curve with a qualitative questionnaire. Results: There were benefits to planning in 54.5% of cases (n=18), improved intraoperative decision-making in 60.6% of cases (n=20). These benefits were reported more frequently earlier in the cases, with improvements to learning reported in 60% of the first five cases and not in subsequent cases. The surgeon commented that the biomodels were more useful on. Conclusions: The rates of preoperative and intraoperative benefits are consistent with existing studies, and the early benefit to the learning curve may be suitable for applications to surgical training. Additional research is required to determine the practicality of biomodels and their impact on patient outcomes for endoscopic spinal surgery.

A bioconvergence study on platinum-free concurrent chemoradiotherapy for the treatment of HPV-negative head and neck carcinoma.

Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is characterized by high rate of recurrence, resulting in a poor survival. Standard treatments are associated with significant toxicities that impact the patient's quality of life, highlighting the urgent need for novel therapies to improve patient outcomes. On this regard, noble metal nanoparticles (NPs) are emerging as promising agents as both drug carriers and radiosensitizers. On the other hand, co-treatments based on NPs are still at the preclinical stage because of the associated metal-persistence.In this bioconvergence study, we introduce a novel strategy to exploit tumour chorioallantoic membrane models (CAMs) in radio-investigations within clinical equipment and evaluate the performance of non-persistent nanoarchitectures (NAs) in combination with radiotherapy with respect to the standard concurrent chemoradiotherapy for the treatment of HPV-negative HNSCCs. A comparable effect has been observed between the tested approaches, suggesting NAs as a potential platinum-free agent in concurrent chemoradiotherapy for HNSCCs. On a broader basis, our bioconvergence approach provides an advance for the translation of Pt-free radiosensitizer to the clinical practice, positively shifting the therapeutic vs. side effects equilibrium for the management of HNSCCs.

Surgical accuracy of CAD/CAM splints using virtual surgical planning in orthognathic surgery: policy implications for healthcare in Australia.

BACKGROUND: This study examines post-surgical outcomes of maxillary position using virtual surgical planning (VSP) with computer designed and manufactured surgical splints, without the use of costly patient specific implants (PSI), in the treatment of routine nonsyndromic orthognathic patients. The cost of these personalized medical devices and their impact in the setting of cranio-maxillofacial surgery is currently under review by The Department of Health and Aged Care in Australia. METHODS: This is a single-centre retrospective analysis of 49 patients who underwent bimaxillary orthognathic surgery by a single surgeon at Epworth Richmond Hospital (Victoria, Australia) over a period spanning 2016 to 2020. Patients were included in the study provided their surgery was facilitated using VSP with manufacture of computer designed occlusal splints. RESULTS: Use of computer designed and manufactured splints were highly reliable in reproducing the virtual surgical plan, when using palatal plane, upper incisor angulation, and anterior upper facial height. CONCLUSION: Use of computer designed and manufactured splints provide a method of leveraging the accuracy of VSP methods, without the additional costs associated with PSI. These findings may assist in appropriate resource allocation and case stratification in patients undergoing orthognathic surgery.

CASBERT: BERT-based retrieval for compositely annotated biosimulation model entities.

Maximising FAIRness of biosimulation models requires a comprehensive description of model entities such as reactions, variables, and components. The COmputational Modeling in BIology NEtwork (COMBINE) community encourages the use of Resource Description Framework with composite annotations that semantically involve ontologies to ensure completeness and accuracy. These annotations facilitate scientists to find models or detailed information to inform further reuse, such as model composition, reproduction, and curation. SPARQL has been recommended as a key standard to access semantic annotation with RDF, which helps get entities precisely. However, SPARQL is unsuitable for most repository users who explore biosimulation models freely without adequate knowledge of ontologies, RDF structure, and SPARQL syntax. We propose here a text-based information retrieval approach, CASBERT, that is easy to use and can present candidates of relevant entities from models across a repository's contents. CASBERT adapts Bidirectional Encoder Representations from Transformers (BERT), where each composite annotation about an entity is converted into an entity embedding for subsequent storage in a list of entity embeddings. For entity lookup, a query is transformed to a query embedding and compared to the entity embeddings, and then the entities are displayed in order based on their similarity. The list structure makes it possible to implement CASBERT as an efficient search engine product, with inexpensive addition, modification, and insertion of entity embedding. To demonstrate and test CASBERT, we created a dataset for testing from the Physiome Model Repository and a static export of the BioModels database consisting of query-entities pairs. Measured using Mean Average Precision and Mean Reciprocal Rank, we found that our approach can perform better than the traditional bag-of-words method.

A High-Fidelity Artificial Urological System for the Quantitative Assessment of Endoscopic Skills.

Minimally-invasive surgery is rapidly growing and has become a standard approach for many operations. However, it requires intensive practice to achieve competency. The current training often relies on animal organ models or physical organ phantoms, which do not offer realistic surgical scenes or useful real-time feedback for surgeons to improve their skills. Furthermore, the objective quantitative assessment of endoscopic skills is also lacking. Here, we report a high-fidelity artificial urological system that allows realistic simulation of endourological procedures and offers a quantitative assessment of the surgical performance. The physical organ model was fabricated by 3D printing and two-step polymer molding with the use of human CT data. The system resembles the human upper urinary tract with a high-resolution anatomical shape and vascular patterns. During surgical simulation, endoscopic videos are acquired and analyzed to quantitatively evaluate performance skills by a customized computer algorithm. Experimental results show significant differences in the performance between professional surgeons and trainees. The surgical simulator offers a unique chance to train endourological procedures in a realistic and safe environment, and it may also lead to a quantitative standard to evaluate endoscopic skills.

SBML to bond graphs: From conversion to composition.

The Systems Biology Markup Language (SBML) is a popular software-independent XML-based format for describing models of biological phenomena. The BioModels Database is the largest online repository of SBML models. Several tools and platforms are available to support the reuse and composition of SBML models. However, these tools do not explicitly assess whether models are physically plausible or thermodynamically consistent. This often leads to ill-posed models that are physically impossible, impeding the development of realistic complex models in biology. Here, we present a framework that can automatically convert SBML models into bond graphs, which imposes energy conservation laws on these models. The new bond graph models are easily mergeable, resulting in physically plausible coupled models. We illustrate this by automatically converting and coupling a model of pyruvate distribution to a model of the pentose phosphate pathway.

The Intersection Between the Oculomotor Nerve and the Internal Carotid Artery to Distinguish Extracavernous and Intracavernous Paraclinoid Aneurysms Using Anatomic Dissections-A New 3T Magnetic Resonance Imaging Protocol Confirmed by Three-Dimensionally Printed Biomodels.

OBJECTIVE: To evaluate the relationship between the oculomotor nerve (CNIII) and the internal carotid artery (ICA) as a new anatomic-radiologic landmark for distinguishing the exact location of a paraclinoid intracranial aneurysm (IA). METHODS: Microanatomic dissections were performed in 20 cavernous sinuses to evaluate the ICA paraclinoid region. Based on anatomic observations, a new magnetic resonance (MRI) protocol to classify paraclinoid aneurysms was proposed. MRI of 42 IAs from 34 patients was independently analyzed and classified as intracavernous, extracavernous, or transitional by 2 neuroradiologists. To validate the proposed MRI protocol, each IA was classified by a three-dimensionally (3D) printed biomodel and agreement with the radiologic classifications was evaluated. Of 42 IAs, 23 undergoing microsurgeries were also classified by direct visualization. RESULTS: We observed that the true cavernous sinus roof is defined by the carotid-oculomotor membrane, which has an intimate relationship with the intersection between the superior limit of the CNIII and the ICA. Based on this intersection, all 42 IAs were radiologically classified and agreement with the 3D printed biomodels was observed in 95% IAs. Concordance tests showed a statistically significant (P < 0.05) agreement between the classifications. All 23 IAs treated had the radiologic and 3D biomodel classification confirmed. CONCLUSIONS: The intersection between the ICA and the CNIII, which crosses it transversely in its entire diameter, is a reliable anatomic-radiologic landmark to correctly classify paraclinoid aneurysms. Through a new MRI protocol, it is possible to radiologically identify this intersection and to easily distinguish the intracavernous and extracavernous ICA paraclinoid aneurysms.

NLIMED: Natural Language Interface for Model Entity Discovery in Biosimulation Model Repositories.

Semantic annotation is a crucial step to assure reusability and reproducibility of biosimulation models in biology and physiology. For this purpose, the COmputational Modeling in BIology NEtwork (COMBINE) community recommends the use of the Resource Description Framework (RDF). This grounding in RDF provides the flexibility to enable searching for entities within models (e.g., variables, equations, or entire models) by utilizing the RDF query language SPARQL. However, the rigidity and complexity of the SPARQL syntax and the nature of the tree-like structure of semantic annotations, are challenging for users. Therefore, we propose NLIMED, an interface that converts natural language queries into SPARQL. We use this interface to query and discover model entities from repositories of biosimulation models. NLIMED works with the Physiome Model Repository (PMR) and the BioModels database and potentially other repositories annotated using RDF. Natural language queries are first "chunked" into phrases and annotated against ontology classes and predicates utilizing different natural language processing tools. Then, the ontology classes and predicates are composed as SPARQL and finally ranked using our SPARQL Composer and our indexing system. We demonstrate that NLIMED's approach for chunking and annotating queries is more effective than the NCBO Annotator for identifying relevant ontology classes in natural language queries.Comparison of NLIMED's behavior against historical query records in the PMR shows that it can adapt appropriately to queries associated with well-annotated models.

Using a Syrian (Golden) Hamster Biological Model for the Evaluation of Recombinant Anthrax Vaccines.

In this paper, we demonstrate that a Syrian hamster biological model can be applied to the study of recombinant anthrax vaccines. We show that double vaccination with recombinant proteins, such as protective antigen (PA) and fusion protein LF1PA4, consisting of lethal factor I domain (LF) and PA domain IV, leads to the production of high titers of specific antibodies and to protection from infection with the toxicogenic encapsulated attenuated strain B. anthracis 71/12. In terms of antibody production and protection, Syrian hamsters were much more comparable to guinea pigs than mice. We believe that Syrian hamsters are still underestimated as a biological model for anthrax research, and, in some cases, they can be used as a replacement or at least as a complement to the traditionally used mouse model.

Female squirrel monkeys as models for research on women's pelvic floor disorders.

Animal models enable research on biological phenomena with controlled interventions not possible or ethical in patients. Among species used as experimental models, squirrel monkeys (Saimiri genus) are phylogenetically related to humans and are relatively easily managed in captivity. Quadrupedal locomotion of squirrel monkeys resembles most other quadrupedal primates in that they utilize a diagonal sequence/diagonal couplets gait when walking on small branches. However, to assume a bipedal locomotion, the human pelvis has undergone evolutionary changes. Therefore, the pelvic bone morphology is not that similar between the female squirrel monkey and woman, but pelvic floor support structures and impacts of fetal size and malpresentation are similar. Thus, this review explores the pelvic floor support structural characteristics of female squirrel monkeys, especially in relation to childbirth to demonstrate similarities to humans.

The production of testis biomodels using three-dimensional (3D) technologies.

This study aimed to investigate the potentiality of biomodels to be produced as alternative tools to slaughterhouse materials in andrology education. For this purpose, testis biomodels were produced with reference to bull testes. The biomodel production was carried out by the following steps: the preparation of the reference organs, 3D modelling, and processing of data sets and stages. The biomodels and reference testes were compared in terms of morphological parameters and tonicity. As a result of quantitative measurements, the average length in the reference testicles was 145.56 ± 21.3 mm, while the thickness was 61.94 ± 17.2 mm. The average length, thickness, volume and tonicity values of the biomodels showed similarity to the values of the reference testicles (p > .05). However, it was recorded that the average weight of the reference testicles was determined as 368.07 ± 40.3 g, while the average weight of the biomodels was 69.02 ± 3.18 g (p < .01). As a result, it has been shown that testis biomodels can be successfully produced using three-dimensional technologies. These biomodels are the first examples in the field. We think that the biomodels produced by using innovative technologies should be considered as serious alternatives, which could contribute to the learning processes of students, especially in andrology education.

Conceptual evolution of 3D printing in orthopedic surgery and traumatology: from "do it yourself" to "point of care manufacturing".

BACKGROUND: 3D printing technology in hospitals facilitates production models such as point-of-care manufacturing. Orthopedic Surgery and Traumatology is the specialty that can most benefit from the advantages of these tools. The purpose of this study is to present the results of the integration of 3D printing technology in a Department of Orthopedic Surgery and Traumatology and to identify the productive model of the point-of-care manufacturing as a paradigm of personalized medicine. METHODS: Observational, descriptive, retrospective and monocentric study of a total of 623 additive manufacturing processes carried out in a Department of Orthopedic Surgery and Traumatology from November 2015 to March 2020. Variables such as product type, utility, time or materials for manufacture were analyzed. RESULTS: The areas of expertise that have performed more processes are Traumatology, Reconstructive and Orthopedic Oncology. Pre-operative planning is their primary use. Working and 3D printing hours, as well as the amount of 3D printing material used, vary according to the type of product or material delivered to perform the process. The most commonly used 3D printing material for manufacturing is polylactic acid, although biocompatible resin has been used to produce surgical guides. In addition, the hospital has worked on the co-design of customized implants with manufacturing companies. CONCLUSIONS: The integration of 3D printing in a Department of Orthopedic Surgery and Traumatology allows identifying the conceptual evolution from "Do-It-Yourself" to "POC manufacturing".

Non-toxic doses of modified titanium dioxide nanoparticles (m-TiO2NPs) in albino CFW mice.

Modified titanium dioxide (m-TiO2NPs) is a novel photocatalytic nanomaterial. Its level of toxicity was evaluated to be used in photodynamic treatment for cervical cancer. In the toxicity studies (Irwin test, acute and repeated doses (10 days)), female albino Swiss Webster (CFW) mice, 28 days old were used; the m-TiO2NPs was administered in single 300, 600 and 5,000 mg/kg of body weight (b.w) doses injected in the peritoneal zone. No adverse events or mortality were produced. Daily intraperitoneal doses of 300 and 600 mg/kg b.w every 24 h for 10 days did not produce adverse effects or mortality. There were no abnormal clinical signs or behavioral changes (neurological or physiological) in any of the mice. All organs exhibited normal architecture, and histological studies determined that m-TiO2NPs does not produce changes in the cells or tissues. Based on the test results, it is concluded that the m-TiO2NPs has not a toxic effect in doses equal to or less than 5,000 mg/kg b.w.

Accurate and cost-effective mandibular biomodels: a standardized evaluation of 3D-Printing via fused layer deposition modeling on soluble support structures.

INTRODUCTION: Medical biomodels can be used for illustration of medical conditions, preoperative planning or to facilitate pre-bending of osteosynthesis material. They have been shown to be an effective and efficient method to reduce operating time, blood loss and wound stress in cranio-maxillo-facial surgery. Lately, new time and cost-efficient 3D-printing methods have been introduced into the mass-market. The aim of this study was to establish a standardized method of evaluation and consequently evaluate Fused Layer Deposition Modeling in combination with soluble support structures for fabrication of medical biomodels regarding precision and cost-effectiveness. MATERIALS & METHODS: Twenty-one biomodels of human mandibles equipped with measuring appliances were printed on a FLDM 3D-printers (Ultimaker 3 Extended) using a polyactate filament and a water-soluble Polyvinyl alcohol-based support structures. Precision of these models was compared to commercial, polyamide sintered models and the planning data. Production costs, printing times and post processing procedures were evaluated. RESULTS: Duration of printing of mandibular biomodels was between 6 h 5 min - 15 h 9 min (mean 9 h 12 min, ±2 h 25 min). The average cost of materials was €5.90 (± €1.28) per model. With an average aberrance of 0.29 mm, FLDM printing delivered a high level of accuracy. It was significantly superior to the polyamide reference models in the area of the semilunar incision, yet inferior at the coronoid process. CONCLUSION: FLDM printers are able to provide very precise biomodels at very low costs. The use of using soluble support structures reduces time, costs and equipment needed for post processing procedures close to zero.

3D Printed Biomodels for Flow Visualization in Stenotic Vessels: An Experimental and Numerical Study.

Atherosclerosis is one of the most serious and common forms of cardiovascular disease and a major cause of death and disability worldwide. It is a multifactorial and complex disease that promoted several hemodynamic studies. Although in vivo studies more accurately represent the physiological conditions, in vitro experiments more reliably control several physiological variables and most adequately validate numerical flow studies. Here, a hemodynamic study in idealized stenotic and healthy coronary arteries is presented by applying both numerical and in vitro approaches through computational fluid dynamics simulations and a high-speed video microscopy technique, respectively. By means of stereolithography 3D printing technology, biomodels with three different resolutions were used to perform experimental flow studies. The results showed that the biomodel printed with a resolution of 50 µm was able to most accurately visualize flow due to its lowest roughness values (Ra = 1.8 µm). The flow experimental results showed a qualitatively good agreement with the blood flow numerical data, providing a clear observation of recirculation regions when the diameter reduction reached 60%.

The Use of a 3D Simulator Software and 3D Printed Biomodels to Aid Autologous Breast Reconstruction.

Aesthetically pleasing and symmetrical breasts are the goal of reconstructive breast surgery. However, multiple procedures are sometimes needed to improve a reconstructed breast's symmetry and appearance. Since all breasts vary in terms of volume, height, width, projection, orientation, and shape, the lack of attention to these details at the moment of flap shaping in autologous reconstruction can lead to poor results. Recent advances in 3-dimensional (3D) surface imaging and printing technologies have allowed for improvement in autologous breast reconstruction symmetry. While 3D printing technology is becoming faster, more accurate, and less expensive, the technology required to obtain proper 3D breast images remains expensive, including laser scanners or 3D photogrammetric cameras. In this study, we present a novel use of an aesthetic surgery simulator software as an affordable alternative to obtaining 3D breast images and creating 3D printed biomodels to aid in the precise shaping of the flap. This approach aims to optimize aesthetic results in autologous breast reconstruction avoiding surgical revisions and reducing surgical times. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Otobone ®: Three-dimensional printed Temporal Bone Biomodel for Simulation of Surgical Procedures

Introduction: The anatomy of the temporal bone is complex due to the large number of structures and functions grouped in this small bone space, which do not exist in any other region in the human body. With the difficulty of obtaining anatomical parts and the increasing number of ear, nose and throat (ENT) doctors, there was a need to create alternatives as real as possible for training otologic surgeons. Objective: Developing a technique to produce temporal bone models that allow them to maintain the external and internal anatomical features faithful to the natural bone. Methods: For this study, we used a computed tomography (CT) scan of the temporal bones of a 30-year-old male patient, with no structural morphological changes or any other pathology detected in the examination, which was later sent to a 3D printer in order to produce a temporal bone biomodel. Results: After dissection, the lead author evaluated the plasticity of the part and its similarity in drilling a natural bone as grade "4" on a scale of 0 to 5, in which 5 is the closest to the natural bone and 0 the farthest from the natural bone. All structures proposed in the method were found with the proposed color. Conclusion: It is concluded that it is feasible to use biomodels in surgical training of specialist doctors. After dissection of the bone biomodel, it was possible to find the anatomical structures proposed, and to reproduce the surgical approaches most used in surgical practice and training implants (AU)

Otobone ® : Three-dimensional printed Temporal Bone Biomodel for Simulation of Surgical Procedures.

Introduction The anatomy of the temporal bone is complex due to the large number of structures and functions grouped in this small bone space, which do not exist in any other region in the human body. With the difficulty of obtaining anatomical parts and the increasing number of ear, nose and throat (ENT) doctors, there was a need to create alternatives as real as possible for training otologic surgeons. Objective Developing a technique to produce temporal bone models that allow them to maintain the external and internal anatomical features faithful to the natural bone. Methods For this study, we used a computed tomography (CT) scan of the temporal bones of a 30-year-old male patient, with no structural morphological changes or any other pathology detected in the examination, which was later sent to a 3D printer in order to produce a temporal bone biomodel. Results After dissection, the lead author evaluated the plasticity of the part and its similarity in drilling a natural bone as grade "4" on a scale of 0 to 5, in which 5 is the closest to the natural bone and 0 the farthest from the natural bone. All structures proposed in the method were found with the proposed color. Conclusion It is concluded that it is feasible to use biomodels in surgical training of specialist doctors. After dissection of the bone biomodel, it was possible to find the anatomical structures proposed, and to reproduce the surgical approaches most used in surgical practice and training implants.

Three-Dimensional Printing in Minimally Invasive Spine Surgery.

PURPOSE OF REVIEW: To summarize the recent advances in 3D printing technology as it relates to spine surgery and how it can be applied to minimally invasive spine surgery. RECENT FINDINGS: Most early literature about 3D printing in spine surgery was focused on reconstructing biomodels based on patient imaging. These biomodels were used to simulate complex pathology preoperatively. The focus has shifted to guides, templates, and implants that can be used during surgery and are specific to patient anatomy. However, there continues to be a lack of long-term outcomes or cost-effectiveness analyses. 3D printing also has the potential to revolutionize tissue engineering applications in the search for the optimal scaffold material and structure to improve bone regeneration without the use of other grafting materials. 3D printing has many potential applications to minimally invasive spine surgery requiring more data for widespread adoption.

Reproducible Research Using Biomodels.

Like other types of computational research, modeling and simulation of biological processes (biomodels) is still largely communicated without sufficient detail to allow independent reproduction of results. But reproducibility in this area of research could easily be achieved by making use of existing resources, such as supplying models in standard formats and depositing code, models, and results in public repositories.