Establishing a 3D In Vitro Hepatic Model Mimicking Physiologically Relevant to In Vivo State.

Three-dimensional (3D) bioprinting is a promising technology to establish a 3D in vitro hepatic model that holds great potential in toxicological evaluation. However, in current hepatic models, the central area suffers from hypoxic conditions, resulting in slow and weak metabolism of drugs and toxins. It remains challenging to predict accurate drug effects in current bioprinted hepatic models. Here, we constructed a hexagonal bioprinted hepatic construct and incorporated a spinning condition with continuous media stimuli. Under spinning conditions, HepG2 cells in the bioprinted hepatic construct exhibited enhanced proliferation capacity and functionality compared to those under static conditions. Additionally, the number of spheroids that play a role in boosting drug-induced signals and responses increased in the bioprinted hepatic constructs cultured under spinning conditions. Moreover, HepG2 cells under spinning conditions exhibited intensive TGFß-induced epithelial-to-mesenchymal transition (EMT) and increased susceptibility to acetaminophen (APAP)-induced hepatotoxicity as well as hepatotoxicity prevention by administration of N-acetylcysteine (NAC). Taken together, the results of our study demonstrate that the spinning condition employed during the generation of bioprinted hepatic constructs enables the recapitulation of liver injury and repair phenomena in particular. This simple but effective culture strategy facilitates bioprinted hepatic constructs to improve in vitro modeling for drug effect evaluation.

Clinical application of patient-specific 3D printing brain tumor model production system for neurosurgery.

The usefulness of 3-dimensional (3D)-printed disease models has been recognized in various medical fields. This study aims to introduce a production platform for patient-specific 3D-printed brain tumor model in clinical practice and evaluate its effectiveness. A full-cycle platform was created for the clinical application of a 3D-printed brain tumor model (3D-printed model) production system. Essential elements included automated segmentation software, cloud-based interactive communication tools, customized brain models with exquisite expression of brain anatomy in transparent material, adjunctive devices for surgical simulation, and swift process cycles to meet practical needs. A simulated clinical usefulness validation was conducted in which neurosurgeons assessed the usefulness of the 3D-printed models in 10 cases. We successfully produced clinically applicable patient-specific models within 4 days using the established platform. The simulated clinical usefulness validation results revealed the significant superiority of the 3D-printed models in surgical planning regarding surgical posture (p = 0.0147) and craniotomy design (p = 0.0072) compared to conventional magnetic resonance images. The benefit was more noticeable for neurosurgeons with less experience. We established a 3D-printed brain tumor model production system that is ready to use in daily clinical practice for neurosurgery.

Use of color-coded, three-dimensional-printed equine carpus models is preferred by students but does not result in statistically different academic performance.

Radiology can be a challenging subject for students and finding new techniques that help improve their understanding could have positive effects in their clinical practice. The purpose of this prospective experimental study was to implement the use of color-coded, three-dimensional-printed, handheld equine carpus models into a radiographic anatomy course and evaluate the impact objectively and subjectively using quizzes and student response surveys. A first-year veterinary class was randomly divided into two similarly sized groups (groups A and B) for an equine normal radiographic anatomy laboratory. Both groups experienced the same laboratory structure; however, each student in group B received a handheld three-dimensional-printed equine carpus. Both groups received a quiz at the end of their laboratory consisting of 10 multiple-choice questions related to the equine carpus. An anonymous survey regarding the laboratory was emailed to students after the laboratory. One week later, the same 10 questions in randomized order were administered via a pop-quiz. Students believed both quizzes would count toward their final course grade. There was no statistically significant difference in grades between groups on either quiz (P > .05). However, based on survey responses, group B students felt the carpus made the laboratory more enjoyable and improved their comprehension of the material, whereas group A students felt the carpus would have increased their enjoyment and improved their comprehension. The implementation of three-dimensional-printed anatomic models may be useful to enhance enjoyment and perceived comprehension of veterinary students; however, there is currently insufficient evidence to suggest these models improve academic performance.

Utility of 3D printed cardiac models in congenital heart disease: a scoping review.

OBJECTIVE: Three-dimensional printing (3DP) is a novel technology with applications in healthcare, particularly for congenital heart disease (CHD). We sought to explore the spectrum of use of 3D printed CHD models (3D-CM) and identify knowledge gaps within the published body of literature to guide future research. METHODS: We conducted a scoping review targeting published literature on the use of 3D-CMs. The databases of MEDLINE, EMBASE and Web of Science were searched from their inception until 19 July 2019. Inclusion criteria were primary research; studies reporting use of 3D-CMs; and human subjects. Exclusion criteria were studies where 3D-CMs were generated for proof of concept but not used; and studies focused on bioprinting or computational 3D-CMs. Studies were assessed for inclusion and data were extracted from eligible articles in duplicate. RESULTS: The search returned 648 results. Following assessment, 79 articles were included in the final qualitative synthesis. The majority (66%) of studies are case reports or series. 15% reported use of a control group. Three main areas of utilisation are for (1) surgical and interventional cardiology procedural planning (n=62), (2) simulation (n=25), and (3) education for medical personnel or patients and their families (n=17). Multiple studies used 3D-CMs for more than one of these areas. CONCLUSIONS: 3DP for CHD is a new technology with an evolving literature base. Most of the published literature are experiential reports as opposed to manuscripts on scientifically robust studies. Our study has identified gaps in the literature and addressed priority areas for future research.

Utility of a Three-Dimensional Printed Pelvic Model for Lateral Pelvic Lymph Node Dissection Education: A Randomized Controlled Trial.

BACKGROUND: Lateral pelvic lymph node dissection for rectal cancer is a difficult technique due to the complex pelvic anatomy involved. Three-dimensional (3D) organ models have been introduced as education tools to study anatomy in some fields. In this study, we educated the participants about pelvic anatomy using a 3D model, and evaluated learning efficiency, comparing the outcomes with those using a traditional textbook. STUDY DESIGN: This study was a randomized, controlled, single-center trial conducted between July 2018 and July 2019. A total of 102 participants (34 medical students, 34 residents, and 34 surgeons) were enrolled. Participants were randomly assigned to the 3D model group or the textbook group. First, they completed a short test to confirm their basic knowledge before further education. After collocated education, they completed the same short test again and another long test to evaluate their learning outcomes. RESULTS: Before education, there was no significant difference in the short test scores between the 3D model group and the textbook group. After education, the short and long test scores of the 3D model group were significantly higher than those of the textbook group for students (short test; p = 0.05, long test; p = 0.03), residents (short test; p = 0.05, long test; p = 0.002), and surgeons (short test; p = 0.009, long test; p < 0.001). CONCLUSIONS: Using a 3D pelvic model is superior to using a textbook when learning pelvic anatomy required for lateral pelvic lymph node dissection.

Long-term Evaluation of Meniscal Tissue Formation in 3-dimensional-Printed Scaffolds With Sequential Release of Connective Tissue Growth Factor and TGF-ß3 in an Ovine Model.

BACKGROUND: Artificial meniscal scaffolds are being developed to prevent development of osteoarthritis after meniscectomy. Previously, it was reported that 3-dimensional (3D) anatomic scaffolds loaded with connective tissue growth factor (CTGF) and transforming growth factor ß3 (TGF-ß3) achieved meniscal regeneration in an ovine model. This was a relatively short-term study (3 months postoperative), and outcome analyses did not include magnetic resonance imaging (MRI). PURPOSE: To evaluate long-term outcome of meniscal replacement with growth factor-laden poly-ε-caprolactone (PCL) scaffolds. STUDY DESIGN: Controlled laboratory study. METHODS: Anatomically shaped ovine meniscal scaffolds were fabricated from PCL with a 3D printer based on MRI data. Skeletally mature sheep (N = 34) were randomly allocated to 3 groups: scaffold without growth factor (0-µg group), scaffold with CTGF microspheres (µS) (5 µg) + TGF-ß3 µS (5 µg) (5-µg group), and scaffold with CTGF µS (10 µg) + TGF-ß3 µS (10 µg) (10-µg group). Unilateral medial meniscal replacement was performed. Animals were euthanized at 6 or 12 months. Regenerated meniscus, articular cartilage status, and synovial reaction were evaluated quantitatively with gross inspection, histology, and MRI. Kruskal-Wallis and Dunn tests were used to compare the 3 groups. RESULTS: Remnants of the PCL scaffold were evident in the 6-month specimens and were decreased but still present at 12 months in most animals. There were no significant differences among groups in gross inspection, histology, or MRI for either meniscal regeneration or articular cartilage protection. All experimental groups exhibited articular cartilage degeneration as compared with control (nonoperated). In terms of synovitis, there were no clear differences among groups, suggesting that growth factors did not increase inflammation and fibrosis. MRI revealed that meniscal extrusion was observed in most animals (82.7%). CONCLUSION: Previously, the combination of CTGF and TGF-ß3 was shown to stimulate mesenchymal stem cells into a fibrochondrocyte lineage. CTGF and TGF-ß3 did not aggravate synovitis, suggesting no adverse response to the combination of 3D-printed PCL scaffold combined with CTGF and TGF-ß3. Further work will be required to improve scaffold fixation to avoid meniscal extrusion. CLINICAL RELEVANCE: A significant advantage of this technique is the ability to print custom-fit scaffolds from MRI-generated templates. In addition, average-size menisci could be printed and available for off-the-shelf applications. Based on the 1-year duration of the study, the approach appears to be promising for meniscal regeneration in humans.

Implementation of 3D Printing Technology in the Field of Prosthetics: Past, Present, and Future.

There is an interesting and long history of prostheses designed for those with upper-limb difference, and yet issues still persist that have not yet been solved. Prosthesis needs for children are particularly complex, due in part to their growth rates. Access to a device can have a significant impact on a child's psychosocial development. Often, devices supporting both cosmetic form and user function are not accessible to children due to high costs, insurance policies, medical availability, and their perceived durability and complexity of control. These challenges have encouraged a grassroots effort globally to offer a viable solution for the millions of people living with limb difference around the world. The innovative application of 3D printing for customizable and user-specific hardware has led to open-source Do It Yourself "DIY" production of assistive devices, having an incredible impact globally for families with little recourse. This paper examines new research and development of prostheses by the maker community and nonprofit organizations, as well as a novel case study exploring the development of technology and the training methods available. These design efforts are discussed further in the context of the medical regulatory framework in the United States and highlight new associated clinical studies designed to measure the quality of life impact of such devices.

Characterization of particulate and gaseous pollutants emitted during operation of a desktop 3D printer.

The emission of ultrafine particles (UFP) and gaseous pollutants from 3D printing has been increasingly gaining attention in recent years due to potential health risks. The physical and chemical properties of the emitted particulate matter, however, remain unclear. In this study, we characterized these particles with a focus on their chemical composition and volatility, and measured the gaseous pollutants from desktop 3D printing in a standardized environmental test chamber. Eight types of filaments were tested, including ABS (acrylonitrile butadiene styrene), ASA (acrylonitrile styrene acrylate), HIPS (high impact polystyrene), PETG (polyethylene terephthalate glycol), and PCABS (polycarbonate & ABS). Particle size distribution (PSD), particle number concentration (PNC), particle chemical composition and particle volatility were measured. In addition, volatile and very volatile organic compounds (VOCs and VVOCs) emitted during 3D printing were analyzed. The specific emission rates (SERs) for particles in the size range of 5.6 to 560 nm ranged from 2.0 × 109 (GLASS, a PETG-based filament) to 1.7 × 1011 (ASA) #/min. The particle SERs for ABS were (4.7 ±â€¯1.1) × 1010 #/min. The SERs for total volatile organic compounds (TVOC) varied from 0.2 µg/min (GLASS) to 40.5 µg/min (ULTRAT, an ABS-based filament). Particles started to evaporate extensively from 150 °C. At 300 °C, only 25% of the particle number remained with the size distribution mode peaked at 11 nm. The particles collected on the quartz filter were mainly composed of semi-volatile organic compounds (SVOCs) associated with the plasticizers, flame-retardants, antioxidants of the thermoplastics, and cyclosiloxanes which may be used as lubricants in the 3D printer.

Surgery of complex craniofacial defects: A single-step AM-based methodology.

BACKGROUND AND OBJECTIVE: The purpose of the present paper is to pave the road to the systematic optimization of complex craniofacial surgical intervention and to validate a design methodology for the virtual surgery and the fabrication of cranium vault custom plates. Recent advances in the field of medical imaging, image processing and additive manufacturing (AM) have led to new insights in several medical applications. The engineered combination of medical actions and 3D processing steps, foster the optimization of the intervention in terms of operative time and number of sessions needed. Complex craniofacial surgical intervention, such as for instance severe hypertelorism accompanied by skull holes, traditionally requires a first surgery to correctly "resize" the patient cranium and a second surgical session to implant a customized 3D printed prosthesis. Between the two surgical interventions, medical imaging needs to be carried out to aid the design the skull plate. Instead, this paper proposes a CAD/AM-based one-in-all design methodology allowing the surgeons to perform, in a single surgical intervention, both skull correction and implantation. METHODS: A strategy envisaging a virtual/mock surgery on a CAD/AM model of the patient cranium so as to plan the surgery and to design the final shape of the cranium plaque is proposed. The procedure relies on patient imaging, 3D geometry reconstruction of the defective skull, virtual planning and mock surgery to determine the hypothetical anatomic 3D model and, finally, to skull plate design and 3D printing. RESULTS: The methodology has been tested on a complex case study. Results demonstrate the feasibility of the proposed approach and a consistent reduction of time and overall cost of the surgery, not to mention the huge benefits on the patient that is subjected to a single surgical operation. CONCLUSIONS: Despite a number of AM-based methodologies have been proposed for designing cranial implants or to correct orbital hypertelorism, to the best of the authors' knowledge, the present work is the first to simultaneously treat osteotomy and titanium cranium plaque.

Three-dimensional Printing of Thermoplastic Materials to Create Automated Syringe Pumps with Feedback Control for Microfluidic Applications.

Microfluidics has become a critical tool in research across the biological, chemical, and physical sciences. One important component of microfluidic experimentation is a stable fluid handling system capable of accurately providing an inlet flow rate or inlet pressure. Here, we have developed a syringe pump system capable of controlling and regulating the inlet fluid pressure delivered to a microfluidic device. This system was designed using low-cost materials and additive manufacturing principles, leveraging three-dimensional (3D) printing of thermoplastic materials and off-the-shelf components whenever possible. This system is composed of three main components: a syringe pump, a pressure transducer, and a programmable microcontroller. Within this paper, we detail a set of protocols for fabricating, assembling, and programming this syringe pump system. Furthermore, we have included representative results that demonstrate high-fidelity, feedback control of inlet pressure using this system. We expect this protocol will allow researchers to fabricate low-cost syringe pump systems, lowering the entry barrier for the use of microfluidics in biomedical, chemical, and materials research.

Software tools for cell culture-related 3D printed structures.

Three-dimensional (3D) printing technology allowed fast and cheap prototype fabrication in numerous segments of industry and it also became an increasingly versatile experimental platform in life sciences. Yet, general purpose software tools to control printer hardware are often suboptimal for bioprinting applications. Here we report a package of open source software tools that we developed specifically to meet bioprinting requirements: Machine movements can be (i) precisely specified using high level programming languages, and (ii) easily distributed across a batch of tissue culture dishes. To demonstrate the utility of the reported technique, we present custom fabricated, biocompatible 3D-printed plastic structures that can control cell spreading area or medium volume, and exhibit excellent optical properties even at 50 ul sample volumes. We expect our software tools to be helpful not only to manufacture customized in vitro experimental chambers, but for applications involving printing cells and extracellular matrices as well.

A Soft Tooling Process Chain for Injection Molding of a 3D Component with Micro Pillars.

The purpose of this paper is to present the method of a soft tooling process chain employing Additive Manufacturing (AM) for fabrication of injection molding inserts with micro surface features. The Soft Tooling inserts are manufactured by Digital Light Processing (vat photo polymerization) using a photopolymer that can withstand relatively high temperaturea. The part manufactured here has four tines with an angle of 60°. Micro pillars (Ø200 µm, aspect ratio of 1) are arranged on the surfaces by two rows. Polyethylene (PE) injection molding with the soft tooling inserts is used to fabricate the final parts. This method demonstrates that it is feasible to obtain injection-molded parts with microstructures on complex geometry by additive manufactured inserts. The machining time and cost is reduced significantly compared to conventional tooling processes based on computer numerical control (CNC) machining. The dimensions of the micro features are influenced by the applied additive manufacturing process. The lifetime of the inserts determines that this process is more suitable for pilot production. The precision of the inserts production is limited by the additive manufacturing process as well.

A 3D-printed Chamber for Organic Optoelectronic Device Degradation Testing.

In this manuscript, we outline the manufacture of a small, portable, easy-to-use atmospheric chamber for organic and perovskite optoelectronic devices, using 3D-printing. As these types of devices are sensitive to moisture and oxygen, such a chamber can aid researchers in characterizing the electronic and stability properties. The chamber is intended to be used as a temporary, reusable, and stable environment with controlled properties (including humidity, gas introduction, and temperature). It can be used to protect air-sensitive materials or to expose them to contaminants in a controlled way for degradation studies. To characterize the properties of the chamber, we outline a simple procedure to determine the water vapor transmission rate (WVTR) using relative humidity as measured by a standard humidity sensor. This standard operating procedure, using a 50% infill density of polylactic acid (PLA), results in a chamber that can be used for weeks without any significant loss of device properties. The versatility and ease of use of the chamber allows it to be adapted to any characterization condition that requires a compact-controlled atmosphere.

3D printing in medical imaging and healthcare services.

Three-dimensional (3D) printing technology has demonstrated a huge potential for the future of medicine. Since its introduction, it has been used in various areas, for example building anatomical models, personalising medical devices and implants, aiding in precision medical interventions and the latest development, 3D bioprinting. This commentary is provided to outline the current use of 3D printing in medical imaging and its future directions for advancing the healthcare services.

A 3-dimensional (3D)-printed Template for High Throughput Zebrafish Embryo Arraying.

The zebrafish is a globally recognized fresh water organism frequently used in developmental biology, environmental toxicology, and human disease related research fields. Thanks to its unique features, including large fecundity, embryo translucency, rapid and simultaneous development, etc., zebrafish embryos are often used for large scale toxicity assessment of chemicals and drug/compound screening. A typical screening procedure involves adult zebrafish spawning, embryos selection, and arraying the embryos into multi-well plates. From there, embryos are subjected to exposure and the toxicity of chemical, or the effectiveness of the drugs/compounds can be evaluated relatively quickly based on phenotypic observations. Among these processes, embryos arraying is one of the most time-consuming and labor-intensive steps that limits the throughput level. In this protocol, we present an innovative approach that makes use of a 3D-printed arraying template coupled with vacuum manipulation to speed up this laborious step. The protocol herein describes the overall design of the arraying template, a detailed experimental setup and step-by-step procedure, followed by representative results. When implemented, this approach should prove beneficial in a variety of research applications using zebrafish embryos as testing subjects.

Clinical value of 3D printing guide plate in core decompression plus porous bioceramics rod placement for the treatment of early osteonecrosis of the femoral head.

BACKGROUND: The conventional method of core decompression combined with porous bioceramics rod is usually performed under C-arm fluoroscopy for the treatment of early osteonecrosis of the femoral head (ONFH). This study was to evaluate the clinical value and efficacy of three-dimensional (3D) printing guide plate in the process of core decompression plus porous bioceramics rod for the treatment of early ONFH. METHODS: Forty patients were enrolled, including 20 patients undergoing the surgery with 3D printing guide plate in the experiment group and 20 controls with C-arm fluoroscopy. The following parameters such as surgery time, blood loss, fluoroscopy times, and the accuracy of core decompression for necrosis area, function outcome according to Harris Hip Score (HHS), and any possible complications were recorded and compared between the two groups. All the patients were followed up at 6, 12, and 18 months postoperatively. RESULTS: The surgery time, fluoroscopy time, and intraoperative blood loss in the experiment group was significantly less (P < 0.05) than those in the control group. There was no statistical significance in the accuracy of core decompression and porous bioceramics rod placement between the two groups (P > 0.05). All patients were followed up for 18 months. There was a significant difference between the preoperative and final follow-up HSS scores in both groups (P < 0.05). In addition, there was also a significant difference between the groups in the last follow-up HSS scores (P < 0.05). CONCLUSIONS: Compared with the traditional method, 3D printing guide plate could shorten the surgery time and fluoroscopy times and decrease intraoperative blood loss. It seems to be an effective method in the combined core decompression with porous bioceramics rod placement for early ONFH.

A 3D printed model for radius curvus surgical treatment planning in a dog / Modelo impresso em 3D usado num planeamento cirúrgico de um cão com radius curvus

An 8 month-old, 10 kg male Azawakh dog was presented due to worsening forelimb gait and exercise intolerance. The right forelimb presented gross angular limb deformity with carpal valgus and radial procurvatum. Surgical planning based on radiographs allowed calculation of the centers of rotation and angularity (CORAs). The computer tomography data were used to generate 3D reconstructions of the antebrachium to aid the detection of the orthopaedic problems. With proper imaging software, the nature of the deformity and its degree were quantified using a previously unreported method based on the CORAs as a 3D printed model of anatomical area of interest. This 3D printed model was used by the surgeon to simulate the surgery with all orthopaedic steps, which included a partial ulna osteotomy and a double cuneiform osteotomy of the radius performed at the level of CORAs and stabilized with bone plates and screws. After 7 weeks, radiographs revealed bone union. At 8 months after surgery the animal presented a complete recovery of the involved forelimb. CORAs method combined with computed tomography and 3D model was useful to plan and simulate surgical procedures, including the corrective surgery of forelimb deformities in a dog which improved the surgical efficiency comparatively to the conventional pre-operative study.(AU)

Um cão com 8 meses de idade, 10kg de peso vivo, macho da raça Azawakh foi apresentado à clínica devido à intolerância ao exercício e agravamento da marcha do membro anterior. O membro anterior direito apresentou uma deformidade angular com valgus carpal e com um procarvatum radial. O planeamento cirúrgico inicialmente baseado em exames radiográficos possibilitou o cálculo dos centros de rotação e angulação articulares (CORAs). O exame de tomografia computadorizada foi utilizado juntamente com um software de imagiologia para obter o modelo 3D virtual da área anatómica de interesse que foi posteriormente impresso em 3D e que permitiu quantificar micrometricamente a deformação óssea presente. Este modelo 3D foi utilizado pelos cirurgiões para executar uma simulação cirúrgica completa que englobou todos os procedimentos cirúrgicos, que incluiu a realização de várias osteotomias e aplicação do material cirúrgico (placas e parafusos). Com base na simulação cirúrgica foi executada a cirurgia ao animal. Decorridas sete semanas, as radiografias demonstraram uma correta regeneração óssea. Oito meses após a cirurgia o animal apresentou uma recuperação completa. O método dos CORAs juntamente com a tomografia computadorizada e com a utilização do modelo 3D revelou-se útil no planeamento e na simulação dos vários procedimentos cirúrgicos, resultando numa melhoria significativa da eficiência cirúrgica.(AU)

A simulated training model for laparoscopic pyloromyotomy: Is 3D printing the way of the future?

BACKGROUND: Hypertrophic pyloric stenosis (HPS) is a common neonatal condition treated with open or laparoscopic pyloromyotomy. 3D-printed organs offer realistic simulations to practice surgical techniques. The purpose of this study was to validate a 3D HPS stomach model and assess model reliability and surgical realism. METHODS: Medical students, general surgery residents, and adult and pediatric general surgeons were recruited from a single center. Participants were videotaped three times performing a laparoscopic pyloromyotomy using box trainers and 3D-printed stomachs. Attempts were graded independently by three reviewers using GOALS and Task Specific Assessments (TSA). Participants were surveyed using the Index of Agreement of Assertions on Model Accuracy (IAAMA). RESULTS: Participants reported their experience levels as novice (22%), inexperienced (26%), intermediate (19%), and experienced (33%). Interrater reliability was similar for overall average GOALS and TSA scores. There was a significant improvement in GOALS (p<0.0001) and TSA scores (p=0.03) between attempts and overall. Participants felt the model accurately simulated a laparoscopic pyloromyotomy (82%) and would be a useful tool for beginners (100%). CONCLUSION: A 3D-printed stomach model for simulated laparoscopic pyloromyotomy is a useful training tool for learners to improve laparoscopic skills. The GOALS and TSA provide reliable technical skills assessments. LEVEL OF EVIDENCE: II.

Anterior Unilateral Plagiocephaly in Patient with Alagille Syndrome: Case Report.

BACKGROUND: The polymalformative syndromes and craniofacial anomalies association is a well-known phenomenon in patients with Crouzon, Pfeiffer, Apert, or Muenke disease. Recently, other less frequent pathologies, such as Alagille syndrome, have shown an association with alterations in the development of cranial sutures, resulting in serious cosmetic defects and neurologic disorders. CASE DESCRIPTION: We report an exceptional case of a 30-month-old girl, a nephroblastoma survivor diagnosed with Alagille syndrome, who was referred to our department with progressive anterior plagiocephaly and premature left coronal suture closure associated with a large compensating right bossing. Despite the patient's age, we offered aggressive surgical treatment performing a new forehead harvested from the skull vertex with orbital rim reconstruction. CONCLUSIONS: Alagille syndrome is a complex multisystem pathology with a poor craniosynostosis association and only 3 cases have been described in the literature.