Point-of-Care 3-Dimensional-Printed Polyetheretherketone Customized Implants for Cranioplastic Surgery of Large Skull Defects.

BACKGROUND AND OBJECTIVES: 3-Dimensional (3D) printing has become a common tool to aid implant molding for cranioplastic surgery of large skull defects. Until now, 3D printing of cranial implants itself has not been used, mainly because of medicolegal concerns. With a 3D printer developed for printing medical applications and with implant-grade polyetheretherketone (PEEK) filament available, we established a workflow (in compliance with medical device regulations) to 3D print cranial implants for cranioplastic surgery directly at the point of care (POC). Here, we describe the implementation of 3D printing these PEEK implants for cranioplastic surgery at our academic hospital. METHODS: A thorough design and 3D printing process, in accordance with local medical device regulations, was developed. Implants are digitally designed based upon pre- and post-craniectomy cranial computed tomography scans by trained 3D printing experts from the department of medical engineering at our institution. Implants are then produced on a medical 3D printer with implant-grade PEEK filament using the fused filament fabrication process. After postprocessing and steam sterilization, implantation for reconstruction of the skull can be performed. RESULTS: Cranioplastic surgery with a 3D-printed PEEK implant was performed at our institution in a patient with a large frontotemporoparietal skull defect after traumatic brain injury with consecutive decompressive craniectomy. No intra- or post-operative complications occurred. Postoperative cranial computed tomography scans showed perfect reconstruction of precraniectomy skull shape. The aesthetic result was promising and satisfactory to the patient. CONCLUSION: This novel 3D printing workflow enables the production of patient-specific cranial implants from PEEK, to reconstruct large skull defects directly at the POC in accordance with the European Medical Device Regulation. This marks an unprecedented technological and legal advancement, enabling the hospital infrastructure not only to deliver the cranioplastic surgery itself, but also additive manufacturing of the implant directly at the POC.

Skull-femoral traction followed by osteotomy correction is a safe and effective treatment for severe scoliosis with split cord malformation.

OBJECTIVE: This study aimed to evaluate the safety and efficacy of skull-femoral traction followed by osteotomy correction in patients with severe spinal scoliosis and split cord malformation. METHODS: We retrospectively analyzed ten cases of severe spinal scoliosis with Pang I type split cord malformation treated between August 2012 and August 2023. Patients underwent skull-femoral traction prior to osteotomy correction. We assessed changes in height, weight, coronal and sagittal Cobb's angles, and physiological indicators such as vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and blood gas levels before, during, and after treatment. RESULTS: Traction duration ranged from 9 to 19 days, with height and weight showing significant increases post-treatment. The coronal Cobb's angle improved from pre-treatment to post-corrective surgery and remained stable at the final follow-up. Similar improvements were observed in the sagittal plane. Physiological indicators such as VC, FVC, and FEV1, as well as blood gas levels, normalized after treatment. Nutritional status, indicated by triceps skinfold thickness, albumin, and transferrin concentrations, also improved. No neurological complications or device-related complications occurred during or after treatment. CONCLUSION: Skull-femoral traction followed by osteotomy correction is a safe and effective treatment for severe spinal scoliosis with split cord malformation, offering an alternative to high-risk procedures.

Covariation of Skull and Brain Morphology in Domestic Dogs.

Despite their distinct embryonic origins, the skull and brain are highly integrated. Understanding the covariation between the skull and brain can shed light on anatomical, cognitive, and behavioral traits in extant and extinct species. Domestic dogs offer a unique opportunity to investigate skull-brain covariation due to their diverse skull morphologies and neural anatomy. To assess this question, we examined T2-weighted MRI studies of 62 dogs from 33 breeds, plus an additional 17 dogs of mixed or unknown breeds. Scans were opportunistically collected from a veterinary teaching hospital of dogs that were referred for neurological examination but did not have grossly observable structural brain abnormalities. As the neurocrania of dogs become broader and shorter, there is a significant decrease in the gray matter volume of the right olfactory bulb, frontal cortex, marginal gyrus, and cerebellum. On the other hand, as the neurocrania of dogs become narrower and longer, there is a significant decrease in the gray matter volume of the olfactory bulb, frontal cortex, temporal cortex, amygdala, hypothalamus, hippocampus, periaqueductal gray, cerebellum, and brainstem. Selective breeding for specific skull shapes may impact canine brain anatomy and function.

The World's first 3D-printed PEEK cranial implant: a new horizon in precision and personalized neurosurgery.

Cranioplasty is a reconstructive neurosurgical procedure that fixes the cranial bone defects after the craniotomy for brain surgeries like tumours, aneurysms, arterio-venous malformations, subdural empyemas and hematomas. Personalized 3D-printed implants offer various advantages, including anatomical accuracy, functional restoration, time-sparing surgery, excellent cosmetic outcomes through their impeccable adjustment to cranial vault defects, and better clinical outcomes. PEEK has a meritorious profile in terms of high success rate, low complication rate, fracture resistance and low toxicity profile, high strength, high toughness, and excellent biocompatibility in cranioplasty. On the other hand, the need for more cost-effective yet ideal biomaterials must be met for nations and patients with financial constraints. Nevertheless, this additively manufactured 3D-printed cranial implant marks the dawn of a new era in precision and personalized neurosurgery.

Ultrasound-triggered piezoelectric polyetheretherketone with boosted osteogenesis via regulating Akt/GSK3ß/ß-catenin pathway.

Maxillofacial bone defects can severely impact quality of life by impairing physiological functions such as chewing, breathing, swallowing, and pronunciation. Polyether ether ketone (PEEK) is commonly used for the repair of maxillofacial defects due to its mechanical adaptability, while its osteogenic properties still need refinement. Herein, we have utilized the piezoelectric effect exhibited by barium titanate (BTO) under low-intensity pulsed ultrasound (LIPUS) to develop an ultrasound responsive PEEK (PDA@BTO-SPEEK, PBSP) through the mediating effect of polydopamine (PDA), for repairing maxillofacial bone defects. After modification by PDA@BTO, PBSP possesses better hydrophilicity, which is conducive to cell growth and adhesion. Simultaneously, by virtue of the piezoelectric characteristics of BTO, PBSP obtains a piezoelectric coefficient that matches the bone cortex. Notably, when PBSP is stimulated by LIPUS, it can generate stable electricity and effectively accelerate the osteogenic differentiation of osteoblasts through the regulation of the Piezo1-induced calcium (Ca2+) influx and Akt/GSK3ß/ß-catenin pathway. In addition, PBSP presents satisfactory therapeutic effects in rat skull defect models, and its osteogenic efficiency can be further improved under LIPUS stimulation with high tissue penetration. Collectively, PBSP + LIPUS exhibits great potential as a promising alternative strategy for the repair of maxillofacial bone defects.

INDIVIDUAL ANATOMICAL VARIABILITY OF THE ANTEROPOSTERIOR LATERAL DIMENSIONS OF THE FACIAL SKULL IN MATURE ADULTS.

Despite the significance of anatomical variability in various specialties, there is currently limited research dedicated to this topic. Most studies focus on the brain, with only a small number examining the human skull, primarily in relation to anatomical variability in childhood. AIM: Therefore, the aim of our work is to determine the individual anatomical variability of the lateral dimensions of the facial section of the adult human skull. MATERIALS AND METHODS: The study included 115 skulls of mature individuals, comprising 35 dry bone specimens from the anatomy museum collection and 80 results from human head CT scans without bone tissue pathologies. To detail the craniometric characteristics of the lateral surface of the facial section of the skull, polygons (polygons) were constructed with dividing of the facial section of the skull is into the orbital-frontal, nasal, and maxillary. The facial profilegram of the skull was formed as a set of predetermined dimensions between facial profile points, presenting a continuous line passing through points gl-n-rhi-ns-pr-id-pg, reflecting the shape, dimensions, and position of the cranial profile of mature adults regardless of sex or cranial type. RESULTS: It was established that the longitudinal anteroposterior dimensions of the facial skull exhibit a certain range of variability in mature individuals depending on gender. For instance, the distance between the points gl-po (glabella-porion) reaches its maximum values in individuals with a brachycranial skull shape, ranging from 107 mm to 130 mm in men and from 104 mm to 128 mm in women. In individuals with a mesocranial skull shape, this parameter gradually decreases to 109-126 mm in men and 107-124 mm in women. A similar decrease is observed in those with a dolichocranial skull shape, where the range is 109-121 mm in men and 109-120 mm in women. The distance between n-po (nasion-porion) in brachycranial and mesocranial individuals remains within 96-123 mm and 102-123 mm, regardless of gender, indicating that this parameter is relatively stable. However, in dolichocranial individuals, this distance decreases to 104-115 mm. CONCLUSIONS: Individual anatomical variability of the anteroposterior lateral dimensions of the facial skeleton in mature individuals has been determined. A more in-depth analysis of the existing range of individual variability in the profile configuration of the facial skull was conducted using sagittal polygons. It was found that the polygons gl-po-n, n-po-rhi, and rhi-po-ns relate to the structure of the bony profile of the orbital-temporal and nasal regions of the facial skull, reflecting the upper, combined orbital-nasal section of the head.

Minimum and early high-energy sonication protocol of MR-guided focused ultrasound thalamotomy for low-skull density ratio patients with essential tremor and Parkinson's disease.

OBJECTIVE: MR-guided focused ultrasound (MRgFUS) thalamotomy is an incisionless neurosurgical treatment for patients with medically refractory essential tremor and tremor-dominant Parkinson's disease. A low skull density ratio (SDR) < 0.40 is a known risk factor for treatment failure. The aim of this study was to identify useful sonication strategies for patients with a low SDR < 0.40 by modifying the standard sonication protocol using maximum high-energy sonication while minimizing the number of sonications. METHODS: The authors retrospectively analyzed the effects of modified MRgFUS sonication on low-SDR tremor patients. All patients underwent head CT scans to calculate their SDR. The SDR threshold for MRgFUS thalamotomy was 0.35. The patients in the early series underwent the standard sonication protocol targeting the ventral intermediate nucleus contralateral to the treated hand side. The patients with a low SDR < 0.40 in the late series underwent a modified sonication protocol, in which the number of alignment sonications was minimized and high-energy treatment sonication (> 36,000 J) was used. The authors evaluated the lesion volume the following day and tremor improvement and adverse events 3 and 12 months after the procedure. The sonication patterns between low-SDR patients treated using different sonication protocols were examined using Fisher's exact test. ANOVA was used to examine the lesion volume and tremor improvement in high- and low-SDR patients treated using different sonication protocols. RESULTS: Among 41 patients with an SDR < 0.40, 14 underwent standard sonication and 27 underwent modified sonication. Fewer alignment sonications and high-energy treatment sonications were used in the modified sonication group compared with the standard group (p < 0.001). The duration of modified sonication was significantly shorter than that of standard sonication (p < 0.001). The lesion volume and tremor improvement significantly differed among the high- and low-SDR groups with different sonication protocols (p < 0.001). Low-SDR patients treated using modified sonication protocols had comparable lesion volume and tremor improvement to the high-SDR group. The modified sonication protocol did not significantly increase adverse intraprocedural and postprocedural events. CONCLUSIONS: Minimizing alignment sonications and applying high-energy sonication in early treatment help to create an optimal lesion volume and control tremor in low-SDR patients.

Multiparametric influence of 3D-printed organo-mineral scaffolds on bone regeneration.

The development of synthetic bone substitutes that equal or exceed the efficacy of autologous graft remains challenging. In this study, a rat calvarial defect model was used as a reference to investigate the influence of composition and architecture of 3D-printed cement, with or without bioactives, on tissue regeneration. Printable cement pastes were formulated by combining hyaluronic acid and cement precursors. Cementitious scaffolds were printed with 3 different patterns. After 7 weeks of implantation with or without bone marrow, multiparametric qualitative and quantitative assessments were performed using µCT, SEM, and histology. None of the set-up strategies was as efficient as autologous cancellous bone graft to repair calvarial defects. Nonetheless, the presence of scaffold improved the skull vault closure, particularly when the scaffold was soaked in total bone marrow before implantation. No significant effect of scaffold macro-architecture was observed on tissue mineralization. Magnesium phosphate-based scaffolds (MgP) seemed to induce higher bone formation than their calcium-phosphate-based counterparts. They also displayed a quicker biodegradation and sparse remaining material was found after 7 weeks of implantation. Although further improvements are required to reach clinical settings, this study demonstrated the potential of organo-mineral cements for bone regeneration and highlighted the peculiar properties of MgP-based cements.

Glioblastoma induces the recruitment and differentiation of dendritic-like "hybrid" neutrophils from skull bone marrow.

Tumor-associated neutrophil (TAN) effects on glioblastoma (GBM) biology remain under-characterized. We show here that neutrophils with dendritic features-including morphological complexity, expression of antigen presentation genes, and the ability to process exogenous peptide and stimulate major histocompatibility complex (MHC)II-dependent T cell activation-accumulate intratumorally and suppress tumor growth in vivo. Trajectory analysis of patient TAN scRNA-seq identifies this "hybrid" dendritic-neutrophil phenotype as a polarization state that is distinct from canonical cytotoxic TANs, and which differentiates from local precursors. These hybrid-inducible immature neutrophils-which we identified in patient and murine glioblastomas-arise not from circulation, but from local skull marrow. Through labeled skull flap transplantation and targeted ablation, we characterize calvarial marrow as a contributor of antitumoral myeloid antigen-presenting cells (APCs), including TANs, which elicit T cell cytotoxicity and memory. As such, agents augmenting neutrophil egress from skull marrow-such as intracalvarial AMD3100, whose survival-prolonging effect in GBM we report-present therapeutic potential.

Postnatal Skull Development Reveals a Conservative Pattern in Living and Fossil Vizcachas Genus Lagostomus (Rodentia, Chinchillidae).

The plains vizcacha, Lagostomus maximus, is the only living species in the genus, being notably larger than fossil congeneric species, such as Lagostomus incisus, from the Pliocene of Argentina and Uruguay. Here, we compare the skull growth allometric pattern and sexual dimorphism of L. maximus and L. incisus, relating shape and size changes with skull function. We also test whether the ontogenetic trajectories and allometric trends between both sexes of L. maximus follow the same pattern. A common allometric pattern between both species was the elongation of the skull, a product of the lengthening of rostrum, and chondrogenesis on the spheno-occipitalis synchondrosis and coronalis suture. We also detected a low proportion of skull suture fusion. In some variables, older male specimens did not represent a simple linear extension of female trajectory, and all dimorphic traits were related to the development of the masticatory muscles. Sexual dimorphism previously attributed to L. incisus would indicate that this phenomenon was present in the genus since the early Pliocene and suggests social behaviors such as polygyny and male-male competition. Ontogenetic changes in L. incisus were similar to L. maximus, showing a conservative condition of the genus. Only two changes were different in the ontogeny of both species, which appeared earlier in L. incisus compared to L. maximus: the development of the frontal process of the nasals in a square shape, and the straight shape of the occipital bone in lateral view. Juveniles of L. maximus were close to adult L. incisus in the morphospace, suggesting a peramorphic process. The sequence of suture and synchondroses fusion showed minor differences in temporozygomatica and frontonasalis sutures, indicating major mechanical stress in L. maximus related to size. We suggest a generalized growth path in Chinchillidae, but further analyses are necessary at an evolutionary level, including Lagidium and Chinchilla.

Endocranial shape variation and allometry in Euarchontoglires.

While brain size in primates and their relatives within Euarchontoglires is well-studied, less research has examined brain shape, or the allometric trajectories that underlie the relationship between size and shape. Defining these patterns is key to understanding evolutionary trends. 3D geometric morphometric analyses of endocranial shape were performed on 140 species of extant euarchontoglirans using digital cranial endocasts. Principal component analyses on Procrustes shape variables show a clear phylogenetic pattern in endocranial shape, supported by an ANOVA which identified significant differences in shape among several groups (e.g., Platyrrhini, Strepsirrhini, Scandentia, Rodentia, and Lagomorpha). ANOVAs of shape and size also indicate that allometry has a small but significant impact on endocranial shape across Euarchontoglires, with homogeneity of slopes tests finding significant differences in the scaling relationship between shape and size among these same groups. While most of these clades possess a distinct endocranial morphotype, the highly derived platyrrhines display the strongest relationship between size and shape. Rodents show the most diversity in endocranial shape, potentially attributed to their comparatively weak relationship between shape and size. These results suggest fundamental differences in how shape and size covary among Euarchontoglires, which may have facilitated the adaptive radiations that characterize members of this group.

Comparative morphology in the context of facial reduction: Modularity in primate, dog, and bat crania.

Biological variation in the mammalian skull is the product of a series of factors including changes in gene expression, developmental timing, and environmental pressures. When considering the diversity of extant mammalian crania, it is important to understand these mechanisms that contribute to cranial growth and in turn, how differences in cranial morphology have been attained. Various researchers, including Dr. Sue Herring, have proposed a variety of mechanisms to explain the process of cranial growth. This work has set the foundation on which modern analysis of craniofacial morphology happens today. This study focused on the analysis of modularity in three mammalian taxa, all of which exhibit facial reduction. Specifically, we examined facial reduction as a morphological phenomenon through the use of two-module and six-module modularity hypotheses. We recorded three-dimensional coordinate data for 55 cranial landmarks that allowed us to analyze differences in cranial shape in these three taxa (primates n = 88, bats n = 64, dogs n = 81). When assessing modularity within the two-module modularity hypothesis specifically, dogs exhibited the lowest levels of modularity, while bats and primates both showed a slightly more modular covariance structure. We further assessed modularity in the same sample using the Goswami six-module model, where again dogs exhibited a low degree of modularity, with bats and primates being more moderate. We then broke the sample into subsets by analyzing each morphotype separately. We hypothesized that the modularity would be more pronounced in the brachycephalic morphotype. Surprisingly, we found that in brachycephalic dogs, normocephalic dogs, brachycephalic primates, and normocephalic primates, there was a moderate degree of modularity. Brachycephalic bats had a low degree of modularity, while normocephalic bats were the most modular group observed in this study. Based on these results, it is evident that facial reduction is a complex and multifaceted phenomenon with unique morphological changes observed in each of the three taxa studied.

Gastrotheca Fitzinger, 1843 tadpole morphology: Larval cranium description and its evolutionary implications (Amphibia: Anura: Hemiphractidae).

Hemiphractids have a singular mode of reproduction that involves maternal care. The Andean-endemic Gastrotheca marsupiata species group includes direct-developing and tadpole-bearing species, the latter trait being unique among Gastrotheca. Larval morphology has proven to be a valuable source of evidence to understand the taxonomy and evolution of frogs but remains understudied in Hemiphractids. Herein, we redescribe the larval cranium of G. espeletia, G. gracilis, G. marsupiata, G. peruana, G. pseustes, and G. riobambae, and describe those of G. aureomaculata, G. chrysosticta, G. litonedis, G. monticola and G. psychrophila. Additionally, based on the data gathered, we explore their phylogenetic significance, expanding the knowledge regarding Gastrotheca larval internal morphology. We suggest that the presence of the posterolateral process of crista parotica, the concave palatoquadrate, the quadratoorbital commissure, and the proximal commissures II and III are putative synapomorphies for Gastrotheca. Furthermore, we suggest the long pseudopterygoid process as a putative synapomorphy for Hemiphractyidae.

From imaging to personalized 3D printed molds in cranioplasty.

Cranioplasty is the surgical repair of a bone defect in the skull resulting from a previous operation or injury, which involves lifting the scalp and restoring the contour of the skull with a graft made from material that is reconstructed from scans of the patient's own skull. The paper introduces a 3D printing technology in creating molds, which are filled with polymethyl methacrylate (PMMA) to reconstruct the missing bone part of the skull. The procedure included several steps to create a 3D model in an STL format, conversion into a G-code which is further used to produce the mold itself using a 3D printer. The paper presents our initial experience with 5 patients who undergone cranioplasty utilizing 3D printed molds. Making a patient-specific model is a very complex process and consists of several steps. The creation of a patient-specific 3D model loading of DICOM images obtained by CT scanning, followed by thresholding-based segmentation and generation of a precise 3D model of part of the patient's skull. Next step is creating the G-code models for 3D printing, after which the actual models are printed using Fused Deposition Modeling printer and PLA material. All surgeries showed good match of the missing bone part and part created using 3D printed mold, without additional steps in refinement. In such a way, 3D printing technology helps in creating personalized and visually appealing bone replacements, at a low cost of the final product.

Characterization and selection of a skull surrogate for the development of a biofidelic head model.

This research paper explores the advancement of physical models simulating the human skull-brain complex, focusing on applications in simulating mild Traumatic Brain Injury (mTBI). Existing models, especially head forms, lack biofidelity in accurately representing the native structures of the skull, limiting the understanding of intracranial injury parameters beyond kinematic head accelerations. This study addresses this gap by investigating the use of additive manufacturing (AM) techniques to develop biofidelic skull surrogates. Materials such as Polylactic Acid (PLA), a bone-simulant PLA variant, and Hydroxyapatite-coated Poly(methyl methacrylate) (PMMA) were used to create models tested for their flexural modulus and strength. The trabecular bone regions were simulated by adjusting infill densities (30%, 50%, 80%) and print raster directions, optimizing manufacturing parameters for biofidelic performance. Among the tested materials, PLA and its bone-simulating variant printed at 80% infill density with a side (tangential) print orientation demonstrated the closest approximation to the mechanical properties of cranial bone, yielding a mean flexural modulus of 1337.2 MPa and a mean ultimate strength of 56.9 MPa. Statistical analyses showed that infill density significantly influenced the moduli and strength of the printed simulants. Digital Image Correlation (DIC) corroborated the comparable performance of the simulants, showing similar strain and displacement behaviors to native skull bone. Notably, the performance of the manufactured cortical and trabecular regions underscored their crucial role in achieving biofidelity, with the trabecular structure providing critical dampening effects when the native bone is loaded. This study establishes PLA, particularly its bone-simulant variant, as an optimal candidate for cranial bone simulants, offering significant potential for developing more accurate biofidelic head models in mTBI research.

RRmorph-a new R package to map phenotypic evolutionary rates and patterns on 3D meshes.

The study of evolutionary rates and patterns is the key to understand how natural selection shaped the current and past diversity of phenotypes. Phylogenetic comparative methods offer an array of solutions to undertake this challenging task, and help understanding phenotypic variation in full in most circumstances. However, complex, three-dimensional structures such as the skull and the brain serve disparate goals, and different portions of these phenotypes often fulfil different functions, making it hard to understand which parts truly were recruited by natural selection. In the recent past, we developed tools apt to chart evolutionary rate and patterns directly on three-dimensional shapes, according to their magnitude and direction. Here, we present further developments of these tools, which now allow to restitute the mapping of rates and patterns with full biological realism. The tools are condensed in a new R software package.