Search Results (123)

Craniosynostosis is the premature fusion of skull bones due to loss of stem/progenitor cells located in non-mineralized tissue between growing cranial bones of infants. We generated scaffolds from a biodegradable biomaterial with small interconnected pores (125–250 μm diameter), previously shown to maintain stemness of a mesenchymal cell population, to further develop a method for the creation of an artificial cranial bone stem cell niche. Polymer scaffolds of consistent pore size were fabricated using a molecular-sieved sugar sphere casting technique with poly-l-lactic acid. A rectangular surgical defect within the parietal bone of juvenile mice was created. The three groups included sham animals with surgery but no scaffold, experimental animals with surgery plus an implanted cell-free scaffold, and experimental animals with surgery plus an implanted bone mesenchymal cell-seeded scaffold. Healing at the surgical site was evaluated at 4 and 12 weeks after surgery by micro-CT and histology. Surgical site bone volume fraction and bone mineral density were significantly greater at twelve than four weeks in the sham group but not in either of the scaffold groups. At twelve weeks, the surgical site bone volume fraction and bone mineral density were significantly lower in the cell-seeded scaffold as compared to the sham animal group. At twelve weeks, the anterior and middle cranial vault widths were significantly greater in the cell-seeded scaffold as compared to the sham animal group on the surgery side of the skulls. Less mineralization was evident within the cell-seeded than the cell-free scaffolds by histology. Based on these findings, scaffolds of sufficiently small pore size seeded with autologous bone mesenchymal stem cells could function as an artificial cranial stem cell niche to inhibit surgical-site mineralization and promote cranial growth. Full article

The accurate reconstruction of craniofacial defects requires the precise segmentation and mirroring of healthy anatomy. Conventional workflows rely on manual interaction, making them time-consuming and subject to operator variability. This study developed and validated a fully automated digital pipeline that integrates deep learning–based segmentation with algorithmic mirroring for craniofacial reconstruction. A total of 388 cranial CT scans were used to train a three-dimensional nnU-Net model for skull and mandible segmentation. A Principal Component Analysis–Iterative Closest Point (PCA–ICP) algorithm was then applied to compute the sagittal symmetry plane and perform mirroring. Automated results were compared with expert-generated segmentations and manually defined symmetry planes using Dice Similarity Coefficient (DSC), Mean Surface Distance (MSD), Hausdorff Distance (HD), and angular deviation. The nnU-Net achieved high segmentation accuracy for both the mandible (mean DSC 0.956) and the skull (mean DSC 0.965). Mirroring results showed minimal angular deviation from expert reference planes (mandible: 1.32° ± 0.71° in defect cases, 1.58° ± 1.12° in intact cases; skull: 1.75° ± 0.84° in defect cases, 1.15° ± 0.81° in intact cases). The presence of defects did not significantly affect accuracy. This automated workflow demonstrated robust performance and clinical applicability, offering standardized, reproducible, and time-efficient planning for craniofacial reconstruction. Full article

Cell population and vascular vessel distribution analysis in membrane-based scaffolds for tissue engineering is crucial. Biomimetic nanostructured membranes of methyl methacrylate/hydroxyethyl methacrylate and methyl acrylate/hydroxyethyl acrylate (MMA)1-co-(HEMA)1/(MA)3-co-(HEA)2 loaded with 5% wt SiO2-nanoparticles (Si-M) were doped with zinc (Zn-M) or doxycycline (Dox-M). Critical bone defects were effectuated on six New Zealand-bred rabbit skulls and then they were covered with the membrane-based scaffolds. After six weeks, bone cell population in terms of osteoblasts, osteoclasts, osteocytes, fibroblasts, and M1 and M2 macrophages and vasculature was determined. The areas of interest were the space above (over) and below (under) the membrane, apart from the interior (inner) compartment. All membranes showed that vasculature and most cell types were more abundant under the membrane than in the inner or above regions. Quantitatively, osteoblast density increased by approximately 35% in Zn-M and 25% in Si-M compared with Dox-M. Osteoclast counts decreased by about 78% in Dox-M, indicating strong inhibition of bone resorption. Vascular structures were nearly twofold more frequent under the membranes, particularly in Si-M, while fibroblast presence remained moderate and evenly distributed. The M1/M2 macrophage ratio was higher in Zn-M, reflecting a transient pro-inflammatory state, whereas Dox-M favored an anti-inflammatory, pro-regenerative profile. These results indicate that the biomimetic electrospun membranes functioned as architectural templates that provided favorable microenvironments for cell colonization, angiogenesis, and early bone regeneration in a preclinical in vivo model. Zn-M membranes appear suitable for early osteogenic stimulation, while Dox-M membranes may be advantageous in clinical contexts requiring modulation of inflammation and osteoclastic activity. Full article

Introduction: Tumors of the lateral skull base, particularly those arising from the external auditory canal and peri-retroauricular regions, present considerable surgical and reconstructive difficulties due to their intricate anatomy and aggressive nature. The anterolateral thigh (ALT) free flap offers a viable reconstruction option, enhancing oncological radicality while minimizing morbidity. Materials and Methods: A retrospective analysis was conducted on five cases of malignant tumors involving the external auditory canal and adjacent soft tissues, treated at a tertiary center from March 2023 to March 2025. All patients underwent radical resection, which included lateral or subtotal temporal bone resection, along with parotidectomy and neck dissection when necessary. Reconstruction was performed using myocutaneous anterolateral thigh free flaps. The study evaluated clinical outcomes, complications, and esthetic results. Results: The ALT flap was used in all cases without major postoperative complications. Two patients received adjuvant radiotherapy; one did not start treatment due to early recurrence. At follow-up, three patients were disease-free, while two had died from unrelated causes. Esthetic and functional outcomes were satisfactory in all patients. Conclusions: The ALT free flap is a universal and reliable option for the reconstruction of complex lateral skull base defects, especially in patients following the radical removal of tumors of the external auditory canal and peri-retroauricular areas. It offers excellent tissue coverage, facilitates adjuvant treatment, and has a low complication rate. While our experience supports its use in aggressive oncological resection, larger studies are needed to confirm these findings. Level of evidence: 4. Full article

Background: Reconstruction of nasal, septal, and nasosinusal defects is challenging when the native mucosa is absent or damaged. Oral mucosal grafts have been proposed as a reconstructive option due to their favorable biological properties, but their use in rhinology remains poorly defined. Objective: To evaluate the clinical efficacy and technical characteristics of oral mucosal grafting for nasal, septal, nasosinusal, and skull base reconstruction. Data Sources: PubMed, Embase, Web of Science, and Cochrane Library were searched for studies published between January 2005 and May 2025. Study Eligibility Criteria: We included original human studies (case reports or series) reporting the use of free or pedicled oral mucosal grafts in nasal, septal, nasosinusal, or skull base reconstruction. Non-original studies, animal or preclinical studies, and articles not in English or Spanish were excluded. Methods of Review: One reviewer screened titles, abstracts, and full texts using Rayyan. Methodological quality was assessed using JBI tools for case reports and case series. A narrative synthesis was conducted due to clinical heterogeneity and absence of comparison groups. The resulting assessments were reviewed by the co-authors to confirm accuracy and resolve any potential discrepancies. Results: Of 467 records identified, 10 studies were included. All were case reports or series involving buccal, palatal, or labial mucosa. Most reported good graft integration, low complication rates, and favorable functional outcomes. No randomized studies or comparative analyses were found. Limitations: Included studies had small sample sizes, lacked control groups, and showed heterogeneous methods and follow-up. The certainty of evidence could not be formally assessed. Conclusions: Oral mucosal grafting is a promising reconstructive option in selected nasosinusal and skull base defects. However, stronger comparative studies are needed to determine its clinical superiority. Registration: This review was not registered in any public database. Full article

Intraosseous hemangiomas (IH) are rare intrabony lesions that represent less than 1% of intraosseous tumors. IH are mostly seen in the axial skeleton and skull. Most commonly, the frontal bone, zygomatic, sphenoid, maxilla, ethmoid, and lacrimal bone can manifest IH. Currently, IH is classified as a developmental condition of endothelial origin. According to WHO, the five histological types of IH are cavernous, capillary, epithelioid, histiocytoid, and sclerosing. IH of the zygoma is an extremely rare condition with female predominance. A systematic review recently estimated that there were 78 cases published in the literature until 2023. The lesion is usually asymptomatic and presents with a gradually deteriorating deformity of the malar area, and the patient might be able to recall a history of trauma. Numbness due to involvement of the infraorbital nerve might also be present; however, atypical skin and bone sensations might also occur. Other symptoms include painful swelling, bone asymmetry, skin irritation, sinus pressure, paresthesia, diplopia, enophthalmos, or atypical neuralgia. A bony lesion with a trabecular pattern in a radiating formation (sunburst pattern) or a multilocal lytic lesion pattern created by the multiple cavernous spaces (honeycomb pattern) is commonly observed during radiologic evaluation. We present a rare case of IH of the zygoma in a 65-year-old generally healthy woman. A cyst-like bone tumor was revealed from the CT scan, which made preoperative biopsy of the lesion problematic. A careful radiological diagnostic differentiation of the lesion should always be conducted in such cases to outline a safe surgical plan and possible alternatives if needed. The patient underwent total tumor resection in the operating room, and the defect was reconstructed with the use of a titanium mesh and a synthetic hydroxyapatite bone graft based on a 3D surgical guide printed model. Full article

Lateral facial clefts are rare and often part of more complex syndromic neurocristopathies. According to Tessier’s classification, they correspond to facial cleft numbers 6, 7 and 8. Using micro-computer tomography (micro-CT), we analyzed their underlying bone defects (resolution 50 and 55 µm/voxel) in the context of the known syndrome-specific genetic background. Lateral facial clefts were diagnosed in three severely affected museum specimens representing mandibulofacial dysostosis type Treacher Collins syndrome (TCS), acrofacial dysostosis syndrome of Rodriguez (AFD-Rod) and tetra-amelia syndrome (TETAMS). The TCS specimen mainly showed an absence of the zygomatic bones and most of the lateral maxilla. The AFD-Rod specimen showed an extensive defect of the lateral maxilla, zygomatic bones, and mandible. The TETAMS specimen showed almost isolated agnathia. Possible relationships are discussed between the diverse facial bone defects due to apoptosis of neural crest-derived cells, known to be associated with ribosomopathies and spliceosomopathies, such as TCS and AFD-Rod, and the more targeted bone defects due to genetic variants known to cause TETAMS. Full article

Background/Objectives: This ex vivo study aimed to evaluate the diagnostic performance of ultra-low-dose (ULD) cone-beam computed tomography (CBCT) protocols in detecting vestibular bone defects for immediate implant planning, using intraoral scan (IOS) data as a reference. Methods: Four CBCT protocols (ENDO, A, B, C) were applied to four dried human skulls using a standardized setup and a single CBCT unit (Planmeca ProMax^® 3D Mid, Planmeca Oy, Helsinki, Finland). All scans were taken at 90 kV, with varying parameters: (1) ENDO (40 × 50 mm, 75 µm, 12 mA, 80–120 µSv, 15 s), (2) A (50 × 50 mm, 75 µm, 9 mA, 20–40 µSv, 5 s), (3) B (100 × 60 mm, 150 µm, 7.1 mA, 22–32 µSv, 5 s), and (4) C (100 × 100 mm, 200 µm, 7.1 mA, 44 µSv, 4 s). Vestibular root surfaces of single-rooted teeth (FDI regions 15–25 and 35–45) were digitized via IOS and exported as STL files. CBCT datasets were superimposed using 3D software (Blender 2.79), and surface defects were measured and compared using one-sample t-tests and Bland–Altman analysis. The level of significance was set at p < 0.05. Results: A total of 330 vestibular surfaces from 66 teeth were analyzed. Compared to the IOS reference, protocols ENDO and A showed minimal differences (p > 0.05). In contrast, protocols B and C exhibited statistically significant deviations (p < 0.05). Protocol B demonstrated a mean difference of −0.477 mm² with limits of agreement (LoA) from −2.04 to 1.09 mm² and significant intra-rater variability (p < 0.05). Protocol C revealed a similar mean deviation (−0.455 mm²) but a wider LoA (−2.72 to 1.81 mm²), indicating greater measurement variability. Overall, larger voxel sizes were associated with increased random error, although deviations remained within clinically acceptable limits. Conclusions: Despite statistical significance, deviations for protocols B and C remained within clinically acceptable limits. ULD CBCT protocols are, thus, suitable for evaluating vestibular bone defects with reduced radiation exposure. Full article

Squid skin decellularized dermal matrix (SADM) is gaining attention in tissue engineering and regenerative medicine due to its mimicking of the extracellular matrix property. Hence, SADM was used to investigate mimicking the microenvironment of cellular growth, inducing cellular infiltration and angiogenesis, and facilitating the repair of acute craniofacial wounds. For this, tissue regeneration membranes from squid skin were prepared by decolorization, degreasing and decellularisation methods. The effect of SADM in guiding bone tissue regeneration was evaluated using the rabbit skull bone defect model. SEM images of SADM had a bilayer membrane architecture characterized by a reticulated porous structure on one side and a dense, non-porous surface on the opposite side. Notably, the water absorption capacity of SADM was approximately eight times higher than its weight, exhibiting a porosity of 58% and a peak average tensile stress of 10.43 MPa. Additionally, simulations of tissue fluid degradation indicated a degradation rate of 70.42% and 88.33% on days 8 and 12, respectively. Following 4 and 8 weeks of animal studies focused on repairing cranial bone defects in rabbits, the findings demonstrated that SADM served as an effective barrier against fibrous connective tissue, promoted the proliferation of osteoblasts, and supported bone regeneration. This was confirmed through micro-CT imaging, and sections were stained with senna solid green. In summary, SADM is capable of directing cell infiltration and bone tissue formation, modulating the expression and secretion of inflammatory and skin repair-related factors, thereby enhancing tissue healing. Full article

In this article, an analysis of the problem of treating bone defects using cranial bone disorders as an example is presented. The study was performed in the context of the development of various implant biomaterials used to fill bone defects. An analysis of the requirements for modern materials is undertaken, indicating the need for their further development. The article focuses particular attention on these biomaterial properties, which have an influence on bioresorbability and promote osteointegration and bone growth. The analysis showed the need for further development of biomaterials, the characteristics of which may be multifunctionality. Multifunctional scaffolds are those that simultaneously fill and stabilize the defect and contribute to the proper process of regeneration and reconstruction of cranial bones. Due to the complex structure of the skull and special protective functions, there is a need to develop innovative implants. Implants with complex geometries can be successfully manufactured using additive technologies. Full article

Syphilis is a disease caused by Treponema pallidum. It is primarily transmitted sexually or vertically during pregnancy. The origin is twofold, namely, it comes from America or Europe. Syphilis was first recorded in a human skeleton in the 11th century. However, signs of treponemal disease were observed in osteological material from a Pleistocene bear. Hence, it is necessary to study syphilis on bone material to better understand the etiology of the above disease and, consequently, introduce preventive measures. Examination of syphilis on skeletal material can be performed at the macroscopic and microscopic levels. Those methods refer to the visual assessment of skeletal material, namely the identification of characteristic pathological changes caused by syphilis, such as periostitis, which manifests itself as thickenings on the bone surface, and syphilis nodules (gummata), which are defects in the bones. Most often, these changes are found on long bones such as the tibia, femur, and skull. Radiological methods may be used, such as X-ray, computed tomography (CT), Micro-CT (ICT), as well as molecular examination. Summarizing, this review is an overview of the latest methodology regarding syphilis research on skeletal material, thanks to which it can better understand its genesis. Full article

Background/Objectives: Surgical removal is the treatment of choice for cholesteatoma control. Depending on the size, the surgery involves partial resection of the ossicular chain and, if necessary, the bony skull base. Titanium foreign materials (prostheses, meshes) can be used to restore sound transmission and to cover larger defects of the skull base. After the operation, recurrence and residual control are necessary. This can be achieved by means of second-look surgery or an MRI examination with a non-EPI DWI sequence. Similarly to other metal implants, artifacts may occur in the image due to the titanium used. In this study, we assessed the magnitude of the MRI hardware differences induced by titanium prostheses and meshes and whether these differences could obscure cholesteatoma detection. Methods: 28 MRI examinations (T1-, T2-, non-EPI DWI sequences) in 14 males and 14 females (5.2–92.4 years) after cholesteatoma surgery and single-staged implantation of a PORP, TORP, or titanium mesh were considered. The size of the respective artifacts was measured, and the mean artifact sizes of the respective prosthesis types were compared. A second look surgery was performed in all cases due to the MRI result or clinical findings. Both were also compared. Results: Artifacts occurred in all titanium foreign bodies depending on the used MRI sequence (PORP, TORP, Mesh). We found a positive association between the size of the prosthesis and the size of the artifact. All subsequent second-look surgeries confirmed the MRI examinations according to a positive control for the presence of cholesteatoma. The detection rate was 82.1%. All false results were false negatives, and there were no positive results. Conclusions: Titanium material-related artifacts might influence the MRI detectability of recurrent cholesteatoma. Small cholesteatoma might be missed by an MRI-based follow-up. This finding supports the reevaluation of single-stage versus staged reconstruction modern approaches. Full article

Cranio-maxillofacial bone defect repair poses significant challenges in oral and maxillofacial surgery due to the complex anatomy of the region and its substantial impact on patients’ physiological function, aesthetic appearance, and quality of life. Inaccurate reconstruction can result in serious complications, including functional impairment and psychological trauma. Traditional methods have notable limitations for complex defects, underscoring the need for advanced computational approaches to achieve high-precision personalized reconstruction. This study presents the Internal Diffusion Network (IDNet), a novel framework that integrates a diffusion model into a standard U-shaped network to extract valuable information from input data and produce high-resolution representations for 3D medical segmentation. A Step-Uncertainty Fusion module was designed to enhance prediction robustness by combining diffusion model outputs at each inference step. The model was evaluated on a dataset consisting of 125 normal human skull 3D reconstructions and 2625 simulated cranio-maxillofacial bone defects. Quantitative evaluation revealed that IDNet outperformed mainstream methods, including UNETR and 3D U-Net, across key metrics: Dice Similarity Coefficient (DSC), True Positive Rate (RECALL), and 95th percentile Hausdorff Distance (HD95). The approach achieved an average DSC of 0.8140, RECALL of 0.8554, and HD95 of 4.35 mm across seven defect types, substantially surpassing comparison methods. This study demonstrates the significant performance advantages of diffusion model-based approaches in cranio-maxillofacial bone defect repair, with potential implications for increasing repair surgery success rates and patient satisfaction in clinical applications. Full article

Background/Objectives: Cranial reconstruction (cranioplasty) is a surgical procedure performed to restore skull function and aesthetics following trauma, oncological conditions, or congenital defects. Magnetic resonance imaging (MRI) is commonly used for the postoperative monitoring and diagnosis of patients with cranial implants. However, MRI artifacts caused by these implants can compromise imaging accuracy and diagnostic precision. This study aims to evaluate the extent of MRI artifacts caused by titanium and polyether ether ketone (PEEK) cranial implants and to identify optimal imaging sequences to minimize these artifacts. Methods: Phantom skull models with cranial defects of varying sizes (one-quarter, one-third, and one-half of the skull) were used to simulate real-world clinical conditions. The defects were filled with a water-based medium containing simulated brain tissue and tumor models. Custom 3D-printed titanium and PEEK cranial implants were fixed onto the phantom skulls and scanned using 1.5 T and 3 T MRI scanners. Various imaging sequences were tested, with a focus on optimizing parameters to reduce artifact formation. Turbo Spin Echo (TSE) sequences with fat saturation were implemented to assess their effectiveness in artifact reduction. Results: The study found that MRI artifacts varied based on the implant material, defect size, and magnetic field strength. A higher field strength (3 T) resulted in more pronounced artifacts. However, the use of TSE sequences with fat saturation significantly reduced artifacts and improved lesion visualization, enhancing diagnostic accuracy. Conclusions: This research highlights the importance of optimized MRI protocols when imaging patients with cranial implants. Proper selection of imaging sequences, particularly TSE with fat saturation, can mitigate artifacts and improve diagnostic precision, ultimately benefiting patient outcomes in clinical radiology. Full article

Cranioplasty enables the restoration of cranial defects caused by traumatic injuries, brain tumour excisions, or decompressive craniectomies. Conventional methods rely on Computer-Aided Design (CAD) for implant design, which requires significant resources and expertise. Recent advancements in Artificial Intelligence (AI) have improved Computer-Aided Diagnostic systems for accurate and faster cranial reconstruction and implant generation procedures. However, these face inherent limitations, including the limited availability of diverse datasets covering different defect shapes spanning various locations, absence of a comprehensive pipeline integrating the preprocessing of medical images, cranial reconstruction, and implant generation, along with mechanical testing and validation. The proposed framework incorporates a robust preprocessing pipeline for easier processing of Computed Tomography (CT) images through data conversion, denoising, Connected Component Analysis (CCA), and image alignment. At its core is CRIGNet (Cranial Reconstruction and Implant Generation Network), a novel deep learning model rigorously trained on a diverse dataset of 2160 images, which was prepared by simulating cylindrical, cubical, spherical, and triangular prism-shaped defects across five skull regions, ensuring robustness in diagnosing a wide variety of defect patterns. CRIGNet achieved an exceptional reconstruction accuracy with a Dice Similarity Coefficient (DSC) of 0.99, Jaccard Similarity Coefficient (JSC) of 0.98, and Hausdorff distance (HD) of 4.63 mm. The generated implants showed superior geometric accuracy, load-bearing capacity, and gap-free fitment in the defected skull compared to CAD-generated implants. Also, this framework reduced the implant generation processing time from 40–45 min (CAD) to 25–30 s, suggesting its application for a faster turnaround time, enabling decisive clinical support systems. Full article