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Graft failure is a common complication of cranioplasty. Revision cranioplasty is required to overcome this complication. However, no previous studies have reported outcomes in revision cranioplasty with 3-dimensional (3D) custom-made titanium implants. We describe our experience with 3D titanium implants in patients with revision cranioplasty. We evaluated 43 consecutive patients between January 2011 and December 2019 who underwent revision cranioplasty using 3D custom-made titanium implants. The 3D image of the patient's cranium and the plan to close the cranium defect were created in a virtual environment using software programs. Demographic and radiologic features were compared based on the materials used in the initial cranioplasty. Previous material was autologous graft (AG) in 27 patients and polymethyl methacrylate (PMMA) in 16 patients. The mean time without revision cranioplasty is longer in patients with PMMA implants than in patients with AG. There was no statistically significant difference in the length of hospital stay between patients with PMMA implants and patients with AG. There were no postoperative adverse events such as infection, wound dehiscence, convulsions, or epidural hematoma in 38 patients during hospitalization. Wound dehiscence developed in 5 patients and surgical repair was required in one. Initial cranioplasty with PMMA provides a longer time period than the AG before the revision. However, both of them have similar outcomes based on length of hospital stay and cranial defect area. Custom-made 3D titanium implant is a good option for revision cranioplasty to prevent implant failure and reduce patients' cosmetic concerns. [ABSTRACT FROM AUTHOR]

BACKGROUND: Platelet-rich fibrin (PRF) has many advantages, such as simple preparation, low production cost, and high safety, and has been widely used in the study of bone defect repair in oral and maxillofacial surgery, but there are problems such as too fast degradation rate and short release time of growth factors. OBJECTIVE: PRF was loaded into gelatin methacryloyl (GelMA) hydrogel and its osteogenic properties were analyzed by in vivo and in vitro experiments. METHODS: (1) New Zealand white rabbit venous blood was extracted to prepare PRF. GelMA hydrogels containing 0, 0.05, 0.075, and 0.1 g PRF were prepared, respectively, and were recorded as GelMA, GelMA/PRF-0.05, GelMA/PRF-0.075, and GelMA/PRF-0.1, respectively, to characterize the micromorphology and in vitro slow-release properties of the hydrogels. (2) Four kinds of hydrogels were co-cultured with MC3T3-E1 cells, respectively, and the cell proliferation activity was detected with the single cultured cells as the control. After osteogenic induction, alkaline phosphatase activity, mineralization ability, mRNA and protein expression levels of osteogenic genes (osteocalcin, osteopontin, RUNX2), ERK1/2-p38 MAPK pathway protein mRNA and protein expression levels were detected. (3) Fifteen New Zealand white rabbits were taken. Four full-layer bone defects of 8 mm diameter were prepared in the skull of each rabbit, one of which was implanted without any material (blank control group), and the other three were implanted with GelMA hydrogel, PRF, and GelMA/PRF-0.1 hydrogel, respectively. The bone defect was detected by Micro-CT and bone morphology was observed at 4, 8, and 12 weeks after operation. RESULTS AND CONCLUSION: (1) Scanning electron microscopy observed that all the hydrogels of the four groups had honeycomb pore structure, and the pore size of the hydrogels decreased slightly with the increase of PRF content, but there was no significant difference between the groups. The three groups of GelMA/PRF hydrogel could release transforming growth factor β1 and insulin-like growth factor 1 at a certain rate, and the cumulative release of transforming growth factor β1 and insulin-like growth factor 1 increased significantly with the extension of time. (2) CCK-8 assay and live/dead staining showed that GelMA/ PRF hydrogel could promote the proliferation of MC3T3-E1 cells. The results of alkaline phosphatase staining, alizarin red staining, and osteogenic gene detection showed that GelMA/PRF hydrogel could promote the osteogenic differentiation of MC3T3-E1 cells, and inhibit the expression of ERK1/2-p38 MAPK pathway protein, and showed a PRF content dependence. (3) Micro-CT scan showed that the bone mineral density and bone volume fraction in the bone defect of GelMA/PRF-0.1 hydrogel group were higher than those in the other three groups (P < 0.05). Hematoxylin-eosin staining showed that compared with the other three groups, GelMA/PRF-0.1 hydrogel group had faster and more mature new bone formation at the bone defect. (4) These findings indicate that GelMA/PRF hydrogel has good osteogenic activity both in vivo and in vitro, which may be related to inhibiting the expression of ERK1/2-p38 MAPK pathway protein. [ABSTRACT FROM AUTHOR]

To study the biocompatibility of nanohydroxyapatite (nmHA)-SiO2 fiber material and its efficacy in guided bone regeneration. ① The cytotoxicity of the nmHA-SiO2 fiber material to MC3T3-E1 cells was determined by CCK-8 assay. The adhesion of cells on the surface of the material was observed. ② Bone defects were prepared in the skull of three groups of New Zealand white rabbits. The following treatments were administered: implantation of nmHA-SiO2, implantation of Bio-Oss, and no treatment. The defects were then covered with nmHA-SiO2 membrane or Hai’ao oral repair membrane. Animal samples were analyzed by gross observation, micro-computed tomography, hematoxylin-eosin staining and Masson staining. The data were statistically analyzed by multivariate analysis of variance to evaluate the repair of bone defects. ① The nmHA-SiO2 fiber material has suitable biocompatibility. ② The nmHA-SiO2 fiber material performed more effectively as a barrier membrane than other bone substitute materials in GBR model rabbits. [ABSTRACT FROM AUTHOR]

Objective To evaluate the bone repair effect of 3D-printed magnesium (Mg)-loaded polycaprolactone (PCL) scaffolds in a rat skull defect model. Methods PCL scaffolds mixed with Mg microparticles were prepared by using 3D printing technology, as were pure PCL scaffolds. The surface morphologies of the two scaffolds were observed by scanning electron microscopy (SEM), and the surface elemental composition was analyzed via energy dispersive spectroscopy (EDS). The physical properties of the scaffolds were characterized through contact angle measurements and an electronic universal testing machine. This study has been reviewed and approved by the Ethics Committee. A critical size defect model was established in the skull of 15 Sprague-Dawley (SD) rats, which were divided into the PCL group, PCL-Mg group, and untreated group, with 5 rats in each group. Micro-CT scanning was performed to detect and analyze skull defect healing at 4 and 8 weeks after surgery, and samples from the skull defect area and major organs of the rats were obtained for histological staining at 8 weeks after surgery. Results The scaffolds had a pore size of (480 ± 25) μm, a fiber diameter of (300 ± 25) μm, and a porosity of approximately 66%. The PCL-Mg scaffolds contained 1.0 At% Mg, indicating successful incorporation of Mg microparticles. The contact angle of the PCL-Mg scaffolds was 68.97° ± 1.39°, indicating improved wettability compared to that of pure PCL scaffolds. Additionally, compared with that of pure PCL scaffolds, the compressive modulus of the PCL-Mg scaffolds was (57.37 ± 8.33) MPa, demonstrating enhanced strength. The PCL-Mg group exhibited the best bone formation behavior in the skull defect area compared with the control group and PCL group at 4 and 8 weeks after surgery. Moreover, quantitative parameters, such as bone volume (BV), bone volume/total volume (BV/TV), bone surface (BS), bone surface/total volume (BS/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and bone mineral density (BMD), of skull defects were better than those in the other groups, indicating the best bone regeneration effect. H&E, Goldner, and VG staining revealed more mineralized new bone formation in the PCL-Mg group than in the other groups, and H&E staining of the major organs revealed good biosafety of the material. Conclusion PCL-Mg scaffolds can promote the repair of bone defects and have clinical potential as a new scaffold material for the repair of maxillofacial bone defects.

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The authors report a case of a patient managed for severe cranial vault depression following combined neurosurgery and radiotherapy. This situation caused major aesthetic discomfort and was potentially dangerous due to the mechanical weakness of the bone flap. The authors had a CAD (computer aided design) silicone elastomer custom-made implant made to fill perfectly the depression. Beforehand, an expansion was performed to cover the implant after removal of the radiated skin. The surgery and post-operative course raised no concerns. After one year of follow-up, the result is very good and the patient very satisfied, proving that this technique certainly has its place in the therapeutic arsenal when faced with a tissue defect of the cranial vault. [ABSTRACT FROM AUTHOR]

Autosomal dominantly inherited neurofibromatosis type I (NF1) is a systemic disorder caused by a mutation of a gene on chromosome 17q11.2 and characterized by multiple café-au-lait spots, lentiginous macules, Lisch nodules of the iris, and tumors of the nervous system. Bony manifestations such as scoliosis, dysplasia of the greater sphenoidal wing, tibial pseudoarthrosis, short stature, and macrocephaly have been reported in approximately 50% of patients. However, calvarial bone defects are rare. After screening 324 articles, 23 cases (12 adult and 11 pediatric patients) of occipital bone defects in NF1 patients were selected. All patients had a single/multiple bone defect over the lambdoid suture. Adjacent benign plexiform neurofibromas were observed in 14 patients (60.8%, 7 adults and 7 children); one adult patient was diagnosed with neurofibrosarcoma. Meningoencephalocele over the occipital defect was noted in 8 cases (34.78%, all adults). Cranioplasty was performed in only 17.39% of patients. Histologic examination was performed in 7 of the 15 patients with associated neurofibromas/neurofibrosarcomas. Biopsy of the bone margins surrounding the defect was performed in only one case. Pathologic examination of the herniated parieto-occipital or cerebellar tissue was not performed in any of the patients studied. We report the case of a 9-year-old girl with NF1 and a significant occipital bone defect and performed a systematic review of the relevant literature to highlight the challenges in treating this condition and to investigate the underlying mechanisms contributing to bone defects or dysplasia in NF1. [ABSTRACT FROM AUTHOR]

BACKGROUND: Our group has demonstrated that the immunomodulatory peptide DP7-C has good immunomodulatory functions and can efficiently transfect and deliver miRNAs into cells to exert regulatory functions. OBJECTIVE: To prepare and screen porous poly(lactic-co-glycolic acid) microspheres of different sizes loaded with immunomodulatory peptide miR-26a complexes, construct and optimize the sustained release system, and verify its biocompatibility and osteogenic ability in vivo. METHODS: Microsphere preparation: Porous poly(lactic-co-glycolic acid) microspheres were prepared by double emulsification with NH4HCO3 as the poreforming agent. Three different sizes of porous poly(lactic-co-glycolic acid) microspheres were prepared by adjusting the rotational speed. The microspheres were dispersed in the solution of immunomodulatory peptide DP7-C/miR-26a complex to prepare drug-loaded microspheres. The physical properties of the microspheres were characterized. The best drug-loaded porous poly(lactic-co-glycolic acid) microspheres were selected by comparing productivity, encapsulation rate and release performance for further use. In vitro cell experiment: Drug-loaded and drug-free microsphere solutions with different mass concentrations were co-cultured with rat bone marrow mesenchymal stem cells. CCK-8 assay was performed to verify biocompatibility. Animal in vivo experiment: Nine adult Sprague-Dawley rats were randomly divided into blank group, control group and experimental group, with three rats in each group. Cranial defect models with a diameter of 5 mm were established in all three groups. The rats of the blank group were not implanted with the material. The rats of the control group were implanted with blank microspheres. The rats of the experimental group were implanted with microspheres loaded with DP7-C/miR26a complex. At 8 weeks after operation, the pathological morphology and immunohistochemical staining for alkaline phosphatase of the main organs and skull defects were performed. RESULTS AND CONCLUSION: Microsphere preparation: According to the relevant detection results, the drug-loaded microspheres prepared at 1 000 r/min compared with 500 and 1 200 r/min had uniform size, higher yield and better sustained release performance, which could be used in subsequent experiments. In vitro cell experiment: CCK-8 assay results exhibited that drug-loaded and drug-free microsphere solutions had no effect on the proliferation of bone marrow mesenchymal stem cells and had no obvious cytotoxicity. In vivo experiments: There were no pathological changes in the viscera on hematoxylineosin staining related to the treatment with the intervention. Hematoxylin-eosin staining and Masson staining demonstrated that in the blank group, the defect site was mainly filled by fibrous connective tissue, with a small amount of angiogenesis, but without obvious new bone formation. In the control group, a small amount of new bone formation, fibrous tissue hyperplasia and new capillaries could be visible at the defect site. In the experimental group, there was obvious new bone formation, different degrees of fibrous tissue hyperplasia and new capillaries in the defect area. Immunohistochemical results displayed that alkaline phosphatase was highly expressed in the experimental group compared to the blank group and the control group (P < 0.05). These findings have concluded that the porous poly(lactic-co-glycolic acid)/DP7-C/miR-26a composite system has good biocompatibility and in vivo osteogenic properties and can promote bone regeneration and repair of critical bone defects in the rat skull. [ABSTRACT FROM AUTHOR]

Our case demonstrates a rare genesis of complex scalp defect with exposed dura mater in the occipital region due to self-mutilation. An early interdisciplinary approach is vital to prevent secondary complications and potentially fatal outcomes, particularly in psychiatric patients with reduced health awareness. [ABSTRACT FROM AUTHOR]

Introduction: Transcranial direct current stimulation (tDCS) has been shown to benefit patients with brain lesions or traumatic brain injury (TBI). These patients usually have skull defects with different sizes and electrical conductivities. There is very little data in the literature that show how to optimally stimulate these patients with the presence of skull defects. Methods: Here we leveraged high-resolution (1 mm) realistic head models to explore the best montages targeting right beneath the skull defects with different sizes and conductivities. Specifically, open-source software ROAST was used to solve for the lead field on the publicly available MIDA model. Four different skull defects/plates were modeled with the center above the right primary motor cortex: a larger defect (10 cm diameter) modeled as either titanium or acrylic plate, and a smaller defect (2.5 cm diameter) modeled as either acute state filled with cerebrospinal fluid (CSF) or chronic state with scar tissue. Optimized stimulation with maximal intensity was run using ROAST targeting the right primary motor cortex. Results: We show that optimized high-definition montages can achieve an average of 0.3 V/m higher stimulation intensities at the target compared to un-optimized montages (M1-SO or 4×1). Large skull defects with titanium or acrylic plates significantly reduce the stimulation intensity by about 80%, while small defects with acute (CSF) or chronic (scar) tissues significantly increase the stimulation intensity by about 200%. Furthermore, one can use M1-SO to achieve almost the same stimulation strength as the optimized montage if the skull has a large defect with titanium plate, and there is no significant difference in stimulation intensity between 4×1 montage and the optimized montage for small skull defects with scar tissue. Discussion: Based on this work, future modeling studies leveraging individual anatomy of skull defects may help guide tDCS practice on patients with skull defects and skull plates. [ABSTRACT FROM AUTHOR]

Background: Studies on reconstructive neurosurgical interventions are always relevant due to the persistence of cranial defects, mainly caused by traumatic brain injuries (TBI). To provide medical care to the patients with cranial defects more efficiently, it is necessary to assess a large number of surgical interventions in studies.Objective: To analyze data on reconstructive neurosurgical interventions performed at Novosibirsk hospitals.Methods: We performed a multicenter observational retrospective non-randomized study of the total cranioplasty surgical interventions from 2016 to 2022. The study involved five neurosurgical departments in Novosibirsk hospitals. In 450 of 673 cases the inclusion criteria were met.Results: The majority of patients (n = 361; 80.2%) underwent surgical interventions in federal health facilities. Urban residents prevailed (n = 260) among the patients who met the inclusion criteria. Craniectomies were mainly indicated for the consequences of TBI (n = 319; 70.9%). Time to cranioplasty ranged from 0.1 to 320 months (mean: 23.9 ± 39.2; median: 11.6 months). There were non-clinically significant differences in terms of primary and reconstructive operations between the defects caused by TBI and other conditions. In 51.1% of cases, we found two features describing the size and complexity of the skull defect. In 19.3% of cases, patients were diagnosed with a skull defect (affected anatomical areas were specified).Conclusions: Over seven years, 450 Novosibirsk residents underwent cranioplasty in five neurosurgical Novosibirsk hospitals (mean: 64.3 surgical interventions a year). Comparing the recent results with previous studies data in terms of performed craniectomies, we found that reconstructive interventions are lacking 99.7 cases per year. To reduce the time to cranioplasty, it is necessary to make a registry of patients with skull defects.

IntroductionTranscranial direct current stimulation (tDCS) has been shown to benefit patients with brain lesions or traumatic brain injury (TBI). These patients usually have skull defects with different sizes and electrical conductivities. There is very little data in the literature that show how to optimally stimulate these patients with the presence of skull defects.MethodsHere we leveraged high-resolution (1 mm) realistic head models to explore the best montages targeting right beneath the skull defects with different sizes and conductivities. Specifically, open-source software ROAST was used to solve for the lead field on the publicly available MIDA model. Four different skull defects/plates were modeled with the center above the right primary motor cortex: a larger defect (10 cm diameter) modeled as either titanium or acrylic plate, and a smaller defect (2.5 cm diameter) modeled as either acute state filled with cerebrospinal fluid (CSF) or chronic state with scar tissue. Optimized stimulation with maximal intensity was run using ROAST targeting the right primary motor cortex.ResultsWe show that optimized high-definition montages can achieve an average of 0.3 V/m higher stimulation intensities at the target compared to un-optimized montages (M1-SO or 4×1). Large skull defects with titanium or acrylic plates significantly reduce the stimulation intensity by about 80%, while small defects with acute (CSF) or chronic (scar) tissues significantly increase the stimulation intensity by about 200%. Furthermore, one can use M1-SO to achieve almost the same stimulation strength as the optimized montage if the skull has a large defect with titanium plate, and there is no significant difference in stimulation intensity between 4×1 montage and the optimized montage for small skull defects with scar tissue.DiscussionBased on this work, future modeling studies leveraging individual anatomy of skull defects may help guide tDCS practice on patients with skull defects and skull plates.

Bone defects caused by trauma, tumors, congenital malformation, or inflammation are very common in orthopedics. In recent years, mimicking the composition and structure of natural bone tissue has become a hot topic in biomaterial research, with the aim of developing an ideal biomaterial for bone defect transplantation. Here, the feasibility of a biphasic calcium phosphate (BCP)/acylated methacrylate gelatin (GelMA) composite hydrogel to repair bone defects was evaluated in vitro and in rats. The biocompatibility of a biphasic calcium phosphate (BCP)/acylated methacrylate gelatin (GelMA) composite hydrogel was evaluated by cytoskeleton staining, live/dead cell staining and cell proliferation assays. The in vitro osteogenic activities of the composite hydrogel were evaluated by alkaline phosphatase and alizarin red staining, as well as osteogenic gene expression analysis at both transcript and protein levels. The in vivo bone repair activities were evaluated using the rat skull defect model. The BCP/GelMA composite hydrogel displayed excellent biocompatibility and promoted osteogenesis of bone marrow mesenchymal stem cells in vitro. In addition, the BCP/GelMA composite hydrogel markedly promoted new bone formation in the rat skull-defect model. BCP/GelMA composite hydrogel may be an effective artificial material for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Abstract Background Tumor treating fields (TTFields) is an FDA‐approved adjuvant therapy for glioblastoma. The distribution of an applied electric field has been shown to be governed by distinct tissue structures and electrical conductivity. Of all the tissues the skull plays a significant role in modifying the distribution of the electric field due to its large impedance. In this study, we studied how remodeling of the skull would affect the therapeutic outcome of TTFields, using a computational approach. Methods Head models were created from the head template ICBM152 and five realistic head models. The electric field distribution was simulated using the default TTFields array layout. To study the impact of the skull on the electric field, we compared three cases, namely, intact skull, defective skull, and insulating process, wherein a thin electrical insulating layer was added between the transducer and the hydrogel. The electric field strength and heating power were calculated using the FEM (finite element method). Results Removing the skull flap increased the average field strength at the tumor site, without increasing the field strength of “brain”. The ATVs of the supratentorial tumors were enhanced significantly. Meanwhile, the heating power of the gels increased, especially those overlapping the skull defect site. Insulation lightly decreased the electric field strength and significantly decreased the heating power in deep tumor models. Conclusion Our simulation results showed that a skull defect was beneficial for superficial tumors but had an adverse effect on deep tumors. Skull removal should be considered as an optional approach in future TTFields therapy to enhance its efficacy. An insulation process could be used as a joint option to reduce the thermogenic effect of skull defect. If excessive increase in heating power is observed in certain patients, insulating material could be used to mitigate overheating without sacrificing the therapeutic effect of TTFields.

Skull defect is a common clinical disease, and the corresponding treatment is still a grand challenge. No artificial product can perfectly integrate with human skull and match the skull defect during growth. Herein, we report a porous polyetheretherketone (PEEK) implant with the microstructures almost identical to natural bones for repairing skull defect. Compared to non-porous PEEK controls, the porous PEEK implants efficiently promote cell adhesion, regenerate skull tissues, and finally achieve perfect healing with surrounding tissues within 6 months. This work suggests the important potential of integrated porous PEEK implants for treating skull defect in clinic, especially for children with rapidly growing skulls.

Context The osteogenic potential of the human dental pulp stromal cells (hDPSCs) was reduced in the state of oxidative stress. Resveratrol (RSV) possesses numerous biological properties, including osteogenic potential, growth-promoting and antioxidant activities. Objective This study investigates the osteogenic potential of RSV by activating the Sirt1/Nrf2 pathway on oxidatively stressed hDPSCs and old mice. Materials and methods The hDPSCs were subjected to reactive oxygen species (ROS) fluorescence staining, cell proliferation assay, ROS activity assay, superoxide dismutase (SOD) enzyme activity, the glutathione (GSH) concentration assay, alkaline phosphatase staining, real-time polymerase chain reaction (RT-PCR) and Sirt1 immunofluorescence labelling to assess the antioxidant stress and osteogenic ability of RSV. Forty female Kunming mice were divided into Old, Old-RSV, Young and Young-RSV groups to assess the repair of calvarial defects of 0.2 mL RSV of 20 mg/kg/d for seven days by injecting intraperitoneally at 4 weeks after surgery using micro-computed tomography, nonlinear optical microscope and immunohistochemical analysis. Results RSV abates oxidative stress by alleviating the proliferation, mitigating the ROS activity, increasing the SOD enzyme activity and ameliorating the GSH concentration (RSV IC50 in hDPSCs is 67.65 ± 9.86). The antioxidative stress and osteogenic capabilities of RSV were confirmed by the up-regulated gene expression of SOD1, xCT, RUNX2 and OCN, as well as Sirt1/Nrf2. The collagen, bone matrix formation and Sirt1 expression, are significantly increased after RSV treatment in mice. Discussion and conclusions For elderly or patients with oxidative stress physiological states such as hypertension, heart disease, diabetes, etc., RSV may potentially improve bone augmentation surgery in regenerative medicine.

The Longobard necropolis of Castel Trosino dates from the 6th to the 8th century CE. Among the tombs excavated, the skull of an older female shows the first evidence of a cross‐shaped bone modification on a living subject. Macroscopic, microscopic, and CT scan analyses revealed signs of at least two sets of scraping marks. Specifically, SEM analysis shows that perimortem bone‐scraping traces are present on the skull. Both healed and non‐healed defects suggest that the woman has received at least twice intentional bone modifications to address her condition. This is the first evidence of a cross‐shaped therapeutic intervention on a living subject. [ABSTRACT FROM AUTHOR]

BACKGROUND: During cranioplasty, the postoperative effects of different cranial repair materials are different, and the occurrence of postoperative complications is also quite different. OBJECTIVE: To study the clinical effect of 3D printed polyetheretherketone material in cranioplasty. METHODS: 112 patients with skull defect admitted to The First Affiliated Hospital of Bengbu Medical College from February 2016 to August 2020, including 67 males and 45 females, were selected and subjected to cranioplasty. The patients were divided into polyetheretherketone group (n=36) and titanium mesh group (n=76). Postoperative follow up was conducted to observe the occurrence of complications in the two groups, including subcutaneous effusion, hydrocephalus, epidural or subdural hematoma, poor wound healing, implant leakage, or infection. RESULTS AND CONCLUSION: (1) The patients in the polyetheretherketone group and titanium mesh group were followed up for (14.64±2.39) and (15.49±2.17) months after surgery, respectively, and there was no significant difference between the groups (P > 0.05). There were no patients with implant failure due to implant material in either group. (2) Complications occurred in 33 patients in the titanium mesh group, including 1 case of hydrocephalus, 9 cases of subcutaneous fluid, 3 cases of epidural/subhematoma, 13 cases of poor wound healing, and 3 cases of implant exposure, and 4 cases of intracranial infection. The complication rate was 43.4%. Totally 10 patients in the polyetheretherketone group had complications, including 6 cases of subcutaneous effusion, 1 case of epidural/subhematoma, and 2 cases of poor wound healing, and 1 case of intracranial infection; the complication rate was 27.8%. There was no significant difference in the total postoperative complication rate between the two groups (P > 0.05), but the incidence of poor wound healing/implant exposure was significantly different (P < 0.05). (3) It is concluded that 3D printed polyetheretherketone repair material has good biocompatibility, safety and accuracy in the application of skull defect repair. Compared with titanium mesh repair material, polyetheretherketone has a better advantage in wound healing. [ABSTRACT FROM AUTHOR]

Background: Tumor treating fields (TTFields) is an FDA‐approved adjuvant therapy for glioblastoma. The distribution of an applied electric field has been shown to be governed by distinct tissue structures and electrical conductivity. Of all the tissues the skull plays a significant role in modifying the distribution of the electric field due to its large impedance. In this study, we studied how remodeling of the skull would affect the therapeutic outcome of TTFields, using a computational approach. Methods: Head models were created from the head template ICBM152 and five realistic head models. The electric field distribution was simulated using the default TTFields array layout. To study the impact of the skull on the electric field, we compared three cases, namely, intact skull, defective skull, and insulating process, wherein a thin electrical insulating layer was added between the transducer and the hydrogel. The electric field strength and heating power were calculated using the FEM (finite element method). Results: Removing the skull flap increased the average field strength at the tumor site, without increasing the field strength of "brain". The ATVs of the supratentorial tumors were enhanced significantly. Meanwhile, the heating power of the gels increased, especially those overlapping the skull defect site. Insulation lightly decreased the electric field strength and significantly decreased the heating power in deep tumor models. Conclusion: Our simulation results showed that a skull defect was beneficial for superficial tumors but had an adverse effect on deep tumors. Skull removal should be considered as an optional approach in future TTFields therapy to enhance its efficacy. An insulation process could be used as a joint option to reduce the thermogenic effect of skull defect. If excessive increase in heating power is observed in certain patients, insulating material could be used to mitigate overheating without sacrificing the therapeutic effect of TTFields. [ABSTRACT FROM AUTHOR]

Human skull is designed to absorb the stress from the chewing forces and trauma to the head region. Teeth transfers the chewing forces to the maxilla and mandible and then to the skull bones. In this study, a skull with a maxillary defect due to surgical treatment of mucormycosis is evaluated for stress distribution from occlusal loading. Finite element model is constructed from a CBCT of an adult male patient with maxillectomy defect. Bilateral occlusal loading was done in the remaining posterior teeth in the asymmetrically present maxillary arch. Stress distribution is visualised and quantified both in frontal and lateral skull views. Results showed more stress on the left side than the right side and varied stress trajectories. Thus, we conclude that reconstruction of the maxillary defect is vital to gain proper morphology and symmetric stress distribution to maintain a functionally healthier craniofacial skeleton. [ABSTRACT FROM AUTHOR]

Abstract Background Patients who undergo decompressive craniectomy (DC) are often fitted with a helmet that protects the craniectomy site from injury during rehabilitation. However, conventional “one-size-fits-all” helmets may not be feasible for certain craniectomy defects. We describe the production and use of a custom 3D-printed helmet for a DC patient where a conventional helmet was not feasible due to the craniectomy defect configuration. Case presentation A 65-year-old male with ethmoid sinonasal carcinoma underwent cranionasal resection and DC with free vastus lateralis flap reconstruction to treat cerebrospinal fluid leakage. He required an external helmet to protect the craniectomy site, however, the rim of a conventional helmet compressed the craniectomy site, and the straps compressed the vascular pedicle of the muscle flap. Computed topography (CT) scans of the patient’s cranium were imported into 3D modelling software and used to fabricate a patient-specific, strapless helmet using fused deposition modelling (FDM). The final helmet fit the patient perfectly and circumvented the compression issues, while also providing better cosmesis than the conventional helmet. Four months postoperatively, the helmet remains intact and in use. Conclusions 3D printing can be used to produce low-volume, patient-specific external devices for rehabilitation where standardized adjuncts are not optimal. Once initial start-up costs and training are overcome, these devices can be produced by surgeons themselves to meet a wide range of clinical needs.

Introduction. Significant cranial defects result from a decompressive craniectomy following head trauma, malignant brain edema, intracranial hemorrhage, or resection of tumor affected bone. Unrepaired cranial defects are not just a tremendous esthetic problem. The underlying brain is unprotected, prone to injury, and this state can lead to the so-called “syndrome of the trephined” with mood instability, headaches, and even a neurological deficit. Currently, there is no widely accepted uniform technique of cranial vault shape restoration. Combining 3D technology with the use of polymethylmethacrylate is a challenging field that can bring good functional and aesthetic results and, in the case of smart design, become efficient, low-cost technology. We offer a possible solution to a problem that would be acceptable in neurosurgical practice. Case outline. We present a 37-year-old male patient with a massive hemicranial defect as a consequence of previous decompressive craniectomy following severe craniocerebral injury the previous year. Together with engineers from the appropriate 3D modeling studio, we have designed a two-part mold by laser printing technology using biocompatible advanced polyamide. We made a customized polymethylmethacrylate graft intraoperatively using this mold and achieved good aesthetic results. Conclusion. Reports of 3D printing assisted cranioplasties are growing, describing different techniques and cost- estimation. We hope to introduce a low-cost and simple method for repairing a skull defect.

BACKGROUND: There are many kinds of skull repair materials, but there is still no one material in high biocompatibility, high cost-effective and low incidence of complications in all aspects of clinical needs. OBJECTIVE: To analyze the difference in postoperative complications of 3D printed plastic polyetherketone and titanium mesh cranioplasty, and point out the improvement directions. METHODS: Data of 207 patients undergoing cranioplasty in Huanggang Central Hospital of Yangtze University from June 2014 to June 2021 were retrospectively analyzed, including 157 males and 50 females, at the age of 16-68 years old. Among them, 42 patients were treated with polyetheretherketone and 165 patients were treated with titanium mesh. The satisfaction survey of the reconstruction of the frontotemporal parietal defect area was carried out at 3 weeks after the operation. Complications were analyzed during postoperative follow-up. RESULTS AND CONCLUSION: (1) There were 32 cases of skull defect repaired with polyetheretherketone, with shaping satisfaction of 56.3%, and 117 cases of skull defect repaired with titanium mesh, with shaping satisfaction of 75.2%. Significant differences in shaping satisfaction were found between the two groups (P < 0.05). (2) Complications occurred in 14 of 42 cases in the polyetheretherketone group, including 12 cases of subcutaneous hydrops (28.6%), 1 case of epilepsy, and 1 case of forehead screw fixation swelling pain; with a complication rate of 33.3%. Among the 165 cases in the titanium mesh group, 28 cases had complications, including 15 cases of subcutaneous hydrops (9.1%), 7 cases of epilepsy, 2 cases of intracranial infection, 2 cases of material exposure, 1 case of intracranial hematoma, 1 case of material loosening, with a complications rate of 17.0%. There was a significant difference in the incidence of subcutaneous hydrops and total complication rate between the two groups (P < 0.05). (3) It is concluded that titanium mesh was better than polyetherketone mesh in repairing bone defect of frontotemporal parietal region, with a high satisfaction. The main improvement direction of polyetheretherketone in cranioplasty is to reduce the incidence of postoperative subcutaneous hydrops. [ABSTRACT FROM AUTHOR]

Syndrome of the trephined, or sinking skin flap syndrome, is a rare complication following craniectomy, showing a variety of neurological symptoms that improve after cranioplasty. Taste disorders can be induced by a variety of causes, while those due to central lesions are rare. We report a case of syndrome of the trephined that developed a taste disorder as a sole manifestation. A 61-year-old man underwent enlarged left craniectomy due to bacterial infection after surgical resection of a convexity meningioma. In six weeks, the patient complained of taste abnormalities. Visual analog scale score, electrogustometry, and a whole-mouth gustatory test revealed impairment of taste perception. As other possible causative factors were excluded, and the symptom improved after the cranioplasty, we made the diagnosis of syndrome of the trephined. Gustatory information from one side of the tongue enters the nucleus of the solitary tract of the medulla, and reaches insular-operculum ipsilaterally through the ventroposterior medial nucleus of the thalamus. Additionally, it is speculated that gustatory information from the left side of the tongue directly reaches the left insula, while information from the right side may also reach the left insula through the right insula. Disturbance of the left hemisphere including the insula due to a skull defect may have caused impairment of taste perception. A taste disorder should bear in mind in the treatment of central nervous system diseases and taken into account as a manifestation of syndrome of the trephined.

Background: Patients who undergo decompressive craniectomy (DC) are often fitted with a helmet that protects the craniectomy site from injury during rehabilitation. However, conventional "one-size-fits-all" helmets may not be feasible for certain craniectomy defects. We describe the production and use of a custom 3D-printed helmet for a DC patient where a conventional helmet was not feasible due to the craniectomy defect configuration. Case presentation: A 65-year-old male with ethmoid sinonasal carcinoma underwent cranionasal resection and DC with free vastus lateralis flap reconstruction to treat cerebrospinal fluid leakage. He required an external helmet to protect the craniectomy site, however, the rim of a conventional helmet compressed the craniectomy site, and the straps compressed the vascular pedicle of the muscle flap. Computed topography (CT) scans of the patient's cranium were imported into 3D modelling software and used to fabricate a patient-specific, strapless helmet using fused deposition modelling (FDM). The final helmet fit the patient perfectly and circumvented the compression issues, while also providing better cosmesis than the conventional helmet. Four months postoperatively, the helmet remains intact and in use. Conclusions: 3D printing can be used to produce low-volume, patient-specific external devices for rehabilitation where standardized adjuncts are not optimal. Once initial start-up costs and training are overcome, these devices can be produced by surgeons themselves to meet a wide range of clinical needs. [ABSTRACT FROM AUTHOR]

Objective Using bioinformatics methods to find genes that are differentially expressed in the dura mater at the skull suture of the young and adult sheep, and to analyze the genes that affect the growth of the skull and their corresponding signal pathways. Methods We took the dura mater of the apical frontal suture and sagittal suture for genetic sequencing from six 51-day-old young sheep and six 12-month-old adult sheep. With adult sheep as the control group and young sheep as the experimental group, the results were analyzed for the differential expression, and the differentially expressed genes were analyzed for GO enrichment. Then, the up-regulated and down-regulated genes that affected the growth of the skull were enriched by the KEGG signaling pathway. Frozen young sheep and adult sheep dura mater tissues were taken, and the top 10 genes with the highest differential expression were verified by fluorescence quantitative PCR. Results Compared with the adult sheep, there were 765 differentially expressed genes in the dural tissues of young sheep, including 417 up-regulated genes and 348 down-regulated genes. Bone mineralization was seen after the enrichment of differentially expressed genes in the dural tissues of young sheep and adult sheep, and the positive regulation of bone mineralization was seen after the enrichment of differentially expressed genes. among the up-regulated genes, bone mineralization included 15 genes, namely ENPPl, HlFlA, IBSP, MMP13, PI'N, OMD, COL1A2, BGLAP, FBN2, ASPN, TMEM119, RFLNB, PHOSPHOl, LOX, and ISG15; among the down-regulated genes, the positive regulation of hone mineralization included 5 genes, namely ISG15, OSRl, BMP4, BMP6, and BMP7. KEGG signaling pathway analysis showed that bone mineralization related genes mainly involved P13K-Akt signaling pathway, and positive regulation of bone mineralization genes mainly involved TGF-~ signaling pathway. Among the up-regulated genes, the first 6 genes with the most up-regulation were COL1A2, MMP13, PHOSPHOl, IBSP, OMD, and PI'N, and the top 2 genes with the most down-regulation were BMP4 and BMP6, which were then selected for fluorescence quantitative PCR detection. The results showed that the difference in the above mentioned differentially expressed genes in the same suture between the young sheep and adult sheep was statistically significant ( P < 0. 05) . Conclusion Bioinformatics analysis showed that there are a large number of differentially expressed genes in the dura mater tissues at the suture of the young and adult sheep, which are involved in the hone mineralization and bone mineralization regulation; bone mineralization genes may promote the growth of the skull through the Pl3K-Akt signaling pathway, and hone morphogenetic protein genes may regulate the closure of sutures through the TGF-~ signaling pathway. [ABSTRACT FROM AUTHOR]

To study the biocompatibility of nanohydroxyapatite (nmHA)-SiO 2 fiber material and its efficacy in guided bone regeneration. ① The cytotoxicity of the nmHA-SiO 2 fiber material to MC3T3-E1 cells was determined by CCK-8 assay. The adhesion of cells on the surface of the material was observed. ② Bone defects were prepared in the skull of three groups of New Zealand white rabbits. The following treatments were administered: implantation of nmHA-SiO 2 , implantation of Bio-Oss, and no treatment. The defects were then covered with nmHA-SiO 2 membrane or Hai'ao oral repair membrane. Animal samples were analyzed by gross observation, micro-computed tomography, hematoxylin-eosin staining and Masson staining. The data were statistically analyzed by multivariate analysis of variance to evaluate the repair of bone defects. ① The nmHA-SiO 2 fiber material has suitable biocompatibility. ② The nmHA-SiO 2 fiber material performed more effectively as a barrier membrane than other bone substitute materials in GBR model rabbits.

Apigenin, a natural compound in celery, is found to have pro-osteogenesis capacity by screening in our previous work. This study is focused on its pro-osteogenesis mechanism evaluation. The pro-osteogenesis effect of apigenin (50 mg/kg/day), was evaluated in skull defected (SD) mice by monitoring changes in bone histomorphometry index, formation of new osteoblasts from MSCs and changes in the synthesis of pro-osteogenic cytokines. Signal pathways were investigated by QPCR, Western blot and immunofluorescence. Apigenin has significant pro-osteogenesis effect in vivo, which can promote osteoblasts formation, the expression of osteoblasts-specific marker genes and osteoblasts marker protein in vitro. From the perspective of molecular biology, apigenin promotes osteoblasts formation and the activation of Wnt pathway as well as the induction and nuclei translocation of β-catenin. Driven by the results of this study, celery might be a useful alternative functional food in helping bone defects regeneration.

Introduction: Reconstruction of cranial defects in children less than 2 years of age, particularly when there is an associated dural defect, is challenging due to the need to accommodate active skull growth, limited options for autologous bone graft and thin calvarial bones. We use a simple remodeling technique that exploits the normal dura's inherent potential for new bone growth while covering the dural defect with adjacent skull. Case Presentation: We describe an alternating, two-piece craniotomy or "switch-cranioplasty technique" to repair an occipital meningocele. The two pieces of craniotomy bone flap created around the existing skull and dural defect are switched in the horizontal plane in order to cover the site of the defect and the abnormal dura of the meningocele closure. The area of the original skull defect is transposed laterally over the normal dura. The healing of the lateral skull defects is facilitated with autologous bone chips and dust and covered by periosteal flaps that stimulate spontaneous re-ossification. Discussion: The advantages of this technique are the use of autologous bone adjacent to the skull defect, incorporation of the autologous bone into the growing skull, an acceptable cosmetic and functional outcome in a simple manner. The indications can be extended to include small to medium-sized calvarial defects secondary to leptomeningeal cyst and trauma. [ABSTRACT FROM AUTHOR]

An 8‐year‐old male intact miniature poodle presented for blindness, obtundation, tetraparesis, and vestibular signs. Magnetic resonance imaging, radiography, and ultrasound revealed a left piriform lobe lesion, right cerebellar and left brainstem lesions, and hydrocephalus and bilateral calvarial defects. Histopathology confirmed a choroid plexus carcinoma with meningeal and intraventricular metastases. The calvarial defect did not show evidence of necrosis, osteoclastic resorption, inflammation or neoplastic infiltration, reflecting a quiescent calvarial atrophy or dysplasia. These novel findings supported inclusion of bone atrophy secondary to chronic increased intracranial pressure as a differential diagnosis for large calvarial defects in dogs with choroid plexus carcinoma. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hydroxyapatite-geltin composite has good biocompatibility and osteoinductivity, and can used be as tissue engineering scaffold to repair bone defects. OBJECTIVE: To observe the effect of three-dimensional (3D) printed hydroxyapatite/gelatin scaffold combined with bone marrow mesenchymal stem cells and umbilical vein endothelial cells in repairing rabbit skull defects. METHODS: Nine male New Zealand white rabbits were taken to establish a skull defect model with a diameter of approximately 0.8 cm, and randomly divided into three groups: blank group: no any treatment; control group: only 3D printed hydroxyapatite-geltin scaffold; experimental group: 3D printed hydroxyapatite-geltin scaffold and bone marrow mesenchymal stem cells and bone marrow mesenchymal stem cells complex group, with three rabbits in each group. At 8 weeks after the operation, CT scan of the skull pyramid beam and histological observation of the skull defect were performed on the white rabbits of each group. Animal experiments were approved by the Ethics Committee of Jining Medical College. RESULTS AND CONCLUSION: (1) CT scan of pyramidal tract: Blank group showed obvious bone defects, and the defect area was slightly radiopaque with the edges of the surrounding normal bone tissue. Control group showed some new bone formation, which was discontinuous and inconsistent with the surrounding bone tissue. Experimental group showed that the new bone tissue was linear and continuous; the thickness was thin; and the defect area merged with the adjacent bone tissue edge. (2) Histological observation: Hematoxylin-eosin staining and Masson trichrome staining showed that fibrous connective tissue formation and a small amount of free bone cells were seen in the defect area of the blank group. A small amount of bone formation was seen in the control group. Bone matrix was deposited at the edge of the material, replacing the material to form small bone trabeculae. The material space of the experimental group was gradually replaced by new bone, and the defect area was filled with new bone and trabecular bone structure-like tissue. (3) The results show that the 3D bionic printing hydroxyapatite-geltin scaffold combined with bone marrow mesenchymal stem cells and bone marrow mesenchymal stem cells can effectively promote the growth of bone tissue and accelerate the repair of bone defects. [ABSTRACT FROM AUTHOR]

In our technical note, we have presented a technique of cranioplasty for large skull defects. A thin-slice computed tomography scan is performed. A model of the skull is constructed using a desktop 3-dimensional printer from the computed tomography scan. The skull model is filled with towels of soft cotton and inserted in a sterile thin plastic bag. The implant is molded intraoperatively on the skull model under sterile conditions. After surgical exposure of the skull defect, the implant is inserted and fixed using miniplates and miniscrews. The technique was used in 6 patients and described in 2 representative cases. The required time and cost are significantly lower than those for other techniques used for preoperative manufacture of implants. No technique-related complications occurred. The radiological and cosmetic results were satisfactory. In the present case series, no early or delayed complications occurred. The presented technique is simple, safe, and time- and cost-effective. The technique and results are reproducible. [ABSTRACT FROM AUTHOR]

Introduction: Subdural effusion is a common complication that occurs after decompressive craniectomy. According to the endoscopy results, the formation mechanism of subdural effusion after decompressive craniectomy was discussed. Aim: The morphological structure of subdural effusion in skull defects was observed with endoscopy, and endoscopic- assisted surgery was performed for subdural effusion. Material and methods: From January 2018 to March 2020, 19 cases of skull repair and treatment of subdural effusion were performed. The external wall of the capsule was kept intact during the operation, subdural effusion and surgical procedure of the subdural effusion under an endoscope could be observed, and the results of endoscopic observation were described and recorded. A hemostasis gauze was placed between the two layers of the subdural effusion cavity. Another 13 cases of skull defects with subdural effusion treated without endoscopy during the same time period were enrolled in the study as the control group. The postoperative disappearance of effusion and the incidence of postoperative complications were compared between the two groups. Results: Analysis with an endoscope revealed that all cases of subdural effusion in skull defects presented capsules. The main structures included the outer wall, boundary, inner wall, and fistula. The outer wall was made up of new tissue that had formed after removing the bone flap under the skin flap by artificial peeling under the condition of keeping the whole cavity. The inner wall consisted of thickened arachnoid, dura, and artificial dura. It presented with neovascularization networks, which showed a tendency to form new membrane structures through mutual adhesion and fusion. The inner and outer wall of the skull had fused to form the boundary of the cavity. Cerebrospinal fluid fistulas were detected in 31.6% of the internal walls. Subdural effusion was effectively treated in both the experimental group and the control group. Compared with the control group, complications in the experimental group were significantly reduced. Conclusions: The effusion cavity can be divided into three types based on its structural characteristics: fistula type, membrane type, and closed type. In this study, the formation mechanism of skull defects combined with subdural effusion was explored. This represents a new method for treating subdural effusion in which hemostasis gauze is placed between the two layers of the effusion cavity and cerebrospinal fluid fistula under an endoscope, which can effectively reduce the incidence of postoperative complications. [ABSTRACT FROM AUTHOR]

Background: Pasteurella multocida is a gram-negative coccobacillus that is primarily found in oropharynx of dogs, cats and other animals. It causes infections in human beings through contact with animal saliva in the form of licks, bites and scratches of animals colonized by the bacteria. Meningitis due to Pasteurella multocida is rare in immunocompetent individuals. We report a case of meningitis due to Pasteurella multocida in an immunocompetent patient. Case report: A 30-year-old gentleman presented with 2-day history of fever and neck stiffness. 6 weeks earlier, he was treated as a case of bacterial meningitis. During that hospital stay, he was diagnosed to have bony defect in the sellar floor based on MRI head performed to evaluate for a prolonged history of CSF rhinorrhea. He was discharged and scheduled for an elective endoscopic endonasal/open repair of the skull base defect after resolution of meningitis. CSF findings during current admission also showed features of bacterial meningitis. CSF culture showed Pasteurella multocida sensitive to penicillin, ampicillin and ceftriaxone. Retrospective history revealed patient’s contact with stray cats as he used to feed them but there was no history of licks, bites. He was treated with intravenous ceftriaxone 2 g twice a day for 14 days with complete resolution of his symptoms. Conclusion: Pasteurella multocida is an important cause of bacterial meningitis in patients with skull defect. Patients with traumatic or non-traumatic bony defect of skull should avoid contact with dogs and cats to prevent the spread of infection the central nervous system.

Abstract Background Cranioplasty is important to cover defects following skull surgery and trauma for restoration of function and cosmoses. The objective of the study is to describe the author’s technical experience with the use of polymethyl methacrylate (PMMA) implant for cranioplasty to achieve the best results and avoid complications. Methods The author describes the indications, locations and operative techniques of cranioplasty using polymethyl methacrylate (PMMA) implant for 75 patients. The implant was used to cover any small- or medium-sized (

Objective To explore the effect of ultrasound scanning in ventriculoperitoneal shunt in patients with hydrocephalus with skull defect after craniotomy. Methods The clinical data of 75 patients with skull defect and hydrocephalus after craniotomy underwent ventriculoperitoneal shunt were analyzed retrospectively. The number of intraoperative puncture, intraoperative blood loss, operative time, related complications, and follow-up recovery were compared between the ultrasound group and the control group groups. Results The number of puncture, intraoperative blood loss and operative time in the ultrasound group were significantly less than those in the control group(P<0.05-0.005). There was no statistically significant difference in the incidence of infection and bleeding complications between the two groups within 2 weeks after surgery(χ2=2.163,P=0.141). The complications of tube blockage and infection in the ultrasound group were less than those in the control group follow up for more than 1 year , but there was no statistical significance. Conclusion VP shunt surgery for hydrocephalus patientswith skull defect, real-time guidance of ultrasound technology can be used to obtain a better and ideal position of the ventricle end of shunt, and the puncture injury, operation time and bleeding were reduced. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Apigenin, a natural compound in celery, is found to have pro-osteogenesis capacity by screening in our previous work. This study is focused on its pro-osteogenesis mechanism evaluation. The pro-osteogenesis effect of apigenin (50 mg/kg/day), was evaluated in skull defected (SD) mice by monitoring changes in bone histomorphometry index, formation of new osteoblasts from MSCs and changes in the synthesis of pro-osteogenic cytokines. Signal pathways were investigated by QPCR, Western blot and immunofluorescence. Apigenin has significant pro-osteogenesis effect in vivo , which can promote osteoblasts formation, the expression of osteoblasts-specific marker genes and osteoblasts marker protein in vitro. From the perspective of molecular biology, apigenin promotes osteoblasts formation and the activation of Wnt pathway as well as the induction and nuclei translocation of β-catenin. Driven by the results of this study, celery might be a useful alternative functional food in helping bone defects regeneration. [ABSTRACT FROM AUTHOR]

We report the case of a boy with partial skull defects in addition to widespread craniotabes due to vitamin D deficiency rickets. He was born at 30 wk and 4 d of gestation (birth weight, 2406 g). At 77 d of age, clinical examination of the head revealed widespread craniotabes of the occipital region centered around the lambda suture, and palpation revealed a defect of about 1 cm in the parietal bone of the left occipital region. Cranial computed tomography showed thinning of the cortex and bone defects in the parietal bones bilaterally, as well as in the left occipital bone. At 3 mo of age, he was diagnosed with vitamin D deficiency rickets and was administered alfacalcidol for 4 mo. Although patients with vitamin D deficiency rickets are prone to fractures, bone defects, as in this case, have not been reported. In addition to vitamin D deficiency rickets, the causes of the bone defects, in this case, are hypothesized to be abnormalities in the Ras-mitogen activated protein kinase pathway associated with Noonan syndrome, and long-term compression of the back of the head. However, there are no other similar reports, and further ones need to be accumulated. [ABSTRACT FROM AUTHOR]

Bone defects have a severe impact on the health and lives of patients due to their long-lasting and difficult-to-treat features. Recent studies have shown that there are complex microenvironments, including excessive production of reactive oxygen species. Herein, a surface functionalization strategy using metal-polyphenolic networks was used, which was found to be beneficial in restoring oxidative balance and enhancing osseointegration. The surface properties, biocompatibility, intracellular ROS scavenging, and osseointegration capacity were evaluated, and the therapeutic effects were confirmed using a skull defect model. This approach has great potential to improve complex microenvironments and enhance the efficiency of bone tissue regeneration.