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Introduction: Replacement of lost soft and hard tissues of the human body has always been a daunting task across all surgical specialties. Reconstruction of a cranial deformity is challenging due to the functional and cosmetic requirements. A major constraint with large cranial bony deformity reconstruction is the nonavailability of graft of a specific shape and size. Materials and Method: A total of four cases of large cranial defects which included three cases of unilateral and one case of midline residual deformity were reconstructed at our center using customized titanium implants. These implants were fabricated using additive manufacturing/3D printing technology utilizing computerized tomographic data. Conclusion: The additively manufactured titanium implants appear to be a viable option in the reconstruction of large cranial defects. [ABSTRACT FROM AUTHOR]

Objectives: CT is the clinical standard for surgical planning of craniofacial abnormalities in pediatric patients. This study evaluated three MRI cranial bone imaging techniques for their strengths and limitations as a radiation-free alternative to CT. Methods: Ten healthy adults were scanned at 3 T with three MRI sequences: dual-radiofrequency and dual-echo ultrashort echo time sequence (DURANDE), zero echo time (ZTE), and gradient-echo (GRE). DURANDE bright-bone images were generated by exploiting bone signal intensity dependence on RF pulse duration and echo time, while ZTE bright-bone images were obtained via logarithmic inversion. Three skull segmentations were derived, and the overlap of the binary masks was quantified using dice similarity coefficient. Craniometric distances were measured, and their agreement was quantified. Results: There was good overlap of the three masks and excellent agreement among craniometric distances. DURANDE and ZTE showed superior air-bone contrast (i.e., sinuses) and soft-tissue suppression compared to GRE. Discussions: ZTE has low levels of acoustic noise, however, ZTE images had lower contrast near facial bones (e.g., zygomatic) and require effective bias-field correction to separate bone from air and soft-tissue. DURANDE utilizes a dual-echo subtraction post-processing approach to yield bone-specific images, but the sequence is not currently manufacturer-supported and requires scanner-specific gradient-delay corrections. [ABSTRACT FROM AUTHOR]

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoimmune inflammatory disease characterized by osteoarticular and dermatological manifestations. The most common osteoarticular manifestations involve the anterior chest wall, axial skeleton, and long bones. Cranial bone involvement is less reported in SAPHO syndrome. We herein present three cases of SAPHO syndrome with cranial bone involvement, and review the previous literature on similar manifestations. It was revealed that SAPHO syndrome could lead to cranial bone involvement, which could involve the dura mater, leading to hypertrophic pachymeningitis, but the outcome is usually good. Janus kinase inhibitors may be a potential treatment option. [ABSTRACT FROM AUTHOR]

Cranial bones constitute a protective shield for the vulnerable brain tissue, bound together as a rigid entity by unique immovable joints known as sutures. Cranial sutures serve as major growth centres for calvarial morphogenesis and have been identified as a niche for mesenchymal stem cells (MSCs) and/or skeletal stem cells (SSCs) in the craniofacial skeleton. Despite the established dogma of cranial bone and suture biology, technological advancements now allow us to investigate these tissues and structures at unprecedented resolution and embrace multiple novel biological insights. For instance, a decrease or imbalance of representation of SSCs within sutures might underlie craniosynostosis; dural sinuses enable neuroimmune crosstalk and are newly defined as immune hubs; skull bone marrow acts as a myeloid cell reservoir for the meninges and central nervous system (CNS) parenchyma in mediating immune surveillance, etc. In this review, we revisit a growing body of recent studies that explored cranial bone and suture biology using cutting‐edge techniques and have expanded our current understanding of this research field, especially from the perspective of development, homeostasis, injury repair, resident MSCs/SSCs, immunosurveillance at the brain's border, and beyond. [ABSTRACT FROM AUTHOR]

Abstract Background Primary Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumors (pPNETs) are aggressive bone tumors that rarely occur in the axial skeleton, including the cranial bone and mobile spine. The purpose of this study was to investigate whether there were any differences in patient characteristics, treatment strategies, and outcomes between patients with ES/pPNETs of the cranial bone and those with ES/pPNETs of the mobile spine. Methods A retrospective study was performed on 33 patients with ES/pPNETs who had been surgically treated and pathologically confirmed at our institution between 2010 and 2020. Patient characteristics were compared using Fisher exact tests or independent t tests. Survival rates were estimated via Kaplan–Meier survival analysis and compared using log-rank tests. Results Thirteen patients had ES/pPNETs of the cranial bone (39.4%), while 20 patients had ES/pPNETs of the mobile spine (60.6%). Patients with ES/pPNETs of the cranial bone had a younger mean age (14.8 vs 22.6 years; p = 0.047) and longer mean disease duration (2.5 vs 1.9 months; p = 0.008) compared with those of patients with ES/pPNETs of the mobile spine. Kaplan–Meier analysis showed that gross total resection (GTR) and radiotherapy resulted in a longer median survival time. The overall survival rates and progression-free survival rates of patients with ES/pPNETs of the cranial bone versus those of the mobile spine were not significantly different (p = 0.386 and p = 0.368, respectively). Conclusions Patients with ES/pPNETs of the cranial bone were younger compared to patients with ES/pPNETs of the mobile spine. There was no significant difference in the prognosis of patients with ES/pPNETs of the cranial bone versus those of the mobile spine. Taken together, our findings suggest that GTR and radiotherapy offer the best prognosis for improved long-term survival.

Background: Biomaterials and biotechnology are becoming increasingly important fields in modern medicine. For cranial bone defects of various aetiologies, artificial materials, such as poly-methyl-methacrylate, are often used. We report our clinical experience with poly-methyl-methacrylate for a novel in vivo bone defect closure and artificial bone flap development in various neurosurgical operations. Methods: The experimental study included 12 patients at a single centre in 2018. They presented with cranial bone defects after various neurosurgical procedures, including tumour, traumatic brain injury and vascular pathologies. The patients underwent an in vivo bone reconstruction from poly-methyl-methacrylate, which was performed immediately after the tumour removal in the tumour group, whereas the trauma and vascular patients required a second surgery for cranial bone reconstruction due to the bone decompression. The artificial bone flap was modelled in vivo just before the skin closure. Clinical and surgical data were reviewed. Results: All patients had significant bony destruction or unusable bone flap. The tumour group included five patients with meningiomas destruction and the trauma group comprised four patients, all with severe traumatic brain injury. In the vascular group, there were three patients. The average modelling time for the artificial flap modelling was approximately 10 min. The convenient location of the bone defect enabled a relatively straightforward and fast reconstruction procedure. No deformations of flaps or other complications were encountered, except in one patient, who suffered a postoperative infection. Conclusions: Poly-methyl-methacrylate can be used as a suitable material to deliver good cranioplasty cosmesis. It offers an optimal dural covering and brain protection and allows fast intraoperative reconstruction with excellent cosmetic effect during the one-stage procedure. The observations of our study support the use of poly-methyl-methacrylate for the ad hoc reconstruction of cranial bone defects. [ABSTRACT FROM AUTHOR]

Vertebrate skin is a remarkable organ that supports and protects the body. It consists of two layers, the epidermis and the underlying dermis. In some tetrapods, the dermis includes mineralised organs known as osteoderms (OD). Lizards, with over 7,000 species, show the greatest diversity in OD morphology and distribution, yet we barely understand what drives this diversity. This multiscale analysis of five species of lizards, whose lineages diverged ∼100–150 million years ago, compared the micro- and macrostructure, material properties, and bending rigidity of their ODs, and examined the underlying bones of the skull roof and jaw (including teeth when possible). Unsurprisingly, OD shape, taken alone, impacts bending rigidity, with the ODs of Corucia zebrata being most flexible and those of Timon lepidus being most rigid. Macroscopic variation is also reflected in microstructural diversity, with differences in tissue composition and arrangement. However, the properties of the core bony tissues, in both ODs and cranial bones, were found to be similar across taxa, although the hard, capping tissue on the ODs of Heloderma and Pseudopus had material properties similar to those of tooth enamel. The results offer evidence on the functional adaptations of cranial ODs, but questions remain regarding the factors driving their diversity. Understanding nature has always been a significant source of inspiration for various areas of the physical and biological sciences. Here we unravelled a novel biomineralization, i.e. calcified tissue, OD, forming within the skin of lizards which show significant diversity across the group. A range of techniques were used to provide an insight into these exceptionally diverse natural structures, in an integrated, whole system fashion. Our results offer some suggestions into the functional and biomechanical adaptations of OD and their hierarchical structure. This knowledge can provide a potential source of inspiration for biomimetic and bioinspired designs, applicable to the manufacturing of light-weight, damage-tolerant and multifunctional materials for areas such as tissue engineering. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Primary Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumors (pPNETs) are aggressive bone tumors that rarely occur in the axial skeleton, including the cranial bone and mobile spine. The purpose of this study was to investigate whether there were any differences in patient characteristics, treatment strategies, and outcomes between patients with ES/pPNETs of the cranial bone and those with ES/pPNETs of the mobile spine. Methods: A retrospective study was performed on 33 patients with ES/pPNETs who had been surgically treated and pathologically confirmed at our institution between 2010 and 2020. Patient characteristics were compared using Fisher exact tests or independent t tests. Survival rates were estimated via Kaplan–Meier survival analysis and compared using log-rank tests. Results: Thirteen patients had ES/pPNETs of the cranial bone (39.4%), while 20 patients had ES/pPNETs of the mobile spine (60.6%). Patients with ES/pPNETs of the cranial bone had a younger mean age (14.8 vs 22.6 years; p = 0.047) and longer mean disease duration (2.5 vs 1.9 months; p = 0.008) compared with those of patients with ES/pPNETs of the mobile spine. Kaplan–Meier analysis showed that gross total resection (GTR) and radiotherapy resulted in a longer median survival time. The overall survival rates and progression-free survival rates of patients with ES/pPNETs of the cranial bone versus those of the mobile spine were not significantly different (p = 0.386 and p = 0.368, respectively). Conclusions: Patients with ES/pPNETs of the cranial bone were younger compared to patients with ES/pPNETs of the mobile spine. There was no significant difference in the prognosis of patients with ES/pPNETs of the cranial bone versus those of the mobile spine. Taken together, our findings suggest that GTR and radiotherapy offer the best prognosis for improved long-term survival. [ABSTRACT FROM AUTHOR]

Cell-based therapies with mesenchymal stem cells (MSCs) are considered as promising strategies for spinal cord injury (SCI). MSCs have unique characteristics due to differences in the derived tissues. However, relatively few studies have focused on differences in the therapeutic effects of MSCs derived from different tissues. In this study, the therapeutic effects of adipose tissue-derived MSCs, bone marrow-derived MSCs, and cranial bone-derived MSCs (cMSCs) on chronic SCI model rats were compared. MSCs were established from the collected adipose tissue, bone marrow, and cranial bone. Neurotrophic factor expression of each MSC type was analyzed by real-time PCR. SCI rats were established using the weight-drop method and transplanted intravenously with MSCs at 4 weeks after SCI. Hindlimb motor function was evaluated from before injury to 4 weeks after transplantation. Endogenous neurotrophic factor and neural repair factor expression in spinal cord (SC) tissue were examined by real-time PCR and western blot analyses. Although there were no differences in the expression levels of cell surface markers and multipotency, expression of Bdnf, Ngf, and Sort1 (Nt-3) was relatively higher in cMSCs. Transplantation of cMSCs improved motor function of chronic SCI model rats. Although there was no difference in the degree of engraftment of transplanted cells in the injured SC tissue, transplantation of cMSCs enhanced Bdnf, TrkB, and Gap-43 messenger RNA expression and synaptophysin protein expression in injured SC tissue. As compared with MSCs derived other tissues, cMSCs highly express many neurotrophic factors, which improved motor function in chronic SCI model rats by promoting endogenous neurotrophic and neural plasticity factors. These results demonstrate the efficacy of cMSCs in cell-based therapy for chronic SCI. [ABSTRACT FROM AUTHOR]

Background: Biomaterials and biotechnology are becoming increasingly important fields in modern medicine. For cranial bone defects of various aetiologies, artificial materials, such as poly-methyl-methacrylate, are often used. We report our clinical experience with poly-methyl-methacrylate for a novel in vivo bone defect closure and artificial bone flap development in various neurosurgical operations. Methods: The experimental study included 12 patients at a single centre in 2018. They presented with cranial bone defects after various neurosurgical procedures, including tumour, traumatic brain injury and vascular pathologies. The patients underwent an in vivo bone reconstruction from poly-methyl-methacrylate, which was performed immediately after the tumour removal in the tumour group, whereas the trauma and vascular patients required a second surgery for cranial bone reconstruction due to the bone decompression. The artificial bone flap was modelled in vivo just before the skin closure. Clinical and surgical data were reviewed. Results: All patients had significant bony destruction or unusable bone flap. The tumour group included five patients with meningiomas destruction and the trauma group comprised four patients, all with severe traumatic brain injury. In the vascular group, there were three patients. The average modelling time for the artificial flap modelling was approximately 10 min. The convenient location of the bone defect enabled a relatively straightforward and fast reconstruction procedure. No deformations of flaps or other complications were encountered, except in one patient, who suffered a postoperative infection. Conclusions: Poly-methyl-methacrylate can be used as a suitable material to deliver good cranioplasty cosmesis. It offers an optimal dural covering and brain protection and allows fast intraoperative reconstruction with excellent cosmetic effect during the one-stage procedure. The observations of our study support the use of poly-methyl-methacrylate for the ad hoc reconstruction of cranial bone defects.

Keywords: transcranial direct current stimulation; sex differences; hormones; cranial bone; cortical excitability EN transcranial direct current stimulation sex differences hormones cranial bone cortical excitability 1 4 4 06/24/20 20200619 NES 200619 Introduction The past 20 years have seen an increased interest in non-invasive brain stimulation, such as transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS) ([1]). The introduction of human brain-imaging techniques, like positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), have heightened awareness of sex differences and revealed sex-related influences on brain functions that were previously thought to be similar between the sexes ([5]). Transcranial direct current stimulation, sex differences, hormones, cranial bone, cortical excitability. [Extracted from the article]

Current cranial repair techniques combine the use of autologous bone grafts and biomaterials. In addition to their association with harvesting morbidity, autografts are often limited by insufficient quantity of bone stock. Biomaterials lead to better outcomes, but their effectiveness is often compromised by the unpredictable lack of integration and structural failure. Bone tissue engineering offers the promising alternative of generating constructs composed of instructive biomaterials including cells or cell-secreted products, which could enhance the outcome of reconstructive treatments. This review focuses on cell-based approaches with potential to regenerate calvarial bone defects, including human studies and preclinical research. Further, we discuss strategies to deliver extracellular matrix, conditioned media and extracellular vesicles derived from cell cultures. Recent advances in 3D printing and bioprinting techniques that appear to be promising for cranial reconstruction are also discussed. Finally, we review cell-based gene therapy approaches, covering both unregulated and regulated gene switches that can create spatiotemporal patterns of transgenic therapeutic molecules. In summary, this review provides an overview of the current developments in cell-based strategies with potential to enhance the surgical armamentarium for regenerating cranial vault defects.

Objective To compare the therapeutic effect of transplantation of cranial mesenchymal stem cells (cMSCs) with that of bone marrow stem cells (bMSCs) on ischemic stroke rats. Methods The bMSCs were isolated from the femur and tibia of male SD rats and cMSCs were isolated from the skull. Real-time PCR was used to detect the mRNA expression of neural crest-related genes (Snail, Slug) and neurotrophic factors (Bduf, Gduf, Ngf). The middle cerebral artery occlusion (MC A O) models were established in SD male rats. Another 20 rats were selected as the sham operation group. The MC AO model rats were randomly divided into the model group, BMSCs group and CMSCs group, with 20 rats in each. The rats in the BMSCs group and CMS Cs group were injected with bMSCs and cMSCs (1. 0 X 106 /300 µL PBS) via caudal vein at 24 h after MC A O. On the 2nd, 7th, 14th and 21st days after modeling, balance beam test and Garcia score were used to evaluate the motor function of rats in each group. After 21 days of modeling, rats were killed and their brains were taken out. HE staining was used to observe the pathological changes of rat hippocampal tissues. Triphenyltetrazolium chloride (TTC) staining was utilized for the calculation of cerebral iufarction (CI) area, and and TUNEL staining for hippocampal neuron apoptosis as well as the apoptosis rate. Results The expression levels of Snail, Slug, Bdnf, and Ngf mRNA in cMSCs were significantly higher than those in bMSCs ( all P < 0. 05 ). The experimental scores of balance beam in the model group, BMSCs group and CMSCs group were higher than those in the sham operation group, and Garcia score was lower than that in the sham operation group ( all P < 0. 05 ). Compared with the model group, the experimental scores of balance beam in the bMSCs group and cMSCs group decreased significantly on the 7th, 14th and 21st days after modeling, while the Garcia score increased significantly ( all P < 0. 05 ), and the improvement degree of the cMSCs group at each time point was significantly higher than that of bMSCs group ( all P < 0. 05 ). At 21st day after modeling, compared with the bMSCs group, the cMSCs group showed relatively less damage, reduced necrotic area, incomplete cell structure, decreased nuclear shrinkage and decreased interstitial edema. The CI area in the bMSCs group and cMSCs group was significantly lower than that in the model group (P < 0. 05 ). The model group, bMSCs group and cMSCs group had higher neuron apoptosis rates than the sham operation group, and the bMSCs group and cMSCs group had lower neuron apoptosis rates than the model group, and the cMSCs group had lower neuron apoptosis rate than the bMSCs group ( all P < 0. 05 ). Conclusions C The cMSCs derived from cranial neural crest cells have significant neurogenic activity. Compared with the bMSCs transplantation, cMSCs transplantation is more beneficial to the recovery of motor function and reduces the hippocampal injury and hippocampal neuron apoptosis. [ABSTRACT FROM AUTHOR]

Cellular therapies represent a new frontier in the treatment of neurological diseases. Accumulating evidence from preclinical studies of animal models suggests that mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, are an effective therapy for neurological diseases. In this study, we established human MSC lines from both cranial bone marrow (cBMMSCs) and iliac crest bone marrow (iBMMSCs) from the same donors and found that cBMMSCs show higher expression of neural crest‐associated genes than iBMMSCs. Moreover, as observed in both mRNA and protein assays, neurogenic‐induced cells from cBMMSCs expressed significantly higher levels of neural markers, such as NESTIN, SLUG, SOX9, and TWIST, than those from iBMMSCs. Thus, cBMMSCs showed a greater tendency than iBMMSCs to differentiate into neuron‐like cells. [ABSTRACT FROM AUTHOR]

Many researches aim to develop different biomaterials that are compatible with natural tissues. In vitro and in vivo tests are used to evaluate this potential. Our aim was to report the importance of the critical defect’s location for in vivo assays, to evaluate this approach; in vivo studies were performed, using different compositions of biomaterials in two critical size defects: tibia and parietal bone. Polycaprolactone was used as the main polymeric matrix with and without addition of hydroxyapatite. In vivo studies on the standard critical size defect in tibia and parietal bone were performed using Wistars models: 3x2 and 5x1 dimensions, respectively. The animals were sacrificed after 32 days; neobone formation was assessed with the histological data. The in vivo data demonstrated differences between the tibia and parietal bone groups: the influence of the bone on the neobone’s formation was notable. All the tibia defect samples had greater neobone volume when compared to the parietal data. Indeed, these bones have distinct embryology, influence of mechanical forces and vascularization rate that are well known; moreover, these characteristics were demonstrated to be critical for neobone formation.

The uneven distributed microstructure featured with plate-like spongy bone in woodpecker’s skull has been found to further help reduce the impact during woodpecker’s pecking behavior. Therefore, this work was to investigate the micro-mechanical properties and composition on different sites of Great Spotted woodpecker’s (GSW) skull. Different sites were selected on forehead, tempus and occiput, which were also compared with those of Eurasian Hoopoe (EH) and Lark birds (LB). Micro structural parameters assessed from micro computed tomography (μCT) occurred significantly difference between GSW, EH and LB. The micro finite element (micro-FE) models were developed and the simulation was performed as a compression process. The maximal stresses of GSW’s micro-FE models were all lower than those of EH and LB respectively and few concentrated stresses were noticed on GSW’s trabecular bone. Fourier transform infrared mapping suggesting a greater organic content in the occiput of GSW’s cranial bone compared with others. The nano-hardness of the GSW’s occiput was decreasing from forehead to occiput. The mechanical properties, site-dependent hardness distribution and special material composition of GSW’s skull bone are newly found in this study. These factors may lead to a new design of bulk material mimicking these characteristics. [ABSTRACT FROM PUBLISHER]

Summary Background While spring-assisted cranioplasty has become a widespread technique to correct scaphocephaly in children with sagittal synostosis, predicting head shape changes induced by the gradual opening of the springs remains challenging. This study aimed to explore the role of cranial bone structure on surgical outcomes. Methods Patients with isolated sagittal synostosis undergoing spring-assisted cranioplasty at GOSH (London, UK) were recruited (n = 18, age: 3–8 months). Surgical outcome was assessed by the change in cephalic index measured on 3D head scans acquired before spring insertion and after their removal using a 3D handheld scanner. Parietal bone samples routinely discarded during spring-assisted cranioplasty were collected and scanned using micro-computed tomography. From visual assessment of such scans, bone structure was classified into one- or three-layered, the latter indicating the existence of a diploë cavity. Bone average thickness, volume fraction and surface density were computed and correlated with changes in cephalic index. Results Cephalic index increased for all patients (p < 0.001), but individual improvement varied. Although the patient age and treatment duration were not significantly correlated with changes in cephalic index, bone structural parameters were. The increase of cephalic index was smaller with increasing bone thickness (Pearson's r = −0.79, p < 0.001) and decreasing bone surface density (r = 0.77, p < 0.001), associated with the three-layered bone structure. Conclusions Variation in parietal bone micro-structure was associated with the magnitude of head shape changes induced by spring-assisted cranioplasty. This suggests that bone structure analysis could be a valuable adjunct in designing surgical strategies that yield optimal patient-specific outcomes. [ABSTRACT FROM AUTHOR]

Conducting in vitro research for forensic, impact and injury simulation modelling generally involves the use of a skull simulant with mechanical properties similar to those found in the human skull. For this study epoxy resin, fibre filled epoxy resin, 3D-printing filaments (PETG, PLA) and self-cure acrylic denture base resin were used to fabricate the specimens (n=20 per material group), according to ISO 527-2 IBB and ISO20795-1. Tensile and flexural testing in a universal testing machine was used to measure their tensile/flexural elastic modulus and strength. The results showed that the epoxy resin and fibre filled epoxy resin had similar tensile elastic moduli (no statistical significant difference) with lower values observed for the other materials. The fibre filled epoxy resin had a considerably higher flexural elastic modulus and strength, possibly attributed to the presence of fibres. Of the simulants tested, epoxy resin had an elastic modulus and flexural strength close to that of mean human skull values reported in the literature, and thus can be considered as a suitable skull simulant for a skin/skull/brain model for lower impact forces that do not exceed the fracture stress. For higher impact forces a 3D printing filament (PLA) may be a more suitable skull simulant material, due to its closer match to fracture stresses found in human skull bone. Influencing factors were also anisotropy, heterogeneity and viscoelasticity of human skull bone and simulant specimens. [ABSTRACT FROM AUTHOR]

The presence of the dense hydroxyapatite matrix within human bone limits the applicability of conventional protocols for protein extraction. This has hindered the complete and accurate characterization of the human bone proteome thus far, leaving many bone-related disorders poorly understood. We sought to refine an existing method of protein extraction from mouse bone to extract whole proteins of varying molecular weights from human cranial bone. Whole protein was extracted from human cranial suture by mechanically processing samples using a method that limits protein degradation by minimizing heat introduction to proteins. The presence of whole protein was confirmed by western blotting. Mass spectrometry was used to sequence peptides and identify isolated proteins. The data have been deposited to the ProteomeXchange with identifier PXD003215. Extracted proteins were characterized as both intra- and extracellular and had molecular weights ranging from 9.4 to 629 kDa. High correlation scores among suture protein spectral counts support the reproducibility of the method. Ontology analytics revealed proteins of myriad functions including mediators of metabolic processes and cell organelles. These results demonstrate a reproducible method for isolation of whole protein from human cranial bone, representing a large range of molecular weights, origins and functions. [ABSTRACT FROM AUTHOR]