Skull Defects Research Articles

Sinking skin syndrome in a decompressive craniectomy series: Clinical and radiological features.

The sinking skin syndrome (SSS) is a particular complication after a decompressive craniectomy (DC). It still remains a poorly understood and underestimated entity. Retrospective case series of craniectomized patients with and without SSS. Clinical and radiological features (DC diameter, shape of craniectomy flap, and midline deviation) were described and relative volumes of intracranial loss were quantified. Twenty-seven patients (63% with SSS). The most common indication for DC was traumatic brain injury: 48.15%. The p50 diameter of DC was 12.8 cm for patients with SSS and 11.1 cm for patients without (Z score = 0.32). DC area was 81.5 cm2 for patients with SSS and 71.43 cm2 for patients without the syndrome (Z score = 0.61). According to the shape of the craniectomy flap, we classified our patients as: «same level» (51.8%), «sunken» (25.9%), and «extracranial herniation» (14.8%). Two patients (7.4%) had paradoxical herniation. Midline deviation was present in 12 (70.6%) patients with SSS. The 3rd ventricle volume average was 1.2 cc for patients with SSS versus 2.35 cc for patients without (Z score = 0.04). About 94.11% of patients (16 out of 17) clearly improved after replacement of the cranial defect. In our series, low 3rd ventricle volumes had a good relation with SSS. The presence of a sunken flap does not guarantee SSS per se and we propose the following radiologic description: A = sunken, B = same level, C = extracranial herniation, and D = paradoxical. Replacement of the skull defect is the main treatment.

Polylactic Glycolic Acid-Based Nano Artificial Bone Stent Loaded with Recombinant Human Bone Morphogenetic Protein-2 and Its Performance

Pearl layer/polylactic glycolic acid (PLGA) stent and recombinant human bone morphogenetic protein-2 (rhBMP-2) were prepared. Its biocompatibility and osteoblast activity were discussed, and it was applied in the clinical repair of skull defect. Firstly, phase separation/salting out load were adopted to compound different proportions of PLGA and pearl layer powder in different proportions. Besides, PLGA-based nano composite stent was prepared. The physical property synthesized by pearl layer and PLGA in different proportions was detected. The nano stent with the best mechanical performance was selected to load rhBMP-2 and analyze its release characteristics in vitro. The material was soaked in MC3T3-E1 cell solution and then analyze its cell activity. A 5 mm critical bone defect model of rat skull was established and the material was implanted into rat skull defect area. At different time periods, cone beam computed tomography (CBCT) was employed to observe the repair effect of the material on defect areas. The results showed that the prepared PLGA-based nano composite stent showed three-dimensional porous structure, porosity reaching above 80%. When the ratio of pearl layer/PLGA was 7:5, it showed good mechanical strength. The release rate of load rhBMP-2 based on the ratio was accelerated in the first 7 days. In contrast, it gradually became stable after 7 days. The relative proliferation rate of cell solution in the material was over 90% during 7 days. The cytotoxicity is low and the material extract could induce MC3T3-E1 cell differentiation. Under electron microscope, the combination of rhBMP-2/pearl layer/PLGA and autogenous bone showed good effects.

WE-176. Scalp HFO rates decrease after successful epilepsy surgery and are not impacted by the skull defect resulting from craniotomy

WE-176. Scalp HFO rates decrease after successful epilepsy surgery and are not impacted by the skull defect resulting from craniotomy

Down-regulation of hsa-circ-0107593 promotes osteogenic differentiation of hADSCs via miR-20a-5p/SMAD6 signaling.

Increasing evidence indicated circRNAs were involved in stem cells osteogenesis differentiation. Herein, we aimed to clarify the role of hsa-circ-0107593 during the osteogenesis process of human adipose-derived stem cells (hADSCs) and the underlying mechanisms. The ring structure of hsa-circ-0107593 was confirmed using RNase R treatment and Sanger sequencing. Nucleoplasmic separation and fluorescence in situ hybridization detected hsa-circ-0107593 distribution. Lentivirus and siRNA were used to modulate the expression of hsa-circ-0107593, and the binding relationship between hsa-circ-0107593 and miR-20a-5p was verified by luciferase assay and RNA immunoprecipitation. We detected the osteogenic activity of hADSCs through alkaline phosphatase staining, alizarin red S staining, real-time polymerase chain reaction (RT-PCR), western blot, and cellular immunofluorescence experiment. In vivo, micro-computed tomography was performed to analyze bone formation around skull defect. RT-PCR results exhibited that hsa-circ-0107593 was downregulated while miR-20a-5p was upregulated during hADSCs osteogenesis. In vivo and in vitro experiments results indicated that knocking down hsa-circ-0107593 promoted the osteogenic differentiation of hADSCs, while overexpression of hsa-circ-0107593 showed an inhibitory effect on hADSCs osteogenic differentiation. In vitro experiment results showed hsa-circ-0107593 acted as a hADSCs osteogenic differentiation negative factor for it inhibited the suppressing effect of miR-20a-5p on SMAD6. Knocking down hsa-circ-0107593 acts as a positive factor of the osteogenic differentiation of hADSCs via miR-20a-5p/SMAD6 signaling.

Microsphere-Gel Composite System with Mesenchymal Stem Cell Recruitment, Antibacterial, and Immunomodulatory Properties Promote Bone Regeneration via Sequential Release of LL37 and W9 Peptides.

Various types of biomaterials have been widely used to treat complex bone defects. However, potential infection risks and inappropriate host immune responses induced by biomaterials can adversely affect the final bone repair outcome. Therefore, the development of novel bone biomaterials with antibacterial and immunomodulatory capabilities is conducive to achieving a good interaction between the host and material, thereby creating a local microenvironment favorable for osteogenesis and ultimately accelerating bone regeneration. In this study, we fabricated a porcine small intestinal submucosa (SIS) hydrogel containing LL37 peptides and polylactic-glycolic acid (PLGA) microspheres encapsulated with WP9QY(W9) peptide (LL37-W9/PLGA-SIS), which can fill irregular bone defects and exhibits excellent mechanical properties. In vitro experiments showed that the microsphere-gel composite system had sequential drug release characteristics. The LL37 peptide released first had good antibacterial performance and BMSC recruitment ability, which could prevent infection at an early stage and increase the number of BMSCs at the injured site. In addition, it also has immunomodulatory properties, showing both pro-inflammatory and anti-inflammatory activities, but its early pro-inflammatory properties are more inclined to activate the M1 phenotype of macrophages. Moreover, the subsequently released W9 peptide not only reduced the expression of pro-inflammatory genes to alleviate inflammation and induced more macrophages to convert to M2 phenotypes but also promoted the osteogenic differentiation of BMSCs. This finely regulated immune response is considered to be more closely related to the physiological bone healing process. When studying the interaction between macrophages and BMSCs mediated by the material, it was found that the immunomodulatory and osteogenic effects were enhanced. In vivo experiments, we constructed rat skull defect models, which further proved that LL37-W9/PLGA-SIS gel can properly regulate the immune response, and has a good ability to promote osteogenesis in situ. In conclusion, the LL37-W9/PLGA-SIS hydrogel has great application prospects in immune regulation and bone therapy.

Naringin Release from a Nano-Hydroxyapatite/Collagen Scaffold Promotes Osteogenesis and Bone Tissue Reconstruction.

Bone fractures and defects are a major health issue and have reportedly affected over 455 million individuals globally to date. Bone tissue engineering has gained great success in bone defect repair and bone reconstruction based on the use of nano-hydroxyapatite (nHA) or collagen (COL). Both nHA and COL exhibit osteogenic induction capacity to support bone tissue regeneration; however, the former suffers from poor flexibility and the latter lacks mechanical strength. Biological scaffolds created by combining nHA and COL (nHA/COL) can overcome the drawbacks imposed by individual materials and, therefore, have become widely applied in tissue engineering. The composite scaffolds can further promote tissue reconstruction by allowing the loading of various growth factors. Naringin (NG) is a natural flavonoid. Its molecular weight is 580.53 Da, lower than that of many growth factors, and it causes minimal immune responses when being introduced in vivo. In addition, naringin is safe, non-toxic, inexpensive to produce, and has superior bio-properties. In this study, we introduced NG into a nHA/COL scaffold (NG/nHA/COL) and exploited the potentials of the NG/nHA/COL scaffold in enhancing bone tissue regeneration. NG/nHA/COL scaffolds were fabricated by firstly combining nHA and collagen at different compositional ratios, followed by NG encapsulation. NG release tests showed that the scaffold with a nHA/COL mass ratio of 7:3 exhibited the optimal property. The in vitro cell study showed the desirable biocompatibility of the NG/nHA/COL scaffold, and its effective promotion for the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), as proved by an increased alkaline phosphatase (ALP) activity, the formation of more calcium nodules, and a higher expression of osteogenic-related genes involving Osteocalcin (OCN), BMP-2, and Osteopontin (OPN), compared with the control and nHA/COL groups. When administered into rats with skull defects, the NG/nHA/COL scaffold significantly promoted the reconstruction of bone tissues and the early repair of skull defects, indicating the great potential of NG/nHA/COL scaffolds in bone tissue engineering.

Frontal intradiploic encephalocele in a 44-year-old male patient: illustrative case.

Encephaloceles are protrusions of the cerebral tissue through a skull defect. They occur mostly in children and very rarely in adults. The authors present a case of a 44-year-old man presenting with a first-time generalized seizure. Computed tomography of the head showed bone destruction associated with a right frontal lesion. Magnetic resonance imaging scans demonstrated a largely isointense lesion in the intradiploic space that contained small, hyperintense nodular components and showed a low to moderate contrast agent enhancement. The patient underwent resection, during which the histological examination found the lesion to be an intradiploic encephalocele. The patient had an uneventful postoperative course with a cessation of seizures. The imaging and neuropathological findings as well as a literature review, together with a discussion on the etiology of intradiploic encephaloceles, are contained in this report.

DLP fabricating of precision GelMA/HAp porous composite scaffold for bone tissue engineering application

The hydrogel composited hydroxyapatite (HAp) scaffold shown biomimetic extracellular matrix and osteogenic activity, which is a promising bone regeneration biomaterial. 3D printing has been widely used in fabrication of customized and complex bone regeneration scaffold. However, it is still a challenge to prepare high-precision HAp reinforced composites by digital light processing (DLP) printing that can effectively promote bone regeneration. In this study, shear-thinning gelatin methacrylamide (GelMA)/hydroxyapatite (HAp) composite inks were prepared to fabricate high-precision scaffolds by DLP printing for bone repair. Firstly, GelMA hydrogels with adjustable mechanical, rheological and printing properties were synthesized to screen hydrogel concentration and degree of substitution. Then carefully selected biocompatible dispersants to reduce the agglomeration of hydroxyapatite. The actual printing resolution of the GelMA/HAp porous composite scaffolds with excellent mechanical strength through DLP 3D printing was up to about 100 μm. In vitro, the 3D printed composite scaffold significantly promoted the adhesion and proliferation of osteoblasts, as well as promoted osteogenic differentiation. In vivo, the GelMA/HAp porous composite scaffolds showed excellent ability in accelerating the formation of new bone in rabbit skull defects. The GelMA/HAp porous composite scaffolds fabricated by the composite inks with good printability, mechanical properties and osteogenic activity have fascinating potential in bone repair application.

Superimposing Pre-Cranioplasty on Pre-Craniectomy Images to Gauge Feasibility of Early Cranioplasty: A Proof of Concept.

Cranioplasty to reconstruct a skull defect after a decompressive craniectomy (DC) is a common neurosurgical procedure. However, cranioplasty is associated with relatively high complication rates, with optimal timing from craniectomy to cranioplasty remaining a controversial matter. Recent studies demonstrated early cranioplasty with appropriate risk mitigation to be a viable option with many clinical advantages, propelling the advocacy for cranioplasty as soon as brain swelling resolves. We report on a 33-year-old male with traumatic brain injury who received an early cranioplasty, 18 days post-DC. The extent of adequate brain swelling resolution was determined by superimposing selected pre-cranioplasty computed tomography (CT) images onto corresponding pre-craniectomy CT images. By ensuring all brain matter lies within the outer table of the skull in superimposed brain images, the extent of brain swelling resolution could be determined reliably and the feasibility of cranioplasty can be assessed objectively.

Bone morphogenetic protein 4 rescues the bone regenerative potential of old muscle-derived stem cells via regulation of cell cycle inhibitors

BackgroundBone morphogenetic protein 4 (BMP4) promotes the osteogenic differentiation and the bone regenerative potential of muscle-derived stem cells (MDSCs). BMP4 also promotes the self-renewal of both embryonic and somatic stem cells; however, BMP4 signaling activity significantly decreases with age. Cyclin-dependent kinase inhibitors P16INK4A (P16) and P18INK4C (P18) induce early G1-phase cell cycle blockade by targeting cyclin-dependent kinase 4/6. It is still unclear if BMP4 affects the bone regenerative potential of old MDSCs through regulation of P16 and P18 expression.MethodsYoung and old MDSCs were isolated from 3 week (young) and 2-year-old (old) mice. In vitro cell proliferation and multipotent differentiation were performed for young and old MDSCs both before and after BMP4/GFP transduction. Cell cycle genes were analyzed using Q-PCR. The bone regenerative potential of young and old MDSCs transduced with BMP4/GFP were compared using Micro-CT and histological analysis. The bone regenerative potential of young and old MDSCs was also compared between single and double transduction (higher BMP4 levels expression). The cell proliferation, mitochondrial function and osteogenic differentiation was also compared in vitro between cells that have been transduced with BMP4GFP (single and double transduction). The correlation of bone regeneration capacity of young and old MDSCs with P16 and P18 expression was further evaluated at 10 days after cell transplantation using histology and western blot analysis.ResultsOld murine MDSCs (MDSCs) exhibit reduced proliferation and multi-lineage differentiation potential with or without BMP4 stimulation, when compared to young murine MDSCs. Old MDSCs express significantly higher P16 and lower P18, with more cells in the G0/1 phase and fewer cells in the G2/M phase, compared to young MDSCs. Old MDSCs retrovirally transduced to express BMP4 regenerated less bone in a critical size skull defect in CD-1 nude mice when compared to young retrovirally transduced MDSCs expressing similar BMP4 levels and contribute less to the new regenerated new bone. Importantly, both young and old MDSCs can regenerate more bone when BMP4 expression levels are increased by double-transduction with the retroviral-BMP4/GFP. However, the bone regeneration enhancement with elevated BMP4 was more profound in old MDSCs (400% at 2 weeks) compared to young MDSCs (200%). Accordingly, P18 is upregulated while P16 is downregulated after BMP4 transduction. Double transduction did not further increase cell proliferation nor mitochondrial function but did significantly increase Osx expression in both young and old MDSCs. Old MDSCs had even significant higher Osx levels as compared to young MDSCs following double transduction, while a similar Alp expression was observed between young and old MDSCs after double transduction. In addition, at 10 days after cell transplantation, old MDSCs having undergone double transduction regenerated bone more rapidly as showed by Alcian blue and Von Kossa staining. Western blot assays demonstrated that old MDSCs after retro-BMP4/GFP double transduction have significantly lower P18 expression levels when compared to young BMP4-transduced MDSCs. In addition, P18 expression was slightly increased in old MDSCs after double transduction when compared to single transduction. P16 expression was not detectable for both young and two old BMP4/GFP transduced MDSCs groups.ConclusionsIn summary, BMP4 can offset the adverse effect of aging on the osteogenic differentiation and the bone regenerative potential of old MDSCs via up-regulation of P18 and down-regulation P16 expression.

Cranioplasty for Skull Defects With Polypropylene Abdominal Wall Mesh

Cranioplasty is a well-established common surgery in the practice of neurosurgery and craniofacial surgery. In young patients, complete skull defect closure by bone splitting may be troublesome due to the difficulty to obtain enough bone area. In such cases, sometimes the authors need to use allografts, which may not be widely available in rural practice. In this study, the authors present the series of cranioplasty with polypropylene mesh, which is widely used in abdominal wall closure. Nine patients with depressed compound skull fracture were treated by performing this technique. Selection criteria were: compound depressed skull fractures in which bones were fragmented in a way not able to be reconstructed with and leaving a skull defect, small-sized or relatively medium-sized skull defects, and skull defects not located on the sharp curvatures of the skull which needs firm bended meshes. All patients were male and their ages ranged between 8 months and 36 years.The skull bone defect was reconstructed with polypropylene abdominal wall mesh, which was sutured circumferentially with the galeal tissue. Skull defects were successfully treated in all patients. The follow-up period ranged from 4 to 13 months. One patient with a history of alcoholism and neglectance developed a wound infection after 3 weeks of surgery. This patient was treated successfully with intravenous antibiotics without the need to remove the mesh. There were no complications in the remaining 8 patients. Polypropylene mesh is a cheap and effective material for the reconstruction of small-sized or medium-sized skull defects. It can be a good alternative in rural practice and/or low economic communities, when other cranioplasty materials are not available.

Skull defect increases the tumor treating fields strength without detrimental thermogenic effect: A computational simulating research.

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. 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). 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. 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.

A novel flexible, conductive, and three-dimensional reduced graphene oxide/polyurethane scaffold for cell attachment and bone regeneration

Development of conductive and three-dimensional scaffolds with elastic properties and shape-recovery capability for bone regeneration within irregular bone cavities has been challenging. Polyurethanes (PUs) are intrinsically elastic polymers; however, their mechanical performance, biocompatibility, and functionality need to be improved for application as implants and biomedical devices. Herein, application of a novel flexible, conductive, and three-dimensional polyurethane scaffold (3DPU), fabricated through coating a commercial PU foam with graphene oxide (GO) and its subsequent reduction with ascorbic acid, described as 3DrGO/PU, is investigated for bone regeneration. The 3DrGO/PU scaffold supported the growth and proliferation of mouse osteoblast cells (MG-63) with strong mineralization and cell attachment. It is likely that the electrically conductive macro-porous 3DrGO/PU scaffold, provides bioactivity and promote nucleation and growth of hydroxyapatite (HA) in the simulated body fluid. Experiments assessing in vivo bone formation in rat calvarial skull defects provided clear evidence for efficacy of the 3D scaffold for treatment of irregular bone defects. The results of this study are promising, as they present easy production of a cost-effective green fabricated scaffold. It also offers a potential for cell attachment and capture, to be used in future tissue engineering and even biosensing applications.

Application of two-stage operation on free latissimus dorsi myocutaneous flap transplantation and skull contour reconstruction in treatment of head titanium mesh exposure with soft tissue infection

To explore the effectiveness of two-stage operation on free latissimus dorsi myocutaneous flap transplantation and skull contour reconstruction in the treatment of head titanium mesh exposure complicated with soft tissue infection. Between January 2015 and December 2021, 13 patients with head titanium mesh exposure complicated with soft tissue infection were admitted. There were 9 males and 4 females with a mean age of 42.9 years (range, 23-64 years). The duration of titanium mesh exposure was 22-609 days (median, 102 days). The wound site located at the frontal part in 3 cases, the parietal part in 1 case, the occipital part in 2 cases, the frontal-parietal part in 1 case, the temporal-parietal part in 4 cases, and the frontotemporal part in 2 cases. The titanium mesh had been taken out in 5 patients before admission, leaving skull defect and shape collapse, with signs of infection. The bacterial culture was positive in 7 cases and negative in 6 cases. The imaging examination revealed that the size of the skull defect ranged from 6 cm×5 cm to 21 cm×17 cm and the scalp defect ranged from 1 cm×1 cm to 15 cm×10 cm. The soft tissue infection did not reach dura in 5 cases, reached dura in 6 cases, and reached frontal sinus in 2 cases. The two-stage surgical protocol was used in all patients. In the first-stage operation, the latissimus dorsi myocutaneous flap was designed to repair the skull and scalp defects after removing the titanium mesh and thorough debridement. The size of muscle flap ranged from 13.5 cm×4.0 cm to 21.0 cm×17.0 cm, and the skin flap ranged from 7.0 cm×4.0 cm to 15.0 cm×10.0 cm. After the flap survived and stabilized, the second-stage operation was performed. The titanium mesh was implanted to reconstruct the skull contour. The size of titanium mesh ranged from 7.0 cm×6.0 cm to 21.5 cm×17.5 cm. The interval between the first- and second-stage operations was 3.7-17.8 months, with an average of 11.4 months. The survival of the skin flap, the appearance of the head, and the presence of re-exposed titanium mesh and infection were observed after operation. At the first-stage operation, venous embolism occurred in 1 case, and no obvious abnormality was observed after treatment. All the flaps survived and the incisions healed by first intention. Besides, the incisions of the second-stage operation healed by first intention. All patients were followed up 1-96 months (median, 14 months). During follow-up, no exposure to titanium mesh, infection, or other complications occurred. The appearance satisfaction rate of the patients was 92.31% (11/13). There was no significant difference in the skull contour between the affected side and the healthy side in all patients. For the head titanium mesh exposure with soft tissue infection, the application of two-stage operation on free latissimus dorsi myocutaneous flap transplantation and skull contour reconstruction can reduce the risks of implant exposure and infection again by increasing the thickness of the scalp and blood supply, filling the wound cavity, and obtain good effectiveness.

Engineered 3D-Printed Polyvinyl Alcohol Scaffolds Incorporating β-Tricalcium Phosphate and Icariin Induce Bone Regeneration in Rat Skull Defect Model.

The skull defects are challenging to self-heal, and autologous bone graft repair has numerous drawbacks. The scaffolds for the rapid and effective repair of skull defects have become an important research topic. In this study, polyvinyl alcohol (PVA)/β-tricalcium phosphate(β-TCP) composite scaffolds containing icariin (ICA) were prepared through direct-ink three-dimensional (3D) printing technology. β-TCP in the composite scaffold had osteoconductive capability, and the ICA molecule had osteoinductive capacity. The β-TCP and ICA components in the composite scaffold can enhance the capability to repair skull defects. We show that ICA exhibited a slow-release behaviour within 80 days. This behaviour helped the scaffold to continuously stimulate the formation of new bone. The results of in vitro cell compatibility experiments showed that the addition of ICA molecules contributed to the adhesion and proliferation of MC-3T3-E1 cells. The level of alkaline phosphatase secretion demonstrated that the slow release of ICA can promote the osteogenic differentiation of MC-3T3-E1 cells. The introduction of ICA molecules accelerated the in situ bone regeneration in in vivo. It is concluded that the 3D-printed PVA scaffold with β-TCP and ICA has a wide range of potential applications in the field of skull defect treatment.

Nano artificial periosteum PLGA/MgO/Quercetin accelerates repair of bone defects through promoting osteogenic − angiogenic coupling effect via Wnt/ β-catenin pathway

Bone nonunion or delayed union, caused by stripping or injuring of periosteum, is the most common sequelae of segmental bone defects. The preservation of periosteum, or the use of periosteal grafts, can significantly improve the integration of bone graft, speeding up the process of bone reconstruction. However, in most cases, periosteum cannot be preserved with bioactivity. Thus, it is pivotal to develop artificial periosteum. In this study, artificial periosteum of PLGA/MgO/Quercetin was prepared by electrospinning. PLGA/MgO/Quercetin membranes were shown to have a highly porous surface and microstructure, as observed by scanning electron microscopy. Along with excellent biocompatibility, PLGA/MgO/Quercetin membranes promoted cell proliferation and migration, as well as osteogenic differentiation of BMSCs (Bone marrow mesenchymal stem cells) in a dose-dependent manner through the activation of Wnt/β-Catenin pathway. The PLGA/MgO/Quercetin membranes, with an appropriate concentration of quercetin (<1 ​wt%), promoted EPCs (Endothelial progenitor cells) angiogenesis. In a subcutaneous implantation model and rat skull defect model, optimal osteogenesis and angiogenesis function were observed for the PLGA/20 ​wt% MgO/0.1 ​wt% Quercetin membrane. In conclusion, PLGA/MgO membranes, with an appropriate concentration of quercetin, show a variety of biological activities and are promising materials for the generation of artificial periosteum.

Porous gelatin microsphere-based scaffolds containing MC3T3-E1 cells and calcitriol for the repair of skull defect

There is an increasing demand for biomaterials with skull regeneration for clinical application. However, most of the current skull repair materials still have limitations, such as inadequate sources, poor cell adherence, differentiation, tissue infiltration, and foreign body sensation. Therefore, this study developed porous microsphere-based scaffolds containing mouse embryonic osteoblast precursor cells (MC3T3-E1 cells) and calcitriol (Cal) using gelatin and gelatin/hydroxyapatite through green freeze-crosslinking and freeze-drying. Gelatin was employed to prepare porous microspheres with a particle size of 100-300μm, containing open pores of 2-70μm and interconnected paths. Furthermore, the addition of Cal to porous gelatin microsphere-based scaffolds containing MC3T3-E1 cells (PGMSs-MC) and porous gelatin/hydroxyapatite composite microspheres containing MC3T3-E1 cells (HPGMSs-MC) improved their osteoinductivity and cell proliferation and promoted the formation of mature and well-organized bone. The developed Cal-HPGMSs-MC and Cal-PGMSs-MC displayed a good porous structure and cytocompatibility, histocompatibility, osteoconductivity, and osteoinduction. Thus, the designed scaffolds provide a promising prospect for tissue-engineered constructs with skull growth and integration, laying a foundation for further research on the reconstruction of skull defects.

Role of personalized 3D printing in brain protection after decompressive craniectomy

Objective: To explore the application value of personalized three-dimensional (3D) printed protective cap in brain protection after decompressive craniectomy (DC). Methods: Fourty-five patients who underwent DC from January 2021 to October 2021 were selected, including 26 males and 19 females, aged 5-73 (50±13) years old. The brain CT data were imported into 3D Slicer software to rebuild the protective cap through 3D printing. The cap was worn on the head of the patient, thereby preventing secondary braindamage. The follow-up results were compared with 53 patients without protective capduring the same period. Results: There were no statistically significant differences in age, skull defect location and follow-up time between the two groups (all P>0.05).Among 45 patients, 47 brain protective caps (2 cases with bilateral skull defects) were successfully designed. The time for image post-processingand 3D printing was (21.2±6.0) min and (62.4±8.3) min, respectively. There were 6 cases of low compliance, 9 cases of moderate compliance, 32 cases of high compliance, respectively. Six cases with low conformity were redesigned and printed, 2 of 9 cases with moderate conformity were redesigned and printed, and the remaining 7 cases reached high compliance after grinding and packaging. In the current study, 45 patients with brain protective caps were followed up for 3 months, and no secondary brain injury occurred. However, among 53 patients without brain protective caps during the same period, 4 patients had secondary accidental brain compression. The incidence of injury was 7.5 %, and the difference was statistically significant (P<0.001). Conclusion: Brain protective cap designed based on cranial CT and 3D printing can be used in patients with skull defects to protect the brain tissue from secondary crush damage and has certain clinical value.

Cranial defect and pneumocephalus are associated with significant postneurosurgical positional brain shift: evaluation using upright computed tomography

Only few studies have assessed brain shift caused by positional change. This study aimed to identify factors correlated with a large postneurosurgical positional brain shift (PBS). Sixty-seven patients who underwent neurosurgical procedures had upright computed tomography (CT) scan using settings similar to those of conventional supine CT. The presence of a clinically significant PBS, defined as a brain shift of ≥ 5 mm caused by positional change, was evaluated. The clinical and radiological findings were investigated to identify factors associated with a larger PBS. As a result, twenty-one patients had a clinically significant PBS. The univariate analysis showed that supratentorial lesion location, intra-axial lesion type, craniectomy procedure, and residual intracranial air were the predictors of PBS. Based on the multivariate analysis, craniectomy procedure (p < 0.001) and residual intracranial air volume (p = 0.004) were the predictors of PBS. In a sub-analysis of post-craniectomy patients, PBS was larger in patients with supratentorial craniectomy site and parenchymal brain injury. A large craniectomy area and long interval from craniectomy were correlated with the extent of PBS. In conclusion, patients who undergo craniectomy and those with residual intracranial air can present with a large PBS. In post-craniectomy patients, the predisposing factors of a large PBS are supratentorial craniectomy, presence of parenchymal injury, large skull defect area, and long interval from craniectomy. These findings can contribute to safe mobilization among postneurosurgical patients and the risk assessment of sinking skin flap syndrome.

Paediatric cranioplasty—Experience from a Singapore children’s hospital

Cranioplasty is a common neurosurgical procedure. Nonetheless, cranioplasty in the paediatric population pose a set of unique challenges owing to their developing craniums. We conducted a single institution, retrospective study of children that underwent cranioplasty; and corroborated our clinical outcomes with current literature. Data was statistically analysed to assess for factors associated with implant complications that required interval intervention. Thirty-two patients were recruited for the study from 01 January 2001 to 31 December 2021. Mean age was 7.9 years. For the cranial implants, there were 16 autologous (43.2%), 7 acrylic (18.9%), 5 titanium mesh (13.5%) and 4 PEEK (10.8%) grafts. Aetiologies for the skull defect include head injury (n = 22; 68.8%), neoplasm (n = 4; 12.5%), spontaneous intracranial haemorrhage (n = 3; 9.4%) and infection (n = 3; 9.4%). Eight patients (25%) required another surgery due to implant-related complications. Here, 3 patients had their implants removed due to infection (6.3%) and extrusion (3.1%); 4 had bone resorption of their autologous grafts (12.5%): and 1 patient (3.1%) had a postoperative acute extradural haematoma. A subgroup analysis was performed for patients (n = 16) with autologous skull implants. We observed that autologous bone cranioplasty at more than 6 weeks post-decompression was associated with higher rates of bone graft resorption (p = 0.008). The mean time for this group of patients to undergo a second surgery was 29.1 months. Overall, our results concur with the difficulties reported in previous publications and highlight the need for long-term followup to monitor for implant-related complications.