Cranial suture lineage and contributions to repair of the mouse skull.

The cranial sutures are proposed to be a stem cell niche, harbouring skeletal stem cells that are directly involved in development, homeostasis and healing. Like the craniofacial bones, the sutures are formed from both mesoderm and neural crest. During cranial bone repair, neural crest cells have been proposed to be key players; however, neural crest contributions to adult sutures are not well defined, and the relative importance of suture proximity is unclear. Here, we use genetic approaches to re-examine the neural crest-mesoderm boundaries in the adult mouse skull. These are combined with calvarial wounding experiments suggesting that suture proximity improves the efficiency of cranial repair. Furthermore, we demonstrate that Gli1+ and Axin2+ skeletal stem cells are present in all calvarial sutures examined. We propose that the position of the defect determines the availability of neural crest-derived progenitors, which appear to be a key element in the repair of calvarial defects.

[Rapid Reconstruction of Craniotomy Defects Based on Surgical Navigation].

In neurosurgery, skull repair caused by surgical approach is one of the important research contents. In this paper, a rapid reconstruction method of the skull defect with optical navigation system is proposed. This method can automatically reconstruct the structure of skull defect with the intraoperative defect edge points and preoperative medical image data. The head model experiment was used to evaluate the effect of the method, the average error of the reconstruction of the defect in the right orbit was 0.424 mm, while the average error of the reconstruction of the defect in the posterior skull base was 0.377 mm. The experimental results show that the structure of the defect is consistent with the actual defect, and the reconstruction accuracy satisfies the clinical requirements in neurosurgery.

Neural crest-derived mesenchymal progenitor cells enhance cranial allograft integration.

Replacement of lost cranial bone (partly mesodermal and partly neural crest-derived) is challenging and includes the use of nonviable allografts. To revitalize allografts, bone marrow-derived mesenchymal stromal cells (mesoderm-derived BM-MSCs) have been used with limited success. We hypothesize that coating of allografts with induced neural crest cell-mesenchymal progenitor cells (iNCC-MPCs) improves implant-to-bone integration in mouse cranial defects. Human induced pluripotent stem cells were reprogramed from dermal fibroblasts, differentiated to iNCCs and then to iNCC-MPCs. BM-MSCs were used as reference. Cells were labeled with luciferase (Luc2) and characterized for MSC consensus markers expression, differentiation, and risk of cellular transformation. A calvarial defect was created in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice and allografts were implanted, with or without cell coating. Bioluminescence imaging (BLI), microcomputed tomography (µCT), histology, immunofluorescence, and biomechanical tests were performed. Characterization of iNCC-MPC-Luc2 vs BM-MSC-Luc2 showed no difference in MSC markers expression and differentiation in vitro. In vivo, BLI indicated survival of both cell types for at least 8 weeks. At week 8, µCT analysis showed enhanced structural parameters in the iNCC-MPC-Luc2 group and increased bone volume in the BM-MSC-Luc2 group compared to controls. Histology demonstrated improved integration of iNCC-MPC-Luc2 allografts compared to BM-MSC-Luc2 group and controls. Human osteocalcin and collagen type 1 were detected at the allograft-host interphase in cell-seeded groups. The iNCC-MPC-Luc2 group also demonstrated improved biomechanical properties compared to BM-MSC-Luc2 implants and cell-free controls. Our results show an improved integration of iNCC-MPC-Luc2-coated allografts compared to BM-MSC-Luc2 and controls, suggesting the use of iNCC-MPCs as potential cell source for cranial bone repair.

Rapid Reconstruction of Craniotomy Defects Based on Surgical Navigation / 中国医疗器械杂志

In neurosurgery, skull repair caused by surgical approach is one of the important research contents. In this paper, a rapid reconstruction method of the skull defect with optical navigation system is proposed. This method can automatically reconstruct the structure of skull defect with the intraoperative defect edge points and preoperative medical image data. The head model experiment was used to evaluate the effect of the method, the average error of the reconstruction of the defect in the right orbit was 0.424 mm, while the average error of the reconstruction of the defect in the posterior skull base was 0.377 mm. The experimental results show that the structure of the defect is consistent with the actual defect, and the reconstruction accuracy satisfies the clinical requirements in neurosurgery.

Super early cranial repair improves the prognosis of patients with craniocerebral injury.

OBJECTIVE: Craniocerebral injury has high disability and mortality rates. The timing of cranioplasty has an important impact on patients' prognosis. This study was performed to compare the functional prognosis between super early repair and conventional repair. METHODS: This observational study included 60 patients who underwent cranioplasty after surgical treatment of severe craniocerebral trauma. The patients were divided into two groups according to the time of cranial repair after the surgical treatment of craniocerebral injury: the super early group and the conventional repair group. Sex, age, Karnofsky performance status (KPS) score, Zubrod performance status (ZPS) score, psychological function score, quality of life score, and complications were recorded. RESULTS: The KPS score, ZPS score, psychological function score, and quality of life score were significantly related to the intervention period. Each of these scores had a clear correlation with the performance of super early treatment. CONCLUSION: Super early cranial repair does not increase the incidence of surgical complications, and it can improve the postoperative KPS, ZPS, and quality of life scores.

Management and prevention of cranioplasty infections.

BACKGROUND: Infection may complicate the outcome of cranial repair with significant additional morbidity, related to hospitalization, surgery and long antibiotic therapy, that may become even dramatic in case of multi-resistant germs and in particular in the paediatric population. Additionally, the economic costs for the health system are obvious. Moreover, surgical decisions concerning the timing of cranioplasty and choice of the material may be strongly affected by the risk of infection. Despite, management and prevention of cranioplasty infections are not systematically treated through the literature so far. METHODS: We reviewed pertinent literature dealing with cranioplasty infection starting from the diagnosis to treatment options, namely conservative versus surgical ones. Our institutional bundle, specific to the paediatric population, is also presented. This approach aims to significantly reduce the risk of infection in first-line cranioplasty and redo cranioplasty after previous infection. CONCLUSIONS: A thorough knowledge and understanding of risk factors may lead to surgical strategies and bundles, aiming to reduce infectious complications of cranioplasty. Finally, innovation in materials used for cranial repair should also aim to enhance the antimicrobial properties of these inert materials.

The growth of the neurocranium: literature review and implications in cranial repair.

BACKGROUND: Postnatal growth of neurocranium is prevalently completed in the first years of life, thus deeply affecting the clinical presentation and surgical management of pediatric neurosurgical conditions involving the skull. This paper aims to review the pertinent literature on the normal growth of neurocranium and critically discuss the surgical implications of this factor in cranial repair. METHODS: A search of the electronic database of Pubmed was performed, using the key word "neurocranium growth", thus obtaining 217 results. Forty-six papers dealing with this topic in humans, limited to the English language, were selected. After excluding a few papers dealing with viscerocranium growth or pathological conditions not related to normal neurocranium growth 18 papers were finally included into the present review. RESULTS AND CONCLUSIONS: The skull growth is very rapid in the first 2 years of life and approximates the adult volume by 7 years of age, with minimal further growth later on, which is warranted by the remodeling of the cranial bones. This factor affects the outcome of cranioplasty. Thus, it is essential to consider age in the planning phase of cranial repair, choice of the material, and critical comparison of results of different cranioplasty solutions.

Craniocerebral disproportion after decompressive craniectomy in infants: The hidden enemy of cranial repair?

INTRODUCTION: Cranioplasty aims at restoring the physiological integrity and volume of the skull. Any disproportion between the intracranial content and the volume of the container may favor the occurrence of complications. A classification of volume mismatches is proposed. A negative mismatch, consisting of intracranial content minor to skull volume, is well represented by the sinking flap. On the other side, a positive mismatch, consisting of intracranial content higher than skull volume, usually depends on CSF collection or hydrocephalus once the brain edema is regressed. Though, in children, this condition may result from physiological brain growth after decompressive craniectomy. Treatment algorithm based on this classification is presented. ILLUSTRATIVE CASE: A 1-year-old boy with a severe traumatic brain injury underwent right decompressive craniectomy, evacuation of subdural hematoma, and dural expansion at another institution. After failure of autologous bone-assisted cranioplasty for infection, a helmet was recommended in order to postpone the cranial repair. Patient was admitted to our institution 3 years later. CT scan showed brain herniation through the cranial defect, associated to a condition of acquired craniocerebral disproportion, due to the condition of "open skull". Augmented hydroxyapatite cranioplasty (CustomBone, Finceramica, Faenza, Italy) was performed in order to manage this rare condition of positive volume mismatch. Subsequent course was uneventful and no complication was recorded at 30-month follow-up. CONCLUSIONS: This illustrative case highlights the possible occurrence of a positive structural mismatch between the skull and the intracranial content after decompressive craniectomy, thus configuring a condition of acquired craniocerebral disproportion, aside of other brain or CSF complications. We firstly recognize this condition in the literature and propose it as a possible factor affecting the outcome of cranioplasty in infants and young children.

Cranioplasty with Adipose-Derived Stem Cells, Beta-Tricalcium Phosphate Granules and Supporting Mesh: Six-Year Clinical Follow-Up Results.

Several alternative techniques exist to reconstruct skull defects. The complication rate of the cranioplasty procedure is high and the search for optimal materials and techniques continues. To report long-term results of patients who have received a cranioplasty using autologous adipose-derived stem cells (ASCs) seeded on beta-tricalcium phosphate (betaTCP) granules. Between 10/2008 and 3/2010, five cranioplasties were performed (four females, one male; average age 62.0 years) using ASCs, betaTCP granules and titanium or resorbable meshes. The average defect size was 8.1 × 6.7 cm2 . Patients were followed both clinically and radiologically. The initial results were promising, with no serious complications. Nevertheless, in the long-term follow-up, three of the five patients were re-operated due to graft related problems. Two patients showed marked resorption of the graft, which led to revision surgery. One patient developed a late infection (7.3 years post-operative) that required revision surgery and removal of the graft. One patient had a successfully ossified graft, but was re-operated due to recurrence of the meningioma 2.2 years post-operatively. One patient had an uneventful clinical follow-up, and the cosmetic result is satisfactory, even though skull x-rays show hypodensity in the borders of the graft. Albeit no serious adverse events occurred, the 6-year follow-up results of the five cases are unsatisfactory. The clinical results are not superior to results achieved by conventional cranial repair methods. The use of stem cells in combination with betaTCP granules and supporting meshes in cranial defect reconstruction need to be studied further before continuing with clinical trials. Stem Cells Translational Medicine 2017;6:1576-1582.