Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration.

Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration. Despite extensive studies on mineralized parenchymal tissue rebuilding, regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet. Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage. But to date, the absence of promising therapeutic biomaterials/scaffolds remains. The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds. To address these issues, in this study, we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds. Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses. A feasible scaffold, polylactic acid electrospinning membrane (PLA), was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center, meanwhile supporting proper osteointegration with defect bony edges. Especially, transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered. This study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing, offering clinicians potential choices for regenerating such complicated injuries.

Subcutaneous preservation versus cryopreservation of autologous bone grafts for cranioplasty: A systematic review and meta-analysis.

BACKGROUND: Cranioplasty corrects cranial bone defects using various bone substitutes or autologous bone flaps created during a previous craniectomy surgery. These autologous bone flaps can be preserved through subcutaneous preservation (SP) or cryopreservation (CP). AIM: We aim to compare outcomes and complications for both SP and CP techniques to enhance the current evidence about autologous bone flap preservation. METHODS: Five electronic databases were searched to collect all relevant studies. Records were screened for eligibility. Data were extracted from the included studies independently. We categorized surgical site infection (SSI) as either due to Traumatic brain injury (TBI) or not to reveal potential variations in SSI incidence. The double-arm meta-analysis utilized risk ratios (RR) and mean differences (MD) with corresponding confidence intervals (CI) to pool categorical and continuous outcomes, respectively. Proportions with their respective 95% CIs were pooled for single-arm meta-analyses to determine outcomes related to SP technique. RESULTS: Seventeen studies involving 1169 patients were analyzed. No significant difference in SSI rates was observed between SP and CP methods in patients with or without TBI. SP was linked to shorter hospital stays in two studies (194 patients). Single-arm analysis showed a 17% revision surgery rate across five studies (375 patients) and infection rates in 17 studies for SP. New bone formation occurred in 13.2% of patients, with 19.9% showing resorption. CONCLUSION: SP and CP methods showed similar SSI rates post-craniectomy in TBI and non-TBI patients. SP was associated with reduced hospitalization time, low infection rates, and a moderate need for revision surgery.

Thickness and design features of clinical cranial implants-what should automated methods strive to replicate?

PURPOSE: New deep learning and statistical shape modelling approaches aim to automate the design process for patient-specific cranial implants, as highlighted by the MICCAI AutoImplant Challenges. To ensure applicability, it is important to determine if the training data used in developing these algorithms represent the geometry of implants designed for clinical use. METHODS: Calavera Surgical Design provided a dataset of 206 post-craniectomy skull geometries and their clinically used implants. The MUG500+ dataset includes 29 post-craniectomy skull geometries and implants designed for automating design. For both implant and skull shapes, the inner and outer cortical surfaces were segmented, and the thickness between them was measured. For the implants, a 'rim' was defined that transitions from the repaired defect to the surrounding skull. For unilateral defect cases, skull implants were mirrored to the contra-lateral side and thickness differences were quantified. RESULTS: The average thickness of the clinically used implants was 6.0 ± 0.5 mm, which approximates the thickness on the contra-lateral side of the skull (relative difference of -0.3 ± 1.4 mm). The average thickness of the MUG500+ implants was 2.9 ± 1.0 mm, significantly thinner than the intact skull thickness (relative difference of 2.9 ± 1.2 mm). Rim transitions in the clinical implants (average width of 8.3 ± 3.4 mm) were used to cap and create a smooth boundary with the skull. CONCLUSIONS: For implant modelers or manufacturers, this shape analysis quantified differences of cranial implants (thickness, rim width, surface area, and volume) to help guide future automated design algorithms. After skull completion, a thicker implant can be more versatile for cases involving muscle hollowing or thin skulls, and wider rims can smooth over the defect margins to provide more stability. For clinicians, the differing measurements and implant designs can help inform the options available for their patient specific treatment.

Customised pre-operative cranioplasty to achieve maximal surgical resection of tumours with osseous involvement-a case series.

PURPOSE: Surgical resection with bony margins would be the treatment of choice for tumours with osseous involvement such as meningiomas and metastasis. By developing and designing pre-operative customised 3D modelled implants, the patient can undergo resection of meningioma and repair of bone defect in the same operation. We present a generalisable method for designing pre-operative cranioplasty in patients to repair the bone defect after the resection of tumours. MATERIALS AND METHODS: We included six patients who presented with a tumour that was associated with overlying bone involvement. They underwent placement of customised cranioplasty in the same setting. A customised implant using a pre-operative imaging was designed with a 2-cm margin to allow for any intra-operative requirements for extending the craniectomy. RESULTS: Six patients were evaluated in this case series. Four patients had meningiomas, 1 patient had metastatic breast cancer on final histology, and 1 patient was found to have an intra-osseous arteriovenous malformation. Craniectomy based on margins provided by a cutting guide was fashioned. After tumour removal and haemostasis, the cranioplasty was then placed. All patients recovered well post-operatively with satisfactory cosmetic results. No wound infection was reported in our series. CONCLUSION: Our series demonstrate the feasibility of utilising pre-designed cranioplasty for meningiomas and other tumours with osseous involvement. Following strict infection protocols, minimal intra-operative handling/modification of the implant, and close follow-up has resulted in good cosmetic outcomes with no implant-related infections.

Predicting the optimal concentration of remifentanil for skull pin fixation with hemodynamic and analgesia nociception index monitoring.

Inadequate antinociception during skull pin fixation may cause hemodynamic instability in intracranial surgery. The optimal concentration of remifentanil to provide adequate antinociception and stable hemodynamics during skull pin fixation under analgesia nociception index monitoring is unknown. This study is to assess the 90% effective concentration of remifentanil for skull pin fixation under hemodynamic and analgesia nociception index monitoring. Twenty-six patients were enrolled for intracranial surgery, anesthesia was induced and maintained under total intravenous anesthesia using target-controlled infusion for remifentanil and propofol under analgesia nociception index and bispectral index monitoring. Skull pin fixation was performed at different effect-site concentrations of remifentanil required for Dixon's up-and-down method with a step size of 0.5 ng/ml under bispectral index 40-60. Inadequate antinociception is defined when either ANI < 30 or > 20% in hemodynamic changes from baseline (e.g. heart rate > 100 beats/min, or blood pressure > 180/100 mmHg) and the effect-site concentration of remifentanil is considered as failure. It is considered success as ANI > 30 and < 20% hemodynamic changes from baseline simultaneously. Seven pairs of failure/success were used for probit analysis. The 90% effective concentration of remifentanil for skull pin fixation with adequate antinociception and hemodynamic stability was 4.7 ng/ml.

Early detection of aseptic bone necrosis post-cranioplasty: A retrospective CT analysis using Hounsfield units.

This study examined the efficacy of computed tomography (CT)-based Hounsfield units (HU) as early predictors of aseptic bone necrosis, a serious post-cranioplasty complication after autologous cranioplasty. In total, 100 patients who underwent decompressive craniectomy and subsequent autologous cranioplasty were included. The radiodensity of the bone flap was evaluated in HU from CT scans at five follow-up timepoints. HU thresholds were established to predict the development of aseptic bone necrosis. HU demonstrated a declining trend throughout the follow-up period in all patients. Necrosis type I patients showed significant differences at all timepoints from 3 months post-procedure onwards, while necrosis type II patients displayed a significant decline in HU at every follow-up. Optimal thresholds with cut-off A (91.23% of initial HU) and cut-off B (78.73% of initial HU) were established to predict the occurrence of bone necrosis and the need for artificial bone replacement, respectively. Our findings demonstrated the utility of CT-based HU measurements as a simple, non-invasive tool for the early prediction of aseptic bone necrosis following autologous cranioplasty. By delineating specific HU thresholds, our study offers a valuable guide for orchestrating timely follow-ups and advising patients on the necessity of proactive interventions.

Soft-tissue, non-osteogenic distraction of the mandible and lower face in bilateral hemifacial microsomia-technical report.

The aim of this study is to present a sequential strategy of soft-tissue, non-osteogenic distraction with a novel device, followed by microvascular bony reconstruction for severe cases of mandibular hypoplasia. The case of a 21-year-old woman with Goldenhar syndrome is presented, whose mandible remained severely hypoplastic despite previous attempts at distraction and was not suitable for further osteogenic distraction. Soft tissue deficiency and pin track scarring prevented free fibular transfers. A personalized distractor, anchored to the cranium and the mandibular symphysis, was designed to expand the soft tissues while allowing for physiological temporomandibular joint (TMJ) movement without compression forces. Internal distractors were placed along the osteotomies to prevent condylar luxation. After completion of the soft tissue distraction, the native mandible was resected except for the condyles and reconstructed with two free fibula flaps. This report represents the proof of concept of a sequential approach to severe lower face soft-tissue and bone deficiency, which preserves TMJ function and avoids the transfer of poorly matched skin to the face.

Comprehensive functional outcome analysis and importance of bone remodelling on personalized cranioplasty treatment using Poly(methyl methacrylate) bone flaps.

Cranioplasty involves the surgical reconstruction of cranial defects arising as a result of various factors, including decompressive craniectomy, cranial malformations, and brain injury due to road traffic accidents. Most of the modern decompressive craniectomies (DC) warrant a future cranioplasty surgery within 6-36 months. The conventional process of capturing the defect impression and polymethyl methacrylate (PMMA) flap fabrication results in a misfit or misalignment at the site of implantation. Equally, the intra-operative graft preparation is arduous and can result in a longer surgical time, which may compromise the functional and aesthetic outcomes. As part of a multicentric pilot clinical study, we recently conducted a cohort study on ten human subjects during 2019-2022, following the human ethics committee approvals from the participating institutes. In the current study, an important aspect of measuring the extent of bone remodelling during the time gap between decompressive craniectomy and cranioplasty was successfully evaluated. The sterilised PMMA bone flaps were implanted at the defect area during the cranioplasty surgery using titanium mini plates and screws. The mean surgery time was 90 ± 20 min, comparable to the other clinical studies on cranioplasty. No signs of intra-operative and post-operative complications, such as cerebrospinal fluid leakage, hematoma, or local and systemic infection, were clinically recorded. Importantly, aesthetic outcomes were excellent for all the patients, except in a few clinical cases, wherein the PMMA bone flap was to be carefully customized due to the remodelling of the native skull bone. The extent of physiological remodelling was evaluated by superimposing the pre-operative and post-operative CT scan data after converting the defect morphology into a 3D model. This study further establishes the safety and efficacy of a technologically better approach to fabricate patient-specific acrylic bone flaps with improved surgical outcomes. More importantly, the study outcome further demonstrates the strategy to address bone remodelling during the patient-specific implant design.

Comparison of different bone substitutes in the repair of rat calvaria critical size defects: questioning the need for alveolar ridge presentation.

OBJECTIVE: This study aimed to evaluate the effectiveness of biomaterials in bone healing of critical bone defects created by piezoelectric surgery in rat calvaria. METHOD AND MATERIALS: Histomorphologic analysis was performed to assess bone regeneration and tissue response. Fifty animals were randomized into five groups with one of the following treatments: Control group (n = 10), spontaneous blood clot formation with no bone fill; BO group (Bio-Oss, Geistlich Pharma; n = 10), defects were filled with bovine medullary bone substitute; BF group (Bonefill, Bionnovation; n = 10), defects were filled with bovine cortical bone substitute; hydroxyapatite group (n = 10), defects were filled with hydroxyapatite; calcium sulfate group (n = 10), defects were filled with calcium sulfate. Five animals from each group were euthanized at 30 and 45 days. The histomorphometry calculated the percentage of the new bone formation in the bone defect. RESULTS: All data obtained were evaluated statistically considering P < .05 as statistically significant. The results demonstrated the potential of all biomaterials for enhancing bone regeneration. The findings showed no statistical differences between all the biomaterials at 30 and 45 days including the control group without bone grafting. CONCLUSION: In conclusion, the tested biomaterials presented an estimated capacity of osteoconduction, statistically nonsignificant between them. In addition, the selection of biomaterial should consider the specific clinical aspect, resorption rates, size of the particle, and desired bone healing responses. It is important to emphasize that in some cases, using no bone filler might provide comparable results with reduced cost and possible complications questioning the very frequent use of ridge presentation procedures.

The transition from cranial surgery to neurosurgery in East London, 1760-1960.

The emergence of neurosurgery from the practice of cranial surgery between the eighteenth and the twentieth centuries in London, UK, is well documented, including the role of Sir Victor Horsley, the first neurosurgical appointee at the National Hospital Queen Square in 1886. The process of this transition elsewhere in London and the subsequent foundation of other neurosurgical units are less well described. In East London, the status of St. Bartholomew's Hospital (Barts) as the oldest London hospital still active on its original site and its comprehensive archives allow an unusually long history of surgical practice in the specialty to be studied. Using these archives and other primary and secondary sources, this article describes the transition of cranial surgery in East London from the general surgeons, limited to the treatment of brain and skull injury, to the specialized discipline of neurosurgery. We discuss the culmination of this process in the foundation of three neurosurgical units at London Hospital, Whitechapel, by Sir Hugh B. Cairns from 1927; at Barts Hospital, Smithfield, by John E. A. O'Connell from 1937; and at Oldchurch Hospital, Romford, by Leslie C. Oliver from 1945. Two modern neurosurgical units, in Whitechapel and Romford, have taken forward the work begun by this group.

Exploring complications following cranioplasty after decompressive hemicraniectomy: A retrospective bicenter assessment of autologous, PMMA and CAD implants.

Cranioplasty (CP) after decompressive hemicraniectomy (DHC) is a common neurosurgical procedure with a high complication rate. The best material for the repair of large cranial defects is unclear. The aim of this study was to evaluate different implant materials regarding surgery related complications after CP. Type of materials include the autologous bone flap (ABF), polymethylmethacrylate (PMMA), calcium phosphate reinforced with titanium mesh (CaP-Ti), polyetheretherketone (PEEK) and hydroxyapatite (HA). A retrospective, descriptive, observational bicenter study was performed, medical data of all patients who underwent CP after DHC between January 1st, 2016 and December 31st, 2022 were analyzed. Follow-up was until December 31st, 2023. 139 consecutive patients with a median age of 54 years who received either PMMA (56/139; 40.3%), PEEK (35/139; 25.2%), CaP-Ti (21/139; 15.1%), ABF (25/139; 18.0%) or HA (2/139; 1.4%) cranial implant after DHC were included in the study. Median time from DHC to CP was 117 days and median follow-up period was 43 months. Surgical site infection was the most frequent surgery-related complication (13.7%; 19/139). PEEK implants were mostly affected (28.6%; 10/35), followed by ABF (20%; 5/25), CaP-Ti implants (9.5%; 2/21) and PMMA implants (1.7%, 1/56). Explantation was necessary for 9 PEEK implants (25.7%; 9/35), 6 ABFs (24.0%; 6/25), 3 CaP-Ti implants (14.3%; 3/21) and 4 PMMA implants (7.1%; 4/56). Besides infection, a postoperative hematoma was the most common cause. Median surgical time was 106 min, neither longer surgical time nor use of anticoagulation were significantly related to higher infection rates (p = 0.547; p = 0.152 respectively). Ventriculoperitoneal shunt implantation prior to CP was noted in 33.8% (47/139) and not significantly associated with surgical related complications. Perioperative lumbar drainage, due to bulging brain, inserted in 38 patients (27.3%; 38/139) before surgery was protective when it comes to explantation of the implant (p = 0.035). Based on our results, CP is still related to a relatively high number of infections and further complications. Implant material seems to have a high effect on postoperative infections, since surgical time, anticoagulation therapy and hydrocephalus did not show a statistically significant effect on postoperative complications in this study. PEEK implants and ABFs seem to possess higher risk of postoperative infection. More biocompatible implants such as CaP-Ti might be beneficial. Further, prospective studies are necessary to answer this question.

Giant Congenital Hemangioma of the Skull: Prenatal Diagnosis and Multimodal Endovascular and Surgical Management.

Introduction: calvarial capillary hemangiomas are vascular tumors rarely seen in newborns. Differential diagnosis may be not straightforward on imaging studies and the management depends on patient and lesion characteristics. Case report: we present the case of a large congenital intracranial extra-axial lesion detected by routine prenatal US screening, a giant calvarial congenital hemangioma, treated with a multimodal strategy. Neonatal MR showed a hemorrhagic solid lesion, causing compression of brain tissue. Conservative treatment was attempted, but a one-month follow-up MR showed growth of the lesion with increased mass effect. Pre-operative endovascular embolization and surgical resection were performed. The pathology was consistent with intraosseous capillary hemangioma. The post-operative course was uneventful. At the 8-month follow-up, the patient had no clinical deficits and MR showed complete resection of the lesion. At the 13-month follow-up, the patient was asymptomatic, showing normal neurological examination and psychophysical development. Conclusions: although wait-and-see policy is feasible for small and asymptomatic lesions, radical resection is indicated when the mass is large, thus causing severe mass effect on the brain. Hypervascularization of the tumor may be responsible for hemorrhagic complications and severe anemia. On these grounds, endovascular treatment is feasible and effective to reduce hemorrhagic complications.

Endoscopy-Assisted Craniosynostosis Surgery Versus Cranial Vault Remodeling for Non-Syndromic Craniosynostosis: Experience of a Single Center.

AIM: To evaluate and compare open cranial vault remodeling (OCVR) and endoscopy-assisted craniosynostosis surgery (EACS) in patients with non-syndromic craniosynostosis and to develop an algorithm to determine the most appropriate surgery for each patient. MATERIAL AND METHODS: Eighty-five children with craniosynostosis who underwent surgery between 2010 and 2022 were retrospectively analyzed. Demographic data, comorbidities, and peri-operative findings of the patients were recorded. Pre- and post-operative comparisons were made between predetermined measurement techniques for each deformation. In addition, measurements were obtained by computed tomography (CT) or 3D stereophotogrammetric (3DSPG) methods from eligible patients and compared with one another. RESULTS: In our study, 61 patients underwent EACS, whereas 24 underwent OCVR. The operating time of OCVR was approximately 54.4 minutes longer than that of EACS (p < 0.001). The intra-operative blood loss was around 139 ml higher in OCVR (p < 0.001). The length of hospital stay for patients who underwent EACS was shorter at 8.4 days on average (p < 0.001). Surprisingly, 5 complications were observed in OCVR compared with 7 in EACS. While the cosmetic outcome of EACS was superior in most of the pathologyspecific measurement techniques, the metopic index increased only in patients with metopic synostosis after both surgical operations. Still, this increase was lower in EACS than in OCVR. CONCLUSION: This study suggests that endoscopic craniosynostosis surgery has lower estimated blood loss and operation and hospitalization times, as well as comparable cosmetic results compared with open vault surgeries on long-term follow-up. CT and 3DSPG methods can help distinguish between different types of measurement techniques for synostoses. However, no significant differences were found in the comparisons since 3DSPG can also provide reliable measurements comparable to those on CT during follow-up.

Skull and Scalp En-Bloc Harvest Protects Calvarial Perfusion: A Cadaveric Study.

BACKGROUND: Calvarial defects are severe injuries that can result from a wide array of etiologies. Reconstructive modalities for these clinical challenges include autologous bone grafting or cranioplasty with biocompatible alloplastic materials. Unfortunately, both approaches are limited by factors such as donor site morbidly, tissue availability, and infection. Calvarial transplantation offers the potential opportunity to address skull defect form and functional needs by replacing "like-with-like" tissue but remains poorly investigated. METHODS: Three adult human cadavers underwent circumferential dissection and osteotomy to raise the entire scalp and skull en-bloc. The vascular pedicles of the scalp were assessed for patency and perfused with color dye, iohexol contrast agent for computed tomography (CT) angiography, and indocyanine green for SPY-Portable Handheld Imager assessment of perfusion to the skull. RESULTS: Gross changes were appreciated to the scalp with color dye, but not to bone. CT angiography and SPY-Portable Handheld Imager assessment confirmed perfusion from the vessels of the scalp to the skull beyond midline. CONCLUSION: Calvarial transplantation may be a technically viable option for skull defect reconstruction that requires vascularized composite tissues (bone and soft tissue) for optimal outcomes.

Fully immersive virtual reality for skull-base surgery: surgical training and beyond.

PURPOSE: A virtual reality (VR) system, where surgeons can practice procedures on virtual anatomies, is a scalable and cost-effective alternative to cadaveric training. The fully digitized virtual surgeries can also be used to assess the surgeon's skills using measurements that are otherwise hard to collect in reality. Thus, we present the Fully Immersive Virtual Reality System (FIVRS) for skull-base surgery, which combines surgical simulation software with a high-fidelity hardware setup. METHODS: FIVRS allows surgeons to follow normal clinical workflows inside the VR environment. FIVRS uses advanced rendering designs and drilling algorithms for realistic bone ablation. A head-mounted display with ergonomics similar to that of surgical microscopes is used to improve immersiveness. Extensive multi-modal data are recorded for post-analysis, including eye gaze, motion, force, and video of the surgery. A user-friendly interface is also designed to ease the learning curve of using FIVRS. RESULTS: We present results from a user study involving surgeons with various levels of expertise. The preliminary data recorded by FIVRS differentiate between participants with different levels of expertise, promising future research on automatic skill assessment. Furthermore, informal feedback from the study participants about the system's intuitiveness and immersiveness was positive. CONCLUSION: We present FIVRS, a fully immersive VR system for skull-base surgery. FIVRS features a realistic software simulation coupled with modern hardware for improved realism. The system is completely open source and provides feature-rich data in an industry-standard format.