Skull Defects Research Articles

Large aplasia cutis congenita of the vertex conservative management.

Aplasia cutis congenita (ACC) of the vertex with bone defect is a rare and begnin anomaly that can involve the epidermis, dermis, and subcutaneous tissues of the scalp with significant bone defect Bajpai and Pal (J Pediatr Surg 38(2):e4, 2003). When associated with skull defect, this rare malformation carries the risk of severe complications such as rupture of the superior sagittal sinus or infections. We report a case of aplasia cutis congenita of the scalp with skull defect measuring 9 × 10cm and an exposed sagittal sinus in a newborn. Both conservative and surgical methods have been proposed to treat this condition. In our case, conservative treatment was planned led to complete epithelization and the patient was healing well at 5years of follow-up. ACC of the vertex with a large scalp defects present a management dilemma Rocha et al. (Clin Case Rep 3(10):841-4, 2015). Based on a review of the literature, we report this case to demonstrate that even for the largest skin and bone defects, an initial conservative approach may allow for complete wound closure without the need for early surgical intervention.

Optimized high-definition tDCS in patients with skull defects and skull plates.

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

Berberine-Encapsulated Poly(lactic-co-glycolic acid)-Hydroxyapatite (PLGA/HA) Microspheres Synergistically Promote Bone Regeneration with DOPA-IGF-1 via the IGF-1R/PI3K/AKT/mTOR Pathway.

Polymer microspheres have recently shown outstanding potential for bone tissue engineering due to their large specific surface area, good porosity, injectable property, good biocompatibility, and biodegradability. Their good load-release function and surface modifiability make them useful as a carrier of drugs or growth factors for the repair of bone defects in irregularly injured or complex microenvironments, such as skull defects. In this study, berberine (BBR)-encapsulated poly(lactic-co-glycolic acid) (PLGA)/hydroxyapatite (HA) microspheres were fabricated using electrified liquid jets and a phase-separation technique, followed by modification with the 3,4-hydroxyphenalyalanine-containing recombinant insulin-like growth-factor-1 (DOPA-IGF-1). Both the BBR and the IGF-1 exhibited sustained release from the IGF-1@PLGA/HA-BBR microspheres, and the composite microspheres exhibited good biocompatibility. The results of the alkaline phosphatase (ALP) activity assays showed that the BBR and IGF-1 in the composite microspheres synergistically promoted the osteogenic differentiation of MC3T3-E1 cells. Furthermore, it was confirmed that immobilized IGF-1 enhances the mRNA expression of an osteogenic-related extracellular matrix and that BBR accelerates the mRNA expression of IGF-1-mediated osteogenic differentiation and cell mineralization. Further cellular studies demonstrate that IGF-1 could further synergistically activate the IGF-1R/PI3K/AKT/mTOR pathway using BBR, thereby enhancing IGF-1-mediated osteogenesis. Rat calvarial defect repair experiments show that IGF-1@PLGA/HA-BBR microspheres can effectively promote the complete bony connection required to cover the defect site and enhance bone defect repair. These findings suggest that IGF-1@PLGA/HA-BBR composite microspheres show a great potential for bone regeneration.

Biomimetic Polyphenolic Scaffolds with Antioxidative Abilities for Improved Bone Regeneration.

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

Results of cranioplasty using individual titanium implants

Background. Despite its long history, cranioplasty remains a topical problem of neurosurgery, due to the increasing number of traumatic brain injury, the consequences of which are the main driver in preserving the population of patients with postcranioectomy skull defects. As a rule, these defects are extensive, and the use of individual implants in these cases is the method of choice. Over the past 5 years, the use of products created by medical additive manufacturing has increased, in this regard, the assessment of long-term results of surgical interventions with their use is an actual issue of modern medicine.Aim. To evaluate the results of surgical treatment of patients with skull defects of various etiologies using individual titanium implants made by three-dimensional printing.Materials and methods. The study analyzed 94 cases of cranioplasty using individual titanium implants made by three-dimensional printing using DMLS (Direct Metal Laser Sintering) technology. The minimum follow-up period was 12 months from the moment of the intervention. Traumatic brain injury and its consequences was the dominant cause of skull bone defects (n = 56, 59.6 %). The average area of defects in the study group was 99.2 ± 43.4 cm2. For men (n = 53), this parameter corresponded to 106.7 ± 44.7 cm2, for women (n = 41) – 89.5 ± 40.1 cm2.Results. The total number of complications in the study group was 12 (12.7 %) cases, of which 5 (5.3 %) cases were recorded during the in hospital stay of patients, 7 (7.4 %) – during outpatient follow-up. One complication was not related to the performed surgical intervention. Removal of the implant was required in 7 (7.4 %) cases. The terms of implant removal varied from 0 to 14 months from the moment of the performed intervention. The survival rate of individual titanium implants for more than 12 months was 92.6 %.Conclusion. The data on the presence of complications after cranioplasty vary from study to study, while the results of reconstructive interventions performed using individual titanium implants are of significant interest, the use of which has increased significantly over the past five years due to the introduction of additive medical production into clinical practice.

AuNP-Loaded Electrospinning Membrane Cooperated with CDs for Periodontal Tissue Engineering.

Guided bone regeneration (GBR) is commonly used to regenerate periodontal tissue. However, the bone inductivity and antibacterial properties of the GBR membranes currently in use are severely limited. This issue can be resolved by loading growth factors and antibiotics. Bioactive substitutes, such as Aunanoparticles (AuNPs) and carbon quantum dots (CDs), were proposed to prevent the denaturation of osteogenic growth factors and the induction of antibacterial drug resistance. Ornidazole was initially used as the raw material to prepare the CDs, followed by the incorporation of an optimal ratio of nanoparticles to produce the electrospun membrane doped with AuNPs and novel traceable antibacterial CDs. The morphology of the membrane was characterized. The adhesion, proliferation, and osteogenic differentiation of cells on the membrane were evaluated in vitro. The antimicrobial characteristics of the membrane were also investigated. The electrospun membrane was implanted into a rat skull defect model in vivo to investigate its osteogenic potential. The blending of nanomaterials did not affect the micro morphology of the fiber, resulting in enhanced mechanical properties. Membranes dopedwith AuNPs and CDs exhibited excellent biocompatibility, increased ALP activity, improved calcified nodules, and increased expression of osteogenic-associated proteins, in addition to pronounced antibacterial effects. The membrane also demonstrated excellent osteogenic characteristics in rat models. The synergistic effect of loaded AuNPs electrospun fiber membrane with CDs can promote periodontal bone regeneration and exert antibacterial activity.

Nondestructive and high-resolution monitoring of inflammation-type skull defects regeneration on adult zebrafish with optical coherence tomography.

Optimized animal models and effective imaging techniques are exceedingly important to study cranial defects in bone loss due to chronic inflammation. In this study, the assessment procedure on a zebrafish inflammation-type skull defects model was monitored in vivo with spectral-domain optical coherence tomography (SD-OCT), and the efficacy of etidronate disodium in bone regeneration was assessed. An acute skull defect injury model was established in adult zebrafish using a stereotaxic craniotomy device. SD-OCT imaging was performed immediately following the mechanical injury. Both SD-OCT and immunohistochemistry results demonstrated an increase in inflammation-induced skull destruction within 5 days, which was confirmed by pathological experiments.

Comparative evaluation of accuracy of cranial prosthesis designed by four different workflow protocols analysed by software

Cranioplasty aims to reconstruct skull defects from tumours, congenital anomalies, decompressive craniectomies, and fractures in a cosmetically acceptable manner. Since the 1970s, polymethyl methacrylate (PMMA) prostheses have been manually prefabricated using a variety of techniques. However, more recent computer-aided design and computer-aided manufacturing (CAD/CAM) techniques appear to have eclipsed these older methods. These techniques essentially involve using imaging from the patient's cranial defect and prefabricating the PMMA prosthesis using a 3D printer. The traditional methods for producing prostheses require a number of intricate stages, can be extremely stressful for the patient, and their success depends on the expertise of the maxillofacial team. Although there have been advances in digital fabrication for prosthetics, there are still some constraints that prevent a full transition to digital fabrication for the final stages of prosthesis construction. Advance training and modification of current treatment procedures are required due to the introduction of new technologies and methods in the field of maxillofacial prosthodontics. The aim of this study is to compare and evaluate the accuracy of cranial prosthesis designed by conventional, digital and two hybrid workflows We will report on 10 consecutive patients who have undergone cranioplasty surgery or had trauma for an extensive skull defect. The final prosthesis will be analyzed using the software CloudCompare for its accuracy by using reverse engineering principle. The purpose of this research is to develop a hybrid protocol for fabricating a prosthesis that is both cost-effective and more dimensionally accurate than its conventional counterpart, thereby providing ease for both the patient and the maxillofacial team.

Polysaccharide-Based Composite Hydrogel with Hierarchical Microstructure for Enhanced Vascularization and Skull Regeneration.

Critical-size skull defects caused by trauma, infection, and tumor resection raise great demands for efficient bone substitutes. Herein, a hybrid cross-linked hierarchical microporous hydrogel scaffold (PHCLS) was successfully assembled by a multistep procedure, which involved (i) the preparation of poly(lactic-co-glycolic)/nanohydroxyapatite (PLGA-HAP) porous microspheres, (ii) embedding the spheres in a solution of dopamine-modified hyaluronic acid and collagen I (Col I) and cross-linking via dopamine polyphenols binding to (i) Col I amino groups (via Michael addition) and (ii) PLGA-HAP (via calcium ion chelation). The introduction of PLGA-HAP not only improved the diversity of pore size and pore communication inside the matrix but also greatly enhanced the compressive strength (5.24-fold, 77.5 kPa) and degradation properties to construct a more stable mechanical structure. In particular, the PHCLS (200 mg, nHAP) promoted the proliferation, infiltration, and angiogenic differentiation of bone marrow mesenchymal stem cells in vitro, as well as significant ectopic angiogenesis and mineralization with a storage modulus enhancement of 2.5-fold after 30 days. Meanwhile, the appropriate matrix microenvironment initiated angiogenesis and early osteogenesis by accelerating endogenous stem cell recruitment in situ. Together, the PHCLS allowed substantial skull reconstruction in the rabbit cranial defect model, achieving 85.2% breaking load strength and 84.5% bone volume fractions in comparison to the natural cranium, 12 weeks after implantation. Overall, this study reveals that the hierarchical microporous hydrogel scaffold provides a promising strategy for skull defect treatment.

Chiari Malformation (CM) type III surgical management in infant: a case report

Background: Chiari Malformations (CM) is a collection of hindbrain abnormalities ranging from simple to complete agenesis of the cerebellum. Type III CM (CM III) is the rarest CM, with herniation of the cerebellum and brainstem into a posterior encephalocele and other intracranial anomalies. Reduction of the viable herniated brain, along with providing intracranial space and inadequate closure, often presents as the main problem. This case study aims to evaluate the Chiari malformation type III surgical management in infants. Case Presentation: A 16-day-old male infant with an intact congenital mass in the occipital, with no neurological deficit. Radiological examination shows a defect in the occipital skull consisting of cystic non-contrast enhancing lesion and parenchymal tissue herniated through the defect. The cele excision and defect closure were performed, and viable neural tissue was found inside the sac. Blossom flower-like trim expanded the fossa posterior space and put the viable neural tissue inside the intracranial room. The defect was then closed with a dura, periosteal patch, and tension-free two-layered scalp closure. Post-operative follow-up presented a good outcome, and 1-year follow-up showed good recovery, with developmental delay, following developmental rehabilitation. Conclusion: CM III is rare and has poor outcomes because neurological deficits and respiratory problems usually follow it. Operative management patient with CM III was presented with occipital encephalocele with no post-operative complication. Occipital bone reconstruction using a blossomed-flower-like technique could be considered to create adequate room for viable neural tissue.

Electrospun sandwich mesh structures loaded with naringenin and vitamin K2 polycaprolactone/gelatin nanofibers synergistically promote bone regeneration

Osteoblasts and osteoclasts play a crucial role in the dynamically coupled balance during bone regeneration and remodeling. They complement and restrict each other in the human body. Decreased osteoblasts lead to insufficient bone formation or excessive formation of osteoclasts, leading to increased bone resorption, which will destroy the structure of the bone tissue. This will greatly increase the risk of diseases such as osteoporosis and nonunions caused by bone defects.Herein, gelatin and polycaprolactone were used as substrates, and biomaterial membranes with mesh and sandwich structures were constructed using the electrospinning technology. Naringenin was loaded into the shell, and vitamin K2 was loaded into the core layer of the nanofibrous membrane. The biocompatibility and osteogenic capacity of the membranes were assessed in vitro using mouse bone marrow mesenchymal stem cells (BMSCs). During osteoclast induction, the receptor activator of nuclear factor kappa-Β ligand (RANKL) was used to coculture RAW264.7 cells with various materials. The regulatory effect of various membranes on osteoclast growth was evaluated by detecting the expression levels of osteoclast-related genes and proteins in the cells.Subsequently, we constructed a model of a rat skull defect and implanted different membranes into the defect. Then, we evaluated the new bone formation in the defect using histological staining and micro-computed tomography after 4 and 8 weeks. The results of in vitro experiments confirmed that the incorporation of naringenin and vitamin K2 stimulated the expression of osteogenesis-related genes and the secretion of osteogenesis-related proteins. Simultaneously, the results showed that naringenin and vitamin K2 inhibited the formation and growth of osteoclasts. Therefore, naringenin and vitamin K2 have a synergistic effect in promoting bone growth and regulating osteoclast growth.

Giant Occipital Encephalocele: Literature Review and Illustrative Case

Background: Encephalocele is defined as a herniation of the neural tube due to skull defect. anterior encephaloceles are common in males while the occipital form occurs in females. We present in this article a case of a giant occipital encephalocele and provide a literature review on the subject. Case description: We report a case of 8 months old female, the third child of a family of 3 children with notion of consanguinity of third degree, the mother had no notion of taking medication during pregnancy, this one was followed to term. the delivery was by caesarean section. on the clinical examination the infant mobilizes the 4 limbs, no sensitive or motor deficits, no occulomotor disorders, cranial perimeter at 37 cm, the general examination does not find any other malformations. we operated the patient with ablation of the encephalocele, the postoperative continuations were simple, the evolution was marked by the stability of the cranial perimeter, and the infant was hospitalized for 5 days, then declared out with a good postoperative evolution. Conclusion: Occipital encephalocele is considered as a very common form of neural tube defect the diagnosis is based on neuroimaging techniques; we believe that its Management includes full investigations for optimum surgical plan.

CASE OF GALVANIC SYNDROME AFTER CRANIOPLASTY BY A TITANIUM IMPLANT WITH DEVELOPMENT OF NEOOSTEOGENESIS CELLS OF THE SKULL BONES

There was a constant searing pain in the right side of the head and a face that was not buying analgesics in a 61-year-old woman, after surgery in 2018 to remove a meningioma in the right frontal lobe followed by a cranioplasty titanium implant. Evaluation of immune status revealed that the allergological test for titanium was positive. According to the results of the MR-study of data for continued growth of the tumor, as well as signs of vasonary conflict of the trigeminal nerve.The possible development of the galvanic syndrome in patient has been suggested. Thus, the decision to remove the titanium implant has been made. During the operation, the presence of galvanic current (from 3–46 μA) on the titanium plate surface was documented and instrumentally confirmed.Under the titanium implant during the operation, ectopic foci of neoosteogenesis were visualized. The condition improved in the form of a complete regression of pain syndrome after removing the titanium implant.The present clinical case is the world’s first description of the development of galvanic syndrome on the surface of titanium cranioplastic mesh. The presence of electroplating repair of bone tissue can be a new step in solving the problem of closing skull defects in neurosurgical patients.

Mechanical behaviour of reconstructed defected skull with custom PEEK implant and Titanium fixture plates under dynamic loading conditions using FEM

Skull reconstruction using cranial implants is often required for repairing skull defects caused due to trauma, diseases, or malignancy to protect intracranial structures. For relieving Intracranial Pressure (ICP) surgeons restore cranial defects either using natural bones or fabricated custom cranial implants. With the increase in Traumatic Brain Injuries (TBI) and challenges faced by TBI patients to regain normalcy, it is imperative to analyse the mechanical behaviour of skull-implant assemblies under some Head Injury Criteria (HIC). Medical grade materials including Titanium Alloys (Ti-6Al-4V) and Polyether-ether-ketone (PEEK) are used by fabricating Patient-Specific Implants (PSI) manufactured using 3D imaging, modelling and printing techniques. 3D technologies are preferred over conventional manufacturing methods, as they enable fabrication of custom shapes, sizes and properties for these PSI.For an effective attachment of PSI with a defective skull, a stable joint and plate arrangement as fixture plates is necessary at their interface. These fixtures can have variable numbers, design shapes, materials and location arrangements.This paper presents the Finite Element Method/Analysis (FEM/FEA) study of PSI attached to a defected skull for reconstruction, with linear shaped fixture configuration, when subjected to an external dynamic loading at 5 m/s, strain rate of 10s−1 to 243s−1 and ICP of 15mm Hg from three sides of the skull faces. Three different materials as Neoprene (soft), Concrete (medium rigid) and E-Glass (highly rigid) have been used, in the form of a rectangular thin cuboidal wall structure, at an angle of 45° with the skull face. Four linear shaped fixture plates which were simplest to design, were used to attach the PSI-skull assembly, to ensure that weight of the PSI-fixation assembly on the patient remains minimal, overall assembly has symmetrical fixations and efforts required by a surgeon for fitment of these plates remain minimal. Placement of these fixture plates has been optimized to encompass the complete PSI-skull interface section, due to which the stresses within all the assembly components (PSI, fixture plate and skull) reduced by nearly 2.5 times than the initial design and remained within yielding limits, thereby, averting any failure under heavy external dynamic loading.

Towards clinical applicability and computational efficiency in automatic cranial implant design: An overview of the AutoImplant 2021 cranial implant design challenge.

Cranial implants are commonly used for surgical repair of craniectomy-induced skull defects. These implants are usually generated offline and may require days to weeks to be available. An automated implant design process combined with onsite manufacturing facilities can guarantee immediate implant availability and avoid secondary intervention. To address this need, the AutoImplant II challenge was organized in conjunction with MICCAI 2021, catering for the unmet clinical and computational requirements of automatic cranial implant design. The first edition of AutoImplant (AutoImplant I, 2020) demonstrated the general capabilities and effectiveness of data-driven approaches, including deep learning, for a skull shape completion task on synthetic defects. The second AutoImplant challenge (i.e., AutoImplant II, 2021) built upon the first by adding real clinical craniectomy cases as well as additional synthetic imaging data. The AutoImplant II challenge consisted of three tracks. Tracks 1 and 3 used skull images with synthetic defects to evaluate the ability of submitted approaches to generate implants that recreate the original skull shape. Track 3 consisted of the data from the first challenge (i.e., 100 cases for training, and 110 for evaluation), and Track 1 provided 570 training and 100 validation cases aimed at evaluating skull shape completion algorithms at diverse defect patterns. Track 2 also made progress over the first challenge by providing 11 clinically defective skulls and evaluating the submitted implant designs on these clinical cases. The submitted designs were evaluated quantitatively against imaging data from post-craniectomy as well as by an experienced neurosurgeon. Submissions to these challenge tasks made substantial progress in addressing issues such as generalizability, computational efficiency, data augmentation, and implant refinement. This paper serves as a comprehensive summary and comparison of the submissions to the AutoImplant II challenge. Codes and models are available at https://github.com/Jianningli/Autoimplant_II.

Custom-made 3D printing-based cranioplasty using a silicone mould and PMMA

All types of cranioplasty techniques restore the morphology of the skull and affect patient aesthetics. Safe and easy techniques are required to enhance patients’ recovery and the rehabilitation process. We propose a new method of cranioplasty. The 3-dimensional (3D) reconstruction of a thin-layer computed tomography (CT) scan of the skull was used to reflect the intact side onto the defect and subtract the overlapping points from one another. In this way, a 3D model of the planned implant can be built in the required shape and size. The precise fit of the implant can be checked by printing the defective part of the skull in case it can be modified. A sterilisable silicone mould based on the finalized model was created afterwards. Polymethyl methacrylate implants were prepared directly in an aseptic environment in the operating room during surgery. Between 2005 and 2020, we performed 54 cranioplasties on 52 patients whose craniotomies were performed previously for indications of traumatic brain injury, stroke or tumour surgeries. No technical problems were noted during the operations. In 2 cases, septic complications that occurred were not connected to the technique itself, and the implants were removed and later replaced. Our proposed technique based on 3D-printed individual silicone moulds is a reliable, safe, easily reproducible and low-cost method to repair different skull defects.

Can locally applied risedronate be an effective agent when combined with xenografts? An animal study

BackgroundTo examine the effects of local risedronate application with xenografts on healing of rabbit skull defects using histological, histomorphometric, immunohistochemical, and three-dimensional radiological methods.MethodsTwo critical-sized defects with a diameter of 10 mm were created in 16 rabbits and filled with xenogenic bone graft and xenogenic bone graft + 5 mg risedronate in the control I and risedronate (RIS) groups, respectively. Residual graft, new bone, soft tissue areas, and bone volume were evaluated in the 4- and 8-week study groups.ResultsIn both the 4- and 8-week samples, the RIS group samples had significantly higher mean new bone area values than the C group (p < 0.05). In both groups, the values for the new bone area were significantly higher in the 8-week-old samples than in the 4-week-old samples (p < 0.05). The h scores obtained for sialoprotein and osteopontin did not differ significantly between the groups at either time point (p > 0.05). The results of radiological evaluation showed that the bone density value was significantly higher in the C group than in the RIS group at either time point (p < 0.05).ConclusionsAlthough this study aimed to demonstrate the effect of risedronate on the osteoconductive properties of xenografts when applied locally, targeted results could not be achieved.

Human nasal mucosa ectomesenchymal stem cells derived extracellular vesicles loaded omentum/chitosan composite scaffolds enhance skull defects regeneration

Engineered bone tissue that can promote osteogenic differentiation is considered an ideal substitute for materials to heal bone defects. Extracellular vesicle (EV)-based cell-free regenerative therapies represent an emerging promising alternative for bone tissue engineering. We hypothesized that EVs derived from human nasal mucosa-derived ectomesenchymal stem cells (hEMSCs) can promote bone tissue regeneration. Herein, hEMSCs were cultured with osteogenic induction medium or normal medium to generate two types of EVs. We first demonstrated that the two EVs exhibited strong potential to promote rat suture mesenchymal stem cell (SMSC) osteogenesis by transferring TG2 to SMSCs and regulating extracellular matrix (ECM) synthesis. Next, we developed a composite hydrogel made of porcine omentum and chitosan into which EVs were adsorbed to enable the effective delivery of EVs with sustained release kinetics. Implantation of the EV-loaded hydrogels in a critical-size rat cranial defect model significantly promoted bone regeneration. Therefore, we suggest that our hEMSC-derived EV-loading system can serve as a new therapeutic paradigm for promoting bone tissue regeneration in the clinic.

PLGA/BGP/Nef porous composite restrains osteoclasts by inhibiting the NF-κB pathway, enhances IGF-1-mediated osteogenic differentiation and promotes bone regeneration

BackgroundNovel bone substitutes are urgently needed in experimental research and clinical orthopaedic applications. There are many traditional Chinese medicines that have effects on bone repair. However, application of natural medicines in traditional Chinese medicine to bone tissue engineering and its mechanism were rarely reported.ResultsIn this study, the osteogenic ability of bioactive glass particles (BGPs) and the osteogenic and osteoclastic ability of neferine (Nef) were fused into PLGA-based bone tissue engineering materials for bone regeneration. BGPs were prepared by spray drying and calcination. Particles and Nef were then mixed with PLGA solution to prepare porous composites by the phase conversion method. Here we showed that Nef inhibited proliferation and enhanced ALP activity of MC3T3-E1 cells in a dose‐ and time‐dependent manner. And the composites containing Nef could also inhibit RANKL‐induced osteoclast formation (p < 0.05). Mechanistically, the PLGA/BGP/Nef composite downregulated the expression of NFATC1 by inhibiting the NF-κB pathway to restrain osteoclasts. In the other hands, PLGA/BGP/Nef composite was first demonstrated to effectively activate the IGF-1R/PI3K/AKT/mTOR pathway to enhance IGF-1-mediated osteogenic differentiation. The results of animal experiments show that the material can effectively promote the formation and maturation of new bone in the skull defect site.ConclusionsThe PLGA/BGP/Nef porous composite can restrain osteoclasts by inhibiting the NF-κB pathway, enhance IGF-1-mediated osteogenic differentiation and promotes bone regeneration, and has the potential for clinical application.

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

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. 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. 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. Calvarial transplantation may be a technically viable option for skull defect reconstruction that requires vascularized composite tissues (bone and soft tissue) for optimal outcomes.