Reconstruction Of Cranial Bone Defects Research Articles

Overexpression of fibroblast growth factor receptor 2 in bone marrow mesenchymal stem cells enhances osteogenesis and promotes critical cranial bone defect regeneration.

Background: Reconstruction of cranial bone defects is one of the most challenging problems in reconstructive surgery, and several biological tissue engineering methods have been used to promote bone repair, such as genetic engineering of bone marrow mesenchymal stem cells (BMSCs). Fibroblast growth factor receptor 2 (Fgfr2) is an important regulator of bone construction and can be used as a potential gene editing site. However, its role in the osteogenesis process of BMSCs remains unclear. This article clarifies the function of Fgfr2 in BMSCs and explores the role of Fgfr2-overexpressed BMSCs carried by light-induced porous hydrogel (GelMA) in the repair of cranial bone defects. Methods: Lenti-virus was used to overexpress Fgfr2 in BMSCs, and cell counting kit-8, transwell, and flow cytometry assays were conducted to investigate the proliferation, migration, and characteristics. After 0, 3, 7, and 10 days of osteogenic or chondrogenic induction, the changes in osteogenic and chondrogenic ability were detected by real-time PCR, western blot, alkaline phosphatase staining, alizarin Red staining, and alcian blue staining. To investigate the viability of BMSCs carried by GelMA, calcein and propyl iodide staining were carried out as well. Finally, a critical cranial bone defect model was established in 6-week-old male mice and micro-computerized tomography, masson staining, and immunohistochemistry of OCN were conducted to test the bone regeneration properties of implanting Fgfr2-overexpressed BMSCs with GelMA in cranial bone defects over 6 weeks. Results: Overexpression of Fgfr2 in BMSCs significantly promoted cell proliferation and migration and increased the percentage of CD200+CD105+ cells. After osteogenic and chondrogenic induction, Fgfr2 overexpression enhanced both osteogenic and chondrogenic ability. Furthermore, in cranial bone defect regeneration, BMSCs carried by light-induced GelMA showed favorable biocompatibility, and Fgfr2-overexpressed BMSCs induced superior cranial bone regeneration compared to a normal BMSCs group and an untreated blank group. Conclusion: In vitro, Fgfr2 enhanced the proliferation, migration, and stemness of BMSCs and promoted osteogenesis and chondrogenesis after parallel induction. In vivo, BMSCs with Fgfr2 overexpression carried by GelMA showed favorable performance in treating critical cranial bone defects. This study clarifies the multiple functions of Fgfr2 in BMSCs and provides a new method for future tissue engineering.

Clinical and patient-reported outcome after patient-specific 3D printer-assisted cranioplasty

Various cranioplasty techniques exist for the reconstruction of cranial bone defects. Patient-specific implants can be produced in-house using a recently developed 3D printer-assisted cranioplasty technique. However, the resulting cosmetic outcomes from the patient’s perspective are underreported. With our case series, we aim to present the clinical outcome, morbidity rate, patient-reported cosmetic results, and cost-effectiveness of patient-specific3D printer-assisted cranioplasty technique. This is a consecutive retrospective case series of adult patients undergoing cranioplasty using the patient-specific 3D printer-assisted technique. As primary endpoint, the functional outcome based on modified Rankin scale (mRS) at discharge and follow-up was assessed. A prospective telephone survey was conducted to collect and provide patient-reported outcomes. Thirty-one patients underwent patient-specific 3D printer-assisted cranioplasty, mostly to reconstruct frontotemporoparietal (61.3%) and frontotemporal defects with orbital involvement (19.4%). Good functional outcome (mRS ≤ 2) at discharge and during the last follow-up was achieved in 54.8% (n = 17) and 58.1% (n = 18) patients. Overall, the rate of clinically relevant surgery-related complications was 35.5% (n = 11). Postoperative epidural hematoma/collection (16.1%) and infections (12.9%) were the most frequent complications. Permanent morbidity occurred in one patient (3.2%) with postoperative acute ipsilateral vision loss after frontotemporal cranioplasty with orbital involvement. No surgery-related mortality occurred. The mean patient-reported cosmetic satisfaction score was 7.8 ± 1.5, with 80% of patients reporting satisfying or very satisfying cosmetic results. No significant differences were seen between the different defect localization regarding the cosmetic outcome. The mean manufacturing costs of a patient-specific 3D printer-assisted implant ranged from 748 to 1129 USD. Based on our case series, patient-specific 3D printer-assisted cranioplasty is cost-effective and leads to satisfying cosmetic results, especially in large defects and/or defects with complex geometry.

Clinical Applications of Poly-Methyl-Methacrylate in Neurosurgery: The In Vivo Cranial Bone Reconstruction.

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

Pulsed radiofrequency energy device (PEAK plasmablade™) and CustomBone® Cranioplasty: an appealing surgical rendez-vous

Background CustomBone® prosthesis is a widely recognized effective and successful technique for the reconstruction of cranial bone defects. Prior the cranioplasty implant, meticulous dissection within thick scar tissue is required. During this delicate surgical manoeuvre is vital to avoid damage to the skin flap itself and to the underlying cerebrovascular structures. We report our experience and potential applications of a novel, pulsed monopolar radiofrequency energy device (PEAK PlasmaBlade™, Medtronic plc). It reduced the incidence of post operativesubgaleal hematoma, the operative times and the intra operative blood loss following cranioplasty compared to the traditional scalpel and scissor dissection. Methods The authors present a one centre case series study to review the indications, safety and efficacy of the PEAK PlasmaBlade™ in adult patientsunderwent cranioplasty. Two surgical techniques for tissue dissection were compared: PEAK PlasmaBlade™ versus scalpel and scissor dissection (SSD). Treatment outcomes following each of these surgical approaches, relative to rate of post-operative subgalealhematoma formation, hospital admission, and operative times were compared. Results A total of 10 patients that had cranioplasty treatment were evaluated. In patients underwent scalp dissection with the PEAKPlasmaBlade™, we observed a reduction in the operative times, in the subgaleal hematoma formation and then in the hospital stay. Conclusion PEAK PlasmaBlade™ revealed to be a safe and effective device in tissues dissection for cranioplasty implant. It provided reduction of the rate of subgaleal hematoma formation, operating times and less potential risk to damage cerebrovascular structures.

Effects of platelet-rich plasma and carbonated hydroxyapatite combination on cranial defect Bone Regeneration: An animal study

Abstract Background Recently, platelet-rich plasma (PRP) has become popular in the tissue engineering field. PRP has a high concentration of platelets that is three to five times above that of normal plasma and contains several growth factors such as platelet-derived growth factor (PDGF), platelet-derived angiogenesis factor (PDAF), platelet-derived endothelial growth factor (PDEGF), transforming growth factor-beta (TGF-β), insulin-like growth factor (IGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF). Standard reconstruction of cranial bone defects involves the use of auto- or allogenic biomaterial, such as carbonated hydroxyapatite (CHA) as a scaffold for the osteogenesis process. The purpose of this study is to investigate whether any additional compound may improve the bone healing process. Methods This study involved animal experiments on white male rats (Rattus norvegicus). Three millimetre diameter were created in rat cranium. Samples were divided into three groups: first group, the cranial defect was grafted with CHA combined with PRP; second group, with CHA alone; and third group, the defect was left as secondary healing wound (control group). The wound healing process was observed for the presence of inflammatory cells and the occurrence of woven bone and lamellar bone. The results among the groups were compared and analysed by the Mann Whitney test using SPSS Statistics Program Package Version 22.0. Results The experimental group of 2 weeks showed no difference between inflammatory response (p = 0.119), woven bone (p = 0094) and lamellar bone (p = 0130). At 4 weeks, a combination of PRP and CHA showed a superior growth of lamellar bone compared to CHA (p = 0008). Conclusion A combination of PRP and CHA as a bone regeneration scaffold showed a histologically increased bone formation.

Split-Rib Cranioplasty Using a Patient-Specific Three-Dimensional Printing Model.

Split-Rib Cranioplasty Using a Patient-Specific Three-Dimensional Printing Model.

Mineralized collagen biomaterial for reconstruction of cranial bone defects and its clinical applications

Event Abstract Back to Event Mineralized collagen biomaterial for reconstruction of cranial bone defects and its clinical applications Zhiye Qiu1, 2, Tianxi Song2*, Yuqi Zhang3 and Xiumei Wang1 1 Tsinghua University, School of Materials Science and Engineering, China 2 Beijing Allgens Medical Science and Technology Co., Ltd., China 3 Yuquan Hospital, Tsinghua University, Department of Neurosurgery, China Introduction: Cranial bone defects result from congenital malformation, trauma, tumor, as well as produced by trephination in craniotomy are common symptoms in neurosurgery. Such defects should be repaired appropriate methods, in order to provide biomechanical stability for the skull, protect the brain, and achieve cosmetic results. Metals, bioceramics and polymers were tried to be used for repairing cranial defects, however, many disadvantages induced by these materials limited their clinical outcomes[1]. Especially for those pediatric patients with growing cranial bone, titanium mesh or polyetheretherketone restrict the growth of the cranial bone and result in high risk of malformation of the skull. Therefore, a biodegradable and osteoconductive biomaterial is required for the reconstruction of cranial bone defects[2]. Materials and Methods: Mineralized collagen was prepared by an in vitro biomimetic mineralization process. Briefly, calcium and phosphorous salts were added into acidic collagen solution, respectively; then the pH value and temperature were adjusted to form mineralized collagen deposition; after washing and freeze-drying, mineralized collagen biomaterial with the same chemical composition and microstructure to the nature bone matrix was obtained. Such mineralized collagen could be fabricated into many bone grafts, such as burr-hole plug, trepanation gap filling strip, as well as patient specific irregular implant according to CT scanning data of the patient. Phase composition and chemical structure were characterized by XRD and FTIR. Clinical outcomes of cranial bone defect reconstructions were evaluated by plain radiographs and CT scanning at the 6th and 12th month post-operation. Results and Discussion: For each patient, there were no inflammatory responses, itching, or exudation at the surgical sites, and the wounds healed well. The defects implanted with mineralized collagen biomaterials healed well. As shown by Figure 1, bone mineral density gradually increased and approximated surrounding host bone. However, the defects as the blank control without any implants unchanged during the follow-up period. Mineralized collagen is the fundamental structural unit of many connective tissues, including bone, the biomimetic mineralized collagen material therefore has the same chemical composition and microstructure to the natural bone[3]. Animal experiments demonstrated that the mineralized collagen could be gradually substituted by newly regenerated bone tissues. For the reconstruction of cranial bone defect, mineralized collagen biomaterial serves as a scaffold for bone regeneration induced by dura matter. Conclusion: Mineralized collagen biomaterial has good biodegradability and osteoconductivity. Clinical outcomes demonstrated mineralized collagen implants promoted bone reconstruction of cranial defects, without any adverse responses. National Basic Research Program (973 Program) of China (2011CB606205); ‘Twelfth Five-Year’ National Science and Technology Support Program (2012BAI17B02) funded by the Ministry of Science and Technology of China; National Natural Science Foundation of China (21371106, 51402167)

Management of Cranial Bone Defects

Reconstruction of cranial bone defects is one of the most challenging problems in reconstructive surgery. The timing of reconstruction, the location of the defect, the materials to be used, and the medical history of the patient are parameters that have been mostly discussed in the literature. To the best of our knowledge, there has not been any published classification for the cranial bone defect reconstruction according to defect size. Twelve patients underwent reconstruction of cranial vault defects. Cranial bone defects were classified into 3 groups according to the size of the defect. The small-sized group included the defects smaller than 25 cm(2), the medium-sized group included the defects between 25 to 200 cm(2), and the large-sized group included the defects larger than 200 cm(2). The small-sized defects were reconstructed with split calvarial graft, demineralized bone matrix, or hydroxyapatite cement; the medium-sized defects were reconstructed with split calvarial graft or allogenic bone graft; and the large-sized defects were reconstructed with methyl methacrylate, autoclaved bone, or porous polyethylene. Two patients needed revision for irregularities with demineralized bone matrix. Other patients had no skull defects or irregularities for which revision was suggested. We believe that the size of the defect is important for the reconstruction of cranial vault defects and that using a standard algorithm can increase the success rate.

Use of acrylic bone cement for reconstruction of cranial bone defects

Use of acrylic bone cement for reconstruction of cranial bone defects

Reconstruction of Cranial Bone Defects Using Struthio camelus Eggshell

There are many synthetic materials for the treatment of bone defects, which have their own advantages and disadvantages. We aimed to compare the efficacy of ostrich eggshell, which is cheap and easily available, and demineralized bone matrix in healing of cranial bone defects. A full-thickness circular bone defect was created in the frontal bone of 40 Wistar rats. Group 1 was the operative control group. In group 2, demineralized bone matrix applied into the defects; in group 3, Struthio camelus (ostrich) eggshell implants (OSIs) were applied into the defects; and in group 4, ostrich eggshell powders were applied into the defects. Computed tomographic analysis was performed to evaluate the healing of bone defects, the bone density, the OSI area measurements, and the OSI volume and density. At the end of the 24th week, all rats were killed. New bone formation, infection, resorption, and tissue reactions were evaluated. Ostrich eggshell implants were slightly resorbed, integrated with bone, stable, and supplied good cranial completeness. Ostrich eggshell powders were totally resorbed at the sixth month. There were no significant differences between control and ostrich eggshell groups in new bone formation. Ostrich eggshell did not seem to be an osteoproductive material, but it has some important advantages as an implant. Ostrich eggshell has a strong structure, is cheap, is shaped easily, and does not cause tissue reaction or infection. Ostrich eggshell could be a good alternative graft material for craniomaxillofacial procedures. Further studies are required to find out the potential use of the ostrich eggshell in craniomaxillofacial reconstructions.

Reconstruction of Cranial Bone Defects Using a Quick-Setting Hydroxyapatite Cement and Absorbable Plates

Reconstruction of Cranial Bone Defects Using a Quick-Setting Hydroxyapatite Cement and Absorbable Plates

In vivo performance of simvastatin‐loaded electrospun spiral‐wound polycaprolactone scaffolds in reconstruction of cranial bone defects in the rat model

Reconstruction of large bone defects is still a major problem. Tissue-engineering approaches have become a focus in regeneration of bone. In particular, critical-sized defects do not ossify spontaneously. The use of electrospinning is attracting increasing attention in the preparation of tissue-engineering scaffolds. Recently, acellular scaffolds carrying bioactive agents have been used as scaffolds in "in situ" tissue engineering for soft and hard tissue repair. Poly(epsilon-caprolactone) (PCL) with two different molecular weights were synthesized, and the blends of these two were electrospun into nonwoven membranes composed of nanofibers/micropores. To stimulate bone formation, an active drug, "simvastatin" was loaded either after the membranes were formed or during electrospinning. The matrices were then spiral-wound to produce scaffolds with 3D-structures having both macro- and microchannels. Eight-millimeter diameter critical size cranial defects were created in rats. Scaffolds with or without simvastatin were then implanted into these defects. Samples from the implant sites were removed after 1, 3, and 6 months postimplantation. Bone regeneration and tissue response were followed by X-ray microcomputed tomography and histological analysis. These in vivo results exhibited osseous tissue integration within the implant and mineralized bone restoration of the calvarium. Both microCT and histological data clearly demonstrated that the more successful results were observed with the "simvastatin-containing PCL scaffolds," in which simvastatin was incorporated into the PCL scaffolds during electrospinning. For these samples, bone mineralization was quite significant when compared with the other groups.

Reconstruction of Cranial Bone Defects Using a Quick-Setting Hydroxyapatite Cement and Absorbable Plates

We examine the 6-month histology of a quick-setting hydroxyapatite cement (Mimix), with and without absorbable plates (LactoSorb), after placement in critical size defects made in the skull of 20 New Zealand white rabbits. Two 10-mm-diameter parietal defects were made in each rabbit. One defect was placed on each side of the sagittal suture. In 10 animals, the left defect was filled with Mimix alone, and in the other 10, an absorbable plate was placed across the base of the left defect before Mimix placement. The right-sided defect served as a control in all animals, with no material placed in or across this defect. The rabbits were killed 6 months postoperatively. A bone pathologist performed histologic examinations of the specimens looking specifically for evidence of inflammatory reaction and bone formation. There was no inflammation around the dura or any other negative histologic reaction in either the study groups or the control. Growth of new bone into the Mimix was found along the periphery in all specimens. We found no migration or displacement of the Mimix from any of the calvarial defects.

Reconstruction of Cranial Bone Defects Using a Compound of Bone Marrow Stromal Cells and Hydroxyapatite-Tricalcium Phosphate

Hydroxyapatite-tricalcium phosphate (HA-TCP) is a new kind of material which shows good biocompatibility, biological degradability, and porosity. This study aimed to determine the effectiveness of HA-TCP as a bone tissue engineering scaffold. In this study, critical size cranial defects were reconstructed with compounds of autogenous bone marrow stromal cells (BMSCs) and HA-TCP. The resulting grafts were examined by X-ray, histological examination, semi-quantitative analysis of osteogenesis, immunochemical examination (collagen type I and III), scanning electron microscopy and transmission electron microscopy. The results showed that HA-TCP is a good bone tissue engineering scaffold and BMSCs/HA-TCP is a promising technique for reconstruction of bone defects.

Cranial Bone Regeneration Using a Composite Scaffold of Beta‐Tricalcium Phosphate, Collagen, and Autologous Bone Fragments

The aim of our study was to examine the tissue response and new bone formation induced by beta-tricalcium phosphate (beta-TCP), collagen, and autologous bone fragments with fibrin glue implanted into a cranial bone defect. Granulated beta-TCP and collagen from porcine skin were mixed and freeze-dried. The weight ratio of both materials was 98:2. The composite scaffold for bone regeneration was composed of this artificial material and autologous bone fragments. Five adult beagle dogs were used. A cranial bone defect (2 cmx2 cm) was created in each dog. The animals were divided into two groups. In group 1 (n=3), the cranial bone defect was closed by replacing the original free bone flap, and the residual fissure and burr holes were filled with the composite scaffold with fibrin glue. In group 2 (n=2), the bone defect was closed only by replacing the original free bone flap. Three months after the treatment, computed tomography and histologic examinations were done in all animals. In all dogs in group 1, the defects were almost closed by new bone; whereas in group 2, the defects were filled with fibrous tissues instead of bone. This study showed that the composite scaffold made of beta-TCP, collagen, and autologous bone fragments with fibrin glue enabled reconstruction of cranial bone defects without the usual fixation materials.

Tissue Engineering Designs for the Future: New Logics, Old Molecules

Tissue Engineering Designs for the Future: New Logics, Old Molecules

Polylactide and polyglycolic acid-reinforced coralline hydroxy-apatite for the reconstruction of cranial bone defects in the rabbit.

The possibility of using coralline hydroxy-apatite in combination with polylactide and polyglcycolic acid instead of a bone graft in the skull region is examinated. Coralline hydroxy-apatite blocks strengthened with a membrane made of a combination of polylactide and polyglycolic acid were inserted into bony defects created in 12 rabbit skulls. The blocks were observed during a follow-up of 12 months. They became fixed to the surrounding bone and no adverse effects or harmful reactions in the nearby tissues could be detected.