Schwann Cells Accelerate Osteogenesis via the Mif/CD74/FOXO1 Signaling Pathway In Vitro.

Schwann cells have been found to promote osteogenesis by an unclear molecular mechanism. To better understand how Schwann cells accelerate osteogenesis, RNA-Seq and LC-MS/MS were utilized to explore the transcriptomic and metabolic response of MC3T3-E1 to Schwann cells. Osteogenic differentiation was determined by ALP staining. Lentiviruses were constructed to alter the expression of Mif (macrophage migration inhibitory factor) in Schwann cells. Western blot (WB) analysis was employed to detect the protein expression. The results of this study show that Mif is essential for Schwann cells to promote osteogenesis, and its downstream CD74/FOXO1 is also involved in the promotion of Schwann cells on osteogenesis. Further, Schwann cells regulate amino acid metabolism and lipid metabolism in preosteoblasts. These findings unveil the mechanism for Schwann cells to promote osteogenesis where Mif is a key factor.

The effect of fluid shear stress on fibroblasts and stem cells on plane and groove topographies.

In this study, we aimed to study the effect of fluid shear stress on fibroblasts and BMSCs on plane and groove topographies. The results showed that 0.6-Hz stress had the greatest influence on the alignment, polarity, migration and adhesion of fibroblasts on plane by increasing the expression of reoriented actin and vinculin; whereas 1.0-Hz stress promoted differentiation of fibroblasts into myofibroblasts by increasing Col-I and α-SMA expression. Interestingly, under the given frequency stress, the groove structure strengthened the above characteristics of fibroblasts beyond adhesion, and promoted differentiation of BMSCs into myofibroblasts. The above results indicate that 0.6 Hz may improve the implant-tissue sealing, while 1.0-Hz stress probably causes the disordered fiber deposition around implants.

Effects of cyclic fluid stress at different frequencies on behaviors of cells incubated on titanium alloy.

The orthopedic external fixation is always in dynamic mechanical environment with the somatic movement. We used a self-designed mini oscillator to simulate this condition by providing the reciprocating cyclic fluid stress, and observed the behavioral responses of fibroblasts implanted on titanium alloy plane to the stress at different frequencies, including 0.2 Hz, 0.6 Hz, and 1.0 Hz. We found that the cell angle, shape index and expression of vinculin were mostly biphasic-dependent with the increase of frequency, with peaks at 0.6 Hz. Whereas the cell area, expression of Col-I and α-SMA were mainly affected by the 1.0 Hz stress. Interestingly, 1.0 Hz stress also promoted Col-I expression of bone marrow mesenchymal stem cells (BMSCs), although it did not increase α-SMA. These results reveal that 0.6 Hz stress improves the alignment, polarity and adherence of fibroblasts on titanium alloy substrates, thus improving the sealing of implants; the 1.0 Hz force activates the differentiation of fibroblasts into myofibroblasts and increases collagen produced by stem cells, which probably cause the formation of fibrous capsules around implants.

Low-Temperature Additive Manufacturing of Biomimic Three-Dimensional Hydroxyapatite/Collagen Scaffolds for Bone Regeneration.

Low-temperature additive manufacturing (AM) holds promise for fabrication of three-dimensional (3D) scaffolds containing bioactive molecules and/or drugs. Due to the strict technical limitations of current approaches, few materials are suitable for printing at low temperature. Here, a low-temperature robocasting method was employed to print biomimic 3D scaffolds for bone regeneration using a routine collagen-hydroxyapatite (CHA) composite material, which is too viscous to be printed via normal 3D printing methods at low temperature. The CHA scaffolds had excellent 3D structure and maintained most raw material properties after printing. Compared to nonprinted scaffolds, printed scaffolds promoted bone marrow stromal cell proliferation and improved osteogenic outcome in vitro. In a rabbit femoral condyle defect model, the interconnecting pores within the printed scaffolds facilitated cell penetration and mineralization before the scaffolds degraded and enhanced repair, compared to nonprinted CHA scaffolds. Additionally, the optimal printing parameters for 3D CHA scaffolds were investigated; 600-µm-diameter rods were optimal in terms of moderate mechanical strength and better repair outcome in vivo. This low-temperature robocasting method could enable a variety of bioactive molecules to be incorporated into printed CHA materials and provides a method of bioprinting biomaterials without compromising their natural properties.

Different effects of implanting sensory nerve or blood vessel on the vascularization, neurotization, and osteogenesis of tissue-engineered bone in vivo.

To compare the different effects of implanting sensory nerve tracts or blood vessel on the osteogenesis, vascularization, and neurotization of the tissue-engineered bone in vivo, we constructed the tissue engineered bone and implanted the sensory nerve tracts (group SN), blood vessel (group VB), or nothing (group Blank) to the side channel of the bone graft to repair the femur defect in the rabbit. Better osteogenesis was observed in groups SN and VB than in group Blank, and no significant difference was found between groups SN and VB at 4, 8, and 12 weeks postoperatively. The neuropeptides expression and the number of new blood vessels in the bone tissues were increased at 8 weeks and then decreased at 12 weeks in all groups and were highest in group VB and lowest in group Blank at all three time points. We conclude that implanting either blood vessel or sensory nerve tract into the tissue-engineered bone can significantly enhance both the vascularization and neurotization simultaneously to get a better osteogenesis effect than TEB alone, and the method of implanting blood vessel has a little better effect of vascularization and neurotization but almost the same osteogenesis effect as implanting sensory nerve.

Neuropeptide substance P improves osteoblastic and angiogenic differentiation capacity of bone marrow stem cells in vitro.

Our previous work showed that implanting a sensory nerve or vascular bundle when constructing vascularized and neurotized bone could promote bone osteogenesis in tissue engineering. This phenomenon could be explained by the regulatory function of neuropeptides. Neuropeptide substance P (SP) has been demonstrated to contribute to bone growth by stimulating the proliferation and differentiation of bone marrow stem cells (BMSCs). However, there have been no prior studies on the association between Wnt signaling and the mechanism of SP in the context of BMSC differentiation. Our results have shown that SP could enhance the differentiation of BMSCs by activating gene and protein expression via the Wnt pathway and by translocating ß-catenin, which can be inhibited by Wnt signaling blocker treatment or by the NK-1 antagonist. SP could also increase the growth factor level of bone morphogenetic protein-2 (BMP-2). Additionally, SP could enhance the migration ability of BMSCs, and the promotion of vascular endothelial growth factor (VEGF) expression by SP has been studied. In conclusion, SP could induce osteoblastic differentiation via the Wnt pathway and promote the angiogenic ability of BMSCs. These results indicate that a vascularized and neurotized tissue-engineered construct could be feasible for use in bone tissue engineering strategies.

PKC-NF-κB are involved in CCL2-induced Nav1.8 expression and channel function in dorsal root ganglion neurons.

CCL2 [chemokine (C-C motif) ligand 2] contributes to the inflammation-induced neuropathic pain through activating VGSC (voltage-gated sodium channel)-mediated nerve impulse conduction, but the underlying mechanism is currently unknown. Our study aimed to investigate whether PKC (protein kinase C)-NF-κB (nuclear factor κB) is involved in CCL2-induced regulation of voltage-gated sodium Nav1.8 currents and expression. DRG (dorsal root ganglion) neurons were prepared from adult male Sprague-Dawley rats and incubated with various concentration of CCL2 for 24 h. Whole-cell patch-clamps were performed to record the Nav1.8 currents in response to the induction by CCL2. After being pretreated with 5 and10 nM CCL2 for 16 h, CCR2 [chemokine (C-C motif) receptor 2] and Nav1.8 expression significantly increased and the peak currents of Nav1.8 elevated from the baseline 46.53±4.53 pA/pF to 64.28±3.12 pA/pF following 10 nM CCL2 (P<0.05). Compared with the control, significant change in Nav1.8 current density was observed when the CCR2 inhibitor INCB3344 (10 nM) was applied. Furthermore, inhibition of PKC by AEB071 significantly eliminated CCL2-induced elevated Nav1.8 currents. In vitro PKC kinase assays and autoradiograms suggested that Nav1.8 within DRG neurons was a substrate of PKC and direct phosphorylation of the Nav1.8 channel by PKC regulates its function in these neurons. Moreover, p65 expression was significantly higher in CCL2-induced neurons (P<0.05), and was reversed by treatment with INCB3344 and AEB071. PKC-NF-κB are involved in CCL2-induced elevation of Nav1.8 current density by promoting the phosphorylation of Nav1.8 and its expression.

Salvianolic acid B attenuates spinal cord ischemia-reperfusion-induced neuronal injury and oxidative stress by activating the extracellular signal-regulated kinase pathway in rats.

BACKGROUND: Salvianolic acid B (SalB), the main bioactive compound isolated from the traditional Chinese medicinal herb broad Radix Salviae Miltiorrhizae exerts a spectrum of pharmacologic activities. We investigated the effects of SalB treatment in a rat model of spinal cord ischemia and reperfusion (I/R) injury and the underlying mechanism. MATERIALS AND METHODS: SalB was administered at 1, 10, or 50 mg/kg after spinal cord ischemia. The potential protective effects on spinal cord injury were determined by spinal cord edema, infarct volume, and motor function assessment of the hind limbs. RESULTS: SalB treatment significantly decreased spinal cord edema and infarct volume and preserved motor function of the hind limbs in a dose-dependent manner. SalB administration ameliorated the generation of oxidative products and preserved antioxidant defense activities in the injured spinal cord at both 4 and 24 h after I/R injury. Moreover, SalB prolonged the I/R injury-induced activation of extracellular signal-regulated kinase (ERK), and blocking ERK activation with PD98059 partially prevented the neuroprotective effects of SalB. CONCLUSIONS: These findings demonstrate the neuroprotective effects of SalB in a spinal cord I/R injury model and suggest that SalB-induced neuroprotection was mediated by ERK activation.

Precise resection and biological reconstruction under navigation guidance for young patients with juxta-articular bone sarcoma in lower extremity: preliminary report.

BACKGROUND: It is a challenge to perform a joint-preserving resection for young patients with juxta-articular bone sarcomas. We determined whether osteotomy under image-guided navigation make joint-saving resection possible for juxta-articular lesions while adhering oncological principles. METHODS: Between June 2008 and July 2010, joint-preserving limb salvage surgeries were performed on 9 patients with juxta-articular bone sarcomas under navigation guidance. Computed tomography/magnetic resonance imaging fusion images were used for real-time navigation. Eight lesions located around the knee and 1 in hip. Six tumors extend to and 3 beyond the epiphyseal line. Planned osteotomy under image-guided navigation was employed for achieving clear surgical margin while maximizing host tissue preservation. All tumors were en bloc removed and intercalary defect were reconstructed by combination of allograft with vascularized fibula graft. All specimens were examined for resection margin. Patients were followed up for an average of 25.2 months for evaluating of functional and oncology outcomes. RESULTS: Entire joint were preserved in 6 patients and part of joint were saved in another 3 patients. The mean registration error for navigation was 0.40 mm (range, 0.31 to 0.62 mm). Clear surgical margin was obtained in all specimens. The average closest distance between the osteotomy line and tumor edge was 9.6 mm (range, 6 to 14 mm). Entire joint cartilage was preserved in 6 patients and portion of joint were saved in 3 patients (2 in proximal tibia, 1 in distal femur). No patient experienced local recurrence. Two patients developed lung metastasis. One died of disease and the other underwent metastasectomy and had no evidence of disease at the most recent follow-up. All reconstruction was in situ with the Musculoskeletal Tumor Society average score of 26.7 at final follow-up. CONCLUSIONS: With careful patient selection, image navigation-assisted surgery made it possible to resect the bone exactly as planned in length and orientation in the magnetic resonance imaging image, yielding a clear margin and preserving the entire or part of the articular cartilage in joint-sparing limb salvage procedures for treating skeletally immature patients with juxta-articular bone sarcomas. LEVEL OF EVIDENCE: Level IV--therapeutic study.

[Establishment of Schatzker classification digital models of tibial plateau fractures and its application on virtual surgery].

OBJECTIVE: To explore the establishment of Schatzker classification digital model of tibial plateau fractures and its application in virtual surgery. METHODS: Proximal tibial of one healthy male volunteer was examined with 64-slice spiral computed tomography (CT). The data were processed by software Mimics 10.01 and a model of proximal tibia was reconstructed. According to the Schatzker classification criteria of tibial plateau fractures, each type of fracture model was simulated.Screen-captures of fracture model were saved from different directions.Each type of fracture model was exported as video mode.Fracture model was imported into FreeForm modeling system.With a force feedback device, a surgeon could conduct virtual fracture operation simulation.Utilizing the GHOST of FreeForm modeling system, the software of virtual cutting, fracture reduction and fixation was developed.With a force feedback device PHANTOM, a surgeon could manipulate virtual surgical instruments and fracture classification model and simulate surgical actions such as assembly of surgical instruments, drilling, implantation of screw, reduction of fracture, bone grafting and fracture fixation, etc. RESULTS: The digital fracture model was intuitive, three-dimensional and realistic and it had excellent visual effect.Fracture could be observed and charted from optional direction and angle.Fracture model could rotate 360 ° in the corresponding video mode. The virtual surgical environment had a strong sense of reality, immersion and telepresence as well as good interaction and force feedback function in the FreeForm modeling system. The user could make the corresponding decisions about surgical method and choice of internal fixation according to the specific type of tibial plateau fracture as well as repeated operational practice in virtual surgery system. CONCLUSION: The digital fracture model of Schatzker classification is intuitive, three-dimensional, realistic and dynamic. The virtual surgery systems of Schatzker classifications make the virtual surgery training more normalized, programmed and standardized.In addition, virtual surgery system can serve as a new tool for preoperative planning and surgeon-patient interactions.

[Three-dimensional flow perfusion culture enhances proliferation of human fetal osteoblasts in large scaffold with controlled architecture].

OBJECTIVE: To demonstrate the feasibility and benefits of custom designed perfusion bioreactor in conjunction with well-defined three-dimensional (3D) environment for enhanced proliferation and homogeneous distribution of human fetal osteoblasts in large scaffold in vitro. METHODS: Large-scale ß-tricalcium phosphate (ß-TCP) scaffolds with tightly controlled architectures were fabricated. And a custom designed perfusion bioreactor was developed. Human fetal osteoblasts were seeded onto the scaffolds, cultured for up to 16 days in static or flow perfusion conditions. At Days 4, 8 & 16 post-incubation, the proliferation and distribution of osteoblasts were determined by daily D-glucose consumption, cell viability (methyl thiazolyl tetrazolium (MTT) assay), histological evaluation and scanning electron microcopy (SEM). Sphere like structures observed in the SEM images were assessed by energy dispersive X-ray (EDX) analysis. RESULTS: In both static and perfusion cultures, the daily D-glucose consumption increased with prolonged time. The daily D-glucose consumption was significantly higher in the perfusion culture than that in static culture (P < 0.05). The increased cell viability with time during the culture was similar to the daily D-glucose consumption under both conditions. There was much greater cell viability under flow perfusion culture compared to static culture (P < 0.05). Flow perfused constructs demonstrated improved cell proliferation and a homogeneous layer composed of cells and extracellular matrix in channels throughout the whole scaffold. However, the cells were biased to periphery in scaffolds culture statically. Sphere like structures present in the matrix were identified as calcium phosphate nodules via EDX analysis. CONCLUSIONS: Flow perfusion culture plus well-defined 3D interconnected channel environments enhances the proliferation and improve the distribution of human fetal osteoblasts in large scaffolds. Scaffolds with controlled architecture may be a potential tool of studying the fluid flow configuration and cell behavior inside scaffold in details. And human fetal osteoblasts can be used as a cell source in large bone graft research.

[Experimental study of repairing femoral bone defects with nHA/RHLC/PLA scaffold composite with endothelial cells and osteoblasts in canines].

OBJECTIVE: To explore whether a tissue-engineered construct composed of autogenous endothelial cells, osteoblasts and a new bioresorbable nano-hydroxyapatite/recombinant human-like collagen/polylactic acid (nHA/RHLC/PLA) would enhance bone regeneration and repair femoral head defects in canine models. METHODS: The bone marrow stem cells (BMSCs) were isolated from bone marrow of canine ilium and cultured in Dulbecco's modified eagle medium:nutrient mixture F-12 culture media for 1 week and the second-generation BMSCs were further induced by osteogenic medium (1×10(-8) mol/L dexamethasone, 10 mmol/L B-sodium glycerophosphate and 50 µg/ml vitamin C) and by endothelial cell grow medium (vascular endothelial growth factor and basic fibroblast growth factor) for 14 days in vitro. Thus BMSCs were induced into ECs and OBs. After the second passage, cells were digested and collected.And cell density was adjusted to 1.0×10(6)/ml.The cells and nHA/RHLC/PLA scaffold were co-cultured for 2-4 hours then nHA/RHLC/PLA scaffold composites prepared. Cavity defects of 8 mm in diameter and 10 mm in height were made in femoral heads.The nHA/RHLC/PLA scaffold composited with ECs and osteoblasts (OBs) (group A) and composited with OBs (group B) were inserted into different defects while cell-free nHA/RHLC/PLA scaffold served as controls (group C). New bone formation and defect repair were evaluated at 3 and 6 months by radiographic examination, histology and bone histomorphometry. RESULTS: New bone formation was evident as early as 3 months in groups A, B and C.At 6 months, abundant bone tissue within defects was observed in group A. The control animals with cell-free scaffold showed less bone formation at both timepoints.The scaffold of nHA/RHLC/PLA was degraded and absorbed gradually with the formation of new bone tissues.Histology and bone histomorphometry further revealed significantly increased trabecular bones in group A compared with groups B and C at 6 months postimplantation (P < 0.01). CONCLUSION: More abundant new bone tissue may be found in the bone defect areas implanted with osteoblast-endotheliocyte composite than osteoblasts composite and scaffold materials only.ECs and osteoblasts derived from BMSC are ideal seed cells for repairing femoral head defects.

Enhancing the bioactivity of Poly(lactic-co-glycolic acid) scaffold with a nano-hydroxyapatite coating for the treatment of segmental bone defect in a rabbit model.

PURPOSE: Poly(lactic-co-glycolic acid) (PLGA) is excellent as a scaffolding matrix due to feasibility of processing and tunable biodegradability, yet the virgin scaffolds lack osteoconduction and osteoinduction. In this study, nano-hydroxyapatite (nHA) was coated on the interior surfaces of PLGA scaffolds in order to facilitate in vivo bone defect restoration using biomimetic ceramics while keeping the polyester skeleton of the scaffolds. METHODS: PLGA porous scaffolds were prepared and surface modification was carried out by incubation in modified simulated body fluids. The nHA coated PLGA scaffolds were compared to the virgin PLGA scaffolds both in vitro and in vivo. Viability and proliferation rate of bone marrow stromal cells of rabbits were examined. The constructs of scaffolds and autogenous bone marrow stromal cells were implanted into the segmental bone defect in the rabbit model, and the bone regeneration effects were observed. RESULTS: In contrast to the relative smooth pore surface of the virgin PLGA scaffold, a biomimetic hierarchical nanostructure was found on the surface of the interior pores of the nHA coated PLGA scaffolds by scanning electron microscopy. Both the viability and proliferation rate of the cells seeded in nHA coated PLGA scaffolds were higher than those in PLGA scaffolds. For bone defect repairing, the radius defects had, after 12 weeks implantation of nHA coated PLGA scaffolds, completely recuperated with significantly better bone formation than in the group of virgin PLGA scaffolds, as shown by X-ray, Micro-computerized tomography and histological examinations. CONCLUSION: nHA coating on the interior pore surfaces can significantly improve the bioactivity of PLGA porous scaffolds.

Use of patient-specific templates in hip resurfacing arthroplasty: experience from sixteen cases.

PURPOSE: Hip resurfacing arthroplasty (HRA) is a technically demanding operation, requiring both accuracy and precision in placement of the acetabular and femoral components. Malalignment of the component can lead to notching and possible femoral neck fractures. We used specific templates created using a rapid prototyping machine based on the patients' anatomy, to aid in accurate intraoperative pin placement. METHODS: A 3D model of the hip was reconstructed using spiral computed tomography (CT) data by Amira 3.1 software in 16 patients in whom HRA was planned for hip osteoarthritis (OA). All of the patients in the study had normal contralateral hips. The rotational centre of femoral head on the normal side was superimposed using Imageware12.0 software to determine the centre of the femoral head on the contralateral side. The data was then used to produce patient-specific templates using a rapid prototyping technique. These templates were designed according to the anatomical features of femoral head surface, the rotation centre and the planned prosthesis shaft angle. The orientation of the prosthesis was determined by matching the model to the femoral head surface during the operation. In addition, a control group of 18 patients with OA was operated upon by the conventional method. RESULTS: The mean prosthesis stem shaft angle (SSA), as determined from postoperative imaging, was 138.68 ± 8.85° for the locating template group, and (118.9 ± 12.8) for the conventional group. CONCLUSIONS: The locating template designed and constructed preoperatively can provide precise and dependable location for hip resurfacing femoral components during arthroplasty and ensure the valgus stem placement necessary for optimal outcomes.

Irregular osteotomy in limb salvage for juxta-articular osteosarcoma under computer-assisted navigation.

BACKGROUND: Joint-preserving limb salvage surgery has been expected to have good functional outcomes. However, it is still a unsolved problem to perform a joint preserving resection for patients with juxta-articular osteosarcoma invading epiphyseal line. We determined whether irregular osteotomy under image-guided navigation make joint-saving resection possible for juxta-articular osteosarcoma while adhering oncological principles. METHODS: We performed joint-preserving limb salvage surgeries on six patients with juxta-articular osteosarcoma of the long bone. Three lesions located in humerus, two in tibia and one in femur. Two tumors extend to and four beyond the epiphyseal line. CT and MRI data fusion images were applied for intraoperative navigation. Planned irregular osteotomy under image-guided navigation was employed for obtaining clear surgical margin while maximizing host tissue preservation. All tumors were en bloc removed and intercalary defect were reconstructed by allograft in one and combination of allograft with vascularized fibula graft in five patients. All specimens were examined for resection margin. Patients were followed up for average of 17.5 months for evaluating of functional and oncology outcomes. RESULT: Entire joint were preserved in three patients and part of joint were saved in another three patients. Clear surgical margin was obtained in all specimens with a minimum of 6-mm distance between tumor and osteotomy line. No patient experienced a local recurrence. One patient developed lung metastasis and had no evidence of disease at the most recent follow-up. All allografts but one healed during the study period. The MSTS average score was 88.8% at final follow-up. CONCLUSIONS: With careful patient selection, the irregular osteotomy under navigation guidance was proved to be an effective and safe technique for precise tumor resection in joint preserving limb salvage procedures for treating patients with juxta-articular osteosarcomas.

The dose-effect of icariin on the proliferation and osteogenic differentiation of human bone mesenchymal stem cells.

Icariin had been reported as a potential agent for osteogenesis, but the dose-effect relationship needed further research to realize the clinical application of icariin. We isolated and purified human bone mesenchymal stem cells (hBMSCs) and stimulated them with different concentrations of icariin. The cytotoxicity of icariin was evaluated by the methylthiazolytetrazolium (MTT) assay method. The proliferation and osteogenic differentiation of such hBMSCs were investigated for different concentrations of icariin. We found that icariin had a dose-dependent effect on the proliferation and osteogenic differentiation of hBMSCs in a suitable concentration range from 10(-9) M to 10(-6) M, but at concentrations above 10(-5) M, the cytotoxicity limited its use. The extremely low cost of icariin and its high abundance make it appealing for bone regeneration.

Biological reconstruction using massive bone allograft with intramedullary vascularized fibular flap after intercalary resection of humeral malignancy.

BACKGROUND: Reconstruction after excision of the humeral malignancy is a challenging issue for the reconstructive surgeon. The combined use of a fibular flap and allograft can provide a reliable reconstructive option. This article describes the authors' experience with this technique for the treatment of segmental bone defects after resection of humeral malignancy. METHODS: From 2005 to 2008, seven patients that had intercalary resection of humeral malignancy underwent reconstruction with an allograft and vascularized fibula construct. Patients were examined clinically and radiographically. RESULT: The average age at time of operation was 16.7 years. The mean follow-up time was 27.7 months. The average length of the resected humeral segment was 10.6 cm and that of the fibula flap was 13.1 cm. The average time of union of fibula was 20.7 weeks and for union of allograft was 26.3 weeks. Incorporation of the fibula into the allograft was seen in three patients. There were no allograft fractures and no infections. Three patients had surgery-related complications including a temporary radial nerve paralysis in 1, wound dehiscence in 1, and clawed toes in 1. The MSTS average score was 95.2% at final follow-up. CONCLUSIONS: Intramedullary fibular flaps in combination with massive allografts provide an excellent option for reconstruction of large bony defects after humeral malignancy extirpation. The viability of the fibula is a cornerstone in success of reconstruction that prevents allograft nonunion and result in decreased time to bone healing, leading to earlier patient recovery and return of function.

The use of massive allograft with intramedullary fibular graft for intercalary reconstruction after resection of tibial malignancy.

Reconstruction after intercalary excision of tibia malignancy is challenging. The combined use of a vascularized fibular flap and allograft can provide a reliable reconstructive option. Eight patients underwent reconstruction with an allograft and vascularized fibula following tibia malignancy resection. Patients were examined clinically and radiographically. The average age of patients was 16.5 years. The mean follow-up time was 38.4 months. Contralateral free fibula flap was used in three patients and ipsilateral pedicle fibula in five. The average length of defect was 11.8 cm and of fibula flap was 15.9 cm. Primary union was achieved in seven patients. The average time for bone union was 5.8 months at fibula-tibia junction and 14.1 months at allograft-tibia junction. Five patients had 10 complications. The Musculoskeletal Tumor Society average score was 90.8% at final follow-up. Intramedullary fibular flap in combination with massive allografts provide an excellent option for reconstruction of large bony defects after tibial malignancy extirpation. Ipsilateral pedicle fibula transportation had the advantages of short operation time and avoidance of donor site complications compared with the contralateral free fibula transfer.