scholarly journals Towards Understanding Therapeutic Failures in Masquelet Surgery: First Evidence that Defective Induced Membrane Properties are Associated with Clinical Failures

2020 ◽  
Vol 9 (2) ◽  
pp. 450 ◽  
Author(s):  
Marjorie Durand ◽  
Laure Barbier ◽  
Laurent Mathieu ◽  
Thomas Poyot ◽  
Thomas Demoures ◽  
...  
Keyword(s):  
Gene Expression ◽  
Predictive Biomarkers ◽  
Membrane Properties ◽  
Cement Spacer ◽  
Expression Ratio ◽  
Ecm Remodeling ◽  
Induced Membrane ◽  
Post Surgery ◽  
Masquelet Technique ◽  
Membrane Technique

The two-stage Masquelet induced-membrane technique (IMT) consists of cement spacer-driven membrane induction followed by an autologous cancellous bone implantation in this membrane to promote large bone defect repairs. For the first time, this study aims at correlating IMT failures with physiological alterations of the induced membrane (IM) in patients. For this purpose, we compared various histological, immunohistochemical and gene expression parameters obtained from IM collected in patients categorized lately as successfully (Responders; n = 8) or unsuccessfully (Non-responders; n = 3) treated with the Masquelet technique (6 month clinical and radiologic post-surgery follow-up). While angiogenesis or macrophage distribution pattern remained unmodified in non-responder IM as compared to responder IM, we evidenced an absence of mesenchymal stem cells and reduced density of fibroblast-like cells in non-responder IM. Furthermore, non-responder IM exhibited altered extracellular matrix (ECM) remodeling parameters such as a lower expression ratio of metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinases (TIMP-1) mRNA as well as an important collagen overexpression as shown by picrosirius red staining. In summary, this study is the first to report evidence that IMT failure can be related to defective IM properties while underlining the importance of ECM remodeling parameters, particularly the MMP-9/TIMP-1 gene expression ratio, as early predictive biomarkers of the IMT outcome regardless of the type of bone, fracture or patient characteristics.

scholarly journals Combined use of the Ilizarov non-free bone plasty and Masquelet technique in patients with acquired bone defects and pseudarthrosis

2020 ◽  
Vol 26 (4) ◽  
pp. 532-538
Author(s):  
D.Yu. Borzunov ◽  
◽  
D.S. Mokhovikov ◽  
S.N. Kolchin ◽  
E.N. Gorbach ◽  
...  
Keyword(s):  
Bone Grafting ◽  
Soft Tissues ◽  
Bone Defects ◽  
Bone Transport ◽  
Long Bone ◽  
Cement Spacer ◽  
Technical Problems ◽  
Induced Membrane ◽  
Masquelet Technique ◽  
Membrane Technique

Introduction The Masquelet induced membrane technique is effective in the management of acquired heterogeneous long bone defects and pseudarthrosis. The combination of the Masquelet technology and Ilizarov non-free bone grafting seems promising and reduces the risks of recurrence at long-term in patients with congenital pseudarthrosis. Purpose Presentation of new technological solutions that allow combining the advantages of the Ilizarov bone transport and Masquelet bone grafting in patients with acquired bone defects. Materials and methods Retrospective assessment of the results of bone reconstruction in 10 patients who were treated by a combination of Ilizarov and Masquelet bone grafting technologies to repair long bone defects after failures of previous treatment. Fragments of the biomembrane formed around the cement spacer temporarily replacing the tibial gap after resection bone defect or pseudarthrosis were examined in all patients. The studies were carried out using a Reichard sledge microtome, an AxioScope stereomicroscope and an AxioCam ICc 5 digital camera, a JSM- 840 scanning electron microscope and an INCA-200 Energy X-ray electron probe microanalyzer. Results and discussion The combined Masquelet technique and Ilizarov non-free bone plasty provide the conditions that are favorable for reparative processes of the transported fragments. After removal of the spacer, there is a tunnel formed in the interfragmental gap, the walls of which are made of the induced membrane. Bone transport is carried out without technical problems through the compromised tissues which are debrided at the time of distraction initiation, outside the scars. At the same time, there are low risks of inflammation around the transosseous elements; there is no danger of cutting and perforation of soft tissues by transported fragments. Conclusions Complete organotypic rearrangement of the distraction regenerate with the use of Ilizarov non-free bone plasty and the Masquelet technique excludes the possibility of deformities or fractures at the level of newly formed bone areas. Active distraction histogenesis ensures the closure of soft tissue defects without additional reconstructive plastic interventions. The revealed dependence of the induced membrane blood supply on the method of treatment previously used might be a criterion for predicting the treatment outcome in patients with acquired bone defects and pseudarthrosis.

scholarly journals Gene expression-based biomarkers designating glioblastomas resistant to multiple treatment strategies

2021 ◽  
Author(s):  
Otília Menyhárt ◽  
János Tibor Fekete ◽  
Balázs Győrffy
Keyword(s):  
Gene Expression ◽  
Treatment Strategies ◽  
Area Under The Curve ◽  
Predictive Biomarkers ◽  
Subsequent Treatment ◽  
Survival Status ◽  
Multiple Treatment ◽  
Post Surgery ◽  
Potential Biomarker ◽  
Elevated Expression

Abstract Despite advances in molecular characterization of glioblastoma multiforme (GBM), only a handful of predictive biomarkers exist with limited clinical relevance. We aimed to identify differentially expressed genes in tumor samples collected at surgery associated with response to subsequent treatment, including temozolomide (TMZ) and nitrosoureas. Gene expression was collected from multiple independent datasets. Patients were categorized as responders/nonresponders based on their survival status at 16 months post-surgery. For each gene, the expression was compared between responders and nonresponders with a Mann-Whitney U test and receiver operating characteristic. The package "roc" was used to calculate the area under the curve (AUC). The integrated database comprises 454 GBM patients from three independent datasets and 10,103 genes. The highest proportion of responders (68%) were among patients treated with TMZ combined with nitrosoureas, where FCGR2B upregulation provided the strongest predictive value (AUC=0.72, p < 0.001). Elevated expression of CSTA and MRPS17 was associated with a lack of response to multiple treatment strategies. DLL3 upregulation was present in subsequent responders to any treatment combination containing TMZ. Three genes (PLSCR1, MX1, and MDM2) upregulated both in the younger cohort and in patients expressing low MGMT delineate a subset of patients with worse prognosis within a population generally associated with a favorable outcome. The identified transcriptomic changes provide biomarkers of responsiveness, offer avenues for preclinical studies, and may enhance future GBM patient stratifications. The described methodology provides a reliable pipeline for the initial testing of potential biomarker candidates for future validation studies.

scholarly journals Immunohistochemical Analysis Revealed the Expression of Bone Morphogenetic Proteins-4, 6, 7, and 9 in Human Induced Membrane Samples Treated With the Masquelet Technique

2021 ◽  
Author(s):  
Takahiro Niikura ◽  
Takahiro Oda ◽  
Naoe Jimbo ◽  
Masato Komatsu ◽  
Keisuke Oe ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Bone Morphogenetic Proteins ◽  
Immunohistochemical Analysis ◽  
Bone Defects ◽  
Positive Control ◽  
Cement Spacer ◽  
Induced Membrane ◽  
Masquelet Technique ◽  
Human Bone Tissue ◽  
Large Bone

Abstract BackgroundInduced membrane (IM) is the key component of Masquelet reconstruction surgery for the treatment of bone defects. It is formed around the cement spacer and is known to secrete growth factors and osteoinductive factors. However, information on the presence of osteoinductive factors in IM is not enough in the literature. The purpose of this study was to investigate the existence of bone morphogenetic proteins (BMPs) in the IM harvested from patients during the treatment of bone defects using the Masquelet technique.MethodsWe included six patients whose bone defects were treated using the Masquelet technique. The affected bone was the femur in three patients and the tibia in three patients. During the second-stage surgery, 1-cm2 pieces of IM were harvested. Histological sections of IM were immunostained with anti-BMP-4, 6, 7, and 9 antibodies. Human bone tissue served as the positive control.ResultsThe existence of BMP-4, 6, 7, and 9 was observed in all IM samples. Further, immunolocalization of BMP-4, 6, 7, and 9 was observed in blood vessels and fibroblasts of all IM samples. Immunolocalization of BMP-4, 6, 7, and 9 was also observed in bone tissue within the IM in one sample, in which osteogenesis inside the IM was observed.ConclusionsThis study revealed that osteoinductive factors BMP-4, 6, 7, and 9 were present in the IM harvested from patients. This helps explain how the Masquelet technique effectively contributes to the healing of large bone defects. It may thus be possible for surgeons to omit the addition of BMPs to bone grafts give the endogenous secretion of BMPs from the IM.Trial registrationNot applicable.

scholarly journals Immunohistochemical analysis revealed the expression of bone morphogenetic proteins-4, 6, 7, and 9 in human induced membrane samples treated with the Masquelet technique

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Takahiro Niikura ◽  
Takahiro Oda ◽  
Naoe Jimbo ◽  
Masato Komatsu ◽  
Keisuke Oe ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Bone Morphogenetic Proteins ◽  
Immunohistochemical Analysis ◽  
Bone Defects ◽  
Positive Control ◽  
Cement Spacer ◽  
Induced Membrane ◽  
Masquelet Technique ◽  
Human Bone Tissue ◽  
Large Bone

Abstract Background Induced membrane (IM) is the key component of Masquelet reconstruction surgery for the treatment of bone defects. IM is formed around the cement spacer and is known to secrete growth factors and osteoinductive factors. However, there is limited evidence available concerning the presence of osteoinductive factors in IM. This study aimed to investigate the existence of bone morphogenetic proteins (BMPs) in IM harvested from patients during the treatment of bone defects using the Masquelet technique. Methods This study involved six patients whose bone defects had been treated using the Masquelet technique. The affected sites were the femur (n = 3) and the tibia (n = 3). During the second-stage surgery, 1 cm2 pieces of IM were harvested. Histological sections of IM were immunostained with anti-BMP-4, 6, 7, and 9 antibodies. Human bone tissue served as the positive control. Results The presence of BMP-4, 6, 7, and 9 was observed in all IM samples. Further, immunolocalization of BMP-4, 6, 7, and 9 was observed in blood vessels and fibroblasts in all IM samples. Immunolocalization of BMP-4, 6, 7, and 9 was also observed in bone tissue within the IM in one sample, in which osteogenesis inside the IM was observed. Conclusions This study showed that osteoinductive factors BMP-4, 6, 7, and 9 were present in the IM harvested from patients, providing evidence indicating that the Masquelet technique effectively contributes to healing large bone defects. Therefore, it may be possible for surgeons to omit the addition of BMPs to bone grafts, given the endogenous secretion of BMPs from the IM.

scholarly journals Modified Masquelet Technique Using Allogeneic Graft for a Gustilo-Anderson Type III-A Open Fracture of the Femur with an 8 cm Bone Defect

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Hichem Issaoui ◽  
Mohammed Reda Fekhaoui ◽  
Moheddin Jamous ◽  
Alain-Charles Masquelet
Keyword(s):  
Bone Graft ◽  
Bone Defect ◽  
Bony Union ◽  
Induced Membrane ◽  
Masquelet Technique ◽  
Membrane Technique ◽  
Defect Area ◽  
Induced Membrane Technique ◽  
Large Bone

The induced membrane technique was initially described by Masquelet et al. in 1986 as a treatment for tibia nonunion; then, it became one of the established methods in the management of bone defects. Several changes have been made to this technique and have been used in different contexts and different methodologies. We present the case of a 16-year-old girl admitted to our department for a polytrauma after a motorcycle accident. She presented a Gustilo III-A open fracture of the right femoral shaft with a large bone defect of 8 centimeters that we treated with a modified Masquelet technique. In the first stage, an Open Reduction and Internal Fixation of the fracture was made using a 4,5 mm Dynamic Compression Plate and a PMMA cement was inserted at the bone defect area. The second stage was done after 11 weeks, and the defect area was filled exclusively with bone allograft from a bone bank. Complete bony union was seen at 60 weeks of follow-up. After the removal of the implants by another surgeon, the patient presented an atraumatic fracture of the neoformed bone that we treated with intramedullary femoral nailing associated with a local autograft using reaming debris. A complete bony union was achieved after 12 weeks with a complete range of motion of the hip and knee. The stability given to the fracture is essential because it influences the quality of the induced membrane and Masquelet has recommended high initial fixation rigidity to promote incorporation of the graft. It is recommended to delay the second stage of this technique after 8 weeks, especially in femoral reconstruction, to optimize the quality of the induced membrane. Several studies used a modified induced membrane technique to recreate a traumatic large bone defect, and all of them used an autologous bone graft alone or an enriched bone graft. In this case, the use of allograft exclusively seems to be as successful as an autologous or enriched bone graft. Now, with the advent of bone banks, it is possible to get an unlimited amount of allograft, so additional research and large studies are necessary before giving recommendations.

scholarly journals Impact of scaffold granule size use in Masquelet technique on periosteal reaction: a study in rat femur critical size bone defect model

2020 ◽  
Author(s):  
Maximilian Leiblein ◽  
Andreas Winkenbach ◽  
Elias Koch ◽  
Alexander Schaible ◽  
Hubert Büchner ◽  
...  
Keyword(s):  
Critical Size ◽  
Callus Formation ◽  
Healing Time ◽  
Granule Size ◽  
Critical Size Defect ◽  
Induced Membrane ◽  
Masquelet Technique ◽  
Membrane Technique ◽  
Induced Membrane Technique

Abstract Purpose The Masquelet technique for the treatment of large bone defects is a two-stage procedure based on an induced membrane. Compared to mature periosteum, the induced membrane differs significantly. However, both play a crucial role in bone regeneration. As part of a histological and radiological post-evaluation of an earlier project, we analyzed the influence of the granule size of the bone void filler Herafill® on development of periosteum regrowth in a critical size defect. Methods We compared three different sizes of Herafill® granules (Heraeus Medical GmbH, Wehrheim) in vivo in a rat femoral critical size defect (10 mm) treated with the induced membrane technique. After 8 weeks healing time, femurs were harvested and taken for histological and radiological analysis. Results A significantly increased regrowth of periosteum into the defect was found when small granules were used. Large granules showed significantly increased occurrence of bone capping. Small granules lead to significant increase in callus formation in the vicinity to the membrane. Conclusion The size of Herafill® granules has significant impact on the development of periosteal-like structures around the defect using Masquelet’s induced membrane technique. Small granules show significantly increased regrowth of periosteum and improved bone formation adjacent to the induced membrane.

scholarly journals Reconstruction of Carpal Bone Loss of Septic Wrist Arthritis Using Induced Membrane Technique

2019 ◽  
Vol 12 (S 01) ◽  
pp. S54-S57
Author(s):  
Atsuyuki Inui ◽  
Yutaka Mifune ◽  
Hanako Nishimoto ◽  
Takahiro Niikura ◽  
Ryosuke Kuroda
Keyword(s):  
Bone Defect ◽  
Cancellous Bone ◽  
Plate Fixation ◽  
Carpal Bone ◽  
Cement Spacer ◽  
Difficult Case ◽  
Induced Membrane ◽  
Membrane Technique ◽  
Induced Membrane Technique ◽  
Segmental Bone

AbstractThe induced membrane technique has been widely used for the reconstruction of the segmental bone defect. The technique requires two-stage surgery. The first surgery is debridement of the affected bone and replacement of the defect by cement spacer. The spacer is removed at the second surgery, and the defect is filled with cancellous bone. The use of the technique for septic wrist arthritis treatment has not been reported. We report two cases of septic wrist arthritis treated by the induced membrane technique. Radical debridement including the carpal bones was performed as a first surgery. The cement spacer was placed into the bone defect after first surgery; then cancellous bone was transplanted into the induced membrane several weeks later. External fixator or plate fixation was performed simultaneously. Bone formation was observed in both cases at several months after the reconstruction surgery. There was no pain or recurrence of infection in both cases. We consider this technique is a possible method for reconstruction, especially in a difficult case.

scholarly journals Masquelet Technique Combined with Tissue Flap Transplantation in The Treatment of Infectious Complex Tissue Defect: A Clinical Analysis

2021 ◽  
Author(s):  
Zun REN ◽  
Yubo ZHANG ◽  
Jiafei DU ◽  
Weijie CAI ◽  
Pengfei CHENG ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Bone Union ◽  
Cement Spacer ◽  
Induced Membrane ◽  
Soft Tissue Envelope ◽  
Tissue Defect ◽  
Masquelet Technique ◽  
Tissue Flap ◽  
Tissue Flaps ◽  
Tissue Defects

Abstract Background: Infectious complex tissue defects have been described as injuries with composite infectious bone defects and extensive soft tissue damage, which are still austere challenges for orthopedists all around the world. The study retrospectively evaluated the Masquelet technique combined with the tissue flap transplantation for the treatment of infectious complex tissue defects and assess key factors of success in this technique.Methods: From December 2016 to December 2019, 22 patients of infectious complex tissue defects were recruited for the study. All the cases experienced a two-stages treatment. Thorough debridement, stabilization of fracture by external fixation and implantation of a cement spacer mixed with antibiotics in the first stage. Simultaneously, suitable tissue flaps were designed and transplanted for the soft tissue defect. 6-8 weeks later, after the elimination of the infection, the cement spacer was removed carefully from the induced membrane and cancellous bone was grafted into the site of bone defect. The average duration of follow-up was 21 months.Results: Infection was eliminated after the first stage intervention without recurrence. All the transplanted tissue flaps were survived. Bone union was achieved in all patients in a period of 16-31 weeks following the second stage surgery. According to the Paley fracture healing score, 17 patients showed excellent results and 5 patients displayed good results regarding bone outcomes. When considering functional outcomes, 14 patients exhibited excellent results and 8 patients displayed good results.Conclusions: This study showed evidences that Masquelet technique combined with tissue flap transplantation was an effective method to repair the infectious complex tissue defects. We also demonstrate that a complete soft-tissue envelope plays an important role in the formation of the induced membrane which promote bone union and in the anti-infection treatment.

scholarly journals Introduction of a New Surgical Method to Improve Bone Healing in a Large Bone Defect by Replacement of the Induced Membrane by a Human Decellularized Dermis Repopulated with Bone Marrow Mononuclear Cells in Rat

Materials ◽  
2020 ◽  
Vol 13 (11) ◽  
pp. 2629
Author(s):  
Maximilian Leiblein ◽  
Tobias Kolb ◽  
Lion Christian ◽  
Katrin Schröder ◽  
Ceyhan Yaman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Healing ◽  
Mononuclear Cells ◽  
Biomechanical Analysis ◽  
Bone Marrow Mononuclear Cells ◽  
Induced Membrane ◽  
Masquelet Technique ◽  
Membrane Technique ◽  
Large Bone ◽  
Decellularized Dermis

The Masquelet technique for the treatment of large bone defects is a two-stage procedure based on an induced membrane. We eliminate the first surgical step by using a decellularized dermal skin graft (Epiflex®) populated with bone marrow mononuclear cells (BMC), as a replacement for the induced membrane. The aim of this study was to demonstrate the feasibility of this technology and provide evidence of equivalent bone healing in comparison to the induced membrane-technique. Therefore, 112 male Sprague–Dawley rats were allocated in six groups and received a 10 mm femoral defect. Defects were treated with either the induced membrane or decellularized dermis, with or without the addition of BMC. Defects were then filled with a scaffold (β-TCP), with or without BMC. After a healing time of eight weeks, femurs were taken for histological, radiological and biomechanical analysis. Defects treated with Epiflex® showed increased mineralization and bone formation predominantly in the transplanted dermis surrounding the defect. No significant decrease of biomechanical properties was found. Vascularization of the defect could be enhanced by addition of BMC. Considering the dramatic reduction of a patient’s burden by the reduced surgical stress and shortened time of treatment, this technique could have a great impact on clinical practice.

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