Establishment and characterization of the Masquelet induced membrane technique in a rat femur critical-sized defect model

Abstract

The Masquelet induced membrane technique for reconstructing large diaphyseal defects has been shown to be a promising clinical treatment, yet relatively little is known about the cellular, histological and biochemical make-up of these membranes and how they produce this positive clinical outcome. We compared cellular make-up, histological changes and growth factor expression in membranes induced around femur bone defects and in subcutaneous pockets at 2, 4 and 6 weeks after induction, and to the periosteum. We found that membranes formed around bone defects were similar to those formed in subcutaneous pockets; however, both were significantly different from periosteum with regard to structural characteristics, location of blood vessels and overall thickness. Membranes induced at the femur defect (at 2 weeks) and in periosteum contain mesenchymal stem cells (MSCs; STRO-1 ) which were not found in membranes induced subcutaneously. BMP-2, TGFβ and VEGF were significantly elevated in membranes induced around femur defects in comparison to subcutaneously induced membranes, whereas SDF-1 was not detectable in membranes induced at either site. We found that osteogenic and neovascular activity had mostly subsided by 6 weeks in membranes formed at both sites. It was conclude that cellular composition and growth factor content in induced membranes depends on the location where the membrane is induced and differs from periosteum. Osteogenic and neovascular activity in the membranes is maximal between 2 and 4 weeks and subsides after 6. Based on this, better and quicker bone healing might be achieved if the PMMA cement were replaced with a bone graft earlier in the Masquelet technique. Copyright © 2013 John Wiley & Sons, Ltd.

Preclinical induced membrane model to evaluate synthetic implants for healing critical bone defects without autograft

“…Other studies have characterized the induced membrane formed by PMMA in rat models . There are clear similarities between human and rat induced membrane with respect to timing of membrane formation, histological composition including osteoprogenitor cells, and presence of important growth factors such as transforming growth factor‐beta (TGF‐β), bone morphogenetic protein‐2 (BMP‐2), and vascular endothelial growth factor (VEGF) .…”

“…A secondary surgery is then performed to remove the spacer and replace it with a bone graft inside the newly induced membrane. This two‐stage technique yields higher rates of bone healing compared to implanting an equivalent bone graft at the critical defect site initially, since the induced membrane provides a privileged environment for bone regeneration, hypothetically, by producing osteoinductive growth factors, supplying a robust source of blood vessels, and sequestering the defect site to prevent bone graft resorption and the invasion of fibrous tissue . However, the entire procedure requires at least two surgeries with around one in four patients requiring further union surgery or another type of re‐intervention .…”

“…Furthermore, synthetic bone void filler alone still faces challenges in healing large bone defects because of limited re‐vascularization. For this reason, we proposed to apply a PCL/β‐TCP scaffold in conjunction with a Masquelet‐inspired procedure, as we hypothesized the induced membrane could furnish the synthetic implant with osteoinductive growth factors and a rich vascular environment to promote bone healing …”

The Current Perspectives of Stem Cell Therapy in Orthopedic Surgery

“…Bone defects are one of the major challenging situations of orthopedic surgery. In this area, the first stem cell study was performed by Masquelet (40, 41) and then by Henrich et al (42), they used membranes that contain MSCs for the femoral defects, and declared vascular endothelial growth factor, BMP-2, TGFβ and were significantly elevated in the membranes. This raises the question of whether BMDSCs can be used to repair bone defects.…”

Effects of Local Antibiotic Delivery from Porous Space Maintainers on Infection Clearance and Induction of an Osteogenic Membrane in an Infected Bone Defect

“…1,3 Intrinsic membrane factors that can ultimately promote bone growth in the second reconstructive stage include osteogenic and angiogenic growth factors and pro-and anti-inflammatory cytokines. [3][4][5] The presence of these factors has been demonstrated in both human and animal induced membranes over PMMA. 3,[5][6][7] Ultimately, this membrane serves as an endogenously derived depot of growth factors for the second stage of reconstruction, which involves the removal of the PMMA construct and definitive reconstruction with a graft or flap.…”