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

Marjorie Durand,Thomas Demoures,Laure Barbier,Jean-Marc Collombet,Jean-Baptiste Souraud,Thomas Poyot,Alain-Charles Masquelet,Laurent Mathieu

doi:10.3390/jcm9020450

Abstract

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.

Highlights

Large bone defects usually originate from injuries resulting from either high velocity impact or heavy weight object crushing as well as bone loss caused by sepsis-triggered osteomyelitis, radiotherapy-induced osteonecrosis, or bone tumor resections [1]
We showed that matrix metalloproteinase-9 (MMP-9)-dependent remodeling of the extracellular collagen matrix in non-responding patients was altered
Induced membrane tissue was collected in sterile conditions during the routine surgical removal of the gentamycin-PMMA spacers (Palacos© R + G) in the second stage of the induced-membrane technique (IMT)

Summary

Introduction

Large bone defects usually originate from injuries resulting from either high velocity impact or heavy weight object crushing (e.g., gun shot, road accident) as well as bone loss caused by sepsis-triggered osteomyelitis, radiotherapy-induced osteonecrosis, or bone tumor resections [1]. Such bone injuries are defined as critical-sized bone defects, since they cannot spontaneously heal and they remain a challenge, even today, in reconstructive trauma surgery. The three most reported surgical techniques are the free vascularized fibular graft, the Ilizarov technique by local bone transportation and the Masquelet induced-membrane technique (IMT). The Ilizarov technique is a slow and painful process and requires a great deal of expertise to perform successfully [3]

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