Restoration of long bone defects treated with the induced membrane technique: protocol and outcomes

Giannoudis, Peter V.; Harwood, Paul; Tosounidis, Theodoros H.; Kanakaris, Nikolaos K.

doi:10.1016/s0020-1383(16)30840-3

Cited by 156 publications

(105 citation statements)

References 21 publications

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“…IMT is considered as the method of choice to address posttraumatic or infected segmental bone loss [13,26]. Regardless of the heterogeneity and features of study populations (age, sex, smoking…) and fractures (osteosynthetic materials, causes of segmental defects…), numerous studies agreed that the IM is the key element of the surgery as it creates a biologically privileged-environment for bone healing [4,10,22,24].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Some clues explaining the complications and failures in IMT are provided in the literature. Data from several sources highlight either the recurrence of sepsis, active smoking, or lack of rigid fixation after the second operative step as participants in IMT clinical failures [13][14][15][16]. However, available studies in the area are, to date, either prospective or retrospective epidemiologic studies.…”

Section: Introductionmentioning

confidence: 99%

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

Durand¹,

Barbier²,

Laurent

et al. 2020

JCM

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Durand¹,

Barbier²,

Laurent

et al. 2020

JCM

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“…Current treatment relies on bone morphogenetic protein BMP2,4 eventually in combination with bone grafts or bone marrow aspirates 5. BMP2 is delivered with an absorbable collagen sponge in dosages ranging from 10 to 12 mg dependent on the patient's anamnesis and treatment site 6, 7, 8.…”

Section: Introductionmentioning

confidence: 99%

“…Current treatment relies on bone morphogenetic protein BMP2, (4) eventually in combination with bone grafts or bone marrow aspirates. (5) BMP2 is delivered with an absorbable collagen sponge in dosages ranging from 10 to 12 mg dependent on the patient's anamnesis and treatment site. (6)(7)(8) Although BMP2 treatment in these dosages typically leads to successful healing, a series of preclinical and clinical studies have employed lower dosages to induce the bone self-healing cascade.…”

Section: Introductionmentioning

confidence: 99%

The Interaction of BMP2‐Induced Defect Healing in Rat and Fixator Stiffness Modulates Matrix Alignment and Contraction

et al. 2018

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Successful fracture healing requires a tight interplay between mechanical and biological cues. In vitro studies illustrated that mechanical loading modulates bone morphogenetic protein (BMP) signaling. However, in the early phases of large bone defect regeneration in vivo, the underlying mechanisms leading to this mechanosensation remained unknown. We investigated the interaction of BMP2 stimulation and mechanical boundary conditions in a rat critical‐sized femoral defect model (5 mm) stabilized with three distinctly different external fixator stiffness. Defects were treated with 5 μg rhBMP2 loaded on an absorbable collagen sponge. Early matrix alignment was monitored by second‐harmonic generation imaging. Bony bridging of defects and successive healing was monitored by histology at day 7 and day 14 as well as in vivo microCT at days 10, 21, and 42 post‐operation. Femora harvested at day 42 were characterized mechanically assessing torsional load to failure ex vivo. At tissue level, differences between groups were visible at day 14 with manifest bone formation in the microCT. Histologically, we observed prolonged chondrogenesis upon flexible fixation, whereas osteogenesis started earlier after rigid and semirigid fixation. At later time points, there was a boost of bone tissue formation upon flexible fixation, whereas other groups already displayed signs of tissue maturation. Based on gene expression profiling, we analyzed the mechanobiological interplay. Already at day 3, these analyses revealed differences in expression pattern, specifically of genes involved in extracellular matrix formation. Gene regulation correlating with fixator stiffness was pronounced at day 7 comprising genes related to immunological processes and cellular contraction. The influence of loading on matrix contraction was further investigated and confirmed in a 3D bioreactor. Taken together, we demonstrate an early onset of mechanical conditions influencing BMP2‐induced defect healing and shed light on gene regulatory networks associated with extracellular matrix organization and contraction that seemed to directly impact healing outcomes. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

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Enzyme‐Photodynamic Adaptive Bionic Periosteum for Bone Revitalization

Chen,

Jin,

et al. 2024

Adv Funct Materials

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The lack of periosteum in bone allografts is considered a major cause of bone graft failure; however, the currently used artificial periosteum has failed to proactively adapt to its chronological role in the repair process. This study designed an adaptive periosteal system with dual‐response mechanisms to enable interactive angiogenic/osteogenic stimulation customized for inflammatory and anabolic stages of bone healing. Utilizing the enzymatic reactions and photodynamic properties of gold nanorod‐porous silicon, angiogenic peptides (QK) are released in response to matrix metalloproteinase 2 (MMP‐2), whereas bone‐forming peptides (BFP) are triggered by timed near‐infrared (NIR) irradiation, providing a portfolio of growth factors that match the dynamics of bone healing. The incorporation of such nanocarriers into a poly(N‐isopropyl acrylamide)/methacrylic acid gel (PNIPAM/GelMA) successfully formed a bionic periosteum that actively adapted to the function of the periosteum in different scenarios, resulting in more than doubled its ability to promote angiogenesis, stem cell migration, and osteogenesis compared to the controls. Furthermore, over 80% of the defects are covered with a new scab after the timed near‐infrared irradiation of large bone defects implanted with the system. The bionic periosteum actively mimicked the role of the periosteum in bone healing and offered a novel selection strategy for adaptability.

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Restoration of long bone defects treated with the induced membrane technique: protocol and outcomes

Cited by 156 publications

References 21 publications

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

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

The Interaction of BMP2‐Induced Defect Healing in Rat and Fixator Stiffness Modulates Matrix Alignment and Contraction

Enzyme‐Photodynamic Adaptive Bionic Periosteum for Bone Revitalization

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