Osteogenic, stem cell and molecular characterisation of the human induced membrane from extremity bone defects

He, Guanghua; Ode, Gabriella E.; Hoelscher, Gretchen L.; Ingram, Jane A.; Bethea, Synthia; Bosse, Michael J.

doi:10.1302/2046-3758.54.2000483

Cited by 64 publications

(84 citation statements)

References 33 publications

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“…As has been noted in basic science studies 21,22 and some case studies, 24 mineralized tissue will sometimes extend from the original cortical bone ends to encase the spacer. There were no differences between groups in maximal bone extent length (~1.7mm) or total bone volumes.…”

Section: Resultsmentioning

confidence: 95%

Masquelet Technique: Effects of Spacer Material and Micro-topography on Factor Expression and Bone Regeneration

et al. 2018

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We and others have shown that changing surface characteristics of the spacer implanted during the first Masquelet stage alters some aspects of membrane development. Previously we demonstrated that titanium spacers create membranes that are better barriers to movement of solutes >70kDa in size than polymethyl methacrylate (PMMA) induced-membranes, and roughening creates more mechanically compliant membranes. However, it is unclear if these alterations affect the membrane’s biochemical environment or bone regeneration during the second stage. Ten-week-old, male Sprague-Dawley rats underwent an initial surgery to create an externally stabilized 6mm femoral defect. PMMA or titanium spacers with smooth (~1um) or roughened (~8um) surfaces were implanted. Four weeks later, rats were either euthanized for membrane harvest or underwent the second Masquelet surgery. Titanium spacers induced thicker membranes that were similar in structure and biochemical expression. All membranes were bilayered with the inner layer having increased factor expression (BMP2, TGFβ, IL6, and VEGF). Roughening increased overall IL6 levels. Ten-weeks post-engraftment, PMMA-smooth induced membranes better supported bone regeneration (60% union). The other groups only had 1 or 2 that united (9–22%). There were no significant differences in any microCT or dynamic histology outcome. In conclusion, this study suggests that the membrane’s important function in the Masquelet technique is not simply as a barrier. There is likely a critical biochemical, cellular, or vascular component as well.

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Section: Resultsmentioning

confidence: 95%

Masquelet Technique: Effects of Spacer Material and Micro-topography on Factor Expression and Bone Regeneration

et al. 2018

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“…11,[34][35][36][37][38] 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-b), bone morphogenetic protein-2 (BMP-2), and vascular endothelial growth factor (VEGF). 27,39,40 We, therefore, differed in depth analysis of the induced membrane itself and focused on bone formation so as to not unnecessarily duplicate previously validated conclusions.…”

Section: Discussionmentioning

confidence: 99%

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

DeBaun

Stahl

Daoud

et al. 2018

Journal Orthopaedic Research

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Critical bone defects pose a formidable orthopaedic problem in patients with bone loss. We developed a preclinical model based on the induced membrane technique using a synthetic graft to replace autograft for healing critical bone defects. Additionally, we used a novel osteoconductive scaffold coupled with a synthetic membrane to evaluate the potential for single‐stage bone regeneration. Three experimental conditions were investigated in critical femoral defects in rats. Group A underwent a two‐stage procedure with insertion of a polymethylmethacrylate (PMMA) spacer followed by replacement with a 3D printed polycaprolactone(PCL)/β‐tricalcium phosphate (β‐TCP) osteoconductive scaffold after 4 weeks. Group B received a single‐stage PCL/β‐TCP scaffold wrapped in a PCL‐based microporous polymer film creating a synthetic membrane. Group C received a single‐stage bare PCL/β‐TCP scaffold. All groups were examined by serial radiographs for callus formation. After 12 weeks, the femurs were explanted and analyzed with micro‐CT and histology. Mean callus scores tended to be higher in Group A. Group A showed statistically significant greater bone formation on micro‐CT compared with other groups, although bone volume fraction was similar between groups. Histology results suggested extensive bone ingrowth and new bone formation within the macroporous scaffolds in all groups and cell infiltration into the microporous synthetic membrane. This study supports the use of a critical size femoral defect in rats as a suitable model for investigating modifications to the induced membrane technique without autograft harvest. Future investigations should focus on bioactive synthetic membranes coupled with growth factors for single‐stage bone healing. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

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“…First, it separates mechanically the bone defect from the surrounding soft tissue and prevents the ingrowth of fibrous tissues into the defect site [9]. Second, the induced Masquelet membrane has pronounced osteogenic and angiogenic properties; it secretes growth factors such as BMP-2, TGF-β1, and VEGF [13] and supports osteoblastic differentiation [19].…”

Section: Introductionmentioning

confidence: 99%

From two stages to one: acceleration of the induced membrane (Masquelet) technique using human acellular dermis for the treatment of non-infectious large bone defects

Verboket

Leiblein

Janko

et al. 2020

Eur J Trauma Emerg Surg

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Introduction The induced membrane technique for the treatment of large bone defects is a two-step procedure. In the first operation, a foreign body membrane is induced around a spacer, then, in the second step, several weeks or months later, the spacer is removed and the Membrane pocket is filled with autologous bone material. Induction of a functional biological membrane might be avoided by initially using a biological membrane. In this study, the effect of a human acellular dermis (hADM, Epiflex, DIZG gGmbH) was evaluated for the treatment of a large (5 mm), plate-stabilised femoral bone defect. Material and MethodsIn an established rat model, hADM was compared to the two-stage induced membrane technique and a bone defect without membrane cover. Syngeneous spongiosa from donor animals was used for defect filling in all groups. The group size in each case was n = 5, the induction time of the membrane was 3-4 weeks and the healing time after filling of the defect was 8 weeks. Results The ultimate loads were increased to levels comparable with native bone in both membrane groups (hADM: 63.2% ± 29.6% of the reference bone, p < 0.05 vs. no membrane, induced membrane: 52.1% ± 25.8% of the reference bone, p < 0.05 vs. no membrane) and were significantly higher than the control group without membrane (21.5%). The membrane groups were radiologically and histologically almost completely bridged by new bone formation, in contrast to the control Group where no closed osseous bridging could be observed. Conclusion The use of the human acellular dermis leads to equivalent healing results in comparison to the two-stage induced membrane technique. This could lead to a shortened therapy duration of large bone defects.

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Osteogenic, stem cell and molecular characterisation of the human induced membrane from extremity bone defects

Cited by 64 publications

References 33 publications

Masquelet Technique: Effects of Spacer Material and Micro-topography on Factor Expression and Bone Regeneration

Masquelet Technique: Effects of Spacer Material and Micro-topography on Factor Expression and Bone Regeneration

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

From two stages to one: acceleration of the induced membrane (Masquelet) technique using human acellular dermis for the treatment of non-infectious large bone defects

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