Scientific Articles   |    
The Mechanism of Action of Induced Membranes in Bone Repair
Olli-Matti Aho, BM1; Petri Lehenkari, MD, PhD1; Jukka Ristiniemi, MD, PhD2; Siri Lehtonen, PhD1; Juha Risteli, MD, PhD1; Hannu-Ville Leskelä, MD, PhD1
1 Clinical Research Center (O.-M.A., P.L., S.L., and H.-V. L), Department of Clinical Chemistry, Institute of Diagnostics (J.R.), Division of Anatomy and Cell Biology, Department of Biomedicine (P.L, S.L., and H.-V. L), P.O. Box 8000, 90014, University of Oulu, Oulu, Finland. E-mail address for O.-M. Aho: olli-matti.aho@oulu.fi. E-mail address for P. Lehenkari: Petri.Lehenkari@oulu.fi. E-mail address for S. Lehtonen: Siri.Lehtonen@oulu.fi. E-mail address for J. Risteli: Juha.Risteli@oulu.fi. E-mail address for H.-V. Leskelä: Hannu-Ville.Leskela@ppshp.fi
2 Division of Orthopedic and Trauma Surgery, Department of Surgery, P.O. Box 21, 90029, Oulu University Hospital, Oulu, Finland. E-mail address: Jukka.Ristiniemi@ppshp.fi
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Investigation performed at the University of Oulu, Oulu, Finland

Disclosure: One or more of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of an aspect of this work. In addition, one or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. No author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Copyright © 2013 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2013 Apr 03;95(7):597-604. doi: 10.2106/JBJS.L.00310
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Inducement of foreign-body granulation tissue is a relatively novel therapeutic modality in bone repair. A two-stage bone reconstruction method, known as the Masquelet technique, combines inducement of a granulation tissue membrane and subsequent bone autografting as a biphasic technique allowing reconstruction of large bone defects. In light of their already well-characterized osteogenesis-improving capabilities in animals, we performed this translational study to investigate these membranes in patients.


Fourteen patients with complicated fractures and bone defects were randomly selected for this study. Biopsy samples of foreign-body-induced membranes were collected at different time points during scheduled surgical procedures. The membranes were co-cultured with mesenchymal stromal cells, and differentiation into the osteoblastic lineage was assessed by measuring alkaline phosphatase activity, aminoterminal propeptide of type-I procollagen (PINP) production, and Ca2+ concentration. Histological characteristics were evaluated with image analysis. Quantitative reverse transcription polymerase chain reaction was used to measure vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and type-I collagen (Col-1) expression.


The induced membranes were characterized histologically by maturating vascularized fibrous tissue. The vascularization was greatest in one-month-old samples and decreased to <60% in three-month-old samples. One-month-old membrane samples had the highest expression of VEGF, IL-6, and Col-1, whereas two-month-old membranes expressed <40% of the levels of the one-month-old membranes. Specific alkaline phosphatase activity, PINP production, and Ca2+ concentration were increased in co-cultures when a membrane sample was present. In cultures of one-month-old membranes, PINP production was more than two times and Ca2+ deposition was four times higher than that in cultures of two-month-old membranes.


The induced membranes have osteogenesis-improving capabilities. These capabilities, however, appear to decrease over time. We speculate that the optimal time for performing second-stage surgery may be within a month after implantation of foreign material.

Clinical Relevance: 

The two-stage bone reconstruction method is an easily adaptable technique for repair of large bone defects. Further understanding of membrane biology and maturation in humans can help to optimize current procedures and improve their overall success rate.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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