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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1488611
This article is part of the Research Topic Organ crosstalk and other responses to an activated immune system in trauma and disease View all 6 articles

Enhancement of a one-step membrane technique for the treatment of large bone defects by pre-seeding the membrane with CD8 lymphocyte depleted bone marrow mononuclear cells in a rat femoral defect model.

Provisionally accepted
Marissa Penna-Martinez Marissa Penna-Martinez 1*Andreas Kammerer Andreas Kammerer 1Pia Stützle Pia Stützle 1Sabatian Fees Sabatian Fees 1Savina Behr Savina Behr 1Inna Schaible Inna Schaible 1Katrin Schröder Katrin Schröder 2René D. Verboket René D. Verboket 1Jonas Neijhoft Jonas Neijhoft 1Ingo Marzi Ingo Marzi 1Christoph Nau Christoph Nau 1Dirk Henrich Dirk Henrich 1
  • 1 Department of Trauma Surgery and Orthopaedics, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany
  • 2 Vascular Research Center, Goethe University Frankfurt, Frankfurt am Main, Germany

The final, formatted version of the article will be published soon.

    Background: The one-step membrane technique, using a human acellular dermal matrix (hADM), is an experimental method for treating large bone defects. This eliminates the need for the Masquelet membrane induction step, shortening the procedure while maintaining effectiveness. However, previous studies showed that colonizing hADM with bone marrow mononuclear cells (BMC) worsens healing, likely due to the presence of CD8+ lymphocytes, which negatively affect bone regeneration. This study aims to investigate whether the negative impact of BMC on bone healing in this technique is due to the CD8+ cell population. Materials and Methods: A 5 mm femoral defect was created in 25 male Sprague-Dawley rats, divided into three groups (G1-G3). BMC were isolated from syngenic donor rats, with CD8+ lymphocytes removed magnetically from the BMC fraction in one group. The defects were filled with bone chips and wrapped with differently treated hADM: G1 received native hADM, G2 received hADM+BMC, and G3 received hADM+BMC-CD8. After 8 weeks, the femurs were evaluated through radiological, biomechanical, and histological examinations. Results: Bone defects and bone mineral density (BMD) were significantly improved in G3 (hADM+BMC-CD8) compared to G2 (hADM+BMC). Bone volume, bone formation, and median bending stiffness were higher in G3. Immunohistological analysis showed a significant decrease in CD8 cell count in G3, with a lower percentage of IFNγ-producing cells compared to G2. Conclusion: Depleting CD8+ cells from BMC before colonizing hADM significantly improved bone healing, likely due to changes in the local mediator environment. This suggests that preoperative colonization with CD8+-depleted BMC could enhance the one-step membrane technique.

    Keywords: Bone marrow-derived mononuclear cells, BMC, CD8 lymphocytes, bone healing, Human acellular dermal matrix (HADM)

    Received: 30 Aug 2024; Accepted: 04 Oct 2024.

    Copyright: © 2024 Penna-Martinez, Kammerer, Stützle, Fees, Behr, Schaible, Schröder, Verboket, Neijhoft, Marzi, Nau and Henrich. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Marissa Penna-Martinez, Department of Trauma Surgery and Orthopaedics, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.