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The Treatment of Capsular Contracture Around Breast Implants Induced by Fractionated Irradiation: The Collagenase of the Bacterium Clostridium Histolyticum as a Novel Therapeutic Approach

  • Original Article
  • Basic Science/Experimental
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Abstract

Background

Irradiation therapy limits the utilization of silicone implants for breast reconstruction due to a significant risk for capsular contracture. The injection of the collagenase of the bacterium Clostridium histolyticum (CCH) might trivialize this risk by providing a minimal-invasive treatment option by capsular contracture degradation. However, efficacy in degrading breast implant capsules induced by fractionated irradiation remains unclear.

Methods

Twenty-four rats in three groups received miniature silicone implants in a submuscular pocket. After 3D dose calculation and treatment field definition, rats of two groups underwent fractionated radiotherapy (6 × 8 Gy) using a linear accelerator. A third group served as control. On day 120, one irradiated group received injections of 0.3 mg/ml collagenase. Administration of plain solvent solution served as control in the two other groups. Outcome parameters included CT-imaging, histology, vessel wall analysis, immunohistochemistry, chemical collagen quantification and gene expression analysis.

Results

Fractioned irradiation leads to a significant increase in collagen deposition around silicone implants with higher capsule thickness and collagen density when comparing all groups. Additionally, significant alterations of collagen fiber deposition were evident. Vessel wall thickness was significantly increased after radiotherapy. The injection of collagenase led to a significant reduction of capsule thickness, collagen density and content. However, the collagenase application induced a significant overexpression of TGFβ1. No side effects were monitored.

Conclusions

The CCH proved to be a safe and effective approach to degrade capsule tissue induced by fractionated irradiation in an animal model. This may pave its way for clinical application in implant-based breast reconstruction patients.

Level of Evidence

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Acknowledgements

We want to acknowledge funding support through an Educational Research Grant from Endo Pharmaceuticals. We would like to thank Polytech (Dieburg, Germany) for providing the miniature silicone implants. Funders did not influence study design, the collection, analysis and interpretation of data, the writing of the manuscript and the decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Department of Hand-, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwig-Guttmann-Strasse 13, 67071, Ludwigshafen, Germany

    Yannick F. Diehm, Yanic Jost, Dimitra Kotsougiani-Fischer, Valentin Haug, Ulrich Kneser & Sebastian Fischer

  2. Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St, Boston, 02115, USA

    Yannick F. Diehm & Valentin Haug

  3. German Cancer Research Center (DKFZ), Im Neuenheimer Feld 223, 69120, Heidelberg, Germany

    Mona Splinter & Peter Häring

  4. Toxicology and Chemotherapy Unit, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany

    Martin R. Berger

  5. Department of Clinical Radiology, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Jürgen Debus

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  1. Yannick F. Diehm
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Correspondence to Sebastian Fischer.

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The authors declare that they have no conflict of interest.

Ethical Approval

All applicable institutional and national guidelines for care and use of animals were followed (AEP No.: 05086).

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For this type of study, informed consent is not applicable.

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Electronic supplementary material

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Supplementary Figure 1: Example picture of minimal-invasive CCH-Injection.

The CCH is injected between implant and capsule in the upper parts of the capsule with a blunt needle. Distribution into the lower capsule parts takes place due to gravity. (PNG 1423 kb)

Supplementary Figure 2: Example Pictures of outcome analysis.

Representative slides of CT-scans (first row), Hematoxylin & Eosin (thickness measurements, second row), Picrosirus Red (density measurements, third row) and Vessels (fourth row) of all study groups. (PNG 3468 kb)

Supplementary Figure 3: Example Pictures of Immunohistochemistry.

Representative slides at 20× magnification of all study groups for collagen I–IV subtype and TGFβ1 analysis. (JPG 245 kb)

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Diehm, Y.F., Jost, Y., Kotsougiani-Fischer, D. et al. The Treatment of Capsular Contracture Around Breast Implants Induced by Fractionated Irradiation: The Collagenase of the Bacterium Clostridium Histolyticum as a Novel Therapeutic Approach. Aesth Plast Surg 45, 1273–1281 (2021). https://doi.org/10.1007/s00266-020-01970-1

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