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Modification of macroporous titanium tracheal implants with biodegradable structures: Tracking in vivo integration for determination of optimal in situ epithelialization conditions

Authors

  • Nihal Engin Vrana,

    1. Institut National de la Santé et de la Recherche Médicale, INSERM Unité 977, 11 Rue Humann, 67085 Strasbourg, France; telephone: +33-3-68-85-30-61; fax: +33-3-68-85-33-79
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  • Agnes Dupret-Bories,

    1. Institut National de la Santé et de la Recherche Médicale, INSERM Unité 977, 11 Rue Humann, 67085 Strasbourg, France; telephone: +33-3-68-85-30-61; fax: +33-3-68-85-33-79
    2. Hôpitaux Universitaires de Strasbourg, Service Oto-Rhino-Laryngologie, 67098 Strasbourg, France
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  • Charlotte Bach,

    1. Institut National de la Santé et de la Recherche Médicale, INSERM Unité 977, 11 Rue Humann, 67085 Strasbourg, France; telephone: +33-3-68-85-30-61; fax: +33-3-68-85-33-79
    2. Faculté de Chirurgie Dentaire, Université de Strasbourg, 1 Place de l'Hôpital, 67000 Strasbourg, France
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  • Christophe Chaubaroux,

    1. Institut National de la Santé et de la Recherche Médicale, INSERM Unité 977, 11 Rue Humann, 67085 Strasbourg, France; telephone: +33-3-68-85-30-61; fax: +33-3-68-85-33-79
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  • Christelle Coraux,

    1. Institut National de la Santé et de la Recherche Médicale, INSERM Unité 903, 51092 Reims, France
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  • Dominique Vautier,

    1. Institut National de la Santé et de la Recherche Médicale, INSERM Unité 977, 11 Rue Humann, 67085 Strasbourg, France; telephone: +33-3-68-85-30-61; fax: +33-3-68-85-33-79
    2. Faculté de Chirurgie Dentaire, Université de Strasbourg, 1 Place de l'Hôpital, 67000 Strasbourg, France
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  • Fouzia Boulmedais,

    1. Centre National de la Recherche Scientifique, UPR 22, Institut Charles Sadron, 23 rue du Loess, BP 84037, 67034 Strasbourg Cedex 2, France
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  • Youssef Haikel,

    1. Institut National de la Santé et de la Recherche Médicale, INSERM Unité 977, 11 Rue Humann, 67085 Strasbourg, France; telephone: +33-3-68-85-30-61; fax: +33-3-68-85-33-79
    2. Faculté de Chirurgie Dentaire, Université de Strasbourg, 1 Place de l'Hôpital, 67000 Strasbourg, France
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  • Christian Debry,

    1. Institut National de la Santé et de la Recherche Médicale, INSERM Unité 977, 11 Rue Humann, 67085 Strasbourg, France; telephone: +33-3-68-85-30-61; fax: +33-3-68-85-33-79
    2. Hôpitaux Universitaires de Strasbourg, Service Oto-Rhino-Laryngologie, 67098 Strasbourg, France
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  • Marie-Helene Metz-Boutigue,

    1. Institut National de la Santé et de la Recherche Médicale, INSERM Unité 977, 11 Rue Humann, 67085 Strasbourg, France; telephone: +33-3-68-85-30-61; fax: +33-3-68-85-33-79
    2. Faculté de Chirurgie Dentaire, Université de Strasbourg, 1 Place de l'Hôpital, 67000 Strasbourg, France
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  • Philippe Lavalle

    Corresponding author
    1. Institut National de la Santé et de la Recherche Médicale, INSERM Unité 977, 11 Rue Humann, 67085 Strasbourg, France; telephone: +33-3-68-85-30-61; fax: +33-3-68-85-33-79
    2. Faculté de Chirurgie Dentaire, Université de Strasbourg, 1 Place de l'Hôpital, 67000 Strasbourg, France
    • Institut National de la Santé et de la Recherche Médicale, INSERM Unité 977, 11 Rue Humann, 67085 Strasbourg, France; telephone: +33-3-68-85-30-61; fax: +33-3-68-85-33-79.
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Abstract

Previously, we showed that macroporous titanium implants, colonized in vivo together with an epithelial graft, are viable options for tracheal replacement in sheep. To decrease the number of operating steps, biomaterial-based replacements for epithelial graft and intramuscular implantation were developed in the present study. Hybrid microporous PLLA/titanium tracheal implants were designed to decrease initial stenosis and provide a surface for epithelialization. They have been implanted in New Zealand white rabbits as tracheal substitutes and compared to intramuscular implantation samples. Moreover, a basement membrane like coating of the implant surface was also designed by Layer-by-Layer (LbL) method with collagen and alginate. The results showed that the commencement of stenosis can be prevented by the microporous PLLA. For determination of the optimum time point of epithelialization after implantation, HPLC analysis of blood samples, C-reactive protein (CRP), and Chromogranin A (CGA) analyses and histology were carried out. Following 3 weeks the implant would be ready for epithelialization with respect to the amount of tissue integration. Calcein-AM labeled epithelial cell seeding showed that after 3 weeks implant surfaces were suitable for their attachment. CRP readings were steady after an initial rise in the first week. Cross-linked collagen/alginate structures show nanofibrillarity and they form uniform films over the implant surfaces without damaging the microporosity of the PLLA body. Human respiratory epithelial cells proliferated and migrated on these surfaces which provided a better alternative to PLLA film surface. In conclusion, collagen/alginate LbL coated hybrid PLLA/titanium implants are viable options for tracheal replacement, together with in situ epithelialization. Biotechnol. Bioeng. 2012; 109:2134–2146. © 2012 Wiley Periodicals, Inc.

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