Liste de Publications

2019

  • [DOI] N. E. Vrana, A. M. Ghaemmaghami, and P. Zorlutuna, « Editorial: adverse reactions to biomaterials: state of the art in biomaterial risk assessment, immunomodulation and in vitro models for biomaterial testing, » Frontiers in bioengineering and biotechnology, vol. 7, p. 15, 2019.
    [Bibtex]
    @ARTICLE{10.3389/fbioe.2019.00015,
    AUTHOR={Vrana, Nihal Engin and Ghaemmaghami, Amir M. and Zorlutuna, Pinar},
    TITLE={Editorial: Adverse Reactions to Biomaterials: State of the Art in Biomaterial Risk Assessment, Immunomodulation and in vitro Models for Biomaterial Testing},
    JOURNAL={Frontiers in Bioengineering and Biotechnology},
    VOLUME={7},
    PAGES={15},
    YEAR={2019},
    URL={https://www.frontiersin.org/article/10.3389/fbioe.2019.00015},
    DOI={10.3389/fbioe.2019.00015},
    ISSN={2296-4185}
    }
  • [DOI] F. Sharifi, S. S. Htwe, M. Righi, H. Liu, A. Pietralunga, O. Yesil-Celiktas, S. Maharjan, B. Cha, S. R. Shin, M. R. Dokmeci, N. E. Vrana, A. M. Ghaemmaghami, A. Khademhosseini, and Y. S. Zhang, « A foreign body response-on-a-chip platform, » Advanced healthcare materials, vol. 8, iss. 4, p. 1801425, 2019.
    [Bibtex]
    @article{doi:10.1002/adhm.201801425,
    author = {Sharifi, Fatemeh and Htwe, Su Su and Righi, Martina and Liu, Hua and Pietralunga, Anna and Yesil-Celiktas, Ozlem and Maharjan, Sushila and Cha, Byung-Hyun and Shin, Su Ryon and Dokmeci, Mehmet Remzi and Vrana, Nihal Engin and Ghaemmaghami, Amir M. and Khademhosseini, Ali and Zhang, Yu Shrike},
    title = {A Foreign Body Response-on-a-Chip Platform},
    journal = {Advanced Healthcare Materials},
    volume = {8},
    number = {4},
    pages = {1801425},
    keywords = {biomaterials, foreign body responses, immune responses, implants, organs-on-a-chip},
    doi = {10.1002/adhm.201801425},
    url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.201801425},
    eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/adhm.201801425},
    abstract = {Abstract Understanding the foreign body response (FBR) and desiging strategies to modulate such a response represent a grand challenge for implant devices and biomaterials. Here, the development of a microfluidic platform is reported, i.e., the FBR-on-a-chip (FBROC) for modeling the cascade of events during immune cell response to implants. The platform models the native implant microenvironment where the implants are interfaced directly with surrounding tissues, as well as vasculature with circulating immune cells. The study demonstrates that the release of cytokines such as monocyte chemoattractant protein 1 (MCP-1) from the extracellular matrix (ECM)-like hydrogels in the bottom tissue chamber induces trans-endothelial migration of circulating monocytes in the vascular channel toward the hydrogels, thus mimicking implant-induced inflammation. Data using patient-derived peripheral blood mononuclear cells further reveal inter-patient differences in FBR, highlighting the potential of this platform for monitoring FBR in a personalized manner. The prototype FBROC platform provides an enabling strategy to interrogate FBR on various implants, including biomaterials and engineered tissue constructs, in a physiologically relevant and individual-specific manner.},,
    year = {2019}
    }

2018

  • [DOI] Y. Fujiso, N. Perrin, J. van der Giessen, N. E. Vrana, F. Neveu, and V. Woisard, « Swall-E: A robotic in-vitro simulation of human swallowing, » Plos one, vol. 13, iss. 12, pp. 1-15, 2018.
    [Bibtex]
    @article{10.1371/journal.pone.0208193,
    author = {Fujiso, Yo AND Perrin, Nicolas AND van der Giessen, Julian AND Vrana, Nihal Engin AND Neveu, Fabrice AND Woisard, Virginie},
    journal = {PLOS ONE},
    publisher = {Public Library of Science},
    title = {Swall-{E}: {A} robotic in-vitro simulation of human swallowing},
    year = {2018},
    month = {12},
    volume = {13},
    url = {https://doi.org/10.1371/journal.pone.0208193},
    pages = {1-15},
    abstract = {Swallowing is a complex physiological function that can be studied through medical imagery techniques such as videofluoroscopy (VFS), dynamic magnetic resonance imagery (MRI) and fiberoptic endoscopic evaluation of swallowing (FEES). VFS is the gold standard although it exposes the subjects to radiations. In-vitro modeling of human swallowing has been conducted with limited results so far. Some experiments were reported on robotic reproduction of oral and esophageal phases of swallowing, but high fidelity reproduction of pharyngeal phase of swallowing has not been reported yet. To that end, we designed and developed a robotic simulator of the pharyngeal phase of human swallowing named Swall-E. 17 actuators integrated in the robot enable the mimicking of important physiological mechanisms occurring during the pharyngeal swallowing, such as the vocal fold closure, laryngeal elevation or epiglottis tilt. Moreover, the associated computer interface allows a control of the actuation of these mechanisms at a spatio-temporal accuracy of 0.025 mm and 20 ms. In this study preliminary experiments of normal pharyngeal swallowing simulated on Swall-E are presented. These experiments show that a 10 ml thick bolus can be swallowed by the robot in less than 1 s without any aspiration of bolus material into the synthetic anatomical laryngo-tracheal conduit.},
    number = {12},
    doi = {10.1371/journal.pone.0208193}
    }
  • [DOI] J. Barthes, C. Dollinger, C. B. Muller, U. Liivas, A. Dupret-Bories, H. Knopf-Marques, and N. E. Vrana, « Immune assisted tissue engineering via incorporation of macrophages in cell-laden hydrogels under cytokine stimulation, » Frontiers in bioengineering and biotechnology, vol. 6, 2018.
    [Bibtex]
    @article{barthes2018immune,
    title={Immune Assisted Tissue Engineering via Incorporation of Macrophages in Cell-Laden Hydrogels Under Cytokine Stimulation},
    author={Barthes, Julien and Dollinger, Camille and Muller, Celine B and Liivas, Urmas and Dupret-Bories, Agnes and Knopf-Marques, Helena and Vrana, Nihal E},
    journal={Frontiers in bioengineering and biotechnology},
    volume={6},
    year={2018},
    publisher={Frontiers Media SA},
    doi={10.3389/fbioe.2018.00108}
    }
  • [DOI] C. Dollinger, S. Ciftci, H. Knopf-Marques, R. Guner, A. M. Ghaemmaghami, C. Debry, J. Barthes, and N. E. Vrana, « Incorporation of resident macrophages in engineered tissues: multiple cell type response to microenvironment controlled macrophage-laden gelatine hydrogels, » Journal of tissue engineering and regenerative medicine, vol. 12, iss. 2, pp. 330-340, 2018.
    [Bibtex]
    @article{doi:10.1002/term.2458,
    author = {Dollinger, Camille and Ciftci, Sait and Knopf-Marques, Helena and Guner, Rabia and Ghaemmaghami, Amir M. and Debry, Christian and Barthes, Julien and Vrana, Nihal Engin},
    title = {Incorporation of resident macrophages in engineered tissues: Multiple cell type response to microenvironment controlled macrophage-laden gelatine hydrogels},
    journal = {Journal of Tissue Engineering and Regenerative Medicine},
    volume = {12},
    number = {2},
    pages = {330-340},
    keywords = {cellcell interactions, foreign body response, gelatine, hydrogel, macrophage, microenvironment},
    doi = {10.1002/term.2458},
    url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/term.2458},
    eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/term.2458},
    abstract = {Abstract The success of tissue engineering strategy is strongly related to the inflammatory response, mainly through the activity of macrophages that are key cells in initial immune response to implants. For engineered tissues, the presence of resident macrophages can be beneficial for maintenance of homeostasis and healing. Thus, incorporation of macrophages in engineered tissues can facilitate the integration upon implantation. In this study, an in-vitro model of interaction was developed between encapsulated naive monocytes, macrophages induced with M1/M2 stimulation and incoming cells for immune assisted tissue engineering applications. To mimic the wound healing cascade, naive THP-1 monocytes, endothelial cells and fibroblasts were seeded on the gels as incoming cells. The interaction was first monitored in the absence of the gels. To mimic resident macrophages, THP-1 cells were encapsulated in the presence or absence of IL-4 to control their phenotype and then these hydrogels were seeded with incoming cells. Without encapsulation, activated macrophages induce apoptosis in endothelial cells. Once encapsulated no adverse effects were seen. Macrophage-laden hydrogels attracted more endothelial cells and fibroblasts compared to monocytes-laden hydrogels. The induction (M2 stimulation) of encapsulated macrophages did not change the overall number of attracted cells; but significantly affected their morphology. M1 stimulation by a defined media resulted in more secretion of both pro- and anti-inflammatory cytokines compared to M2 stimulation. It was demonstrated that there is a distinct effect of encapsulated macrophages on the behaviour of the incoming cells; this effect can be harnessed to establish a microenvironment more prone to regeneration upon implantation.},,
    year = {2018}
    }
  • [DOI] J. Bystroñová, I. Ščigalková, L. Wolfová, M. Pravda, N. E. Vrana, and V. Velebný, « Creating a 3d microenvironment for monocyte cultivation: ecm-mimicking hydrogels based on gelatine and hyaluronic acid derivatives, » Rsc adv., vol. 8, pp. 7606-7614, 2018.
    [Bibtex]
    @Article{C7RA13739G,
    author ="Bystro{\~n}ov{\'a}, Julie and \v{S}\v{c}igalkov{\'a}, Ivana and Wolfov{\'a}, Lucie and Pravda, Martin and Vrana, Nihal Engin and Velebn{\'y}, Vladimir",
    title ="Creating a 3D microenvironment for monocyte cultivation: ECM-mimicking hydrogels based on gelatine and hyaluronic acid derivatives",
    journal ="RSC Adv.",
    year ="2018",
    volume ="8",
    issue ="14",
    pages ="7606-7614",
    publisher ="The Royal Society of Chemistry",
    doi ="10.1039/C7RA13739G",
    url ="http://dx.doi.org/10.1039/C7RA13739G",
    abstract ="Macrophages play a critical role in the initial response to foreign materials in the body. As most biomaterial-based implantable devices would be treated as a foreign body by the immune system{,} there is a need for systems that can establish a favourable interaction between the implanted biomaterial and the host. Herein{,} we describe such a system that can be used as an ECM-like microenvironment for macrophage polarization. The hydrogel system was designed to provide a co-crosslinkable microenvironment containing both protein and glycosaminoglycan components{,} a hydroxyphenyl derivative of gelatine (GTNHPA) and tyraminated hyaluronic acid (HATA). Both polymers can undergo a crosslinking reaction between polymer chains via the same polymerisation initiation system where the polymer network is formed by crosslinks between phenols in GTNHPA and HATA. The mechanical properties and swelling of the hydrogel can be easily controlled as a function of the crosslinking mode and by the ratio of GTNHPA and HATA compounds used. THP-1 monocytes were successfully encapsulated in the gels and cultured for up to 28 days. Cells exhibited higher metabolic activity when encapsulated in softer hydrogels (E  10 kPa) compared to stiffer (E  20 kPa) material in which monocytes tended to form large clusters. Encapsulation of monocytes in the material with HATA content enhanced the expression of macrophage-related genes. We demonstrated a co-crosslinkable GTNHPA and HATA matrix microenvironment that is suitable for in vitro micro t
    }
  • [DOI] J. Barthes, S. Ciftci, F. Ponzio, H. Knopf-Marques, L. Pelyhe, A. Gudima, I. Kientzl, E. Bognár, M. Weszl, J. Kzhyshkowska, and N. E. Vrana, « Review: the potential impact of surface crystalline states of titanium for biomedical applications, » Critical reviews in biotechnology, vol. 38, iss. 3, pp. 423-437, 2018.
    [Bibtex]
    @article{doi:10.1080/07388551.2017.1363707,
    author = {Julien Barthes and Sait Ciftci and Florian Ponzio and Helena Knopf-Marques and Liza Pelyhe and Alexandru Gudima and Imre Kientzl and Eszter Bogn{\'a}r and Mikl{\'o}s Weszl and Julia Kzhyshkowska and Nihal Engin Vrana},
    title = {Review: the potential impact of surface crystalline states of titanium for biomedical applications},
    journal = {Critical Reviews in Biotechnology},
    volume = {38},
    number = {3},
    pages = {423-437},
    year = {2018},
    publisher = {Taylor & Francis},
    doi = {10.1080/07388551.2017.1363707},
    note ={PMID: 28882077},
    URL = {
    https://doi.org/10.1080/07388551.2017.1363707
    },
    eprint = {
    https://doi.org/10.1080/07388551.2017.1363707
    }
    }
  • [DOI] M. Reggente, P. Masson, C. Dollinger, H. Palkowski, S. Zafeiratos, L. Jacomine, D. Passeri, M. Rossi, N. E. Vrana, G. Pourroy, and A. Carradò, « Novel alkali activation of titanium substrates to grow thick and covalently bound pmma layers, » Acs applied materials & interfaces, vol. 10, iss. 6, pp. 5967-5977, 2018.
    [Bibtex]
    @article{doi:10.1021/acsami.7b17008,
    author = {Reggente, Melania and Masson, Patrick and Dollinger, Camille and Palkowski, Heinz and Zafeiratos, Spyridon and Jacomine, Leandro and Passeri, Daniele and Rossi, Marco and Vrana, Nihal Engin and Pourroy, Genevive and Carrad{\`o}, Adele},
    title = {Novel Alkali Activation of Titanium Substrates To Grow Thick and Covalently Bound PMMA Layers},
    journal = {ACS Applied Materials \& Interfaces},
    volume = {10},
    number = {6},
    pages = {5967-5977},
    year = {2018},
    doi = {10.1021/acsami.7b17008},
    note ={PMID: 29338177},
    URL = {
    https://doi.org/10.1021/acsami.7b17008
    },
    eprint = {
    https://doi.org/10.1021/acsami.7b17008
    }
    }
  • [DOI] N. Nagarajan, A. Dupret-Bories, E. Karabulut, P. Zorlutuna, and N. E. Vrana, « Enabling personalized implant and controllable biosystem development through 3d printing, » Biotechnology advances, vol. 36, iss. 2, pp. 521-533, 2018.
    [Bibtex]
    @article{NAGARAJAN2018521,
    title = "Enabling personalized implant and controllable biosystem development through 3D printing",
    journal = "Biotechnology Advances",
    volume = "36",
    number = "2",
    pages = "521 - 533",
    year = "2018",
    issn = "0734-9750",
    doi = "https://doi.org/10.1016/j.biotechadv.2018.02.004",
    url = "http://www.sciencedirect.com/science/article/pii/S073497501830020X",
    author = "Neerajha Nagarajan and Agnes Dupret-Bories and Erdem Karabulut and Pinar Zorlutuna and Nihal Engin Vrana",
    keywords = "Biomedical devices, Personalized medicine, Bioprinting, Biorobotics, Implants",
    abstract = "The impact of additive manufacturing in our lives has been increasing constantly. One of the frontiers in this change is the medical devices. 3D printing technologies not only enable the personalization of implantable devices with respect to patient-specific anatomy, pathology and biomechanical properties but they also provide new opportunities in related areas such as surgical education, minimally invasive diagnosis, medical research and disease models. In this review, we cover the recent clinical applications of 3D printing with a particular focus on implantable devices. The current technical bottlenecks in 3D printing in view of the needs in clinical applications are explained and recent advances to overcome these challenges are presented. 3D printing with cells (bioprinting); an exciting subfield of 3D printing, is covered in the context of tissue engineering and regenerative medicine and current developments in bioinks are discussed. Also emerging applications of bioprinting beyond health, such as biorobotics and soft robotics, are introduced. As the technical challenges related to printing rate, precision and cost are steadily being solved, it can be envisioned that 3D printers will become common on-site instruments in medical practice with the possibility of custom-made, on-demand implants and, eventually, tissue engineered organs with active parts developed with biorobotics techniques."
    }
  • N. E. Vrana, « Introduction to immune response and biomaterials, » in Biomaterials and immune response, CRC Press, 2018, p. 1–16.
    [Bibtex]
    @incollection{vrana2018introduction,
    title={Introduction to Immune Response and Biomaterials},
    author={Vrana, Nihal Engin},
    booktitle={Biomaterials and Immune Response},
    pages={1--16},
    year={2018},
    publisher={CRC Press}
    }

2017

  • [DOI] J. Barthes, A. Mutschler, C. Dollinger, G. Gaudinat, P. Lavalle, V. L. Houerou, G. B. McGuinness, and N. E. Vrana, « Establishing contact between cell-laden hydrogels and metallic implants with a biomimetic adhesive for cell therapy supported implants, » Biomedical materials, vol. 13, iss. 1, p. 15015, 2017.
    [Bibtex]
    @article{Barthes_2017,
    doi = {10.1088/1748-605x/aa895b},
    url = {https://doi.org/10.1088%2F1748-605x%2Faa895b},
    year = 2017,
    month = {dec},
    publisher = {{IOP} Publishing},
    volume = {13},
    number = {1},
    pages = {015015},
    author = {Julien Barthes and Angela Mutschler and Camille Dollinger and Guillaume Gaudinat and Philippe Lavalle and Vincent Le Houerou and Garrett Brian McGuinness and Nihal Engin Vrana},
    title = {Establishing contact between cell-laden hydrogels and metallic implants with a biomimetic adhesive for cell therapy supported implants},
    journal = {Biomedical Materials},
    abstract = {For in-dwelling implants, controlling the biological interface is a crucial parameter to promote tissue integration and prevent implant failure. For this purpose, one possibility is to facilitate the establishment of the interface with cell-laden hydrogels fixed to the implant. However, for proper functioning, the stability of the hydrogel on the implant should be ensured. Modification of implant surfaces with an adhesive represents a promising strategy to promote the adhesion of a cell-laden hydrogel on an implant. Herein, we developed a peptidic adhesive based on mussel foot protein (L-DOPA-L-lysine)2-L-DOPA that can be applied directly on the surface of an implant. At physiological pH, unoxidized (L-DOPA-L-lysine)2-L-DOPA was supposed to strongly adhere to metallic surfaces but it only formed a very thin coating (less than 1 nm). Once oxidized at physiological pH, (L-DOPA-L-lysine)2-L-DOPA forms an adhesive coating about 20 nm thick. In oxidized conditions, L-lysine can adhere to metallic substrates via electrostatic interaction. Oxidized L-DOPA allows the formation of a coating through self-polymerization and can react with amines so that this adhesive can be used to fix extra-cellular matrix based materials on implant surfaces through the reaction of quinones with amino groups. Hence, a stable interface between a soft gelatin hydrogel and metallic surfaces was achieved and the strength of adhesion was investigated. We have shown that the adhesive is non-cytotoxic to encapsulated cells and enabled the adhesion of gelatin soft hydrogels for 21 days on metallic substrates in liquid conditions. The adhesion properties of this anchoring peptide was quantified by a 180 peeling test with a more than 60% increase in peel strength in the presence of the adhesive. We demonstrated that by using a biomimetic adhesive, for the application of cell-laden hydrogels to metallic implant surfaces, the hydrogel/implant interface can be ensured without relying on the properties of the deposited biomaterials.}
    }
  • [DOI] C. Debry, E. N. Vrana, and A. Dupret-Bories, « Implantation of an artificial larynx after total laryngectomy, » New england journal of medicine, vol. 376, iss. 1, pp. 97-98, 2017.
    [Bibtex]
    @article{doi:10.1056/NEJMc1611966,
    author = {Debry, Christian and Vrana, N. Engin and Dupret-Bories, Agn{\`e}s},
    title = {Implantation of an Artificial Larynx after Total Laryngectomy},
    journal = {New England Journal of Medicine},
    volume = {376},
    number = {1},
    pages = {97-98},
    year = {2017},
    doi = {10.1056/NEJMc1611966},
    note ={PMID: 28052218},
    URL = {
    https://doi.org/10.1056/NEJMc1611966
    },
    eprint = {
    https://doi.org/10.1056/NEJMc1611966
    }
    }
  • [DOI] M. Pokorny, J. Klemes, O. Zidek, C. Dollinger, G. Ozcebe, S. Singh, V. Velebny, A. M. Ghaemmaghami, L. Wolfova, and N. E. Vrana, « Electrohydrodynamic printing as a method to micropattern large titanium implant surfaces with photocrosslinkable structures, » Biomedical physics & engineering express, vol. 3, iss. 1, p. 15002, 2017.
    [Bibtex]
    @article{Pokorny_2017,
    doi = {10.1088/2057-1976/3/1/015002},
    url = {https://doi.org/10.1088%2F2057-1976%2F3%2F1%2F015002},
    year = 2017,
    month = {jan},
    publisher = {{IOP} Publishing},
    volume = {3},
    number = {1},
    pages = {015002},
    author = {Marek Pokorny and Jan Klemes and Ondrej Zidek and Camille Dollinger and Gulberk Ozcebe and Sonali Singh and Vladimir Velebny and Amir M Ghaemmaghami and Lucie Wolfova and Nihal Engin Vrana},
    title = {Electrohydrodynamic printing as a method to micropattern large titanium implant surfaces with photocrosslinkable structures},
    journal = {Biomedical Physics {\&} Engineering Express},
    abstract = {Metallic implants are widely used in orthopaedic and orthodontic applications. However, generally surface treatment of the metallic surfaces is necessary to render them more biologically active. Herein, we describe a direct write printing method to modify metallic implant surfaces with biocompatible polymers with microscale precision. Application of polymeric micropatterns on metallic implant surfaces can (i) improve their interaction with the host tissue, (ii) enable the delivery of growth factors, antibiotics, anti-inflammatory cytokines etc from the implant surface and (iii) can control the immune responses to the implant via controlling the attachment of immune cells, such as macrophages. Surface patterns with a resolution of less than 50 m can be created using an electro hydrodynamic (EHD) printing, a template-free and single-step process. We present a revised EHD printing method for the deposition of parallel strips of photocrosslinkable, cell adhesive polymeric composites with spacing of around 20 m onto medical grade titanium substrates. Optimization of voltage, feeding rate and collection speed resulted in regular structures via very rapid movement of the grounded rotating collector driven to equivalent of the linear surface speed of above 100 cm s-1. In the experimental part a mixture of chemically modified PEG /gelatin was deposited onto a conductive titanium substrate with different surface pretreatments with an area of 400 mm2. Acid etched or UV treated titanium surfaces improved the stability of the printed structures. Polymeric lines induced temporary orientation of human monocytes (THP-1) and induced a thicker cell multilayer formation by 3T3 fibroblasts (p<0.05). Staining of the monocytes for M1(CD80) and M2 (CD206) macrophage markers on the patterned surface showed mixed populations with higher anti-inflammatory cytokine secretion compared to tissue culture plastic control. The results demonstrate the suitability of this method for the preparation of biomaterials with structured surfaces on large areas and with desired chemical composition.}
    }
  • [DOI] H. Knopf-Marques, J. Barthes, L. Wolfova, B. Vidal, G. Koenig, J. Bacharouche, G. Francius, H. Sadam, U. Liivas, P. Lavalle, and N. E. Vrana, "Auxiliary biomembranes as a directional delivery system to control biological events in cell-laden tissue-engineering scaffolds," Acs omega, vol. 2, iss. 3, pp. 918-929, 2017.
    [Bibtex]
    @article{doi:10.1021/acsomega.6b00502,
    author = {Knopf-Marques, Helena and Barthes, Julien and Wolfova, Lucie and Vidal, B{\'e}reng{\`e}re and Koenig, Geraldine and Bacharouche, Jalal and Francius, Gr{\'e}gory and Sadam, Helle and Liivas, Urmas and Lavalle, Philippe and Vrana, Nihal Engin},
    title = {Auxiliary Biomembranes as a Directional Delivery System To Control Biological Events in Cell-Laden Tissue-Engineering Scaffolds},
    journal = {ACS Omega},
    volume = {2},
    number = {3},
    pages = {918-929},
    year = {2017},
    doi = {10.1021/acsomega.6b00502},
    URL = {
    https://doi.org/10.1021/acsomega.6b00502
    },
    eprint = {
    https://doi.org/10.1021/acsomega.6b00502
    }
    }
  • [DOI] "More on implantation of an artificial larynx after total laryngectomy," New england journal of medicine, vol. 376, iss. 14, p. e29, 2017.
    [Bibtex]
    @article{doi:10.1056/NEJMc1701193,
    title = {More on Implantation of an Artificial Larynx after Total Laryngectomy},
    journal = {New England Journal of Medicine},
    volume = {376},
    number = {14},
    pages = {e29},
    year = {2017},
    doi = {10.1056/NEJMc1701193},
    note ={PMID: 28379791},
    URL = {
    https://doi.org/10.1056/NEJMc1701193
    },
    eprint = {
    https://doi.org/10.1056/NEJMc1701193
    }
    }
  • [DOI] A. Mutschler, C. Betscha, V. Ball, B. Senger, N. E. Vrana, F. Boulmedais, A. Schroder, P. Schaaf, and P. Lavalle, "Nature of the polyanion governs the antimicrobial properties of poly(arginine)/polyanion multilayer films," Chemistry of materials, vol. 29, iss. 7, pp. 3195-3201, 2017.
    [Bibtex]
    @article{doi:10.1021/acs.chemmater.7b00334,
    author = {Mutschler, Angela and Betscha, Cosette and Ball, Vincent and Senger, Bernard and Vrana, Nihal Engin and Boulmedais, Fouzia and Schroder, Andr{\'e} and Schaaf, Pierre and Lavalle, Philippe},
    title = {Nature of the Polyanion Governs the Antimicrobial Properties of Poly(arginine)/Polyanion Multilayer Films},
    journal = {Chemistry of Materials},
    volume = {29},
    number = {7},
    pages = {3195-3201},
    year = {2017},
    doi = {10.1021/acs.chemmater.7b00334},
    URL = {
    https://doi.org/10.1021/acs.chemmater.7b00334
    },
    eprint = {
    https://doi.org/10.1021/acs.chemmater.7b00334
    }
    }
  • [DOI] V. Riabov, F. Salazar, S. S. Htwe, A. Gudima, C. Schmuttermaier, J. Barthes, H. Knopf-Marques, H. Klüter, A. M. Ghaemmaghami, N. E. Vrana, and J. Kzhyshkowska, "Generation of anti-inflammatory macrophages for implants and regenerative medicine using self-standing release systems with a phenotype-fixing cytokine cocktail formulation," Acta biomaterialia, vol. 53, pp. 389-398, 2017.
    [Bibtex]
    @article{RIABOV2017389,
    title = "Generation of anti-inflammatory macrophages for implants and regenerative medicine using self-standing release systems with a phenotype-fixing cytokine cocktail formulation",
    journal = "Acta Biomaterialia",
    volume = "53",
    pages = "389 - 398",
    year = "2017",
    issn = "1742-7061",
    doi = {10.1016/j.actbio.2017.01.071},
    url = "http://www.sciencedirect.com/science/article/pii/S1742706117300806",
    author = "Vladimir Riabov and Fabin Salazar and Su Su Htwe and Alexandru Gudima and Christina Schmuttermaier and Julien Barthes and Helena Knopf-Marques and Harald Kl{\"u}ter and Amir M. Ghaemmaghami and Nihal Engin Vrana and Julia Kzhyshkowska",
    keywords = "Gelatin, Cytokine, Macrophage phenotype control, Controlled release, Wound healing",
    abstract = "The immediate tissue microenvironment of implanted biomedical devices and engineered tissues is highly influential on their long term fate and efficacy. The creation of a long-term anti-inflammatory microenvironment around implants and artificial tissues can facilitate their integration. Macrophages are highly plastic cells that define the tissue reactions on the implanted material. Local control of macrophage phenotype by long-term fixation of their healing activities and suppression of inflammatory reactions are required to improve implant acceptance. Herein, we describe the development of a cytokine cocktail (M2Ct) that induces stable M2-like macrophage phenotype with significantly decreased pro-inflammatory cytokine and increased anti-inflammatory cytokine secretion profile. The positive effect of the M2Ct was shown in an in vitro wound healing model; where M2Ct facilitated wound closure by human fibroblasts in co-culture conditions. Using a model for induction of inflammation by LPS we have shown that the M2Ct phenotype is stable for 12days. However, in the absence of M2Ct in the medium macrophages underwent rapid pro-inflammatory re-programming upon IFNg stimulation. Therefore, loading and release of the cytokine cocktail from a self-standing, transferable gelatin/tyraminated hyaluronic acid based release system was developed to stabilize macrophage phenotype for in vivo applications in implantation and tissue engineering. The M2Ct cytokine cocktail retained its anti-inflammatory activity in controlled release conditions. Our data indicate that the direct application of a potent M2 inducing cytokine cocktail in a transferable release system can significantly improve the long term functionality of biomedical devices by decreasing pro-inflammatory cytokine secretion and increasing the rate of wound healing.
    Statement of Significance
    Uncontrollable activation of macrophages in the microenvironment of implants and engineered tissues is a significant problem leading to poor integration of implants and artificial tissues. In the current manuscript we demonstrate that self-standing, transferable gelatin/tyraminated hyaluronic acid based thin films are perspective tools for controlled release of anti-inflammatory cytokine combinations and can be used to down-modulate macrophage activation on implant surfaces. We also show that optimized cytokine cocktail consisting of IL4/IL10/TGF1 (M2Ct) induces long-term anti-inflammatory and pro-healing phenotype in human primary monocyte-derived macrophages. This cocktail formulation could be loaded on gelatin/tyraminated films and promoted favorable M2-like macrophage phenotype with low responsiveness to pro-inflammatory stimuli. Such self-standing release systems can be used for prolonged local control of macrophage phenotype upon implantation."
    }
  • [DOI] M. Weszl, K. L. Tóth, I. Kientzl, P. Nagy, D. Pammer, L. Pelyhe, N. E. Vrana, D. Scharnweber, C. Wolf-Brandstetter, Á. J. F., and E. Bognár, "Investigation of the mechanical and chemical characteristics of nanotubular and nano-pitted anodic films on grade 2 titanium dental implant materials," Materials science and engineering: c, vol. 78, pp. 69-78, 2017.
    [Bibtex]
    @article{WESZL201769,
    title = "Investigation of the mechanical and chemical characteristics of nanotubular and nano-pitted anodic films on grade 2 titanium dental implant materials",
    journal = "Materials Science and Engineering: C",
    volume = "78",
    pages = "69 - 78",
    year = "2017",
    issn = "0928-4931",
    doi = {10.1016/j.msec.2017.04.032},
    url = "http://www.sciencedirect.com/science/article/pii/S0928493117305398",
    author = "Mikl{\'o}s Weszl and Kriszti{\'a}n L{\'a}szl{\'o} T{\'o}th and Imre Kientzl and P{\'e}ter Nagy and D{\'a}vid Pammer and Liza Pelyhe and Nihal E. Vrana and Dieter Scharnweber and Cornelia Wolf-Brandstetter and {\'A}rp{\'a}d Jo{\'o}b F. and Eszter Bogn{\'a}r",
    keywords = "Anodization, Nanotubes, Nano-pitted, Mechanical integrity, Titanium-oxide film",
    abstract = "Objective
    The objective of this study was to investigate the reproducibility, mechanical integrity, surface characteristics and corrosion behavior of nanotubular (NT) titanium oxide arrays in comparison with a novel nano-pitted (NP) anodic film.
    Methods
    Surface treatment processes were developed to grow homogenous NT and NP anodic films on the surface of grade 2 titanium discs and dental implants. The effect of process parameters on the surface characteristics and reproducibility of the anodic films was investigated and optimized. The mechanical integrity of the NT and NP anodic films were investigated by scanning electron microscopy, surface roughness measurement, scratch resistance and screwing tests, while the chemical and physicochemical properties were investigated in corrosion tests, contact angle measurement and X-ray photoelectron spectroscopy (XPS).
    Results and discussion
    The growth of NT anodic films was highly affected by process parameters, especially by temperature, and they were apt to corrosion and exfoliation. In contrast, the anodic growth of NP film showed high reproducibility even on the surface of 3-dimensional screw dental implants and they did not show signs of corrosion and exfoliation. The underlying reason of the difference in the tendency for exfoliation of the NT and NP anodic films is unclear; however the XPS analysis revealed fluorine dopants in a magnitude larger concentration on NT anodic film than on NP surface, which was identified as a possible causative. Concerning other surface characteristics that are supposed to affect the biological behavior of titanium implants, surface roughness values were found to be similar, whereas considerable differences were revealed in the wettability of the NT and NP anodic films.
    Conclusion
    Our findings suggest that the applicability of NT anodic films on the surface of titanium bone implants may be limited because of mechanical considerations. In contrast, it is worth to consider the applicability of nano-pitted anodic films over nanotubular arrays for the enhancement of the biological properties of titanium implants."
    }
  • [DOI] S. Singh, D. Awuah, H. M. Rostam, R. D. Emes, N. K. Kandola, D. Onion, S. S. Htwe, B. Rajchagool, B. Cha, D. Kim, P. J. Tighe, N. E. Vrana, A. Khademhosseini, and A. Ghaemmaghami, "Unbiased analysis of the impact of micropatterned biomaterials on macrophage behavior provides insights beyond predefined polarization states," Acs biomaterials science & engineering, vol. 3, iss. 6, pp. 969-978, 2017.
    [Bibtex]
    @article{doi:10.1021/acsbiomaterials.7b00104,
    author = {Singh, Sonali and Awuah, Dennis and Rostam, Hassan M. and Emes, Richard D. and Kandola, Navrohit K. and Onion, David and Htwe, Su Su and Rajchagool, Buddharaksa and Cha, Byung-Hyun and Kim, Duckjin and Tighe, Patrick J. and Vrana, Nihal E. and Khademhosseini, Ali and Ghaemmaghami, Amir},
    title = {Unbiased Analysis of the Impact of Micropatterned Biomaterials on Macrophage Behavior Provides Insights beyond Predefined Polarization States},
    journal = {ACS Biomaterials Science \& Engineering},
    volume = {3},
    number = {6},
    pages = {969-978},
    year = {2017},
    doi = {10.1021/acsbiomaterials.7b00104},
    URL = {
    https://doi.org/10.1021/acsbiomaterials.7b00104
    },
    eprint = {
    https://doi.org/10.1021/acsbiomaterials.7b00104
    }
    }
  • [DOI] C. Dollinger, A. Ndreu-Halili, A. Uka, S. Singh, H. Sadam, T. Neuman, M. Rabineau, P. Lavalle, M. R. Dokmeci, A. Khademhosseini, A. M. Ghaemmaghami, and N. E. Vrana, "Controlling incoming macrophages to implants: responsiveness of macrophages to gelatin micropatterns under m1/m2 phenotype defining biochemical stimulations," Advanced biosystems, vol. 1, iss. 6, p. 1700041, 2017.
    [Bibtex]
    @article{doi:10.1002/adbi.201700041,
    author = {Dollinger, Camille and Ndreu-Halili, Albana and Uka, Arban and Singh, Sonali and Sadam, Helle and Neuman, Toomas and Rabineau, Morgane and Lavalle, Philippe and Dokmeci, Mehmet R. and Khademhosseini, Ali and Ghaemmaghami, Amir M. and Vrana, Nihal E.},
    title = {Controlling Incoming Macrophages to Implants: Responsiveness of Macrophages to Gelatin Micropatterns under M1/M2 Phenotype Defining Biochemical Stimulations},
    journal = {Advanced Biosystems},
    volume = {1},
    number = {6},
    pages = {1700041},
    keywords = {contact guidance, cytokines, gelatin, macrophages, micropatterning},
    doi = {10.1002/adbi.201700041},
    url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/adbi.201700041},
    eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/adbi.201700041},
    abstract = {Adverse immune reactions to implanted devices can seriously hamper the efficacy of implants. Monocyte derived macrophages play a crucial role in both initiation and resolution of the inflammatory response toward foreign bodies. As the surface microtopography is shown to exert significant effects on cell phenotype, it is hypothesized that the presence of micropatterns on implant/medical device surfaces can attenuate the immune response. To this end, enzymatically crosslinked micropatterned gelatin films of varying groove widths (2, 5, 10, 20, and 40 m) are tested for their effect on incoming monocyte behavior. In order to distinguish the effect of cytokine microenvironment on pattern presence, monocytes are seeded on micropatterned films in normal culture medium or M1/M2 inducing media and their morphology and cytokine secretions are observed for 6 d. The presence of the patterns induces microenvironment-specific changes on the secretions of the attached cells and also on their size. IL-1, IL-4, IL-12, TNF-a, and CCL-18 secretions are significantly affected particularly in M1 induction media by pattern presence. It is demonstrated for the first time that micropatterned surfaces can be used to control the initial attachment and cytokine secretion of incoming macrophages if they are linked with a polarization inducing cytokine microenvironment.},,
    year = {2017}
    }
  • [DOI] A. Uka, X. Polisi, A. Halili, C. Dollinger, and N. E. Vrana, "Analysis of cell behavior on micropatterned surfaces by image processing algorithms," in Ieee eurocon 2017 -17th international conference on smart technologies, 2017, pp. 75-78.
    [Bibtex]
    @INPROCEEDINGS{8011080,
    author={A. {Uka} and X. {Polisi} and A. {Halili} and C. {Dollinger} and N. E. {Vrana}},
    booktitle={IEEE EUROCON 2017 -17th International Conference on Smart Technologies},
    title={Analysis of cell behavior on micropatterned surfaces by image processing algorithms},
    year={2017},
    volume={},
    number={},
    pages={75-78},
    keywords={biology computing;cellular biophysics;image filtering;image segmentation;pattern clustering;micropatterned surfaces;image processing algorithms;cell behavior;multimedia elements;image analysis algorithm;cellular shape quantification;cellular size quantification;cell clustering;cell segmentation;cell counting;frequency domain;spatial domain;quantitative analysis;cellular features;substrate topography;cellular metrics;Algorithm design and analysis;Clustering algorithms;Shape;Image segmentation;Surface topography;Biomedical imaging;Image analysis;Monocyte;micropatterned surface;segmentation},
    doi={10.1109/EUROCON.2017.8011080},
    ISSN={},
    month={July},}
  • [DOI] B. Cha, S. R. Shin, J. Leijten, Y. Li, S. Singh, J. C. Liu, N. Annabi, R. Abdi, M. R. Dokmeci, N. E. Vrana, A. M. Ghaemmaghami, and A. Khademhosseini, "Integrin-mediated interactions control macrophage polarization in 3d hydrogels," Advanced healthcare materials, vol. 6, iss. 21, p. 1700289, 2017.
    [Bibtex]
    @article{doi:10.1002/adhm.201700289,
    author = {Cha, Byung-Hyun and Shin, Su Ryon and Leijten, Jeroen and Li, Yi-Chen and Singh, Sonali and Liu, Julie C. and Annabi, Nasim and Abdi, Reza and Dokmeci, Mehmet R. and Vrana, Nihal Engin and Ghaemmaghami, Amir M. and Khademhosseini, Ali},
    title = {Integrin-Mediated Interactions Control Macrophage Polarization in 3D Hydrogels},
    journal = {Advanced Healthcare Materials},
    volume = {6},
    number = {21},
    pages = {1700289},
    keywords = {hydrogels, immune modulation, integrin, M1, M2, macrophage polarization},
    doi = {10.1002/adhm.201700289},
    url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.201700289},
    eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/adhm.201700289},
    abstract = {Abstract Adverse immune reactions prevent clinical translation of numerous implantable devices and materials. Although inflammation is an essential part of tissue regeneration, chronic inflammation ultimately leads to implant failure. In particular, macrophage polarity steers the microenvironment toward inflammation or wound healing via the induction of M1 and M2 macrophages, respectively. Here, this paper demonstrates that macrophage polarity within biomaterials can be controlled through integrin-mediated interactions between human monocytic THP-1 cells and collagen-derived matrix. Surface marker, gene expression, biochemical, and cytokine profiling consistently indicate that THP-1 cells within a biomaterial lacking cell attachment motifs yield proinflammatory M1 macrophages, whereas biomaterials with attachment sites in the presence of interleukin-4 (IL-4) induce an anti-inflammatory M2-like phenotype and propagate the effect of IL-4 in induction of M2-like macrophages. Importantly, integrin a21 plays a pivotal role as its inhibition blocks the induction of M2 macrophages. The influence of the microenvironment of the biomaterial over macrophage polarity is further confirmed by its ability to modulate the effect of IL-4 and lipopolysaccharide, which are potent inducers of M2 or M1 phenotypes, respectively. Thus, this study represents a novel, versatile, and effective strategy to steer macrophage polarity through integrin-mediated 3D microenvironment for biomaterial-based programming.},,
    year = {2017}
    }
  • P. Kumar, N. E. Vrana, and A. M. Ghaemmaghami, "Prospects and challenges in engineering functional respiratory epithelium for in vitro and in vivo applications," Microphysiological systems, vol. 1, iss. 2, 2017.
    [Bibtex]
    @article{MPS4175,
    author = {Pramod Kumar and Nihal E. Vrana and Amir M. Ghaemmaghami},
    title = {Prospects and challenges in engineering functional respiratory epithelium for in vitro and in vivo applications},
    journal = {Microphysiological Systems},
    volume = {1},
    number = {2},
    year = {2017},
    keywords = {},
    abstract = {Respiratory diseases are amongst the leading causes of morbidity and mortality worldwide. There is therefore significant interest in developing more efficient treatment strategies for respiratory diseases particularly where there is irreversible tissue damage and loss of function. Despite recent advances in tissue engineering and stem cell technologies the reconstruction of large defects of upper airway and similar pathologies in respiratory system remains an unmet clinical need. The complex organisation of respiratory epithelium still has not been completely recapitulated in vitro. Therefore, novel strategies for the regeneration of functional ciliated respiratory epithelium are required to address the need for the treatment of life threatening respiratory diseases as well as developing biomimetic in vitro models that can be used in drug discovery and disease modelling. This review primarily focuses on current cell based approaches including available cell sources which have shown potential for developing biomimetic models/replacements of upper respiratory epithelium. Most of the tissue engineering approaches for the development of airway epithelium use epithelial basal cells, autologous or allogenic adult stem cells, induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs) or other stromal cells to induce the organised epithelial differentiation. However, the viability and function of injected/implanted cells could suffer from the host immune response and fail to perform the desired therapeutic functions. Also, given the key role of immune cells in the respiratory epithelium in maintaining defense against external insults, the importance of immune-competency of engineered respiratory epithelia is also discussed. To this end, modulation of immune system and application of biomaterials could play an important role in improving the therapeutic value of cell based respiratory epithelium regeneration. Overall, efforts for reconstruction of functional airway epithelium can be further improved by using optimal cell sources, biomaterials and modulation of immune response. The ability to engineer organised, functional respiratory epithelium can not only provide a remedy for several debilitating diseases but also provide a strong tool for in vitro drug assessment and disease modelling.},
    url = {http://mps.amegroups.com/article/view/4175}
    }
  • [DOI] M. B. Evangelista, S. Ciftci, P. Milad, E. Martinod, A. Dupret-Bories, C. Debry, and N. E. Vrana, "Engineering trachea and larynx," Tissue engineering for artificial organs: regenerative medicine, smart diagnostics and personalized medicine, vol. 2, p. 363–387, 2017.
    [Bibtex]
    @article{evangelista2017engineering,
    title={Engineering Trachea and Larynx},
    author={Evangelista, Marta B and Ciftci, Sait and Milad, Peter and Martinod, Emmanuel and Dupret-Bories, Agnes and Debry, Christian and Vrana, Nihal E},
    journal={Tissue Engineering for Artificial Organs: Regenerative Medicine, Smart Diagnostics and Personalized Medicine},
    volume={2},
    pages={363--387},
    year={2017},
    publisher={Wiley Online Library},
    doi={10.1002/9783527689934.ch11}
    }

2016

  • [DOI] S. Ciftci, J. Barthes, P. Lavalle, H. Özçelik, C. Debry, A. Dupret-Bories, and N. E. Vrana, "Double thin film-based sandwich-cell carrier design for multicellular tissue engineering," Materials & design, vol. 95, pp. 648-655, 2016.
    [Bibtex]
    @article{CIFTCI2016648,
    title = "Double thin film-based sandwich-cell carrier design for multicellular tissue engineering",
    journal = "Materials & Design",
    volume = "95",
    pages = "648 - 655",
    year = "2016",
    issn = "0264-1275",
    doi = "https://doi.org/10.1016/j.matdes.2016.01.120",
    url = "http://www.sciencedirect.com/science/article/pii/S0264127516301204",
    author = "Sait Ciftci and Julien Barthes and Philippe Lavalle and Hayriye {\"O}z\c{c}elik and Christian Debry and Agnes Dupret-Bories and Nihal Engin Vrana",
    keywords = "Gelatin, Respiratory epithelium, Implants, Larynx, Tissue patch",
    abstract = "Many organs are multicellular and each cell type requires a different microenvironment. Thus, there is a need for modular structures where the microenvironment of each cell type can be tuned separately. Herein, we describe enzymatically crosslinked gelatin based double layered film structures where each layer can be loaded with growth factors separately. As a model, we have developed a bi-layer system to produce a respiratory epithelium. This system constitutes an in vitro epithelial patch that can be adhered to the lumen of any implant. Crosslinking of the patches with transglutaminase resulted in 7days of stability at 37C. The film layer was first used to release growth factors and it was shown that the release significantly improved the proliferation over 5days. A549 human lung epithelial cells were used and under the release of an epithelial growth supplement mix, there was a significant improvement on the epithelial proliferation (p<0.01). The designed substrate was successfully attached to titanium implants and we demonstrated the stability of the epithelial patch under in vitro conditions for 7days without deterioration. Under co-culture conditions for three days both cell types were alive. Such patches can be used to obtain fast epithelialization of large implant surfaces."
    }
  • [DOI] G. Koenig, H. Ozcelik, L. Haesler, M. Cihova, S. Ciftci, A. Dupret-Bories, C. Debry, M. Stelzle, P. Lavalle, and N. E. Vrana, "Cell-laden hydrogel/titanium microhybrids: site-specific cell delivery to metallic implants for improved integration," Acta biomaterialia, vol. 33, pp. 301-310, 2016.
    [Bibtex]
    @article{KOENIG2016301,
    title = "Cell-laden hydrogel/titanium microhybrids: Site-specific cell delivery to metallic implants for improved integration",
    journal = "Acta Biomaterialia",
    volume = "33",
    pages = "301 - 310",
    year = "2016",
    issn = "1742-7061",
    doi = "https://doi.org/10.1016/j.actbio.2016.01.023",
    url = "http://www.sciencedirect.com/science/article/pii/S1742706116300228",
    author = "Geraldine Koenig and Hayriye Ozcelik and Lisa Haesler and Martina Cihova and Sait Ciftci and Agnes Dupret-Bories and Christian Debry and Martin Stelzle and Philippe Lavalle and Nihal Engin Vrana",
    keywords = "Titanium, model, Hydrogel, PVA, Dextran, Hybrid, Co-culture",
    abstract = "Porous titanium implants are widely used in dental, orthopaedic and otorhinolaryngology fields to improve implant integration to host tissue. A possible step further to improve the integration with the host is the incorporation of autologous cells in porous titanium structures via cell-laden hydrogels. Fast gelling hydrogels have advantageous properties for in situ applications such as localisation of specific cells and growth factors at a target area without dispersion. The ability to control the cell types in different regions of an implant is important in applications where the target tissue (i) has structural heterogeneity (multiple cell types with a defined spatial configuration with respect to each other); (ii) has physical property gradients essential for its function (such as in the case of osteochondral tissue transition). Due to their near immediate gelation, such gels can also be used for site-specific modification of porous titanium structures, particularly for implants which would face different tissues at different locations. Herein, we describe a step by step design of a model system: the model cell-laden gel-containing porous titanium implants in the form of titanium microbead/hydrogel (maleimide-dextran or maleimide-PVA based) microhybrids. These systems enable the determination of the effect of titanium presence on gel properties and encapsulated cell behaviour as a miniaturized version of full-scale implants, providing a system compatible with conventional analysis methods. We used a fibroblast/vascular endothelial cell co-cultures as our model system and by utilising single microbeads we have quantified the effect of gel microenvironment (degradability, presence of RGD peptides within gel formulation) on cell behaviour and the effect of the titanium presence on cell behaviour and gel formation. Titanium presence slightly changed gel properties without hindering gel formation or affecting cell viability. Cells showed a preference to move towards the titanium beads and fibroblast proliferation was significantly higher in hybrids compared to gel only controls. The MMP (Matrix Metalloproteinase)-sensitive hydrogels induced sprouting by cells in co-culture configuration which was quantified by fluorescence microscopy, confocal microscopy and qRT-PCR (Quantitative Reverse transcription polymerase chain reaction). When the microhybrid up-scaled to 3D thick structures, cellular localisation in specific areas of the 3D titanium structures was achieved, without decreasing overall cell proliferation compared to titanium only scaffolds. Microhybrids of titanium and hydrogels are useful models for deciding the necessary modifications of metallic implants and they can be used as a modelling system for the study of tissue/titanium implant interactions.
    Statement of Significance
    This article demonstrates a method to apply cell-laden hydrogels to porous titanium implants and a model of titanium/hydrogel interaction at micro-level using titanium microbeads. The feasibility of site-specific modification of titanium implants with cell-laden microgels has been demonstrated. Use of titanium microbeads in combination with hydrogels with conventional analysis techniques as described in the article can facilitate the characterisation of surface modification of titanium in a relevant model system."
    }
  • [DOI] H. Knopf-Marques, M. Pravda, L. Wolfova, V. Velebny, P. Schaaf, N. E. Vrana, and P. Lavalle, "Hyaluronic acid and its derivatives in coating and delivery systems: applications in tissue engineering, regenerative medicine and immunomodulation," Advanced healthcare materials, vol. 5, iss. 22, pp. 2841-2855, 2016.
    [Bibtex]
    @article{doi:10.1002/adhm.201600316,
    author = {Knopf-Marques, Helena and Pravda, Martin and Wolfova, Lucie and Velebny, Vladimir and Schaaf, Pierre and Vrana, Nihal Engin and Lavalle, Philippe},
    title = {Hyaluronic Acid and Its Derivatives in Coating and Delivery Systems: Applications in Tissue Engineering, Regenerative Medicine and Immunomodulation},
    journal = {Advanced Healthcare Materials},
    volume = {5},
    number = {22},
    pages = {2841-2855},
    keywords = {biomedical, coatings, delivery systems, hyaluronic acid, immunomodulation, tissue engineering},
    doi = {10.1002/adhm.201600316},
    url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.201600316},
    eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/adhm.201600316},
    abstract = {As an Extracellular Matrix (ECM) component, Hyaluronic acid (HA) plays a multi-faceted role in cell migration, proliferation and differentiation at micro level and system level events such as tissue water homeostasis. Among its biological functions, it is known to interact with cytokines and contribute to their retention in ECM microenvironment. In addition to its biological functions, it has advantageous physical properties which result in the industrial endeavors in the synthesis and extraction of HA for variety of applications ranging from medical to cosmetic. Recently, HA and its derivatives have been the focus of active research for applications in biomedical device coatings, drug delivery systems and in the form of scaffolds or cell-laden hydrogels for tissue engineering. A specific reason for the increase in use of HA based structures is their immunomodulatory and regeneration inducing capacities. In this context, this article reviews recent literature on modulation of the implantable biomaterial microenvironment by systems based on HA and its derivatives, particularly hydrogels and microscale coatings that are able to deliver cytokines in order to reduce the adverse immune reactions and promote tissue healing.},,
    year = {2016}
    }
  • [DOI] A. Mutschler, L. Tallet, M. Rabineau, C. Dollinger, M. Metz-Boutigue, F. Schneider, B. Senger, N. E. Vrana, P. Schaaf, and P. Lavalle, "Unexpected bactericidal activity of poly(arginine)/hyaluronan nanolayered coatings," Chemistry of materials, vol. 28, iss. 23, pp. 8700-8709, 2016.
    [Bibtex]
    @article{doi:10.1021/acs.chemmater.6b03872,
    author = {Mutschler, Angela and Tallet, Lorne and Rabineau, Morgane and Dollinger, Camille and Metz-Boutigue, Marie-Hlne and Schneider, Francis and Senger, Bernard and Vrana, Nihal Engin and Schaaf, Pierre and Lavalle, Philippe},
    title = {Unexpected Bactericidal Activity of Poly(arginine)/Hyaluronan Nanolayered Coatings},
    journal = {Chemistry of Materials},
    volume = {28},
    number = {23},
    pages = {8700-8709},
    year = {2016},
    doi = {10.1021/acs.chemmater.6b03872},
    URL = {
    https://doi.org/10.1021/acs.chemmater.6b03872
    },
    eprint = {
    https://doi.org/10.1021/acs.chemmater.6b03872
    }
    }
  • [DOI] N. E. Vrana, "Immunomodulatory biomaterials and regenerative immunology," Future science oa, vol. 2, iss. 4, p. FSO146, 2016.
    [Bibtex]
    @article{doi:10.4155/fsoa-2016-0060,
    author = {Vrana, Nihal Engin},
    title = {Immunomodulatory biomaterials and regenerative immunology},
    journal = {Future Science OA},
    volume = {2},
    number = {4},
    pages = {FSO146},
    year = {2016},
    doi = {10.4155/fsoa-2016-0060},
    note ={PMID: 28116128},
    URL = {
    https://doi.org/10.4155/fsoa-2016-0060
    },
    eprint = {
    https://doi.org/10.4155/fsoa-2016-0060
    }
    }
  • [DOI] H. M. Rostam, S. Singh, F. Salazar, P. Magennis, A. Hook, T. Singh, N. E. Vrana, M. R. Alexander, and A. M. Ghaemmaghami, "The impact of surface chemistry modification on macrophage polarisation," Immunobiology, vol. 221, iss. 11, pp. 1237-1246, 2016.
    [Bibtex]
    @article{ROSTAM20161237,
    title = "The impact of surface chemistry modification on macrophage polarisation",
    journal = "Immunobiology",
    volume = "221",
    number = "11",
    pages = "1237 - 1246",
    year = "2016",
    issn = "0171-2985",
    doi = "https://doi.org/10.1016/j.imbio.2016.06.010",
    url = "http://www.sciencedirect.com/science/article/pii/S0171298516300973",
    author = "Hassan M. Rostam and Sonali Singh and Fabian Salazar and Peter Magennis and Andrew Hook and Taranjit Singh and Nihal E. Vrana and Morgan R. Alexander and Amir M. Ghaemmaghami",
    keywords = "Macrophage, Monocyte, M1, M2, Macrophage polarisation, Biomaterials, Surface chemistry, Oxygen plasma etching, Water contact angle, Foreign body response",
    abstract = "Macrophages are innate immune cells that have a central role in combating infection and maintaining tissue homeostasis. They exhibit remarkable plasticity in response to environmental cues. At either end of a broad activation spectrum are pro-inflammatory (M1) and anti-inflammatory (M2) macrophages with distinct functional and phenotypical characteristics. Macrophages also play a crucial role in orchestrating immune responses to biomaterials used in the fabrication of implantable devices and drug delivery systems. To assess the impact of different surface chemistries on macrophage polarisation, human monocytes were cultured for 6 days on untreated hydrophobic polystyrene (PS) and hydrophilic O2 plasma-etched polystyrene (O2-PS40) surfaces. Our data clearly show that monocytes cultured on the hydrophilic O2-PS40 surface are polarised towards an M1-like phenotype, as evidenced by significantly higher expression of the pro-inflammatory transcription factors STAT1 and IRF5. By comparison, monocytes cultured on the hydrophobic PS surface exhibited an M2-like phenotype with high expression of mannose receptor (MR) and production of the anti-inflammatory cytokines IL-10 and CCL18. While the molecular basis of such different patterns of cell differentiation is yet to be fully elucidated, we hypothesise that it is due to the adsorption of different biomolecules on these surface chemistries. Indeed our surface characterisation data show quantitative and qualitative differences between the protein layers on the O2-PS40 surface compared to PS surface which could be responsible for the observed differential macrophage polarisation on each surface."
    }
  • [DOI] H. Knopf-Marques, S. Singh, S. S. Htwe, L. Wolfova, R. Buffa, J. Bacharouche, G. Francius, J. Voegel, P. Schaaf, A. M. Ghaemmaghami, N. E. Vrana, and P. Lavalle, "Immunomodulation with self-crosslinked polyelectrolyte multilayer-based coatings," Biomacromolecules, vol. 17, iss. 6, pp. 2189-2198, 2016.
    [Bibtex]
    @article{doi:10.1021/acs.biomac.6b00429,
    author = {Knopf-Marques, Helena and Singh, Sonali and Htwe, Su Su and Wolfova, Lucie and Buffa, Radovan and Bacharouche, Jalal and Francius, Grgory and Voegel, Jean-Claude and Schaaf, Pierre and Ghaemmaghami, Amir M. and Vrana, Nihal Engin and Lavalle, Philippe},
    title = {Immunomodulation with Self-Crosslinked Polyelectrolyte Multilayer-Based Coatings},
    journal = {Biomacromolecules},
    volume = {17},
    number = {6},
    pages = {2189-2198},
    year = {2016},
    doi = {10.1021/acs.biomac.6b00429},
    note ={PMID: 27183396},
    URL = {
    https://doi.org/10.1021/acs.biomac.6b00429
    },
    eprint = {
    https://doi.org/10.1021/acs.biomac.6b00429
    }
    }

2015

  • [DOI] J. Kzhyshkowska, A. Gudima, V. Riabov, C. Dollinger, P. Lavalle, and N. E. Vrana, "Macrophage responses to implants: prospects for personalized medicine," Journal of leukocyte biology, vol. 98, iss. 6, pp. 953-962, 2015.
    [Bibtex]
    @article{doi:10.1189/jlb.5VMR0415-166R,
    author = {Kzhyshkowska, Julia and Gudima, Alexandru and Riabov, Vladimir and Dollinger, Camille and Lavalle, Philippe and Vrana, Nihal Engin},
    title = {Macrophage responses to implants: prospects for personalized medicine},
    journal = {Journal of Leukocyte Biology},
    volume = {98},
    number = {6},
    pages = {953-962},
    keywords = {cytokine, biomarker, biomaterial, titanium, coating},
    doi = {10.1189/jlb.5VMR0415-166R},
    url = {https://jlb.onlinelibrary.wiley.com/doi/abs/10.1189/jlb.5VMR0415-166R},
    eprint = {https://jlb.onlinelibrary.wiley.com/doi/pdf/10.1189/jlb.5VMR0415-166R},
    abstract = {Review of how macrophage response to implants results in adverse inflammatory reactions needing prediction and correction by personalized selection of implant coatings.},,
    year = {2015}
    }
  • [DOI] H. M. Rostam, S. Singh, N. E. Vrana, M. R. Alexander, and A. M. Ghaemmaghami, "Impact of surface chemistry and topography on the function of antigen presenting cells," Biomater. sci., vol. 3, pp. 424-441, 2015.
    [Bibtex]
    @Article{C4BM00375F,
    author ="Rostam, H. M. and Singh, S. and Vrana, N. E. and Alexander, M. R. and Ghaemmaghami, A. M.",
    title ="Impact of surface chemistry and topography on the function of antigen presenting cells",
    journal ="Biomater. Sci.",
    year ="2015",
    volume ="3",
    issue ="3",
    pages ="424-441",
    publisher ="The Royal Society of Chemistry",
    doi ="10.1039/C4BM00375F",
    url ="http://dx.doi.org/10.1039/C4BM00375F",
    abstract ="Antigen presenting cells (APCs) such as macrophages and dendritic cells (DCs) play a crucial role in orchestrating immune responses against foreign materials. The activation status of APCs can determine the outcome of an immune response following implantation of synthetic materials{,} towards either healing or inflammation. A large range of biomaterials are used in the fabrication of implantable devices and drug delivery systems. These materials will be in close contact with APCs and characteristics such as surface chemistry and topography may have a critical role in initiating pro- or anti-inflammatory immune responses. Controlling biomaterial surface attributes provides a powerful tool for modulating the phenotype and function of immune cells with the aim of reducing detrimental pro-inflammatory responses and promoting beneficial healing responses. In this article{,} we review recent literature on how biomaterial surface topography and chemistry can modulate APC populations towards distinct pro- or anti-inflammatory phenotypes with specific examples of how these properties can be used to control host response in vivo. Topographical and/or chemical design of biomaterial surfaces with respect to the APC responses can pave the way for a new generation of cell instructive materials with immunomodulatory properties with a wide range of clinical applications.
    }
  • H. Özçelik, N. E. Vrana, A. Gudima, V. Riabov, A. Gratchev, Y. Haikel, M. Metz-Boutigue, A. Carradò, J. Faerber, T. Roland, H. Klüter, J. Kzhyshkowska, P. Schaaf, and P. Lavalle, ."
    [Bibtex]
    @article{doi:10.1002/adhm.201500546,
    author = {\"O}z\c{c}elik, Hayriye and Vrana, Nihal Engin and Gudima, Alexandru and Riabov, Vladimir and Gratchev, Alexei and Haikel, Youssef and Metz-Boutigue, Marie-Hlne and Carrad{\`o}, Adele and Faerber, Jacques and Roland, Thierry and Kl{\"u}ter, Harald and Kzhyshkowska, Julia and Schaaf, Pierre and Lavalle, Philippe}
  • [DOI] J. Barthes, N. E. Vrana, H. Özçelik, R. Gahoual, Y. N. François, J. Bacharouche, G. Francius, J. Hemmerlé, M. Metz-Boutigue, P. Schaaf, and P. Lavalle, "Priming cells for their final destination: microenvironment controlled cell culture by a modular ecm-mimicking feeder film," Biomater. sci., vol. 3, pp. 1302-1311, 2015.
    [Bibtex]
    @Article{C5BM00172B,
    author ="Barthes, Julien and Vrana, Nihal E. and \"Oz\c{c}elik, Hayriye and Gahoual, Rabah and Fran\c{c}ois, Yannis N. and Bacharouche, Jalal and Francius, Grgory and Hemmerl{\'e}, Joseph and Metz-Boutigue, Marie-Hlne and Schaaf, Pierre and Lavalle, Philippe",
    title ="Priming cells for their final destination: microenvironment controlled cell culture by a modular ECM-mimicking feeder film",
    journal ="Biomater. Sci.",
    year ="2015",
    volume ="3",
    issue ="9",
    pages ="1302-1311",
    publisher ="The Royal Society of Chemistry",
    doi ="10.1039/C5BM00172B",
    url ="http://dx.doi.org/10.1039/C5BM00172B"
    }
  • [DOI] S. Dietemann, C. Debry, A. Onea, I. J. Namer, and A. Imperiale, "Epiglottic Squamous Cell Carcinoma Showing Unexpected 18F-FDOPA Uptake on PET/CT Investigation.," Clinical nuclear medicine, vol. 40, iss. 7, p. e370–1, 2015.
    [Bibtex]
    @article{dietemann2015epiglottic,
    title={{Epiglottic Squamous Cell Carcinoma Showing Unexpected 18F-FDOPA Uptake on PET/CT Investigation.}},
    author={Dietemann, Sebastien and Debry, Christian and Onea, Aline and Namer, Izzie Jacques and Imperiale, Alessio},
    journal={Clinical nuclear medicine},
    volume={40},
    number={7},
    pages={e370--1},
    year={2015},
    doi={10.1097/RLU.0000000000000818}
    }

2014

  • [DOI] N. E. Vrana, A. Dupret-Bories, P. Schultz, C. Debry, D. Vautier, and P. Lavalle, "Titanium microbead-based porous implants: bead size controls cell response and host integration," Advanced healthcare materials, vol. 3, iss. 1, pp. 79-87, 2014.
    [Bibtex]
    @article{doi:10.1002/adhm.201200369,
    author = {Vrana, Nihal Engin and Dupret-Bories, Agn{\`e}s and Schultz, Philippe and Debry, Christian and Vautier, Dominique and Lavalle, Philippe},
    title = {Titanium Microbead-Based Porous Implants: Bead Size Controls Cell Response and Host Integration},
    journal = {Advanced Healthcare Materials},
    volume = {3},
    number = {1},
    pages = {79-87},
    keywords = {host integration, in vivo, porous implants, titanium, trachea},
    doi = {10.1002/adhm.201200369},
    url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.201200369},
    eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/adhm.201200369},
    abstract = {Abstract Openly porous structures in implants are desirable for better integration with the host tissue. Sintered microbead-based titanium implants for oto-rhinolaryngology applications, which create an environment where the cells can migrate in the areas between the microbeads, are developed. This structure promotes fibrovascular tissue formation within the implant in vivo. In this study, it is determine to what extent these events can be controlled by changing the physical environment of the implants both in vitro and in vivo. By cell tracking, it is observed that the size of the beads and the distance between the neighboring beads significantly affect the ability of cells to develop cell-to-cell contacts and to bridge the pores. Live cell staining shows that as the bead size gets smaller, the probability to observe cells that fill the porous areas is higher. This also affects the initial attachment and distribution of the cells and collagen secretion by fibroblasts. Obtaining a fast coverage of the system also enables co-culture systems where, the number and the distribution of the second cell type are boosted by the presence of the first. This concept is utilized to increase the attachment of vascular endothelial cells by an initial layer of fibroblasts. By decreasing the bead diameter, the overall colonization of the implant can be significantly increased in vivo. The effect of bead size has a similar pattern both in rats and rabbits, with faster colonization of smaller bead-based structures. Using smaller beads would improve clinical outcomes as faster integration facilitates the attainment of functionality by the implant.},,
    year = {2014}
    }
  • [DOI] N. E. Vrana, O. Erdemli, G. Francius, A. Fahs, M. Rabineau, C. Debry, A. Tezcaner, D. Keskin, and P. Lavalle, "Double entrapment of growth factors by nanoparticles loaded into polyelectrolyte multilayer films," J. mater. chem. b, vol. 2, pp. 999-1008, 2014.
    [Bibtex]
    @Article{C3TB21304H,
    author ="Vrana, N. E. and Erdemli, O. and Francius, G. and Fahs, A. and Rabineau, M. and Debry, C. and Tezcaner, A. and Keskin, D. and Lavalle, P.",
    title ="Double entrapment of growth factors by nanoparticles loaded into polyelectrolyte multilayer films",
    journal ="J. Mater. Chem. B",
    year ="2014",
    volume ="2",
    issue ="8",
    pages ="999-1008",
    publisher ="The Royal Society of Chemistry",
    doi ="10.1039/C3TB21304H",
    url ="http://dx.doi.org/10.1039/C3TB21304H",
    abstract ="Delivery of growth factors and control of vascularization are prominent problems in regenerative medicine. Vascular endothelial growth factor (VEGF) has been used both in vitro and in vivo to promote angiogenesis but due to its short half-life its controlled delivery is a sought after method. In this study we present a new concept of degradable drug loaded nanoparticles entrapped into exponentially growing multilayer films. Through hydrolysis of the nanoparticles{,} the drug can be delivered over long periods in a controlled manner. Poly(e-caprolactone) nanoparticles were loaded with VEGF and in turn the release of VEGF from a surface is controlled by a thick layer-by-layer polyelectrolyte film. Direct loading of VEGF inside the film was not efficient for long-term applications. When VEGF loaded nanoparticles were introduced into the film{,} the particles were equally distributed inside and were stable after several washes. Moreover{,} the presence of the film sustained the release of VEGF for 7 days. Addition of the nanoparticles to the film promoted endothelial cell proliferation{,} mainly due to the presence of VEGF. Mechanical properties of the film (Young{'}s moduli) were also improved by the presence of nanoparticles. However{,} in the presence of the film loaded with nanoparticles and without any direct contact with this film{,} endothelial cell growth was also enhanced on polystyrene and on Transwell insert surfaces which demonstrates the effectiveness of the nanoparticles not only to improve the mechanical properties of the film but also to deliver active VEGF. An increase in nitric oxide levels as an indicator of endothelial cell activity was monitored and was correlated with the release of VEGF from the nanoparticle/film platform. Finally{,} such a system can be used as an auxiliary delivery body within implants to finely control the release of bioactive agent containing nanoparticles."}
  • [DOI] N. Sananès, R. Ruano, A. Weingertner, P. Regnard, Y. Salmon, A. Kohler, C. Miry, C. Mager, F. Guerra, A. Schneider, F. Becmeur, J. Leroy, J. Dimarcq, C. Debry, and R. Favre, "Experimental fetal endoscopic tracheal occlusion in rhesus and cynomolgus monkeys: nonhuman primate models," The journal of maternal-fetal & neonatal medicine, vol. 28, iss. 15, pp. 1822-1827, 2015.
    [Bibtex]
    @article{doi:10.3109/14767058.2014.969234,
    author = {Nicolas Sanan{\`e}s and Rodrigo Ruano and Anne-Sophie Weingertner and Pierrick Regnard and Yves Salmon and Anne Kohler and Claire Miry and C{\'e}cile Mager and Fernando Guerra and Anne Schneider and Franois Becmeur and Jol Leroy and Jean-Luc Dimarcq and Christian Debry and Romain Favre},
    title = {Experimental fetal endoscopic tracheal occlusion in rhesus and cynomolgus monkeys: nonhuman primate models},
    journal = {The Journal of Maternal-Fetal \& Neonatal Medicine},
    volume = {28},
    number = {15},
    pages = {1822-1827},
    year = {2015},
    publisher = {Taylor & Francis},
    doi = {10.3109/14767058.2014.969234},
    note ={PMID: 25260124},
    URL = {
    https://doi.org/10.3109/14767058.2014.969234
    },
    eprint = {
    https://doi.org/10.3109/14767058.2014.969234
    }
    }
  • [DOI] A. Hasan, A. Paul, N. E. Vrana, X. Zhao, A. Memic, Y. Hwang, M. R. Dokmeci, and A. Khademhosseini, "Microfluidic techniques for development of 3d vascularized tissue," Biomaterials, vol. 35, iss. 26, pp. 7308-7325, 2014.
    [Bibtex]
    @article{HASAN20147308,
    title = "Microfluidic techniques for development of 3D vascularized tissue",
    journal = "Biomaterials",
    volume = "35",
    number = "26",
    pages = "7308 - 7325",
    year = "2014",
    issn = "0142-9612",
    doi = "https://doi.org/10.1016/j.biomaterials.2014.04.091",
    url = "http://www.sciencedirect.com/science/article/pii/S014296121400489X",
    author = "Anwarul Hasan and Arghya Paul and Nihal E. Vrana and Xin Zhao and Adnan Memic and Yu-Shik Hwang and Mehmet R. Dokmeci and Ali Khademhosseini",
    keywords = "Vascularization, Tissue engineering, Vasculogenesis, Angiogenesis, Microfluidics, Micromolding",
    abstract = "Development of a vascularized tissue is one of the key challenges for the successful clinical application of tissue engineered constructs. Despite the significant efforts over the last few decades, establishing a gold standard to develop three dimensional (3D) vascularized tissues has still remained far from reality. Recent advances in the application of microfluidic platforms to the field of tissue engineering have greatly accelerated the progress toward the development of viable vascularized tissue constructs. Numerous techniques have emerged to induce the formation of vascular structure within tissues which can be broadly classified into two distinct categories, namely (1) prevascularization-based techniques and (2) vasculogenesis and angiogenesis-based techniques. This review presents an overview of the recent advancements in the vascularization techniques using both approaches for generating 3D vascular structure on microfluidic platforms."
    }
  • [DOI] C. Debry, A. Dupret-Bories, N. E. Vrana, P. Hemar, P. Lavalle, and P. Schultz, "Laryngeal replacement with an artificial larynx after total laryngectomy: the possibility of restoring larynx functionality in the future," Head & neck, vol. 36, iss. 11, pp. 1669-1673, 2014.
    [Bibtex]
    @article{doi:10.1002/hed.23621,
    author = {Debry, Christian and Dupret-Bories, Agn{\`e}s and Vrana, Nihal E. and Hemar, Patrick and Lavalle, Philippe and Schultz, Philippe},
    title = {Laryngeal replacement with an artificial larynx after total laryngectomy: The possibility of restoring larynx functionality in the future},
    journal = {Head \& Neck},
    volume = {36},
    number = {11},
    pages = {1669-1673},
    keywords = {laryngectomy, tracheostomy, titanium, artificial larynx, cancer},
    doi = {10.1002/hed.23621},
    url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/hed.23621},
    eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/hed.23621},
    abstract = {Abstract Background Most patients perceive total laryngectomy as a mutilation carrying with it a loss of physical and psychological integrity. Thus, an artificial larynx system that can replace the laryngeal functions would significantly improve the quality of life for the afflicted patients. Methods This report, with accompanying video, presents the first case in an ongoing clinical trial of laryngeal rehabilitation using an artificial larynx after total laryngectomy for squamous cell carcinoma, for an 8-month follow-up period. We depict the prosthesis' features, our 2-step surgical procedure, and the outcome. The prosthesis is formed of 2 parts: (1) a tracheal prosthesis with a porous titanium junction with trachea, which was implanted in the first step to ensure its colonization, and (2) a removable part composed of concentric valves that enable inhalation and exhalation. The second part was implanted endoscopically. The implant was monitored with a retrograde nasofibroscopy of the tracheal prosthesis lumen and CT scans over a course of 8 months. Results The patient's functioning in the relevant postoperative problem areas, such as swallowing, breathing, and smelling, has significantly improved. The patient was able to talk in a whispering fashion while the tracheostomy was temporarily closed. The implant's porous part was in the process of being colonized by the surrounding tissue and no fistulas were observed as evidenced by barium swallow. Conclusion As the current case shows, tracheotomy closure can be performed, and laryngeal functions are restored, by means of an implant. With further improvements, this system can alleviate the need for a permanent tracheostomy after total laryngectomy, while maintaining important larynx functions intact.  2014 Wiley Periodicals, Inc. Head Neck 36: 16691673, 2014},,
    year = {2014}
    }
  • [DOI] N. E. Vrana, V. Hasirci, G. B. McGuinness, and A. Ndreu-Halili, "Cell/tissue microenvironment engineering and monitoring in tissue engineering, regenerative medicine, and in vitro tissue models," Biomed research international, vol. 2014, 2014.
    [Bibtex]
    @article{vrana2014cell,
    title={Cell/tissue microenvironment engineering and monitoring in tissue engineering, regenerative medicine, and in vitro tissue models},
    author={Vrana, Nihal Engin and Hasirci, Vasif and McGuinness, Garrett Brian and Ndreu-Halili, Albana},
    journal={BioMed research international},
    volume={2014},
    year={2014},
    publisher={Hindawi},
    doi={10.1155/2014/951626}
    }
  • [DOI] J. Barthes, H. Özçelik, M. Hindié, A. Ndreu-Halili, A. Hasan, and N. E. Vrana, "Cell microenvironment engineering and monitoring for tissue engineering and regenerative medicine: the recent advances," Biomed research international, vol. 2014, 2014.
    [Bibtex]
    @article{barthes2014cell,
    title={Cell microenvironment engineering and monitoring for tissue engineering and regenerative medicine: the recent advances},
    author={Barthes, Julien and {\"O}z{\c{c}}elik, Hayriye and Hindi{\'e}, Mathilde and Ndreu-Halili, Albana and Hasan, Anwarul and Vrana, Nihal Engin},
    journal={BioMed research international},
    volume={2014},
    year={2014},
    publisher={Hindawi},
    doi={10.1155/2014/921905}
    }
  • [DOI] N. E. Vrana, A. Dupret-Bories, P. Schultz, C. Debry, D. Vautier, and P. Lavalle, "Titanium microbead-based porous implants: bead size controls cell response and host integration," Advanced healthcare materials, vol. 3, iss. 1, pp. 79-87, 2014.
    [Bibtex]
    @article{doi:10.1002/adhm.201200369,
    author = {Vrana, Nihal Engin and Dupret-Bories, Agns and Schultz, Philippe and Debry, Christian and Vautier, Dominique and Lavalle, Philippe},
    title = {Titanium Microbead-Based Porous Implants: Bead Size Controls Cell Response and Host Integration},
    journal = {Advanced Healthcare Materials},
    volume = {3},
    number = {1},
    pages = {79-87},
    keywords = {host integration, in vivo, porous implants, titanium, trachea},
    doi = {10.1002/adhm.201200369},
    url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.201200369},
    eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/adhm.201200369},
    abstract = {Abstract Openly porous structures in implants are desirable for better integration with the host tissue. Sintered microbead-based titanium implants for oto-rhinolaryngology applications, which create an environment where the cells can migrate in the areas between the microbeads, are developed. This structure promotes fibrovascular tissue formation within the implant in vivo. In this study, it is determine to what extent these events can be controlled by changing the physical environment of the implants both in vitro and in vivo. By cell tracking, it is observed that the size of the beads and the distance between the neighboring beads significantly affect the ability of cells to develop cell-to-cell contacts and to bridge the pores. Live cell staining shows that as the bead size gets smaller, the probability to observe cells that fill the porous areas is higher. This also affects the initial attachment and distribution of the cells and collagen secretion by fibroblasts. Obtaining a fast coverage of the system also enables co-culture systems where, the number and the distribution of the second cell type are boosted by the presence of the first. This concept is utilized to increase the attachment of vascular endothelial cells by an initial layer of fibroblasts. By decreasing the bead diameter, the overall colonization of the implant can be significantly increased in vivo. The effect of bead size has a similar pattern both in rats and rabbits, with faster colonization of smaller bead-based structures. Using smaller beads would improve clinical outcomes as faster integration facilitates the attainment of functionality by the implant.},,
    year = {2014}
    }

2013

  • [DOI] P. Zorlutuna, N. E. Vrana, and A. Khademhosseini, "The expanding world of tissue engineering: the building blocks and new applications of tissue engineered constructs," Ieee reviews in biomedical engineering, vol. 6, pp. 47-62, 2013.
    [Bibtex]
    @ARTICLE{6384673,
    author={P. {Zorlutuna} and N. E. {Vrana} and A. {Khademhosseini}},
    journal={IEEE Reviews in Biomedical Engineering},
    title={The Expanding World of Tissue Engineering: The Building Blocks and New Applications of Tissue Engineered Constructs},
    year={2013},
    volume={6},
    number={},
    pages={47-62},
    keywords={biological tissues;biomedical materials;biomimetics;cellular biophysics;drugs;medical robotics;medicine;molecular biophysics;physiological models;proteins;reviews;self-assembly;tissue engineering;regenerative medicine;drug discovery;tissue engineered constructs;nonclinical applications;tissue engineering scaffolds;recombinant proteins;self assembling polypeptides;scaffold-free production methods;cell sheets;cell aggregates;cell sources;cell behavior;biomimetic microenvironments;cell differentiation;model tissues;cancer research;biorobotics applications;Computer architecture;Microprocessors;Electronic countermeasures;Biological tissues;Tissue engineering;Medical robots;Circulatory system;Biorobotics;cell aggregates;modular tissue engineering;organ models;organ-on-a-chip;pre-vascularization;synthetic polypeptides;Animals;Drug Discovery;Humans;Models, Biological;Regenerative Medicine;Robotics;Tissue Engineering},
    doi={10.1109/RBME.2012.2233468},
    ISSN={1937-3333},
    month={},}
  • [DOI] N. E. Vrana, A. Dupret-Bories, C. Chaubaroux, E. Rieger, C. Debry, D. Vautier, M. Metz-Boutigue, and P. Lavalle, "Multi-scale modification of metallic implants with pore gradients, polyelectrolytes and their indirect monitoring in vivo," Journal of visualized experiments: jove, iss. 77, 2013.
    [Bibtex]
    @article{vrana2013multi,
    title={Multi-scale modification of metallic implants with pore gradients, polyelectrolytes and their indirect monitoring in vivo},
    author={Vrana, Nihal E and Dupret-Bories, Agnes and Chaubaroux, Christophe and Rieger, Elisabeth and Debry, Christian and Vautier, Dominique and Metz-Boutigue, Marie-Helene and Lavalle, Philippe},
    journal={Journal of visualized experiments: JoVE},
    number={77},
    year={2013},
    publisher={MyJoVE Corporation},
    doi={
    10.3791%2F50533
    }
    }
  • [DOI] C. Chaubaroux, E. Vrana, C. Debry, P. Schaaf, B. Senger, J. Voegel, Y. Haikel, C. Ringwald, J. Hemmerlé, P. Lavalle, and F. Boulmedais, "Collagen-based fibrillar multilayer films cross-linked by a natural agent," Biomacromolecules, vol. 13, iss. 7, pp. 2128-2135, 2012.
    [Bibtex]
    @article{doi:10.1021/bm300529a,
    author = {Chaubaroux, Christophe and Vrana, Engin and Debry, Christian and Schaaf, Pierre and Senger, Bernard and Voegel, Jean-Claude and Haikel, Youssef and Ringwald, Christian and Hemmerl{\'e}, Joseph and Lavalle, Philippe and Boulmedais, Fouzia},
    title = {Collagen-Based Fibrillar Multilayer Films Cross-Linked by a Natural Agent},
    journal = {Biomacromolecules},
    volume = {13},
    number = {7},
    pages = {2128-2135},
    year = {2012},
    doi = {10.1021/bm300529a},
    note ={PMID: 22662909},
    URL = {
    https://doi.org/10.1021/bm300529a
    },
    eprint = {
    https://doi.org/10.1021/bm300529a
    }
    }
  • [PDF] A. D. Dupret Bories, "Laryngeal replacement after total laryngectomy," Theses PhD Thesis, 2013.
    [Bibtex]
    @phdthesis{dupretbories:tel-01024143,
    TITLE = {{Laryngeal replacement after total laryngectomy}},
    AUTHOR = {Dupret Bories, Agn{\`e}s Dupret},
    URL = {https://tel.archives-ouvertes.fr/tel-01024143},
    NUMBER = {2013STRAJ028},
    SCHOOL = {{Universit{\'e} de Strasbourg}},
    YEAR = {2013},
    MONTH = Sep,
    KEYWORDS = {Total laryngectomy ; Tracheal prosthesis ; Respiratory epithelium ; Polymer ; Porous titanium ; Artificial larynx ; {\'E}pith{\'e}lium respiratoire ; Titane poreux ; Proth{\`e}se de trach{\'e}e ; Larynx artificiel ; Laryngectomie totale},
    TYPE = {Theses},
    PDF = {https://tel.archives-ouvertes.fr/tel-01024143/file/Dupret-Bories_Agnes_2013_ED414.pdf},
    HAL_ID = {tel-01024143},
    HAL_VERSION = {v1},
    }

2012 et antérieures

  • [DOI] N. E. Vrana, A. Dupret-Bories, C. Bach, C. Chaubaroux, C. Coraux, D. Vautier, F. Boulmedais, Y. Haikel, C. Debry, M. Metz-Boutigue, and P. Lavalle, "Modification of macroporous titanium tracheal implants with biodegradable structures: tracking in vivo integration for determination of optimal in situ epithelialization conditions," Biotechnology and bioengineering, vol. 109, iss. 8, pp. 2134-2146, 2012.
    [Bibtex]
    @article{doi:10.1002/bit.24456,
    author = {Vrana, Nihal Engin and Dupret-Bories, Agnes and Bach, Charlotte and Chaubaroux, Christophe and Coraux, Christelle and Vautier, Dominique and Boulmedais, Fouzia and Haikel, Youssef and Debry, Christian and Metz-Boutigue, Marie-Helene and Lavalle, Philippe},
    title = {Modification of macroporous titanium tracheal implants with biodegradable structures: Tracking in vivo integration for determination of optimal in situ epithelialization conditions},
    journal = {Biotechnology and Bioengineering},
    volume = {109},
    number = {8},
    pages = {2134-2146},
    keywords = {titanium, trachea, implant, epithelialization, porosity, in vivo, CGA, collagen},
    doi = {10.1002/bit.24456},
    url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.24456},
    eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/bit.24456},
    abstract = {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; 109:21342146.  2012 Wiley Periodicals, Inc.},,
    year = {2012}
    }
  • [DOI] N. E. Vrana, A. Dupret, C. Coraux, D. Vautier, C. Debry, and P. Lavalle, "Hybrid titanium/biodegradable polymer implants with an hierarchical pore structure as a means to control selective cell movement," Plos one, vol. 6, iss. 5, pp. 1-10, 2011.
    [Bibtex]
    @article{10.1371/journal.pone.0020480,
    author = {Vrana, Nihal Engin AND Dupret, Agns AND Coraux, Christelle AND Vautier, Dominique AND Debry, Christian AND Lavalle, Philippe},
    journal = {PLOS ONE},
    publisher = {Public Library of Science},
    title = {Hybrid Titanium/Biodegradable Polymer Implants with an Hierarchical Pore Structure as a Means to Control Selective Cell Movement},
    year = {2011},
    month = {05},
    volume = {6},
    url = {https://doi.org/10.1371/journal.pone.0020480},
    pages = {1-10},
    abstract = {In order to improve implant success rate, it is important to enhance their responsiveness to the prevailing conditions following implantation. Uncontrolled movement of inflammatory cells and fibroblasts is one of these in vivo problems and the porosity properties of the implant have a strong effect on these. Here, we describe a hybrid system composed of a macroporous titanium structure filled with a microporous biodegradable polymer. This polymer matrix has a distinct porosity gradient to accommodate different cell types (fibroblasts and epithelial cells). The main clinical application of this system will be the prevention of restenosis due to excessive fibroblast migration and proliferation in the case of tracheal implants. Methodology/Principal Findings A microbead-based titanium template was filled with a porous Poly (L-lactic acid) (PLLA) body by freeze-extraction method. A distinct porosity difference was obtained between the inner and outer surfaces of the implant as characterized by image analysis and Mercury porosimetry (9.82.2 m vs. 36.711.4 m, p=0.05). On top, a thin PLLA film was added to optimize the growth of epithelial cells, which was confirmed by using human respiratory epithelial cells. To check the control of fibroblast movement, PKH26 labeled fibroblasts were seeded onto Titanium and Titanium/PLLA implants. The cell movement was quantified by confocal microscopy: in one week cells moved deeper in Ti samples compared to Ti/PLLA. Conclusions In vitro experiments showed that this new implant is effective for guiding different kind of cells it will contact upon implantation. Overall, this system would enable spatial and temporal control over cell migration by a gradient ranging from macroporosity to nanoporosity within a tracheal implant. Moreover, mechanical properties will be dependent mainly on the titanium frame. This will make it possible to create a polymeric environment which is suitable for cells without the need to meet mechanical requirements with the polymeric structure.},
    number = {5},
    doi = {10.1371/journal.pone.0020480}
    }
  • [DOI] C. Debry, X. Charles, M. Frenot, and A. Gentine, "Intra-laryngeal endoprosthesis: an alternative therapeutic approach to surgical procedures of laryngeal exclusion," The journal of laryngology & otology, vol. 114, iss. 10, pp. 760-764, 2000.
    [Bibtex]
    @article{debry_charles_frenot_gentine_2000, title={Intra-laryngeal endoprosthesis: an alternative therapeutic approach to surgical procedures of laryngeal exclusion}, volume={114}, DOI={10.1258/0022215001904095}, number={10}, journal={The Journal of Laryngology & Otology}, publisher={Cambridge University Press}, author={Debry, Christian and Charles, Xavier and Frenot, Marc and Gentine, Andr}, year={2000}, pages={760-764}}
  • [DOI] O. Chambres, P. Schultz, and C. Debry, "The larynxane st? intralaryngeal endoprosthesis for laryngotracheal pathologies," The journal of laryngology & otology, vol. 120, iss. 11, pp. 942-948, 2006.
    [Bibtex]
    @article{chambres_schultz_debry_2006, title={The Larynxane ST intralaryngeal endoprosthesis for laryngotracheal pathologies}, volume={120}, DOI={10.1017/S0022215106000466}, number={11}, journal={The Journal of Laryngology & Otology}, publisher={Cambridge University Press}, author={Chambres, O and Schultz, P and Debry, C}, year={2006}, pages={942-948}}
  • P. Schultz, M. Wiorowski, O. Chambres, and C. Debry, "Polychondrite chronique atrophiante de localisation laryngo-trachéale," Annales françaises d'oto-rhino-laryngologie et de pathologie cervico-faciale, vol. 119, iss. 6-C1, p. 369–372, 2002.
    [Bibtex]
    @article{schultz2002polychondrite,
    title={Polychondrite chronique atrophiante de localisation laryngo-trach{\'e}ale},
    author={Schultz, P and Wiorowski, M and Chambres, O and Debry, C},
    journal={Annales Fran{\c{c}}aises d'Oto-Rhino-Laryngologie et de pathologie cervico-faciale},
    volume={119},
    number={6-C1},
    pages={369--372},
    year={2002}}
  • [DOI] P. Schultz, D. Vautier, J. Chluba, L. Marcellin, and C. Debry, "Survival analysis of rats implanted with porous titanium tracheal prosthesis.," The annals of thoracic surgery, vol. 73 6, pp. 1747-51, 2002.
    [Bibtex]
    @article{Schultz2002SurvivalAO,
    title={Survival analysis of rats implanted with porous titanium tracheal prosthesis.},
    author={Philippe Schultz and Dominique Vautier and Johanna Chluba and Luc Marcellin and Christian Debry},
    journal={The Annals of thoracic surgery},
    year={2002},
    volume={73 6},
    pages={
    1747-51
    },
    doi={10.1016/S0003-4975(02)03569-5}
    }