Martin A Birchall

London Centre for Nanotechnology, Londinium, England, United Kingdom

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Publications (138)764.73 Total impact

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    ABSTRACT: Introduction: Prosthetic materials, autologous tissues, cryopreserved homografts and allogeneic tissues have thus far proven unsuccessful in providing long-term functional solutions to extensive upper airway disease and damage. Research is therefore focusing on the rapidly expanding fields of regenerative medicine and tissue engineering in order to provide stem cell-based constructs for airway reconstruction, substitution and/or regeneration.Areas covered: Advances in stem cell technology, biomaterials and growth factor interactions have been instrumental in guiding optimization of tissue-engineered airways, leading to several first-in-man studies investigating stem cell-based tissue-engineered tracheal transplants in patients. Here, we summarize current progress, outstanding research questions, as well as future directions within the field.Expert opinion: The complex immune interaction between the transplant and host in vivo is only beginning to be untangled. Recent progress in our understanding of stem cell biology, decellularization techniques, biomaterials and transplantation immunobiology offers the prospect of transplanting airways without the need for lifelong immunosuppression. In addition, progress in airway revascularization, reinnervation and ever-increasingly sophisticated bioreactor design is opening up new avenues for the construction of a tissue-engineered larynx. Finally, 3D printing is a novel technique with the potential to render microscopic control over how cells are incorporated and grown onto the tissue-engineered airway.
    Expert Opinion on Biological Therapy. 08/2014;
  • Martin A Birchall, Alexander M Seifalian
    The Lancet 04/2014; · 39.06 Impact Factor
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    ABSTRACT: α-Helical peptide hydrogels are decorated with a cell-binding peptide motif (RGDS), which is shown to promote adhesion, proliferation, and differentiation of PC12 cells. Gel structure and integrity are maintained after functionalization. This opens possibilities for the bottom-up design and engineering of complex functional scaffolds for 2D and 3D cell cultures.
    Advanced Healthcare Materials 03/2014;
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    ABSTRACT: Front Cover: Amine functionalized fumed-silica nanoparticles can be used, on page 307, to integrate bioactive molecules. Alexander Seifalian and colleagues show that these can be introduced to materials used for fabricating surgical implants and therefore induce biomimicry for greater cell-material interactions.
    Macromolecular Bioscience 03/2014; 14(3):299. · 3.74 Impact Factor
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    ABSTRACT: Today, tracheal lesions occupying < 30% of the trachea in children and < 50% in adults can be treated with primary resection, followed by end-to-end anastomosis. However, lesions larger than this require a tracheal replacement, of which there are currently few options available. The recent advancement of tissue-engineering principles in tracheal research is quickly opening up new vistas for airway reconstruction and creating a very promising future for medical science. This review discusses the main criteria required for the development of a tissue-engineered tracheal replacement. The criteria include: (a) appropriate cell types and sources; (b) biomolecules to direct the differentiation of the cells to the desired lineage; (c) a suitable scaffold for a cellular matrix; and (d) a bioreactor to facilitate cell attachment and proliferation and construct transport to theatre. Our group has designed and developed the world's first synthetic tracheal replacement, using a novel nanocomposite material, also developed in our laboratory. It was implanted clinically in June 2011 with a successful outcome. The application of tissue-engineering approaches to tracheal replacement development is the first step towards the much-anticipated 'off-the-shelf' tissue-engineered technology, contributing extensively to the advancement in treatment and rehabilitation of patients afflicted with tracheal pathology. Copyright © 2014 John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 01/2014; · 4.43 Impact Factor
  • Jonathan M. Fishman, Mark Lowdell, Martin A. Birchall
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    ABSTRACT: Tissue engineering requires the use of cells seeded onto scaffolds, often in conjunction with bioactive molecules, to regenerate or replace tissues. Significant advances have been made in recent years within the fields of stem cell biology and biomaterials, leading to some exciting developments in airway tissue engineering, including the first use of stem cell-based tissue-engineered tracheal replacements in humans. In addition, recent advances within the fields of scaffold biology and decellularization offer the potential to transplant patients without the use of immunosuppression.
    Seminars in Pediatric Surgery. 01/2014;
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    ABSTRACT: Replacement of irreversibly damaged organs due to chronic disease, with suitable tissue engineered implants is now a familiar area of interest to clinicians and multidisciplinary scientists. Ideal tissue engineering approaches require scaffolds to be tailor made to mimic physiological environments of interest with specific surface topographical and biological properties for optimal cell-material interactions. This study demonstrates a single-step procedure for inducing biomimcry in a novel nanocomposite base material scaffold, to re-create the extracellular matrix, which is required for stem cell integration and differentiation to mature cells. Fumed silica nanoparticle mediated procedure of scaffold functionalization, can be potentially adapted with multiple bioactive molecules to induce cellular biomimicry, in the development human organs. The proposed nanocomposite materials already in patients for number of implants, including world first synthetic trachea, tear ducts and vascular bypass graft.
    Macromolecular Bioscience 11/2013; · 3.74 Impact Factor
  • Clinical Immunology 11/2013; 150(2):140-142. · 3.77 Impact Factor
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    ABSTRACT: Objectives. While numerical and functional defects of invariant NKT cells have been demonstrated in rheumatoid arthritis (RA), the detailed characterization of proliferative and secretory responses following CD1d-mediated presentation is lacking; the presence of non-invariant populations has never been assessed in human autoimmunity. We have evaluated both invariant and non-invariant populations in the blood and synovial fluid from patients to assess feasibility of NKT cell-directed manipulations in RA. Methods. NKT cell populations were quantified by anti-CD4/anti-Vα24 staining and/or CD1d tetramers. Proliferation was measured in cultures of mononuclear cells following stimulations with αGalCer and cytokine secretion determined by multi-bead assay. Results. We have confirmed a proliferative defect of iNKT cells in both peripheral blood and synovial fluid from RA patients, but no changes in baseline frequencies. Moreover, we have detected an enlargement of non-invariant cell pool in synovial fluid samples. In addition, we noted an evident Th2 shift following exposure to αGalCer and pronounced IL-6 secretion. Conclusions. While RA patients suffer from defective proliferative responses of invariant NKT cells, non-invariant cells accumulate at the site of inflammation. While stimulation with αGalCer results in reduced TNF-α and increased suppressive IL-10, abundantly produced IL-6 could potentially contribute to the induction of Th17 cells in the joints.
    Modern Rheumatology 11/2013; · 1.72 Impact Factor
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    ABSTRACT: Objective Effective treatments for hollow organ stenosis, scarring or agenesis are suboptimal or lacking. Tissue engineered implants may provide a solution but those performed to date are limited by poor mucosalization after transplantation. We aimed to perform a systematic review of the literature on tissue engineered airway mucosa. Our objectives were to assess the success of this technology, its potential application to airway regenerative medicine and determine the direction of future research to maximise its therapeutic and commercial potential. Data Sources and Review Methods A systematic review of the literature was performed searching Medline (1996 - December 2012) and Embase (1980 - December 2012) using search terms "tissue engineering" or "tissue" and "engineering" or "tissue engineered" and "mucous membrane" or "mucous" and "membrane" or "mucosa". Original studies utilising tissue engineering to regenerate airway mucosa within the trachea or main bronchi in animal models or human studies were included. Results 719 papers matched the search criteria with 17 fulfilling the entry criteria. Of these 17, four investigated mucosal engineering in humans with the remaining 13 studies investigating mucosal engineering in animal models. The review demonstrated how an intact mucosal layer protects against infection and suggests a role for fibroblasts in facilitating epithelial regeneration in-vitro. A range of scaffold materials were used but no one material was clearly superior to the others. Conclusion The review highlights gaps in the literature and recommends key directions for future research as epithelial tracking and the role of the extracellular environment.
    The Laryngoscope 10/2013; · 1.98 Impact Factor
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    ABSTRACT: The use of human stem cells (SCs) in tissue engineering holds promise in revolutionising the treatment of numerous diseases. There is a pressing need to comprehend the distribution, movement and role of SCs once implanted onto scaffolds. Nanotechnology has provided a platform to investigate this through the development of inorganic magnetic nanoparticles (MNPs). MNPs can be used to label and track SCs by magnetic resonance imaging (MRI) since this clinically available imaging modality has high spatial resolution. In this review, we highlight recent applications of iron oxide and gadolinium based MNPs in SC labelling and MRI; and offer novel considerations for their future development.
    Nanoscale 10/2013; · 6.73 Impact Factor
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    ABSTRACT: Objective: The functional neurotrophic effects of systemic tacrolimus in a sub-immunosuppressive regimen in the minipig model of laryngeal reinnervation were investigated. Methods: Right recurrent laryngeal nerve transection and phrenic-abductor branch of recurrent la-ryngeal nerve anastomosis were performed in two minipigs that were administered low-dose oral tac-rolimus (0.125 mg/kg) for one month. Vocal cord abduction at four months was rated by two blinded expert assessors on a four-point Likert scale from poor (1) to complete (4), and compared with five fully matched historical control animals that received the same surgery but no other interventions. Results: Right vocal cord abduction was more complete in tacrolimus-treated animals than controls (mean abduction score 2.3 vs. 1.5, p=0.019). Conclusion: Tacrolimus may have an important role in laryngeal reinnervation following allograft transplantation, and low-dose regimens may have applications in cranial and peripheral nerve injuries or in the reinnervation of tissue-engineered laryngeal constructs, but further studies are required.
    Archives of Clinical and Experimental Surgery. 09/2013;
  • European Society for Biomaterials 2013; 09/2013
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    ABSTRACT: Decellularized (acellular) scaffolds, composed of natural extracellular matrix, form the basis of an emerging generation of tissue-engineered organ and tissue replacements capable of transforming healthcare. Prime requirements for allogeneic, or xenogeneic, decellularized scaffolds are biocompatibility and absence of rejection. The humoral immune response to decellularized scaffolds has been well documented, but there is a lack of data on the cell-mediated immune response toward them in vitro and in vivo. Skeletal muscle scaffolds were decellularized, characterized in vitro, and xenotransplanted. The cellular immune response toward scaffolds was evaluated by immunohistochemistry and quantified stereologically. T-cell proliferation and cytokines, as assessed by flow cytometry using carboxy-fluorescein diacetate succinimidyl ester dye and cytometric bead array, formed an in vitro surrogate marker and correlate of the in vivo host immune response toward the scaffold. Decellularized scaffolds were free of major histocompatibility complex class I and II antigens and were found to exert anti-inflammatory and immunosuppressive effects, as evidenced by delayed biodegradation time in vivo; reduced sensitized T-cell proliferative activity in vitro; reduced IL-2, IFN-γ, and raised IL-10 levels in cell-culture supernatants; polarization of the macrophage response in vivo toward an M2 phenotype; and improved survival of donor-derived xenogeneic cells at 2 and 4 wk in vivo. Decellularized scaffolds polarize host responses away from a classical TH1-proinflammatory profile and appear to down-regulate T-cell xeno responses and TH1 effector function by inducing a state of peripheral T-cell hyporesponsiveness. These results have substantial implications for the future clinical application of tissue-engineered therapies.
    Proceedings of the National Academy of Sciences 08/2013; · 9.81 Impact Factor
  • Achala de Mel, Martin A Birchall, Alexander M Seifalian
    Angiology 08/2013; 64(6):409-10. · 2.37 Impact Factor
  • E Warner, M Birchall, M W Lowdell
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    ABSTRACT: Background: Biobanking is the process of storing high quality human biospecimens alongside linked clinical data, for research purposes. The aim is to identify novel biomarkers with prognostic or diagnostic significance. However, the challenges implicit in the collection and storage of human tissue for research have curtailed the impact of this technique to date. Aim: This paper aims to summarise the challenges faced by biobanking within the ENT specialty in the UK, and to present protocols used for the routine collection, freezing and storage of tissue specimens at the Royal National Throat, Nose and Ear Hospital. These protocols could be used to guide other ENT departments (in the UK and worldwide) wishing to initiate the routine collection and storage of tissue samples. Their publication could also help to establish basic standards and ensure consistency in ENT tissue storage. Methods: Interviews conducted with industry experts, and a literature review of 'best practice' in biobanking. Conclusion: The ENT specialty must stay abreast of progress in human tissue research in order to ensure the best possible management of its patients. Our protocol for the routine banking of ENT tissue at the Royal National Throat, Nose and Ear Hospital could be used as a template for other ENT departments (in the UK and worldwide) to encourage widespread implementation of high quality tissue banking.
    The Journal of Laryngology & Otology 06/2013; · 0.68 Impact Factor
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    ABSTRACT: Auricular reconstruction using sculpted autologous costal cartilage is effective, but complex, time consuming and may incur donor site sequelae and morbidity. Conventional synthetic alternatives are associated with infection and extrusion in up to 15% of cases. We present a novel POSS-PCU nanocomposite auricular scaffold, which aims to reduce extrusion rates by mimicking the elastic modulus of human ears and by encouraging desirable cellular interactions. The fabrication, physicochemical properties (including nanoscale topography) and cellular interactions of these scaffolds were compared to Medpor®, the current synthetic standard. Our scaffold had a more similar elastic modulus (5.73± 0.17 MPa) to ear cartilage (5.02± 0.17 MPa) compared with Medpor®, which was much stiffer (140.9±0.04 MPa). POSS-PCU supported fibroblast ingrowth and proliferation, significantly higher collagen production was also produced by cells on the POSS-PCU than those on Medpor®. This porous POSS-PCU nanocomposite scaffold is therefore a promising alternative biomaterial for auricular surgical reconstruction.
    Nanomedicine: nanotechnology, biology, and medicine 06/2013; · 6.93 Impact Factor
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    ABSTRACT: Tissue engineering of autologous lung tissue aims to become a therapeutic alternative to transplantation. Efforts published so far in creating scaffolds have used harsh decellularization techniques that damage the extracellular matrix (ECM), deplete its components and take up to 5 weeks to perform. The aim of this study was to create a lung natural acellular scaffold using a method that will reduce the time of production and better preserve scaffold architecture and ECM components. Decellularization of rat lungs via the intratracheal route removed most of the nuclear material when compared to the other entry points. An intermittent inflation approach that mimics lung respiration yielded an acellular scaffold in a shorter time with an improved preservation of pulmonary micro-architecture. Electron microscopy demonstrated the maintenance of an intact alveolar network, with no evidence of collapse or tearing. Pulsatile dye injection via the vasculature indicated an intact capillary network in the scaffold. Morphometry analysis demonstrated a significant increase in alveolar fractional volume, with alveolar size analysis confirming that alveolar dimensions were maintained. Biomechanical testing of the scaffolds indicated an increase in resistance and elastance when compared to fresh lungs. Staining and quantification for ECM components showed a presence of collagen, elastin, GAG and laminin. The intratracheal intermittent decellularization methodology could be translated to sheep lungs, demonstrating a preservation of ECM components, alveolar and vascular architecture. Decellularization treatment and methodology preserves lung architecture and ECM whilst reducing the production time to 3 h. Cell seeding and in vivo experiments are necessary to proceed towards clinical translation.
    Biomaterials 05/2013; · 8.31 Impact Factor

Publication Stats

1k Citations
764.73 Total Impact Points


  • 2014
    • London Centre for Nanotechnology
      Londinium, England, United Kingdom
  • 2011–2014
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
  • 2012–2013
    • Great Ormond Street Hospital for Children NHS Foundation Trust
      • Department of Cardiothoracic Surgery
      Londinium, England, United Kingdom
  • 2009–2013
    • University College London
      • Division of Surgery and Interventional Science
      London, ENG, United Kingdom
    • University of Wisconsin, Madison
      • Department of Surgery
      Madison, MS, United States
  • 1997–2012
    • University of Bristol
      • School of Veterinary Sciences
      Bristol, ENG, United Kingdom
  • 2010
    • Baylor College of Medicine
      • Center for Cell and Gene Therapy
      Houston, TX, United States
    • University of Florence
      Florens, Tuscany, Italy
  • 2008–2009
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain
    • Yale University
      New Haven, Connecticut, United States
  • 2006–2008
    • The University of Manchester
      Manchester, England, United Kingdom
    • The Australian Society of Otolaryngology Head & Neck Surgery
      Evans Head, New South Wales, Australia
  • 2004–2008
    • Aintree University Hospital NHS Foundation Trust
      Liverpool, England, United Kingdom
  • 2004–2007
    • University of Liverpool
      Liverpool, England, United Kingdom
  • 2005
    • University of Wales
      Cardiff, Wales, United Kingdom
  • 2003
    • Royal College of Surgeons of England
      Londinium, England, United Kingdom
  • 1998
    • Cardiff University
      Cardiff, Wales, United Kingdom