Martin Birchall

University College London, Londinium, England, United Kingdom

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Publications (122)623.89 Total impact

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    ABSTRACT: As the global health burden of chronic disease increases, end-stage organ failure has become a costly and intractable problem. De novo organ creation is one of the long-term goals of the medical community. One of the promising avenues is that of tissue engineering: the use of biomaterials to create cells, structures, or even whole organs. Tissue engineering has emerged from its nascent stage, with several proof-of-principle trials performed across various tissue types. As tissue engineering moves from the realm of case trials to broader clinical study, three major questions have emerged: 1) Can the production of biological scaffolds be scaled up accordingly to meet current and future demands without generating an unfavourable immune response? 2) Are biological scaffolds plus or minus the inclusion of cells replaced by scar tissue or native functional tissue? 3) Can tissue-engineered organs be grown in children and adolescents given the different immune profile of children? In this review, we highlight current research in the immunological response to tissue engineered biomaterials, cells, and whole organs and attempt to provide the answers to these questions.
    No preview · Article · Dec 2015 · Tissue Engineering Part B Reviews
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    Full-text · Dataset · Oct 2015
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    Full-text · Dataset · Oct 2015
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    ABSTRACT: Iron oxide nanoparticles (IONPs) of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods such as thermal decomposition or co-precipitation, this process yields nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere. For example, IONPs with a diameter of ca. 8 nm could be made in a reproducible manner and with good crystallinity as evidenced by X-ray diffraction analysis and high saturation magnetization value (84.5 emu g(-1)). The surface of the IONPs could be tailored post synthesis with two different ligands which provided functionality and stability in water and phosphate buffer saline (PBS). Their potential as a magnetic resonance imaging (MRI) contrast agent was confirmed as they exhibited high r1 and r2 relaxivities of 7.95 mM(-1) s(-1) and 185.58 mM(-1) s(-1) respectively at 1.4 T. Biocompatibility and viability of IONPs in primary human mesenchymal stem cells (hMSCs) was studied and confirmed.
    Full-text · Article · Oct 2015 · Nanoscale
  • Jonathan Fishman · De Coppi P · Birchall MA

    No preview · Chapter · Oct 2015
  • Fishman JM · De Coppi P · Birchall MA

    No preview · Chapter · Oct 2015

  • No preview · Article · Oct 2015 · Journal of Pediatric Gastroenterology and Nutrition
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    ABSTRACT: Tissue engineered organs require effective and validated cell seeding protocols when translated clinically. To adequately design these protocols, simple, reliable and reproducible cell-tracking techniques are required. Techniques already available are often either invasive, overly labour intensive, not entirely specific or limited to analysis of a small segment of the graft. Bioluminescence imaging (BLI) is a well-established method of in vivo imaging that is commonly used in real-time analysis of disease and efficacy of drugs. We determined the applicability of BLI as a method to track cells in bioreactor cultures and eventually in vivo, in the development of tissue engineering applications. Lentiviral transduction of various cell types was performed using a transfer vector that constitutively expresses a florescent protein and luciferase. The BLI system was characterised through comparison to pre-established techniques (Alamar Blue and CyQuant). The potential of the system as a cell tracking method in tissue engineering applications was examined by tracking cells on both synthetic and biological tubular scaffolds in a closed bioreactor system and in vivo. BLI was comparable to well-established techniques for cell tracking in vitro. Viable transduced cells could be accurately detected and tracked when seeded in all conditions tested. In addition, BLI was shown to deliver information on cell distribution on the scaffold and could provide a comprehensive assessment of the cells over the entire duration of the experiment. This is an effective, non-invasive and simple cell tracking method that is proven to be a valuable tool in tissue engineering of bioartificial complex organs.
    Full-text · Conference Paper · Sep 2015
  • J C R Wormald · J M Fishman · S Juniat · N Tolley · M A Birchall
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    ABSTRACT: Tissue engineering using biocompatible scaffolds, with or without cells, can permit surgeons to restore structure and function following tissue resection or in cases of congenital abnormality. Tracheal regeneration has emerged as a spearhead application of these technologies, whilst regenerative therapies are now being developed to treat most other diseases within otolaryngology. Methods and results: A systematic review of the literature was performed using Ovid Medline and Ovid Embase, from database inception to 15 November 2014. A total of 561 papers matched the search criteria, with 76 fulfilling inclusion criteria. Articles were predominantly pre-clinical animal studies, reflecting the current status of research in this field. Several key human research articles were identified and discussed. Conclusion: The main issues facing research in regenerative surgery are translation of animal model work into human models, increasing stem cell availability so it can be used to further research, and development of better facilities to enable implementation of these advances.
    No preview · Article · Jun 2015 · The Journal of Laryngology & Otology
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    ABSTRACT: In 2010, a tissue-engineered trachea was transplanted into a 10-year-old child using a decellularized deceased donor trachea repopulated with the recipient's respiratory epithelium and mesenchymal stromal cells. We report the child's clinical progress, tracheal epithelialization and costs over the 4 years. A chronology of events was derived from clinical notes and costs determined using reference costs per procedure. Serial tracheoscopy images, lung function tests and anti-HLA blood samples were compared. Epithelial morphology and T cell, Ki67 and cleaved caspase 3 activity were examined. Computational fluid dynamic simulations determined flow, velocity and airway pressure drops. After the first year following transplantation, the number of interventions fell and the child is currently clinically well and continues in education. Endoscopy demonstrated a complete mucosal lining at 15 months, despite retention of a stent. Histocytology indicates a differentiated respiratory layer and no abnormal immune activity. Computational fluid dynamic analysis demonstrated increased velocity and pressure drops around a distal tracheal narrowing. Cross-sectional area analysis showed restriction of growth within an area of in-stent stenosis. This report demonstrates the long-term viability of a decellularized tissue-engineered trachea within a child. Further research is needed to develop bioengineered pediatric tracheal replacements with lower morbidity, better biomechanics and lower costs. © 2015 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.
    Full-text · Article · Jun 2015 · American Journal of Transplantation
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    ABSTRACT: Tissue engineered tracheae have been successfully implanted to treat a small number of patients on compassionate grounds. The treatment has not become mainstream due to the time taken to produce the scaffold and the resultant financial costs. We have developed a method for decellularization (DC) based on vacuum technology, which when combined with an enzyme/detergent protocol significantly reduces the time required to create clinically suitable scaffolds. We have applied this technology to prepare porcine tracheal scaffolds and compared the results to scaffolds produced under normal atmospheric pressures. The principal outcome measures were the reduction in time (9 days to prepare the scaffold) followed by a reduction in residual DNA levels (DC no-vac: 137.8±48.82 ng/mg vs. DC vac 36.83±18.45 ng/mg, p<0.05.). Our approach did not impact on the collagen or glycosaminoglycan content or on the biomechanical properties of the scaffolds. We applied the vacuum technology to human tracheae, which, when implanted in vivo showed no significant adverse immunological response. The addition of a vacuum to a conventional decellularization protocol significantly reduces production time, whilst providing a suitable scaffold. This increases clinical utility and lowers production costs. To our knowledge this is the first time that vacuum assisted decellularization has been explored. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    No preview · Article · Feb 2015 · Journal of Tissue Engineering and Regenerative Medicine
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    G. Z. Teoh · C. Crowley · M. A. Birchall · A. M. Seifalian
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    ABSTRACT: Congenital tracheal defects and prolonged intubation following premature birth have resulted in an unmet clinical need for tracheal replacement. Advances in stem cell technology, tissue engineering and material sciences have inspired the development of a resorbable, nanocomposite tracheal and bronchial scaffold. A bifurcated scaffold was designed and constructed using a novel, resorbable nanocomposite polymer, polyhedral oligomeric silsesquioxane poly(ϵ-caprolactone) urea urethane (POSS-PCL). Material characterization studies included tensile strength, suture retention and surface characteristics. Bone marrow-derived mesenchymal stem cells (bmMSCs) and human tracheobronchial epithelial cells (HBECs) were cultured on POSS-PCL for up to 14 days, and metabolic activity and cell morphology were assessed. Quantum dots conjugated to RGD (l-arginine, glycine and l-aspartic acid) tripeptides and anticollagen type I antibody were then employed to observe cell migration throughout the scaffold. POSS-PCL exhibited good mechanical properties, and the relationship between the solid elastomer and foam elastomer of POSS-PCL was comparable to that between the cartilaginous U-shaped rings and interconnective cartilage of the native human trachea. Good suture retention was also achieved. Cell attachment and a significant, steady increase in proliferation were observed for both cell types (bmMSCs, P = 0·001; HBECs, P = 0·003). Quantum dot imaging illustrated adequate cell penetration throughout the scaffold, which was confirmed by scanning electron microscopy. This mechanically viable scaffold successfully supports bmMSC and HBEC attachment and proliferation, demonstrating its potential as a tissue-engineered solution to tracheal replacement. © 2015 BJS Society Ltd. Published by John Wiley & Sons Ltd.
    Full-text · Article · Jan 2015 · British Journal of Surgery
  • Lange P · Fishman JM · De Coppi P · Birchall MA

    No preview · Chapter · Jan 2015
  • Lange P · Jonathan Fishman · De Coppi P · Birchall MA

    No preview · Chapter · Jan 2015

  • No preview · Article · Dec 2014 · European Journal of Surgical Oncology
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    ABSTRACT: There has been significant and exciting recent progress in the development of bioengineering approaches for generating tracheal tissue that can be used for congenital and acquired tracheal diseases. This includes a growing clinical experience in both pediatric and adult patients with life-threatening tracheal diseases. However, not all of these attempts have been successful, and there is ongoing discussion and debate about the optimal approaches to be used. These include considerations of optimal materials, particularly use of synthetic versus biologic scaffolds, appropriate cellularization of the scaffolds, optimal surgical approaches and optimal measure of both clinical and biologic outcomes. To address these issues, the International Society of Cell Therapy convened a first-ever meeting of the leading clinicians and tracheal biologists, along with experts in regulatory and ethical affairs, to discuss and debate the issues. A series of recommendations are presented for how to best move the field ahead.
    No preview · Article · Nov 2014 · Cytotherapy
  • Jonathan Fishman · De Coppi P · Birchall MA

    No preview · Chapter · May 2014
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    ABSTRACT: Objectives/hypothesis: 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 and its potential application to airway regenerative medicine and to determine the direction of future research to maximize its therapeutic and commercial potential. Data sources and review methods: A systematic review of the literature was performed searching Medline (January 1996) and Embase (January 1980) using search terms "tissue engineering" or "tissue" and "engineering" or "tissue engineered" and "mucous membrane" or "mucous" and "membrane" or "mucosa." Original studies utilizing tissue engineering to regenerate airway mucosa within the trachea or the main bronchi in animal models or human studies were included. Results: A total of 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 single material was clearly superior to the others. Conclusion: The review highlights gaps in the literature and recommends key directions for future research such as epithelial tracking and the role of the extracellular environment.
    Full-text · Article · Apr 2014 · The Laryngoscope
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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.
    Full-text · Article · Mar 2014 · Macromolecular Bioscience
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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.
    No preview · Article · Mar 2014 · Macromolecular Bioscience

Publication Stats

1k Citations
623.89 Total Impact Points

Institutions

  • 2009-2015
    • University College London
      • • Ear Institute
      • • Division of Surgery and Interventional Science
      • • Centre for Stem Cells and Regenerative Medicine
      Londinium, England, United Kingdom
  • 2014
    • London Centre for Nanotechnology
      Londinium, England, United Kingdom
  • 2013
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
  • 2012
    • Royal Free London NHS Foundation Trust
      Londinium, England, United Kingdom
    • University of California, Davis
      Davis, California, United States
  • 2000-2012
    • University of Bristol
      • • School of Veterinary Sciences
      • • School of Cellular and Molecular Medicine
      Bristol, England, United Kingdom
  • 2011
    • Umeå University
      • Department of Integrative Medical Biology (IMB)
      Umeå, Västerbotten, Sweden
  • 2008
    • Yale University
      New Haven, Connecticut, United States
  • 2007
    • Royal United Hospital Bath NHS Trust
      Bath, England, United Kingdom
  • 2006
    • The Australian Society of Otolaryngology Head & Neck Surgery
      Evans Head, New South Wales, Australia
  • 2004-2006
    • University of Liverpool
      Liverpool, England, United Kingdom
    • Aintree University Hospital NHS Foundation Trust
      Liverpool, England, United Kingdom
  • 2003
    • Royal College of Surgeons of England
      Londinium, England, United Kingdom
  • 1998-2000
    • Bristol Hospital
      Bristol, Connecticut, United States