Martin A Birchall

University College London Hospitals NHS Foundation Trust, Londinium, England, United Kingdom

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Publications (182)983.85 Total impact

  • Owain R Hughes · Sarah M Ayling · Martin A Birchall ·
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    ABSTRACT: Objective: The aim of this study was to measure the effects of endotracheal intubation on innate immune response within the pig laryngeal mucosa. Study design: Prospective controlled basic science study. Setting: The animal experiments and analyses were conducted at the University of Bristol. Samples and methods: Eighteen pigs, matched at the major histocompatibility complex (MHC), were used in the study. The pigs were divided into 9 pairs. One of each pair (9 pigs in total) was intubated with an endotracheal tube under general anesthesia for 90 minutes. Two days later, pinch biopsies were taken from the supraglottis (specifically the false cords) and subglottis of both pigs. The experiment was repeated 8 more times. Based on quantitative immunohistochemistry, percentage areas of positive staining for CD172a, CD163, MHC class II, CD14, and CD16 were calculated separately for the epithelium and lamina propria of each biopsy. Results: Total areas of laryngeal mucosa (epithelium and lamina propria) expressing CD172a and coexpressing CD163 and CD172a were significantly reduced at 2 days following endotracheal intubation (P = .039 and P = .037, respectively). MHC class II expression and MHC class II coexpression with CD172a were similarly reduced following intubation (P = .003 and P = .005, respectively). In the supraglottis, MHC class II coexpression with CD16 and CD14 was also reduced following endotracheal intubation (P = .037). Conclusions: Our results indicate that endotracheal intubation reduces the number of innate immune cells within the upper airway mucosa. This may be an important first step in a cascade leading to chronic wound and scar formation causing airway stenosis.
    Otolaryngology Head and Neck Surgery 11/2015; DOI:10.1177/0194599815617125 · 2.02 Impact Factor
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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.
    Nanoscale 10/2015; DOI:10.1039/C5NR03867G · 7.39 Impact Factor

  • Journal of Pediatric Gastroenterology and Nutrition 10/2015; 61(4):509. DOI:10.1097/MPG.0000000000000923 · 2.63 Impact Factor

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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.
    2015 4th TERMIS World Congress, Boston, Massachusetts, USA; 09/2015
  • M Mat Baki · R Yu · J S Rubin · E Chevretton · G Sandhu · M A Birchall ·
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    ABSTRACT: To explore unilateral vocal fold paralysis patients' perception of a proposed randomised, controlled trial of laryngeal reinnervation versus thyroplasty, and to identify patients' concerns regarding their voice. Seventeen patients from five voice clinics in London were identified as being eligible for the randomised, controlled trial. Eleven of these patients (9 females and 2 males; age range, 18-65 years) were interviewed using a semi-structured topic guide (they were given a minimum of 2 weeks to read through the study information sheet). The interviews were recorded, transcribed and analysed using thematic analysis. The patients were satisfied with the clarity of the information sheet. Most of them perceived that reinnervation was a more 'attractive' option than thyroplasty. This may have been the result of certain phraseology used in the information sheet and by recruiters. Patients' main concern was reduced voice strength and the effects of this on work and social life. Phraseology that needed changing was identified; these changes may optimise the recruitment process for a trial. We propose using the voice handicap index 10 as the primary measure of outcome in the proposed randomised, controlled trial.
    The Journal of Laryngology & Otology 07/2015; 129(7):693-701. DOI:10.1017/S0022215115000985 · 0.67 Impact Factor
  • 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.
    The Journal of Laryngology & Otology 06/2015; 129(8):1-8. DOI:10.1017/S0022215115001577 · 0.67 Impact Factor
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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.
    American Journal of Transplantation 06/2015; 15(10). DOI:10.1111/ajt.13318 · 5.68 Impact Factor
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    ABSTRACT: Stem cell-based tissue-engineered tracheas are at an early stage in their product development cycle. Tens of patients have been treated worldwide in predominantly compassionate use settings, demonstrating significant promise. This potentially life-saving treatment is complex, and the cost and its implications for such treatments are yet to be fully understood. The costs are compounded by varying strategies for graft preparation and transplant, resulting in differing clinical and laboratory costs from different research groups. Here we present a detailed breakdown of the clinical and manufacturing costs for three of the UK patients treated with such transplants. All three patients were treated under Compassionate Use legislation, within the UK National Health Service (NHS) hospital setting. The total costs for the three UK patients treated ranged from approximately $174,420 to $740,500. All three patients were in a state of poor health at time of treatment and had a number of complexities in addition to the restricted airway. This is the first time a cost-analysis has been made for a tissue-engineered organ and provides a benchmark for future studies, as well as comparative data for use in reimbursement considerations.
    Cytotherapy 06/2015; 17(6):S14-S15. DOI:10.1016/j.jcyt.2015.03.332 · 3.29 Impact Factor

  • Cytotherapy 06/2015; 17(6):S69. DOI:10.1016/j.jcyt.2015.03.541 · 3.29 Impact Factor
  • M Rollin · A Jaulim · F Vaz · G Sandhu · S Wood · M Birchall · K Dawas ·
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    ABSTRACT: Adult ingestion of caustic substances is an unusual but serious surgical problem, with injuries likely to be more extensive than those in the corresponding paediatric population. After initial stabilisation and airway management, clinicians are presented with a complex multisystemic problem, frequently requiring a multidisciplinary approach involving several surgical disciplines and associated therapies. A new multidisciplinary team was convened to discuss complex ingestion injury in adults and established techniques were used to bring forward a proposed treatment algorithm. An algorithm may potentially improve clinical efficacy and risk in the management of these complex patients.
    Annals of The Royal College of Surgeons of England 05/2015; 97(4). DOI:10.1308/003588415X14181254789286 · 1.27 Impact Factor
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    ABSTRACT: Trauma to the central and peripheral nervous systems often lead to serious morbidity. Current surgical methods for repairing or replacing such damage have limitations. Tissue engineering offers a potential alternative. Here we show that functionalized α-helical-peptide hydrogels can be used to induce attachment, migration, proliferation and differentiation of murine embryonic neural stem cells (NSCs). Specifically, compared with undecorated gels, those functionalized with Arg-Gly-Asp-Ser (RGDS) peptides increase the proliferative activity of NSCs; promote their directional migration; induce differentiation, with increased expression of microtubule-associated protein-2, and a low expression of glial fibrillary acidic protein; and lead to the formation of larger neurospheres. Electrophysiological measurements from NSCs grown in RGDS-decorated gels indicate developmental progress toward mature neuron-like behavior. Our data indicate that these functional peptide hydrogels may go some way toward overcoming the limitations of current approaches to nerve-tissue repair.
    04/2015; 1(6). DOI:10.1021/acsbiomaterials.5b00051
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    ABSTRACT: Children suffer from damaged or loss of hollow organs i.e. trachea, oesophagus or arteries from birth defects or diseases. Generally these organs possess an outer matrix consisting of collagen, elastin, and cells such as smooth muscle cells (SMC) and a luminal layer consisting of endothelial or epithelial cells, whilst presenting a barrier to luminal content. Tissue engineering research enables the construction of such organs and this study explores this possibility with a bioabsorbable nanocomposite biomaterial, polyhedral oligomeric silsesquioxane poly(ε-caprolactone) urea urethane (POSS–PCL).Our established methods of tubular graft extrusion were modified using a porogen-incorporated POSS–PCL and a new lamination method was explored. Porogen (40, 60 or 105 µm) were introduced to POSS–PCL, which were fabricated into a bilayered, dual topography matching the exterior and luminal interior of tubular organs. POSS–PCL with different amounts of porogen were tested for their suitability as a SMC layer by measuring optimal interactions with human adipose derived stem cells. Angiogenesis potential was tested with the chorioallantoic membrane assay. Tensile strength and burst pressures of bilayared tubular grafts were determined. Scaffolds made with 40 µm porogen demonstrated optimal adipose derived stem cell integration and the scaffolds were able to accommodate angiogenesis. Mechanical properties of the grafts confirmed their potential to match the relevant physiological and biophysical parameters. This study presents a platform for the development of hollow organs for transplantation based on POSS–PCL. These bilayered-tubular structures can be tailor-made for cellular integration and match physico-mechanical properties of physiological systems of interest. More specific luminal cell integration and sources of SMC for the external layer could be further explored.
    Journal of Materials Science Materials in Medicine 03/2015; 26(3):5477. DOI:10.1007/s10856-015-5477-4 · 2.59 Impact Factor
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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.
    Journal of Tissue Engineering and Regenerative Medicine 02/2015; DOI:10.1002/term.1979 · 5.20 Impact Factor
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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.
    British Journal of Surgery 01/2015; 102(2):e140-e150. DOI:10.1002/bjs.9700 · 5.54 Impact Factor
  • Lange P · Fishman JM · De Coppi P · Birchall MA ·

    Gene and Cell Therapy: Therapeutic Mechanisms and Strategies, Fourth Edition, 4th 01/2015: chapter 32: pages 819-832; CRC Press., ISBN: 9781466572003
  • Lange P · Jonathan Fishman · De Coppi P · Birchall MA ·

    Gene and Cell Therapy: Therapeutic Mechanisms and Strategies, Fourth Edition, 4th 01/2015: chapter Surgical and Translational Aspects of Tissue Engineering: pages 819-832; CRC Press., ISBN: 9781466572003
  • Kate Heathcote · Martin Birchall · Yakubu Karagama · Jean-Paul Marie ·

    European Journal of Surgical Oncology 12/2014; 40(12):S6–S7. DOI:10.1016/j.ejso.2014.11.026 · 3.01 Impact Factor

Publication Stats

3k Citations
983.85 Total Impact Points


  • 2015
    • University College London Hospitals NHS Foundation Trust
      Londinium, England, United Kingdom
  • 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
  • 2010-2014
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
    • Baylor College of Medicine
      • Center for Cell and Gene Therapy
      Houston, TX, United States
  • 2013
    • Royal Free London NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2012
    • University of California, Davis
      Davis, California, United States
  • 1998-2012
    • 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
  • 2004-2007
    • University of Liverpool
      Liverpool, England, United Kingdom
    • Aintree University Hospital NHS Foundation Trust
      Liverpool, England, United Kingdom
  • 2006
    • The Australian Society of Otolaryngology Head & Neck Surgery
      Evans Head, New South Wales, Australia
  • 2003
    • Royal College of Surgeons of England
      Londinium, England, United Kingdom
  • 1998-2000
    • Bristol Hospital
      Bristol, Connecticut, United States