Martin A Birchall

University College London, Londinium, England, United Kingdom

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Publications (159)860.6 Total impact

  • [Show abstract] [Hide abstract]
    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 · 1.22 Impact Factor
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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 · 2.38 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 · 4.43 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
  • 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
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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 · 5.21 Impact Factor
  • European Journal of Surgical Oncology 12/2014; 40:S6–S7. DOI:10.1016/j.ejso.2014.11.026 · 2.89 Impact Factor
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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.
    Cytotherapy 11/2014; DOI:10.1016/j.jcyt.2014.10.012 · 3.10 Impact Factor
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    ABSTRACT: Tissue engineering ex vivo and direct cellular application with bioscaffolds in vivo has allowed surgeons to restore and establish function throughout the human body. The evidence for regenerative surgery is growing, and consequently there is a need for the development of more advanced regenerative surgery facilities. Regenerative medicine in the surgical field is changing rapidly and this must be reflected in the design of any future operating suite. The theater environment needs to be highly adaptable to account for future significant advances within the field. Development of purpose built, combined operating suites and tissue-engineering laboratories will provide the facility for modern surgeons to treat patients with organ deficits, using bespoke, regenerated constructs without the need for immunosuppression.
    Regenerative Medicine 11/2014; 9(6):785-791. DOI:10.2217/rme.14.46 · 3.50 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 09/2014; 3(9). DOI:10.1002/adhm.201400065 · 4.88 Impact Factor
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    ABSTRACT: Objective To evaluate the agreement between OperaVOX and MDVP.DesignCross sectional reliability study.SettingUniversity Teaching Hospital.Methods Fifty healthy volunteers and 50 voice disorder patients had supervised recordings in a quiet room using OperaVOX by the iPod's internal microphone with sampling rate of 45kHz. A five seconds recording of vowel /a/ was used to measure fundamental frequency (F0), jitter, shimmer and noise–to–harmonic ratio (NHR). All healthy volunteers and 21 patients had a second recording. The recorded voices was also analysed using the MDVP. The inter- and intra-software reliability was analysed using intraclass correlation (ICC) test and Bland Altman (BA) method. Mann Whitney test was used to compare the acoustic parameters between healthy volunteers and patients.ResultsNine of 50 patients had severe aperiodic voice. The ICC was high with a confidence interval of >0.75 for the inter- and intra-software reliability except for the NHR. For the inter-software BA analysis, excluding the severe aperiodic voice datasets, the bias (95% LOA) of F0, jitter, shimmer and NHR was 0.81(11.32, -9.71); -0.13 (1.26, -1.52); -0.52 (1.68, -2.72); and 0.08 (0.27, -0.10). For the intra-software reliability, it was -1.48 (18.43, -21.39); 0.05 (1.31, -1.21); -0.01 (2.87, -2.89); and 0.005 (0.20, -0.18), respectively. Normative data from the healthy volunteers was obtained. There was a significant difference in all acoustic parameters between volunteers and patients measured by the OperaVOX (p<0.001) except for F0 in females (p=0.87).Conclusion OperaVOX is comparable to MDVP and has high internal consistency for measuring the F0, jitter and shimmer of voice except for the NHR.This article is protected by copyright. All rights reserved.
    Clinical otolaryngology: official journal of ENT-UK; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery 09/2014; 40(1). DOI:10.1111/coa.12313 · 2.27 Impact Factor
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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; 14(10). DOI:10.1517/14712598.2014.938631 · 3.65 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 06/2014; DOI:10.1053/j.sempedsurg.2014.04.002 · 1.94 Impact Factor
  • Diagnosis and Treatment of Voice Disorders, 4th edited by JS Rubin, RT Sataloff, GS Korovin, 05/2014: chapter Emerging approaches to laryngeal replacement and reconstruction: pages 871-886; Plural publishing., ISBN: 9781597565530
  • Martin A Birchall, Alexander M Seifalian
    The Lancet 04/2014; 384(9940). DOI:10.1016/S0140-6736(14)60533-X · 39.21 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 04/2014; 124(4). DOI:10.1002/lary.24469 · 2.03 Impact Factor
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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. DOI:10.1002/mabi.201470009 · 3.65 Impact Factor
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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 03/2014; 14(3). DOI:10.1002/mabi.201300382 · 3.65 Impact Factor
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    ABSTRACT: There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community.
    01/2014; 5:2041731414551764. DOI:10.1177/2041731414551764
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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; 9(4). DOI:10.1002/term.1847 · 4.43 Impact Factor

Publication Stats

2k Citations
860.60 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
  • 2011–2014
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
    • Umeå University
      • Department of Integrative Medical Biology (IMB)
      Umeå, Västerbotten, Sweden
  • 2012–2013
    • Royal Free London NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2000–2012
    • University of Bristol
      • • School of Veterinary Sciences
      • • School of Cellular and Molecular Medicine
      Bristol, England, United Kingdom
  • 2010
    • Baylor College of Medicine
      • Center for Cell and Gene Therapy
      Houston, TX, United States
    • University of Florence
      Florens, Tuscany, Italy
  • 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
  • 2006
    • The Australian Society of Otolaryngology Head & Neck Surgery
      Evans Head, New South Wales, Australia
  • 2004–2005
    • Aintree University Hospital NHS Foundation Trust
      Liverpool, England, United Kingdom
  • 2003
    • Royal College of Surgeons of England
      Londinium, England, United Kingdom
  • 1998
    • Bristol Hospital
      Bristol, Connecticut, United States