42 results on '"Greg Lemon"'
Search Results
2. Retraction Note: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
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Sebastian Sjöqvist, Philipp Jungebluth, Mei Ling Lim, Johannes C. Haag, Ylva Gustafsson, Greg Lemon, Silvia Baiguera, Miguel Angel Burguillos, Costantino Del Gaudio, Antonio Beltrán Rodríguez, Alexander Sotnichenko, Karolina Kublickiene, Henrik Ullman, Heike Kielstein, Peter Damberg, Alessandra Bianco, Rainer Heuchel, Ying Zhao, Domenico Ribatti, Cristián Ibarra, Bertrand Joseph, Doris A. Taylor, and Paolo Macchiarini
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Science - Abstract
Nature Communications 5: Article number: 3562 (2014); Published 15 April 2014; Updated 21 March 2017 This Article is retracted by the authors. Nature Communications previously issued an Editorial Expression of Concern (http://www.nature.com/articles/ncomms13310) related to this Article, following the publication of a report commissioned by The Karolinska Institute and prepared by the Expert Group for Misconduct in Research at the Swedish Central Ethical Review Board.
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- 2017
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3. Characterization of stem-like cells in mucoepidermoid tracheal paediatric tumor.
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Mei Ling Lim, Brandon Nick Sern Ooi, Philipp Jungebluth, Sebastian Sjöqvist, Isabell Hultman, Greg Lemon, Ylva Gustafsson, Jurate Asmundsson, Silvia Baiguera, Iyadh Douagi, Irina Gilevich, Alina Popova, Johannes Cornelius Haag, Antonio Beltrán Rodríguez, Jianri Lim, Agne Liedén, Magnus Nordenskjöld, Evren Alici, Duncan Baker, Christian Unger, Tom Luedde, Ivan Vassiliev, Jose Inzunza, Lars Ahrlund-Richter, and Paolo Macchiarini
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Medicine ,Science - Abstract
Stem cells contribute to regeneration of tissues and organs. Cells with stem cell-like properties have been identified in tumors from a variety of origins, but to our knowledge there are yet no reports on tumor-related stem cells in the human upper respiratory tract. In the present study, we show that a tracheal mucoepidermoid tumor biopsy obtained from a 6 year-old patient contained a subpopulation of cells with morphology, clonogenicity and surface markers that overlapped with bone marrow mesenchymal stromal cells (BM-MSCs). These cells, designated as MEi (mesenchymal stem cell-like mucoepidermoid tumor) cells, could be differentiated towards mesenchymal lineages both with and without induction, and formed spheroids in vitro. The MEi cells shared several multipotent characteristics with BM-MSCs. However, they displayed differences to BM-MSCs in growth kinectics and gene expression profiles relating to cancer pathways and tube development. Despite this, the MEi cells did not possess in vivo tumor-initiating capacity, as proven by the absence of growth in situ after localized injection in immunocompromised mice. Our results provide an initial characterization of benign tracheal cancer-derived niche cells. We believe that this report could be of importance to further understand tracheal cancer initiation and progression as well as therapeutic development.
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- 2014
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4. Editorial Expression of Concern: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
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Sebastian Sjöqvist, Philipp Jungebluth, Mei Ling Lim, Johannes C. Haag, Ylva Gustafsson, Greg Lemon, Silvia Baiguera, Miguel Angel Burguillos, Costantino Del Gaudio, Antonio Beltran Rodriguez, Alexander Sotnichenko, Karolina Kublickiene, Henrik Ullman, Heike Kielstein, Peter Damberg, Alessandra Bianco, Rainer Heuchel, Ying Zhao, Domenico Ribatti, Cristián Ibarra, Bertrand Joseph, Doris A. Taylor, and Paolo Macchiarini
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Science - Published
- 2016
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5. Interconnectivity analysis of supercritical CO2-foamed scaffolds.
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Greg Lemon, Yvonne Reinwald, Lisa J. White, Steven M. Howdle, Kevin M. Shakesheff, and John R. King
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- 2012
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6. Individual-based modelling of angiogenesis inside three-dimensional porous biomaterials.
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Greg Lemon, Daniel Howard 0002, Felicity R. A. J. Rose, and John R. King
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- 2011
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7. A model of inositol 1, 4, 5-trisphosphate and calcium dynamics in single cells following metabotropic receptor activation.
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Greg Lemon, William G. Gibson, and Max R. Bennett
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- 2003
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8. Bladder biomechanics and the use of scaffolds for regenerative medicine in the urinary bladder
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Greg Lemon, Magdalena Fossum, Ioannis S. Chronakis, Fatemeh Ajalloueian, and Jöns Hilborn
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Bladder compliance ,Urology ,media_common.quotation_subject ,Urinary Bladder ,0206 medical engineering ,02 engineering and technology ,Regenerative Medicine ,urologic and male genital diseases ,Models, Biological ,Regenerative medicine ,Urination ,Tissue engineering ,Animals ,Humans ,Regeneration ,Medicine ,Computer Simulation ,Intestinal Mucosa ,media_common ,Urinary bladder ,Tissue Engineering ,Tissue Scaffolds ,business.industry ,Regeneration (biology) ,Biomechanics ,Models, Theoretical ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,Biomechanical Phenomena ,medicine.anatomical_structure ,Bladder augmentation ,0210 nano-technology ,business ,Algorithms ,Biomedical engineering - Abstract
The urinary bladder is a complex organ with the primary functions of storing urine under low and stable pressure and micturition. Many clinical conditions can cause poor bladder compliance, reduced capacity, and incontinence, requiring bladder augmentation or use of regenerative techniques and scaffolds. To replicate an organ that is under frequent mechanical loading and unloading, special attention towards fulfilling its biomechanical requirements is necessary. Several biological and synthetic scaffolds are available, with various characteristics that qualify them for use in bladder regeneration in vitro and in vivo, including in the treatment of clinical conditions. The biomechanical properties of the native bladder can be investigated using a range of mechanical tests for standardized assessments, as well as mathematical and computational bladder biomechanics. Despite a large body of research into tissue engineering of the bladder wall, some features of the native bladder and the scaffolds used to mimic it need further elucidation. Collection of comparable reference data from different animal models would be a helpful tool for researchers and will enable comparison of different scaffolds in order to optimize characteristics before entering preclinical and clinical trials.
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- 2018
9. The Use of Mathematical Modelling for Improving the Tissue Engineering of Organs and Stem Cell Therapy
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Annika Stuewer, Philipp Jungebluth, Alexandra B. Firsova, Paolo Macchiarini, Johannes C. Haag, Risul Amin, E. A. Gubareva, Sebastian Sjöqvist, Mei Ling Lim, Greg Lemon, Neus Feliu, and Ylva Gustafsson
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Science and engineering ,0206 medical engineering ,Medicine (miscellaneous) ,02 engineering and technology ,Biology ,Regenerative Medicine ,Models, Biological ,Regenerative medicine ,03 medical and health sciences ,Tissue scaffolds ,Tissue engineering ,medicine ,Animals ,Humans ,Tissue Engineering ,Tissue Scaffolds ,Management science ,General Medicine ,Stem-cell therapy ,030104 developmental biology ,Organ Specificity ,020602 bioinformatics ,Stem Cell Transplantation - Abstract
Regenerative medicine is a multidisciplinary field where continued progress relies on the incorporation of a diverse set of technologies from a wide range of disciplines within medicine, science and engineering. This review describes how one such technique, mathematical modelling, can be utilised to improve the tissue engineering of organs and stem cell therapy. Several case studies, taken from research carried out by our group, ACTREM, demonstrate the utility of mechanistic mathematical models to help aid the design and optimisation of protocols in regenerative medicine.
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- 2016
10. Retraction notice to:'Verification of cell viability in bioengineered tissues and organs before clinical transplantation ' [BIOMATERIALS (2013) 4057-4067]
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Oscar E. Simonson, Sebastian Sjöqvist, Greg Lemon, Ylva Gustafsson, Karl H. Grinnemo, Costantino Del Gaudio, Mei Ling Lim, Staffan Strömblad, Johannes C. Haag, Paolo Macchiarini, I. V. Gilevich, Philipp Jungebluth, Matthias Corbascio, Fatemeh Ajalloueian, and Silvia Baiguera
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Biomaterials ,Transplantation ,Pathology ,medicine.medical_specialty ,Notice ,Mechanics of Materials ,business.industry ,Biophysics ,Ceramics and Composites ,Medicine ,Bioengineering ,Viability assay ,business - Published
- 2019
11. Publisher Correction: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
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Johannes C. Haag, Greg Lemon, Philipp Jungebluth, Silvia Baiguera, Cristian Ibarra, Paolo Macchiarini, Rainer Heuchel, Karolina Kublickiene, Doris A. Taylor, Peter Damberg, Bertrand Joseph, Alessandra Bianco, Domenico Ribatti, Antonio B. Rodriguez, Ylva Gustafsson, Miguel Angel Burguillos, Sebastian Sjöqvist, Mei Ling Lim, Costantino Del Gaudio, Alexander Sotnichenko, Ying Zhao, Heike Kielstein, and Henrik Ullman
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medicine.medical_specialty ,Science ,Myocytes, Smooth Muscle ,MEDLINE ,General Physics and Astronomy ,General Biochemistry, Genetics and Molecular Biology ,Orthotopic transplantation ,Esophagus ,Medicine ,Animals ,Regeneration ,Multidisciplinary ,Tissue engineered ,Tissue Engineering ,Tissue Scaffolds ,business.industry ,Published Erratum ,General surgery ,Correction ,Cell Differentiation ,Mesenchymal Stem Cells ,General Chemistry ,Rats ,business ,Immunocompetence - Abstract
A tissue-engineered oesophageal scaffold could be very useful for the treatment of pediatric and adult patients with benign or malignant diseases such as carcinomas, trauma or congenital malformations. Here we decellularize rat oesophagi inside a perfusion bioreactor to create biocompatible biological rat scaffolds that mimic native architecture, resist mechanical stress and induce angiogenesis. Seeded allogeneic mesenchymal stromal cells spontaneously differentiate (proven by gene-, protein and functional evaluations) into epithelial- and muscle-like cells. The reseeded scaffolds are used to orthotopically replace the entire cervical oesophagus in immunocompetent rats. All animals survive the 14-day study period, with patent and functional grafts, and gain significantly more weight than sham-operated animals. Explanted grafts show regeneration of all the major cell and tissue components of the oesophagus including functional epithelium, muscle fibres, nerves and vasculature. We consider the presented tissue-engineered oesophageal scaffolds a significant step towards the clinical application of bioengineered oesophagi.
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- 2018
12. Retraction Note: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
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Silvia Baiguera, Johannes C. Haag, Henrik Ullman, Bertrand Joseph, Paolo Macchiarini, Alessandra Bianco, Doris A. Taylor, Karolina Kublickiene, Costantino Del Gaudio, Mei Ling Lim, Domenico Ribatti, Ying Zhao, Ylva Gustafsson, Philipp Jungebluth, Heike Kielstein, Cristian Ibarra, Antonio Beltrán Rodríguez, Alexander Sotnichenko, Rainer Heuchel, Peter Damberg, Greg Lemon, Miguel Angel Burguillos, and Sebastian Sjöqvist
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Multidisciplinary ,Tissue engineered ,business.industry ,Science ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology ,Retraction ,03 medical and health sciences ,030104 developmental biology ,Orthotopic transplantation ,Medicine ,business - Abstract
Nature Communications 5: Article number: 3562 (2014); Published 15 April 2014; Updated 21 March 2017 This Article is retracted by the authors. Nature Communications previously issued an Editorial Expression of Concern (http://www.nature.com/articles/ncomms13310) related to this Article, following the publication of a report commissioned by The Karolinska Institute and prepared by the Expert Group for Misconduct in Research at the Swedish Central Ethical Review Board.
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- 2017
13. Tracheal tissue engineering in rats
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Philipp Jungebluth, Paolo Macchiarini, Greg Lemon, Johannes C. Haag, Ivar Dehnisch, Alessandra Bianco, Per Uhlén, Mei Ling Lim, Silvia Baiguera, Antonio Beltrán Rodríguez, Ylva Gustafsson, Costantino Del Gaudio, and Sebastian Sjöqvist
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Decellularization ,Tissue Engineering ,Tissue Scaffolds ,Guided Tissue Regeneration ,business.industry ,Settore ING-IND/22 - Scienza e Tecnologia dei Materiali ,Cellular differentiation ,Regeneration (biology) ,Rat model ,Nanofibers ,General Biochemistry, Genetics and Molecular Biology ,Biomechanical Phenomena ,Rats ,Trachea ,Orthotopic transplantation ,Tissue engineering ,Electrospun nanofibers ,Animals ,Medicine ,Colorimetry ,Viability assay ,business ,Biomedical engineering - Abstract
Tissue-engineered tracheal transplants have been successfully performed clinically. However, before becoming a routine clinical procedure, further preclinical studies are necessary to determine the underlying mechanisms of in situ tissue regeneration. Here we describe a protocol using a tissue engineering strategy and orthotopic transplantation of either natural decellularized donor tracheae or artificial electrospun nanofiber scaffolds into a rat model. The protocol includes details regarding how to assess the scaffolds' biomechanical properties and cell viability before implantation. It is a reliable and reproducible model that can be used to investigate the crucial aspects and pathways of in situ tracheal tissue restoration and regeneration. The model can be established in
- Published
- 2014
14. RETRACTED: Biomechanical and biocompatibility characteristics of electrospun polymeric tracheal scaffolds
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Paolo Macchiarini, Silvia Baiguera, Alessandra Bianco, Costantino Del Gaudio, Sebastian Sjöqvist, Greg Lemon, Philipp Jungebluth, Fatemeh Ajalloueian, Ylva Gustafsson, Mei Ling Lim, Antonio Beltrán-Rodríguez, and Johannes C. Haag
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Male ,Scaffold ,Materials science ,Biocompatibility ,Polymers ,Polyurethanes ,Biophysics ,Biocompatible Materials ,Cell Count ,Bioengineering ,Rats, Sprague-Dawley ,Biomaterials ,chemistry.chemical_compound ,Bioreactors ,Orthotopic transplantation ,Tissue engineering ,In vivo ,Cell Adhesion ,Polyethylene terephthalate ,Animals ,Tissue Engineering ,Tissue Scaffolds ,Polyethylene Terephthalates ,Mesenchymal Stem Cells ,Electrospinning ,Rats ,Trachea ,Transplantation ,chemistry ,Mechanics of Materials ,Microscopy, Electron, Scanning ,Ceramics and Composites ,Biomedical engineering - Abstract
The development of tracheal scaffolds fabricated based on electrospinning technique by applying different ratios of polyethylene terephthalate (PET) and polyurethane (PU) is introduced here. Prior to clinical implantation, evaluations of biomechanical and morphological properties, as well as biocompatibility and cell adhesion verifications are required and extensively performed on each scaffold type. However, the need for bioreactors and large cell numbers may delay the verification process during the early assessment phase. Hence, we investigated the feasibility of performing biocompatibility verification using static instead of dynamic culture. We performed bioreactor seeding on 3-dimensional (3-D) tracheal scaffolds (PET/PU and PET) and correlated the quantitative and qualitative results with 2-dimensional (2-D) sheets seeded under static conditions. We found that an 8-fold reduction for 2-D static seeding density can essentially provide validation on the qualitative and quantitative evaluations for 3-D scaffolds. In vitro studies revealed that there was notably better cell attachment on PET sheets/scaffolds than with the polyblend. However, the in vivo outcomes of cell seeded PET/PU and PET scaffolds in an orthotopic transplantation model in rodents were similar. They showed that both the scaffold types satisfied biocompatibility requirements and integrated well with the adjacent tissue without any observation of necrosis within 30 days of implantation.
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- 2014
15. Editorial Expression of Concern: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
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Paolo Macchiarini, Ylva Gustafsson, Silvia Baiguera, Cristian Ibarra, Domenico Ribatti, Greg Lemon, Miguel Angel Burguillos, Alessandra Bianco, Sebastian Sjöqvist, Karolina Kublickiene, Heike Kielstein, Bertrand Joseph, Peter Damberg, Costantino Del Gaudio, Philipp Jungebluth, Alexander Sotnichenko, Doris A. Taylor, Rainer Heuchel, Ying Zhao, Johannes C. Haag, Henrik Ullman, Antonio B. Rodriguez, and Mei Ling Lim
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0301 basic medicine ,Multidisciplinary ,Tissue engineered ,business.industry ,Science ,digestive, oral, and skin physiology ,General Physics and Astronomy ,General Chemistry ,digestive system ,digestive system diseases ,General Biochemistry, Genetics and Molecular Biology ,Addendum ,03 medical and health sciences ,surgical procedures, operative ,030104 developmental biology ,Orthotopic transplantation ,otorhinolaryngologic diseases ,Cancer research ,Medicine ,business - Abstract
Editorial Expression of Concern: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
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- 2016
16. Retraction notice to: 'Biomechanical and biocompatibility characteristics of electrospun polymeric tracheal scaffolds '[BIOMATERIALS 35/20 (2014) 5307-5315]
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Antonio Beltrán-Rodríguez, Costantino Del Gaudio, Silvia Baiguera, Alessandra Bianco, Greg Lemon, Ylva Gustafsson, Johannes C. Haag, Sebastian Sjöqvist, Paolo Macchiarini, Philipp Jungebluth, Mei Ling Lim, and Fatemeh Ajalloueian
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Biomaterials ,Materials science ,Biocompatibility ,Notice ,Mechanics of Materials ,Biophysics ,Ceramics and Composites ,Bioengineering ,Biomedical engineering - Published
- 2019
17. The development of the bioartificial lung
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Fatemeh Ajalloueian, Greg Lemon, Paolo Macchiarini, and Mei Ling Lim
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Lung Diseases ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Models, Biological ,Artificial lung ,Tissue engineering ,medicine ,Humans ,Lung transplantation ,Computer Simulation ,Progenitor cell ,Lung ,Bioartificial Organs ,Tissue Engineering ,Tissue Scaffolds ,business.industry ,General Medicine ,respiratory system ,Embryonic stem cell ,respiratory tract diseases ,medicine.anatomical_structure ,Lung disease ,Chronic Disease ,Stem cell ,business ,Lung Transplantation ,Stem Cell Transplantation - Abstract
The incidence of chronic lung disease is increasing worldwide due to the spread of risk factors and ageing population. An important advance in treatment would be the development of a bioartificial lung where the blood-gas exchange surface is manufactured from a synthetic or natural scaffold material that is seeded with the appropriate stem or progenitor cells to mimic the functional tissue of the natural lung.Articles relating to bioartificial lungs were sourced through PubMed and ISI Web of Knowledge.There is a consensus that advances in bioartificial lung engineering will be beneficial to patients with chronic lung failure. Ultimate success will require the concerted efforts of researchers drawn from a broad range of disciplines, including clinicians, cell biologists, materials scientists and engineers.As a source of cells for use in bioartificial lungs it is proposed to use human embryonic stem cells; however, there are ethical and safety concerns regarding the use of these cells.There is a need to identify the optimum strategies for differentiating progenitor cells into functional lung cells; a need to better understand cell-biomaterial/ECM interactions and a need to understand how to harness the body's natural capacity to regenerate the lung.Biomaterial technologies for recreating the natural lung ECM and architecture need further development. Mathematical modelling techniques should be developed for determining optimal scaffold seeding strategies and predicting gas exchange performance.
- Published
- 2013
18. RETRACTED: Verification of cell viability in bioengineered tissues and organs before clinical transplantation
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Philipp Jungebluth, Matthias Corbascio, Silvia Baiguera, Sebastian Sjöqvist, I. V. Gilevich, Oscar E. Simonson, Staffan Strömblad, Paolo Macchiarini, Greg Lemon, Costantino Del Gaudio, Ylva Gustafsson, Mei Ling Lim, Johannes C. Haag, Karl H. Grinnemo, and Fatemeh Ajalloueian
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Male ,Pathology ,medicine.medical_specialty ,Cell Survival ,Cell seeding ,Polyurethanes ,Biophysics ,Cell Count ,Bioengineering ,Biology ,Rats, Sprague-Dawley ,Translational Research, Biomedical ,Biomaterials ,Young Adult ,chemistry.chemical_compound ,Cell Adhesion ,medicine ,Animals ,Humans ,DAPI ,Viability assay ,Engineered tissue ,Synthetic scaffold ,Transplantation ,Bioartificial Organs ,Tissue Scaffolds ,Reproducibility of Results ,Mesenchymal Stem Cells ,Rats ,Trachea ,chemistry ,Mechanics of Materials ,Microscopy, Electron, Scanning ,Ceramics and Composites ,Female ,Colorimetric Cell Viability Assay ,Biomedical engineering - Abstract
The clinical outcome of transplantations of bioartificial tissues and organs depends on the presence of living cells. There are still no standard operative protocols that are simple, fast and reliable for confirming the presence of viable cells on bioartificial scaffolds prior to transplantation. By using mathematical modeling, we have developed a colorimetric-based system (colorimetric scale bar) to predict the cell viability and density for sufficient surface coverage. First, we refined a method which can provide information about cell viability and numbers in an in vitro setting: i) immunohistological staining by Phalloidin/DAPI and ii) a modified colorimetric cell viability assay. These laboratory-based methods and the developed colorimetric-based system were then validated in rat transplantation studies of unseeded and seeded tracheal grafts. This was done to provide critical information on whether the graft would be suitable for transplantation or if additional cell seeding was necessary. The potential clinical impact of the colorimetric scale bar was confirmed using patient samples. In conclusion, we have developed a robust, fast and reproducible colorimetric tool that can verify and warrant viability and integrity of an engineered tissue/organ prior to transplantation. This should facilitate a successful transplantation outcome and ensure patient safety.
- Published
- 2013
19. A FUNCTIONAL DIFFERENTIAL EQUATION MODEL FOR BIOLOGICAL CELL SORTING DUE TO DIFFERENTIAL ADHESION
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John R. King and Greg Lemon
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Cell type ,Continuum (topology) ,Differential equation ,Applied Mathematics ,Modeling and Simulation ,Mathematical analysis ,Sorting ,Adhesion ,Cell sorting ,Biological system ,Continuum Modeling ,Differential (mathematics) ,Mathematics - Abstract
This paper presents a mathematical model to describe the sorting of two different types of cells, arising from differential adhesion mechanisms within biological tissue. The model is based on a continuum approach that takes into account individual cell behavior including aspects of the cell-migration process, dynamics of the adhesions between contacting cells, and finite cell size. Numerical solutions and bifurcation analyses for the case of a collection of two different cell types show a variety of behaviors observed in experiments, including spatially uniform mixing of cells and the formation of two distinct, containing both types of cells or just one. The mathematical model, which is in the form of a set of functional differential equations, represents a novel approach to continuum modeling of cell sorting and migration within biological tissue.
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- 2012
20. Growth of the chorioallantoic membrane into a rapid-prototyped model pore system: experiments and mathematical model
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Felicity R. A. J. Rose, Daniel Howard, Joel Segal, Svetan Ratchev, Hongyi Yang, John R. King, Greg Lemon, Sarah L. Waters, and Oliver E. Jensen
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Scaffold ,Materials science ,Tissue Scaffolds ,Mechanical Engineering ,Isotropy ,Pore system ,Models, Biological ,Chorioallantoic Membrane ,Membrane tension ,Porous scaffold ,Biomechanical Phenomena ,Chorioallantoic membrane ,Membrane ,Tissue engineering ,Modeling and Simulation ,Biophysics ,Animals ,Chickens ,Porosity ,Biotechnology ,Biomedical engineering - Abstract
This paper presents a mathematical model to describe the growth of tissue into a rapid-prototyped porous scaffold when it is implanted onto the chorioallantoic membrane (CAM). The scaffold was designed to study the effects of the size and shape of pores on tissue growth into conventional tissue engineering scaffolds, and consists of an array of pores each having a pre-specified shape. The experimental observations revealed that the CAM grows through each pore as an intact layer of tissue, provided the width of the pore exceeds a threshold value. Based on these results a mathematical model is described to simulate the growth of the membrane, assuming that the growth is a function of the local isotropic membrane tension. The model predictions are compared against measurements of the extent of membrane growth through the pores as a function of time for pores with different dimensions.
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- 2016
21. Interconnectivity analysis of supercritical CO2-foamed scaffolds
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Yvonne Reinwald, Steven M. Howdle, John R. King, Greg Lemon, Kevin M. Shakesheff, and Lisa J. White
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chemistry.chemical_classification ,Scaffold ,Micro-computed tomography ,Materials science ,Characterisation of pore space in soil ,Health Informatics ,Polymer ,Interconnectivity ,Supercritical fluid ,Computer algorithm ,Computer Science Applications ,PLGA ,chemistry.chemical_compound ,Tissue engineering ,chemistry ,Digital image processing ,Software ,Biomedical engineering - Abstract
This paper describes a computer algorithm for the determination of the interconnectivity of the pore space inside scaffolds used for tissue engineering. To validate the algorithm and its computer implementation, the algorithm was applied to a computer-generated scaffold consisting of a set of overlapping spherical pores, for which the interconnectivity was calculated exactly. The algorithm was then applied to micro-computed X-ray tomography images of supercritical CO2-foamed scaffolds made from poly(lactic-co-glycolic acid) (PLGA), whereby the effect of using different weight average molecular weight polymer on the interconnectivity was investigated.
- Published
- 2012
- Full Text
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22. Individual-based modelling of angiogenesis inside three-dimensional porous biomaterials
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Daniel Howard, Felicity R. A. J. Rose, Greg Lemon, and John R. King
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Statistics and Probability ,Scaffold ,Materials science ,Tissue engineered ,Tissue Engineering ,Tissue Scaffolds ,Angiogenesis ,Applied Mathematics ,Neovascularization, Physiologic ,Biocompatible Materials ,Nanotechnology ,General Medicine ,Models, Biological ,Regenerative medicine ,General Biochemistry, Genetics and Molecular Biology ,Capillaries ,Individual based ,Tissue engineering ,Cell Movement ,Modeling and Simulation ,Animals ,Porosity ,Cell Proliferation ,Biomedical engineering ,Rate of growth - Abstract
This paper presents a simulation modelling framework to study the growth of blood vessels and cells through a porous tissue engineering scaffold. The model simulates the migration of capillaries and the formation of a vascular network through a single pore of a tissue engineering scaffold when it is embedded in living tissue. The model also describes how the flow of blood through the network changes as growth proceeds. Results are given for how the different strategies of seeding the pore with cells affects the extent of vascularisation. Also simulations are made to compare results where the values of different model parameters are varied such as the pore dimensions, the density of endothelial cells seeded into the pore, and the release rate of growth factor from the scaffold into the pore. The modelling framework described in this paper is useful for exploring experimental strategies for producing well-vascularised tissue engineered constructs, and is therefore potentially important to the field of regenerative medicine.
- Published
- 2011
23. On the population dynamics of the Australian bushfly
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Greg Lemon
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education.field_of_study ,Ecology ,biology ,Advection ,Ecological Modeling ,Population ,Simulation modeling ,Stable equilibrium ,Musca vetustissima ,biology.organism_classification ,Atmospheric sciences ,Population density ,Geography ,Bifurcation analysis ,Insect migration ,education ,Physics::Atmospheric and Oceanic Physics - Abstract
Each spring, the Australian bushfly (Musca vetustissima Walker) migrates from its over-wintering areas located in central Australia and repopulates the south-eastern parts of the continent. In this paper, a simple size-structured model, in the form of a reaction–advection equation with delay, is presented for the evolution of the population density of the bushfly. The model takes into account the important role of cattle dung in its life cycle and includes the effects of wind-borne migration. Bifurcation analyses of the model equations in the absence of wind advection reveals the environmental conditions under which the fly population will die out, reach a stable equilibrium or explode. Numerical simulations which include advection reveal the importance of wind-borne migration in building up the population of flies in south-eastern Australia during the summer months.
- Published
- 2009
24. Mathematical modelling of human mesenchymal stem cell proliferation and differentiation inside artificial porous scaffolds
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Felicity R. A. J. Rose, John R. King, Greg Lemon, and Sarah L. Waters
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Statistics and Probability ,Biocompatible Materials ,Matrix (biology) ,Biology ,Models, Biological ,Regenerative medicine ,General Biochemistry, Genetics and Molecular Biology ,Downregulation and upregulation ,Tissue engineering ,Humans ,Mesenchymal stem cell proliferation ,Cell Proliferation ,Tissue Engineering ,General Immunology and Microbiology ,Cell growth ,Applied Mathematics ,Mesenchymal stem cell ,Cell Differentiation ,Mesenchymal Stem Cells ,General Medicine ,Cell Hypoxia ,Extracellular Matrix ,Cell biology ,Oxygen ,Cell culture ,Modeling and Simulation ,General Agricultural and Biological Sciences - Abstract
We present a mathematical model for the proliferation and differentiation of human mesenchymal stem cells grown inside artificial porous scaffolds under different oxygen concentrations. The values of parameters in the model are determined by comparison of the model solutions to published experimental data, complemented with a sensitivity analysis of the fitted parameters. It is shown that a simple hypothesis whereby the secretion of extra-cellular matrix (ECM) is oxygen dependent and that ECM itself stimulates cell proliferation is sufficient to explain the experimental data, which under conditions of low oxygen reveals increased total cell proliferation, upregulation of the numbers of undifferentiated cells, and extended lag phase. These results may help further to understand how cells proliferate inside artificial materials and are of importance to the field of tissue engineering.
- Published
- 2007
25. Travelling-wave behaviour in a multiphase model of a population of cells in an artificial scaffold
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Greg Lemon and John R. King
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Scaffold ,Materials science ,Quantitative Biology::Tissues and Organs ,Population ,Biocompatible Materials ,Nanotechnology ,Context (language use) ,Cell Growth Processes ,Models, Biological ,Quantitative Biology::Cell Behavior ,Tissue engineering ,Exponential growth ,Cell Movement ,Humans ,education ,Porosity ,Wavefront ,education.field_of_study ,Tissue Engineering ,Applied Mathematics ,Water ,Numerical Analysis, Computer-Assisted ,Mechanics ,Agricultural and Biological Sciences (miscellaneous) ,Drag ,Modeling and Simulation - Abstract
This paper analyses travelling-wave behaviour in a recently-formulated multiphase model for the growth of biological tissue that comprises motile cells and water inside a porous scaffold. The model arises in the context of tissue engineering, and its purpose is to study how cells migrate and proliferate inside porous biomaterials. In suitable limits, tissue growth in the model is shown to occur in the form of travelling waves that can propagate either forwards or backwards, depending on the values of the parameters. In the case where the drag force between the scaffold and the cells is non-zero, the growth of the aggregate can be analysed in terms of the propagation of a constant-speed wavefront in a semi-infinite domain. A numerical (shooting) method is described for calculating the wave speed, and detailed results for how the speed varies with respect to the parameters are given. In the case where the drag force is zero, the size of the aggregate is shown either to grow or to shrink exponentially with time. These results may be of importance in determining the experimental factors that control tissue invasiveness in scaffolds thereby allowing greater control over engineered tissue growth.
- Published
- 2007
26. Orthotopic transplantation of a tissue engineered diaphragm in rats
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Philipp Jungebluth, S. S. Dzhimak, Geoanna Bautista, Konstantin A. Danilenko, Sergei N. Chvalun, I. S. Gumenyuk, I. V. Gilevich, Mei Ling Lim, Paolo Macchiarini, Mark J. Holterman, E. A. Gubareva, Timofei E. Grigoriev, Greg Lemon, Doris A. Taylor, Antonio Beltrán Rodríguez, Sebastian Sjöqvist, E. V. Kuevda, A. S. Sotnichenko, Alexander G. Pokhotko, Ylva Gustafsson, Vladimir M. Pokrovsky, R. Z. Nakokhov, Neus Feliu, A. A. Basov, and S. V. Krasheninnikov
- Subjects
0301 basic medicine ,Male ,Pathology ,medicine.medical_specialty ,Transplantation, Heterotopic ,Diaphragm ,Biophysics ,Diaphragmatic breathing ,Neovascularization, Physiologic ,Transplants ,Bioengineering ,Mesenchymal Stem Cell Transplantation ,Biomaterials ,03 medical and health sciences ,0302 clinical medicine ,Bioreactors ,Tissue engineering ,Absorbable Implants ,medicine ,Cell Adhesion ,Animals ,Wound Healing ,Decellularization ,Tissue Engineering ,Tissue Scaffolds ,business.industry ,Electromyography ,Regeneration (biology) ,Macrophages ,Mesenchymal stem cell ,Graft Survival ,Cell Differentiation ,Allografts ,Diaphragm (structural system) ,Rats ,Transplantation ,Radiography ,030104 developmental biology ,medicine.anatomical_structure ,Mechanics of Materials ,Rats, Inbred Lew ,030220 oncology & carcinogenesis ,Ceramics and Composites ,Bone marrow ,business ,Hernias, Diaphragmatic, Congenital - Abstract
The currently available surgical options to repair the diaphragm are associated with significant risks of defect recurrence, lack of growth potential and restored functionality. A tissue engineered diaphragm has the potential to improve surgical outcomes for patients with congenital or acquired disorders. Here we show that decellularized diaphragmatic tissue reseeded with bone marrow mesenchymal stromal cells (BM-MSCs) facilitates in situ regeneration of functional tissue. A novel bioreactor, using simultaneous perfusion and agitation, was used to rapidly decellularize rat diaphragms. The scaffolds retained architecture and mechanical properties and supported cell adhesion, proliferation and differentiation. Biocompatibility was further confirmed in vitro and in vivo. We replaced 80% of the left hemidiaphragm with reseeded diaphragmatic scaffolds. After three weeks, transplanted animals gained 32% weight, showed myography, spirometry parameters, and histological evaluations similar to native rats. In conclusion, our study suggested that reseeded decellularized diaphragmatic tissue appears to be a promising option for patients in need of diaphragmatic reconstruction.
- Published
- 2015
27. Generierung eines trachealen Grafts und klinischer Transfer From bench to bedside and back to bench
- Author
-
S Sjöqvist, P Jungebluth, H Dienemann, Ylva Gustafsson, Mei Ling Lim, J.C. Haag, Greg Lemon, P Macchiarini, and Silvia Baiguera
- Subjects
business.industry ,Medicine ,Surgery ,business ,Nuclear medicine ,Bench to bedside - Published
- 2014
28. Characterization of Stem-Like Cells in Mucoepidermoid Tracheal Paediatric Tumor
- Author
-
Jianri Lim, Paolo Macchiarini, Silvia Baiguera, Antonio Beltrán Rodríguez, Greg Lemon, Brandon Nick Sern Ooi, Tom Luedde, Lars Ährlund-Richter, Magnus Nordenskjöld, Evren Alici, Ivan Vassiliev, Ylva Gustafsson, Agne Liedén, José Inzunza, Iyadh Douagi, Johannes C. Haag, Philipp Jungebluth, Duncan Baker, Alina Popova, I. V. Gilevich, Sebastian Sjöqvist, Christian Unger, Mei Ling Lim, Isabell Hultman, and Jurate Asmundsson
- Subjects
Male ,Pathology ,Microarrays ,Cellular differentiation ,lcsh:Medicine ,Cell Separation ,Cell Fate Determination ,Pediatrics ,Mice ,Animal Cells ,Molecular Cell Biology ,Medicine and Health Sciences ,lcsh:Science ,Child ,Stem cell transplantation for articular cartilage repair ,Multidisciplinary ,Stem Cells ,Amniotic stem cells ,Cell Differentiation ,Genomics ,3. Good health ,Mucoepidermoid Tumor ,medicine.anatomical_structure ,Bioassays and Physiological Analysis ,Oncology ,Neoplastic Stem Cells ,Female ,Stem cell ,Cellular Types ,Research Article ,medicine.medical_specialty ,Research and Analysis Methods ,Cancer stem cell ,medicine ,Animals ,Humans ,business.industry ,Gene Expression Profiling ,Mesenchymal stem cell ,lcsh:R ,Biology and Life Sciences ,Computational Biology ,Mesenchymal Stem Cells ,Cell Biology ,Pediatric Oncology ,lcsh:Q ,Tracheal Neoplasms ,Bone marrow ,business ,Developmental Biology - Abstract
Stem cells contribute to regeneration of tissues and organs. Cells with stem cell-like properties have been identified in tumors from a variety of origins, but to our knowledge there are yet no reports on tumor-related stem cells in the human upper respiratory tract. In the present study, we show that a tracheal mucoepidermoid tumor biopsy obtained from a 6 year-old patient contained a subpopulation of cells with morphology, clonogenicity and surface markers that overlapped with bone marrow mesenchymal stromal cells (BM-MSCs). These cells, designated as MEi (mesenchymal stem cell-like mucoepidermoid tumor) cells, could be differentiated towards mesenchymal lineages both with and without induction, and formed spheroids in vitro. The MEi cells shared several multipotent characteristics with BM-MSCs. However, they displayed differences to BM-MSCs in growth kinectics and gene expression profiles relating to cancer pathways and tube development. Despite this, the MEi cells did not possess in vivo tumor-initiating capacity, as proven by the absence of growth in situ after localized injection in immunocompromised mice. Our results provide an initial characterization of benign tracheal cancer-derived niche cells. We believe that this report could be of importance to further understand tracheal cancer initiation and progression as well as therapeutic development.
- Published
- 2014
29. Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
- Author
-
Alessandra Bianco, Greg Lemon, Henrik Ullman, Alexander Sotnichenko, Silvia Baiguera, Karolina Kublickiene, Cristian Ibarra, Antonio Beltrán Rodríguez, Rainer Heuchel, Costantino Del Gaudio, Paolo Macchiarini, Ying Zhao, Philipp Jungebluth, Miguel Angel Burguillos, Sebastian Sjöqvist, Heike Kielstein, Bertrand Joseph, Domenico Ribatti, Johannes C. Haag, Doris A. Taylor, Peter Damberg, Ylva Gustafsson, and Mei Ling Lim
- Subjects
Pathology ,medicine.medical_specialty ,Angiogenesis ,Settore ING-IND/22 - Scienza e Tecnologia dei Materiali ,Cellular differentiation ,General Physics and Astronomy ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Esophagus ,0302 clinical medicine ,Tissue engineering ,medicine ,Animals ,Myocyte ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Tissue Engineering ,Tissue Scaffolds ,Regeneration (biology) ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,General Chemistry ,Anatomy ,Epithelium ,medicine.anatomical_structure ,030220 oncology & carcinogenesis - Abstract
A tissue-engineered oesophageal scaffold could be very useful for the treatment of pediatric and adult patients with benign or malignant diseases such as carcinomas, trauma or congenital malformations. Here we decellularize rat oesophagi inside a perfusion bioreactor to create biocompatible biological rat scaffolds that mimic native architecture, resist mechanical stress and induce angiogenesis. Seeded allogeneic mesenchymal stromal cells spontaneously differentiate (proven by gene-, protein and functional evaluations) into epithelial- and muscle-like cells. The reseeded scaffolds are used to orthotopically replace the entire cervical oesophagus in immunocompetent rats. All animals survive the 14-day study period, with patent and functional grafts, and gain significantly more weight than sham-operated animals. Explanted grafts show regeneration of all the major cell and tissue components of the oesophagus including functional epithelium, muscle fibres, nerves and vasculature. We consider the presented tissue-engineered oesophageal scaffolds a significant step towards the clinical application of bioengineered oesophagi., Patients with oesophageal diseases may require surgical removal and replacement of the oesophagus. Here the authors seed mesenchymal stromal cells on a decellularized rat oesophagus and show that this bioengineered tissue construct restores swallowing function after transplantation into rats.
- Published
- 2014
30. Preservation of aortic root architecture and properties using a detergent-enzymatic perfusion protocol
- Author
-
Ana I. Teixeira, Greg Lemon, Bertrand Joseph, Paolo Macchiarini, Philipp Jungebluth, Johannes C. Haag, Alexander Sotnichenko, Ylva Gustafsson, Vanessa Lundin, Fatemeh Ajalloueian, Mei Ling Lim, Linda Helen Friedrich, Heike Kielstein, Miguel Angel Burguillos, and Sebastian Sjöqvist
- Subjects
Aortic valve ,medicine.medical_specialty ,Materials science ,Biocompatibility ,Cell Survival ,medicine.medical_treatment ,Detergents ,Biophysics ,Bioengineering ,Biomaterials ,Valve replacement ,Tissue engineering ,medicine ,Cell Adhesion ,Animals ,Cells, Cultured ,Decellularization ,Tissue Engineering ,Tissue Processing ,Mesenchymal Stem Cells ,Immunohistochemistry ,Surgery ,Tissue Degeneration ,medicine.anatomical_structure ,Mechanics of Materials ,Aortic Valve ,Ceramics and Composites ,Cell activation ,Biomedical engineering - Abstract
Aortic valve degeneration and dysfunction is one of the leading causes for morbidity and mortality. The conventional heart-valve prostheses have significant limitations with either life-long anticoagulation therapeutic associated bleeding complications (mechanical valves) or limited durability (biological valves). Tissue engineered valve replacement recently showed encouraging results, but the unpredictable outcome of tissue degeneration is likely associated to the extensive tissue processing methods. We believe that optimized decellularization procedures may provide aortic valve/root grafts improved durability. We present an improved/innovative decellularization approach using a detergent-enzymatic perfusion method, which is both quicker and has less exposure of matrix degenerating detergents, compared to previous protocols. The obtained graft was characterized for its architecture, extracellular matrix proteins, mechanical and immunological properties. We further analyzed the engineered aortic root for biocompatibility by cell adhesion and viability in vitro and heterotopic implantation in vivo. The developed decellularization protocol was substantially reduced in processing time whilst maintaining tissue integrity. Furthermore, the decellularized aortic root remained bioactive without eliciting any adverse immunological reaction. Cell adhesion and viability demonstrated the scaffold's biocompatibility. Our optimized decellularization protocol may be useful to develop the next generation of clinical valve prosthesis with a focus on improved mechanical properties and durability.
- Published
- 2013
31. Whole organ and tissue reconstruction in thoracic regenerative surgery
- Author
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Paolo Macchiarini, Linda Helen Friedrich, Greg Lemon, Fatemeh Ajalloueian, I. V. Gilevich, Karl-Henrik Grinnemo, Arthur L. Caplan, Philipp Jungebluth, Mei Ling Lim, J.C. Haag, E. A. Gubareva, and Sebastian Sjöqvist
- Subjects
Pathology ,medicine.medical_specialty ,Tissue replacement ,MEDLINE ,Tissue reconstruction ,030204 cardiovascular system & hematology ,Biology ,Regenerative Medicine ,Organ transplantation ,03 medical and health sciences ,Immune System Phenomena ,0302 clinical medicine ,Bioreactors ,Tissue engineering ,medicine ,Humans ,Cardiac Surgical Procedures ,Intensive care medicine ,Adverse effect ,Lung ,Digestive System Surgical Procedures ,030304 developmental biology ,0303 health sciences ,Tissue Engineering ,Tissue Scaffolds ,Respiratory dysfunction ,General Medicine ,Organ Transplantation ,Thoracic Surgical Procedures ,3. Good health ,Transplantation ,Trachea ,Larynx ,Stem Cell Transplantation - Abstract
Development of novel prognostic, diagnostic, and treatment options will provide major benefits for millions of patients with acute or chronic respiratory dysfunction, cardiac-related disorders, esophageal problems, or other diseases in the thorax. Allogeneic organ transplant is currently available. However, it remains a trap because of its dependency on a very limited supply of donated organs, which may be needed for both initial and subsequent transplants. Furthermore, it requires lifelong treatment with immunosuppressants, which are associated with adverse effects. Despite early clinical applications of bioengineered organs and tissues, routine implementation is still far off. For this review, we searched the PubMed, MEDLINE, and Ovid databases for the following keywords for each tissue or organ: tissue engineering, biological and synthetic scaffold/graft, acellular and decelluar(ized), reseeding, bioreactor, tissue replacement, and transplantation. We identified the current state-of-the-art practices in tissue engineering with a focus on advances during the past 5 years. We discuss advantages and disadvantages of biological and synthetic solutions and introduce novel strategies and technologies for the field. The ethical challenges of innovation in this area are also reviewed.
- Published
- 2012
32. Decellularized Lung Approach to Understand Cell-Matrix Cues
- Author
-
Paolo Macchiarini, Greg Lemon, Mei Ling Lim, Philipp Jungebluth, Sebastian Sjöqvist, and R. Amin
- Subjects
Cancer Research ,Transplantation ,Decellularization ,Lung ,Chemistry ,Immunology ,Cell Biology ,Cell biology ,Extracellular matrix ,medicine.anatomical_structure ,Oncology ,medicine ,Immunology and Allergy ,Genetics (clinical) - Published
- 2016
33. Individualized Decellularization for Tissue Engineering Tissues and Organs in Animals and Humans
- Author
-
Paolo Macchiarini, R. Amin, Sebastian Sjöqvist, Greg Lemon, and Mei Ling Lim
- Subjects
Cancer Research ,Transplantation ,Pathology ,medicine.medical_specialty ,Decellularization ,Immunology ,Cell ,Adipose tissue ,Cell Biology ,Pet imaging ,Anatomy ,Biology ,In vitro ,medicine.anatomical_structure ,Oncology ,Tissue engineering ,medicine ,Immunology and Allergy ,Bone marrow ,Stem cell ,health care economics and organizations ,Genetics (clinical) - Abstract
coding the human or species specific NIS genes. NIS function in transduced MSC was first validated in vitro; NIS expressing MSC (MSC_NIS) from multiple species concentrated high levels of I-125 with no side effects. The sensitivity of cell detection was determined by transplanting a known number of MSC_NIS subcutaneously into mice. We can reliably detect 2x105 MSC_NIS in mice using the newly acquired U-SPECT II machine. Canine MSC derived from the bone marrow were surprisingly robust; viable cells were still detected (albeit lower numbers) at day 28 in the athymic mice. In contrast, NIS signals from adipose tissue derived rat or human MSC disappeared by day 7 post transplantation. Using PET imaging and F18-TFB, sensitivity of imaging could be significantly improved to detect lower numbers of cells. We are currently evaluating the use of NIS for tracking natural killer cells and transplanted hemapoietic stem cells and results will be presented.
- Published
- 2016
34. Modelling biological cell attachment and growth on adherent surfaces
- Author
-
Philipp Jungebluth, Sebastian Sjöqvist, Johannes C. Haag, Greg Lemon, Ylva Gustafsson, Paolo Macchiarini, Fatemeh Ajalloueian, and Mei Ling Lim
- Subjects
Materials science ,Thin layers ,Applied Mathematics ,Mesenchymal stem cell ,Nanotechnology ,Mesenchymal Stem Cells ,Numerical Analysis, Computer-Assisted ,Agricultural and Biological Sciences (miscellaneous) ,Models, Biological ,Rats ,chemistry.chemical_compound ,chemistry ,Tissue engineering ,Cell culture ,Modeling and Simulation ,Monolayer ,Polyethylene terephthalate ,Biophysics ,Cell Adhesion ,Deposition (phase transition) ,Animals ,Seeding ,Cell Proliferation - Abstract
A mathematical model, in the form of an integro-partial differential equation, is presented to describe the dynamics of cells being deposited, attaching and growing in the form of a monolayer across an adherent surface. The model takes into account that the cells suspended in the media used for the seeding have a distribution of sizes, and that the attachment of cells restricts further deposition by fragmenting the parts of the domain unoccupied by cells. Once attached the cells are assumed to be able to grow and proliferate over the domain by a process of infilling of the interstitial gaps; it is shown that without cell proliferation there is a slow build up of the monolayer but if the surface is conducive to cell spreading and proliferation then complete coverage of the domain by the monolayer can be achieved more rapidly. Analytical solutions of the model equations are obtained for special cases, and numerical solutions are presented for parameter values derived from experiments of rat mesenchymal stromal cells seeded onto thin layers of collagen-coated polyethylene terephthalate electrospun fibers. The model represents a new approach to describing the deposition, attachment and growth of cells over adherent surfaces, and should prove useful for studying the dynamics of the seeding of biomaterials.
- Published
- 2012
35. Viability and proliferation of rat MSCs on adhesion protein-modified PET and PU scaffolds
- Author
-
Alessandra Bianco, Vanessa Lundin, Greg Lemon, Philipp Jungebluth, Ylva Gustafsson, Fatemeh Ajalloueian, Guido Moll, Sebastian Sjöqvist, Mei Ling Lim, Silvia Baiguera, Johannes C. Haag, Paolo Macchiarini, Costantino Del Gaudio, and Ana I. Teixeira
- Subjects
Male ,Materials science ,Cell Survival ,Settore ING-IND/22 - Scienza e Tecnologia dei Materiali ,Polyurethanes ,Biophysics ,Bioengineering ,Biomaterials ,Extracellular matrix ,Coated Materials, Biocompatible ,Tissue engineering ,Cell Adhesion ,Animals ,RNA, Messenger ,Viability assay ,Cell adhesion ,Cells, Cultured ,Cell Proliferation ,Tissue Engineering ,Tissue Scaffolds ,biology ,Polyethylene Terephthalates ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Adhesion ,Extracellular Matrix ,Rats ,Fibronectin ,Transplantation ,Rats, Inbred Lew ,Mechanics of Materials ,Ceramics and Composites ,biology.protein ,Biomedical engineering - Abstract
In 2011, the first in-man successful transplantation of a tissue engineered trachea-bronchial graft, using a synthetic POSS-PCU nanocomposite construct seeded with autologous stem cells, was performed. To further improve this technology, we investigated the feasibility of using polymers with a three dimensional structure more closely mimicking the morphology and size scale of native extracellular matrix (ECM) fibers. We therefore investigated the in vitro biocompatibility of electrospun polyethylene terephthalate (PET) and polyurethane (PU) scaffolds, and determined the effects on cell attachment by conditioning the fibers with adhesion proteins. Rat mesenchymal stromal cells (MSCs) were seeded on either PET or PU fiber-layered culture plates coated with laminin, collagen I, fibronectin, poly-D-lysine or gelatin. Cell density, proliferation, viability, morphology and mRNA expression were evaluated. MSC cultures on PET and PU resulted in similar cell densities and amounts of proliferating cells, with retained MSC phenotype compared to data obtained from tissue culture plate cultures. Coating the scaffolds with adhesion proteins did not increase cell density or cell proliferation. Our data suggest that both PET and PU mats, matching the dimensions of ECM fibers, are biomimetic scaffolds and, because of their high surface area-to-volume provided by the electrospinning procedure, makes them per se suitable for cell attachment and proliferation without any additional coating.
- Published
- 2012
36. Mathematical Modelling of Regeneration of a Tissue-Engineered Trachea
- Author
-
John R. King, Greg Lemon, and Paolo Macchiarini
- Subjects
Transplantation ,Engineering ,Tissue engineered ,Tissue engineering ,business.industry ,Regeneration (biology) ,Biochemical engineering ,business ,Regenerative medicine ,Tracheal segment ,Tracheal lumen - Abstract
One of the most promising recent achievements in the field of regenerative medicine was the first successful transplantation of a tissue-engineered trachea (Macchiarini et al. The Lancet 372(9655), 2023–2030). This land-mark operation has paved the way for developing a host of successful stem cell-based therapies for treating disease, and the exciting possibility of the tissue engineering of whole organs. It has also provided the opportunity for new directions in mathematical and computational modelling for tissue engineering. By way of describing an approach to modelling the regeneration of a tissue-engineered trachea seeded with cells in situ this chapter will highlight some of the opportunities and challenges involved in applying mathematical models to these new therapies.
- Published
- 2012
37. Interconnectivity analysis of supercritical CO₂-foamed scaffolds
- Author
-
Greg, Lemon, Yvonne, Reinwald, Lisa J, White, Steven M, Howdle, Kevin M, Shakesheff, and John R, King
- Subjects
Tissue Engineering ,Tissue Scaffolds ,Polymers ,Viscosity ,Biocompatible Materials ,Carbon Dioxide ,Molecular Weight ,Polylactic Acid-Polyglycolic Acid Copolymer ,Image Processing, Computer-Assisted ,Lactic Acid ,Tomography, X-Ray Computed ,Porosity ,Algorithms ,Polyglycolic Acid - Abstract
This paper describes a computer algorithm for the determination of the interconnectivity of the pore space inside scaffolds used for tissue engineering. To validate the algorithm and its computer implementation, the algorithm was applied to a computer-generated scaffold consisting of a set of overlapping spherical pores, for which the interconnectivity was calculated exactly. The algorithm was then applied to micro-computed X-ray tomography images of supercritical CO(2)-foamed scaffolds made from poly(lactic-co-glycolic acid) (PLGA), whereby the effect of using different weight average molecular weight polymer on the interconnectivity was investigated.
- Published
- 2010
38. Mathematical modelling of tissue-engineered angiogenesis
- Author
-
Greg Lemon, John R. King, Lee D.K. Buttery, Matthew J. Tomlinson, Daniel Howard, Felicity R. A. J. Rose, and Sarah L. Waters
- Subjects
Vascular Endothelial Growth Factor A ,Statistics and Probability ,Scaffold ,Time Factors ,Angiogenesis ,Neovascularization, Physiologic ,Transplants ,Chick Embryo ,Biology ,Models, Biological ,Chorioallantoic Membrane ,General Biochemistry, Genetics and Molecular Biology ,Chick chorioallantoic membrane ,Tissue engineering ,In vivo ,Animals ,Computer Simulation ,Vascular tissue ,Tissue engineered ,Cell Death ,Tissue Engineering ,Tissue Scaffolds ,General Immunology and Microbiology ,Macrophages ,Applied Mathematics ,Endothelial Cells ,General Medicine ,Anatomy ,Fibroblasts ,Cell Hypoxia ,Extracellular Matrix ,Oxygen ,Modeling and Simulation ,Ordinary differential equation ,Microvessels ,Pericytes ,General Agricultural and Biological Sciences ,Biological system ,Algorithms - Abstract
We present a mathematical model for the vascularisation of a porous scaffold following implantation in vivo. The model is given as a set of coupled non-linear ordinary differential equations (ODEs) which describe the evolution in time of the amounts of the different tissue constituents inside the scaffold. Bifurcation analyses reveal how the extent of scaffold vascularisation changes as a function of the parameter values. For example, it is shown how the loss of seeded cells arising from slow infiltration of vascular tissue can be overcome using a prevascularisation strategy consisting of seeding the scaffold with vascular cells. Using certain assumptions it is shown how the system can be simplified to one which is partially tractable and for which some analysis is given. Limited comparison is also given of the model solutions with experimental data from the chick chorioallantoic membrane (CAM) assay.
- Published
- 2009
39. 1003 Evaluation of a fast-track decellularization protocol for tubularized ureteral graft tissue engineering in a rat model
- Author
-
P Jungebluth, Mei Ling Lim, Greg Lemon, S Sjöqvist, Felix Wezel, J. von Hardenberg, P Macchiarini, J.C. Haag, and Ylva Gustafsson
- Subjects
medicine.medical_specialty ,Decellularization ,business.industry ,Urology ,Rat model ,medicine ,Fast track ,business ,Tissue Graft ,Surgery - Published
- 2015
40. Multiphase modelling of cell behaviour on artificial scaffolds: effects of nutrient depletion and spatially nonuniform porosity
- Author
-
Greg Lemon and John R. King
- Subjects
Drag coefficient ,Scaffold ,Materials science ,Cell Culture Techniques ,Mitosis ,Cell behaviour ,Apoptosis ,Biocompatible Materials ,Models, Biological ,General Biochemistry, Genetics and Molecular Biology ,Diffusion ,Cell Mobility ,Cell Movement ,Pressure ,Animals ,Humans ,Porosity ,General Environmental Science ,Cell Aggregation ,Cell Proliferation ,Pharmacology ,General Immunology and Microbiology ,Tissue Engineering ,Ecology ,Applied Mathematics ,General Neuroscience ,Water ,General Medicine ,Biological tissue ,Kinetics ,Cartilage ,Modeling and Simulation ,Scaffold material ,Seeding ,Biological system ,Algorithms - Abstract
This paper contains analysis of a recently formulated multiphase model for the growth of biological tissue that comprises motile cells and water inside a rigid scaffold material. The model is extended here to include a term describing cell proliferation which is mediated by the supply of a diffusible nutrient and to include the case where the scaffold porosity varies in space. Numerical solutions of the model equations are presented for different values of the parameters. Comparison is drawn between the different types of growth that arise when using static or dynamic methods for seeding the scaffold with cells. Analytical solutions are presented for the limiting cases in which the coefficient of drag between the cells and the scaffold is very large or zero. In the limit of large time, solutions reveal preferential tissue growth in the vicinity of the scaffold edge due to depletion of nutrient by the cells, consistent with experimental results. However, it is shown that reducing the coefficient of drag between the scaffold and the cells overcomes the effects of nutrient depletion by increasing cell mobility, thereby leading to improved uniformity of the cell distribution within the scaffold.
- Published
- 2006
41. Mathematical modelling of engineered tissue growth using a multiphase porous flow mixture theory
- Author
-
John R. King, Oliver E. Jensen, Helen M. Byrne, Greg Lemon, and Kevin M. Shakesheff
- Subjects
Scaffold ,Materials science ,Polymers ,Population ,Cell Count ,Models, Biological ,Mixture theory ,Cell Movement ,Phase (matter) ,Pressure ,Animals ,Humans ,education ,Cell Aggregation ,Cell Proliferation ,education.field_of_study ,Partial differential equation ,Continuum mechanics ,Tissue Engineering ,Component (thermodynamics) ,Applied Mathematics ,Water ,Agricultural and Biological Sciences (miscellaneous) ,Modeling and Simulation ,Biological system ,Material properties ,Algorithms - Abstract
This paper outlines the framework of a porous flow mixture theory for the mathematical modelling of in vitro tissue growth, and gives an application of this theory to an aspect of tissue engineering. The problem is formulated as a set of partial differential equations governing the space and time dependence of the amounts of each component of the tissue (phase), together with the physical stresses in each component. The theory requires constitutive relations to specify the material properties of each phase, and also requires relations to specify the stresses developed due to mechanical interactions, both within each phase and between different phases. An application of the theory is given to the study of the mobility and aggregation of a population of cells seeded into an artificial polymeric scaffold. Stability analysis techniques show that the interplay of the forces between the tissue constituents results in two different regimes: either the cells form aggregates or disperse through the scaffold.
- Published
- 2004
42. Mathematical modelling of engineered tissue growth using a multiphase porous flow mixture theory.
- Author
-
Greg Lemon, John R. King, Helen M. Byrne, Oliver E. Jensen, and Kevin M. Shakesheff
- Abstract
This paper outlines the framework of a porous flow mixture theory for the mathematical modelling of in vitro tissue growth, and gives an application of this theory to an aspect of tissue engineering. The problem is formulated as a set of partial differential equations governing the space and time dependence of the amounts of each component of the tissue (phase), together with the physical stresses in each component. The theory requires constitutive relations to specify the material properties of each phase, and also requires relations to specify the stresses developed due to mechanical interactions, both within each phase and between different phases. An application of the theory is given to the study of the mobility and aggregation of a population of cells seeded into an artificial polymeric scaffold. Stability analysis techniques show that the interplay of the forces between the tissue constituents results in two different regimes: either the cells form aggregates or disperse through the scaffold. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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