Esophageal tissue engineering: An in‐depth review on scaffold design

Treatment of esophageal cancer often requires surgical procedures that involve removal. The current approaches to restore esophageal continuity however, are known to have limitations which may not result in full functional recovery. In theory, using a tissue engineered esophagus developed from the patient's own cells to replace the removed esophageal segment can be the ideal method of reconstruction. One of the key elements involved in the tissue engineering process is the scaffold which acts as a template for organization of cells and tissue development. While a number of scaffolds range from traditional non‐biodegradable tubing to bioactive decellularized matrix have been proposed to engineer the esophagus in the past decade, results are still not yet favorable with many challenges relating to tissue quality need to be met improvements. The success of new esophageal tissue formation will ultimately depend on the success of the scaffold being able to meet the essential requirements specific to the esophageal tissue. Here, the design of the scaffold and its fabrication approaches are reviewed. In this paper, we review the current state of development in bioengineering the esophagus with particular emphasis on scaffold design. Biotechnol. Bioeng. 2012;109: 1–15. © 2011 Wiley Periodicals, Inc.

[1]  W. Rawlinson,et al.  TRANSMISSION OF PORCINE ENDOGENOUS RETROVIRUSES IN SEVERE COMBINED IMMUNODEFICIENT MICE XENOTRANSPLANTED WITH FETAL PORCINE PANCREATIC CELLS1 , 2000, Transplantation.

[2]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[3]  K. Papadopoulos,et al.  Novel targeted therapies for advanced esophageal cancer. , 2007, Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus.

[4]  B D Boyan,et al.  Role of material surfaces in regulating bone and cartilage cell response. , 1996, Biomaterials.

[5]  Hans Gregersen,et al.  Determination of homeostatic elastic moduli in two layers of the esophagus. , 2008, Journal of biomechanical engineering.

[6]  D. Kohane,et al.  Engineering vascularized skeletal muscle tissue , 2005, Nature Biotechnology.

[7]  D. Kohn,et al.  Effects of pH on human bone marrow stromal cells in vitro: implications for tissue engineering of bone. , 2002, Journal of biomedical materials research.

[8]  D. Mooney,et al.  Vascular endothelial growth factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl-2 expression. , 1999, The American journal of pathology.

[9]  Herwig Ainödhofer,et al.  Esophagus Tissue Engineering: Hybrid Approach with Esophageal Epithelium and Unidirectional Smooth Muscle Tissue Component Generation In Vitro , 2009, Journal of Gastrointestinal Surgery.

[10]  Matthias P Lutolf,et al.  Biopolymeric delivery matrices for angiogenic growth factors. , 2003, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[11]  M. Kitajima,et al.  Basic studies on the application of an artificial esophagus using cultured epidermal cells , 2006, Surgery Today.

[12]  M. Kotaki,et al.  Aligned biodegradable nanofibrous structure: a potential scaffold for blood vessel engineering. , 2004, Biomaterials.

[13]  Joyce Y. Wong,et al.  Aligned Cell Sheets Grown on Thermo‐Responsive Substrates with Microcontact Printed Protein Patterns , 2009 .

[14]  D. Kidron,et al.  Comparative experimental study of esophageal wall regeneration after prosthetic replacement. , 1999, Journal of biomedical materials research.

[15]  Y. Fung,et al.  Biomechanics: Mechanical Properties of Living Tissues , 1981 .

[16]  S. Glagov,et al.  Transmural Organization of the Arterial Media: The Lamellar Unit Revisited , 1985, Arteriosclerosis.

[17]  B. Ratner,et al.  Esophageal epithelial cell interaction with synthetic and natural scaffolds for tissue engineering. , 2005, Biomaterials.

[18]  Sing Yian Chew,et al.  The application of nanofibrous scaffolds in neural tissue engineering. , 2009, Advanced drug delivery reviews.

[19]  Chad Johnson,et al.  The effect of scaffold degradation rate on three-dimensional cell growth and angiogenesis. , 2004, Biomaterials.

[20]  P. Carmeliet Mechanisms of angiogenesis and arteriogenesis , 2000, Nature Medicine.

[21]  C. Mariette,et al.  Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities. , 2007, The Lancet. Oncology.

[22]  M. Kitajima,et al.  An artificial esophagus consisting of cultured human esophageal epithelial cells, polyglycolic acid mesh, and collagen. , 1994, ASAIO journal.

[23]  Dai Fukumura,et al.  Engineering vascularized tissue , 2005, Nature Biotechnology.

[24]  Jing-Cong Luo,et al.  Grafts of Porcine Small Intestinal Submucosa with Cultured Autologous Oral Mucosal Epithelial Cells for Esophageal Repair in a Canine Model , 2009, Experimental biology and medicine.

[25]  Y. Ikada,et al.  Porous collagen sponge for esophageal replacement. , 1993, Journal of biomedical materials research.

[26]  Donald O Freytes,et al.  Esophageal reconstruction with ECM and muscle tissue in a dog model. , 2005, The Journal of surgical research.

[27]  S. Hsu,et al.  Oriented Schwann cell growth on microgrooved surfaces , 2005, Biotechnology and bioengineering.

[28]  L G Griffith,et al.  Effect of pore size and void fraction on cellular adhesion, proliferation, and matrix deposition. , 2001, Tissue engineering.

[29]  Guoping Chen,et al.  Regeneration of the esophagus using gastric acellular matrix: an experimental study in a rat model , 2006, Pediatric Surgery International.

[30]  Hossein Baharvand,et al.  Application of conductive polymers, scaffolds and electrical stimulation for nerve tissue engineering , 2011, Journal of tissue engineering and regenerative medicine.

[31]  Amit Bandyopadhyay,et al.  Pore size and pore volume effects on alumina and TCP ceramic scaffolds , 2003 .

[32]  L. Bonavina,et al.  Results of Surgical Therapy in Patients with Barrett’s Adenocarcinoma , 2003, World Journal of Surgery.

[33]  M. Posner,et al.  The role of surgery in the management of oesophageal cancer. , 2003, The Lancet. Oncology.

[34]  S. Badylak,et al.  An extracellular matrix scaffold for esophageal stricture prevention after circumferential EMR. , 2008, Gastrointestinal endoscopy.

[35]  F. Watt,et al.  Asymmetric stem-cell divisions define the architecture of human oesophageal epithelium , 2000, Current Biology.

[36]  M. Chan-Park,et al.  The growth improvement of porcine esophageal smooth muscle cells on collagen-grafted poly(DL-lactide-co-glycolide) membrane. , 2005, Journal of biomedical materials research. Part B, Applied biomaterials.

[37]  C. V. van Blitterswijk,et al.  Engineering vascularised tissues in vitro. , 2008, European cells & materials.

[38]  S. Engum,et al.  Patch esophagoplasty using AlloDerm as a tissue scaffold. , 2001, Journal of pediatric surgery.

[39]  M. Conconi,et al.  Autologous satellite cell seeding improves in vivo biocompatibility of homologous muscle acellular matrix implants. , 2002, International journal of molecular medicine.

[40]  R Langer,et al.  Stabilized polyglycolic acid fibre-based tubes for tissue engineering. , 1996, Biomaterials.

[41]  Martin Ehrbar,et al.  Endothelial cell proliferation and progenitor maturation by fibrin-bound VEGF variants with differential susceptibilities to local cellular activity. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[42]  T. Skalak,et al.  Vascular Assembly in Natural and Engineered Tissues , 2002, Annals of the New York Academy of Sciences.

[43]  N. Bachrach,et al.  Effects of carbodiimide crosslinking conditions on the physical properties of laminated intestinal submucosa. , 2001, Journal of biomedical materials research.

[44]  Kam W Leong,et al.  The effect of the alignment of electrospun fibrous scaffolds on Schwann cell maturation. , 2008, Biomaterials.

[45]  S. Law,et al.  Colonic interposition after esophagectomy for cancer. , 2003, Archives of surgery.

[46]  Uma Maheswari Krishnan,et al.  Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration , 2009, Journal of Biomedical Science.

[47]  David J. Mooney,et al.  Spatio–temporal VEGF and PDGF Delivery Patterns Blood Vessel Formation and Maturation , 2007, Pharmaceutical Research.

[48]  Marianne J Ellis,et al.  Poly(lactic‐co‐glycolic acid) hollow fibre membranes for use as a tissue engineering scaffold , 2007, Biotechnology and bioengineering.

[49]  Rajiv Midha,et al.  Axonal guidance channels in peripheral nerve regeneration , 2004 .

[50]  H. Gregersen,et al.  Impedance Planimetric Characterization of Esophagus in Systemic Sclerosis Patients with Severe Involvement of Esophagus , 1997, Digestive Diseases and Sciences.

[51]  M. Kitajima,et al.  An artificial esophagus constructed of cultured human esophageal epithelial cells, fibroblasts, polyglycolic acid mesh, and collagen. , 1999, ASAIO journal.

[52]  James G Brasseur,et al.  Function of longitudinal vs circular muscle fibers in esophageal peristalsis, deduced with mathematical modeling. , 2007, World journal of gastroenterology.

[53]  A. Cabrita,et al.  Esophageal replacement in rat using porcine intestinal submucosa as a patch or a tube-shaped graft. , 2006, Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus.

[54]  L. Ghasemi‐Mobarakeh,et al.  Electrical stimulation of nerve cells using conductive nanofibrous scaffolds for nerve tissue engineering. , 2009, Tissue engineering. Part A.

[55]  Janis Gardovskis,et al.  Biomechanical properties of oesophagus wall under loading. , 2003, Journal of biomechanics.

[56]  D. Ribatti,et al.  In vitro and in vivo proposal of an artificial esophagus. , 2006, Journal of biomedical materials research. Part A.

[57]  S. Fernández,et al.  Experimental Study Using PTFE (Goretex) Patches for Replacement of the Oesophageal Wall , 2003 .

[58]  A. Cabrita,et al.  Grafts of Porcine Intestinal Submucosa for Repair of Cervical and Abdominal Esophageal Defects in the Rat , 2006, Journal of investigative surgery : the official journal of the Academy of Surgical Research.

[59]  J. Seery Stem cells of the oesophageal epithelium. , 2002, Journal of cell science.

[60]  J. Conklin,et al.  Neuromuscular control of esophageal peristalsis , 1999, Current gastroenterology reports.

[61]  D. Kaplan,et al.  Porosity of 3D biomaterial scaffolds and osteogenesis. , 2005, Biomaterials.

[62]  J. Hunt,et al.  The angiogenic potential of three-dimensional open porous synthetic matrix materials. , 2007, Biomaterials.

[63]  Jae Young Lee,et al.  Polypyrrole-coated electrospun PLGA nanofibers for neural tissue applications. , 2009, Biomaterials.

[64]  Shyue-Yih Chang,et al.  Reconstruction of the Hypopharynx After Surgical Treatment of Squamous Cell Carcinoma , 2009, Journal of the Chinese Medical Association : JCMA.

[65]  Hans Gregersen,et al.  Stress distribution in the layered wall of the rat oesophagus. , 2003, Medical engineering & physics.

[66]  M. Palkovits,et al.  Gastrointestinal immunology: cell types in the lamina propria--a morphological review. , 2000, Acta physiologica Hungarica.

[67]  B. Brown,et al.  Evidence of innervation following extracellular matrix scaffold‐mediated remodelling of muscular tissues , 2009, Journal of tissue engineering and regenerative medicine.

[68]  V. Egorov,et al.  Mechanical properties of the human gastrointestinal tract. , 2002, Journal of biomechanics.

[69]  Buddy D. Ratner,et al.  Biomaterials with tightly controlled pore size that promote vascular in-growth , 2004 .

[70]  Lauran R. Madden,et al.  Proangiogenic scaffolds as functional templates for cardiac tissue engineering , 2010, Proceedings of the National Academy of Sciences.

[71]  E Ruoslahti,et al.  New perspectives in cell adhesion: RGD and integrins. , 1987, Science.

[72]  B. Ratner,et al.  Effect of electrospun poly(D,L-lactide) fibrous scaffold with nanoporous surface on attachment of porcine esophageal epithelial cells and protein adsorption. , 2009, Journal of biomedical materials research. Part A.

[73]  Robert Langer,et al.  Biodegradable Polymer Scaffolds for Tissue Engineering , 1994, Bio/Technology.

[74]  S. Waldman,et al.  Are micropatterned substrates for directed cell organization an effective method to create ordered 3D tissue constructs? , 2008, Journal of tissue engineering and regenerative medicine.

[75]  B. Ratner,et al.  Protein bonding on biodegradable poly(L-lactide-co-caprolactone) membrane for esophageal tissue engineering. , 2006, Biomaterials.

[76]  C. Mariette,et al.  Surgical management of carcinoma of the hypopharynx and cervical esophagus: analysis of 209 cases. , 2001, Archives of surgery.

[77]  Ashok Srinivasan,et al.  Tissue-engineered esophagus: experimental substitution by onlay patch or interposition. , 2003, The Journal of thoracic and cardiovascular surgery.

[78]  M. J. Moore,et al.  Multiple-channel scaffolds to promote spinal cord axon regeneration. , 2006, Biomaterials.

[79]  M. Hinds,et al.  Successful Repair of Esophageal Injury Using an Elastin Based Biomaterial Patch , 2000 .

[80]  David G Simpson,et al.  Tissue-engineering scaffolds: can we re-engineer mother nature? , 2006, Expert review of medical devices.

[81]  W. B. van den Berg,et al.  Chondrocyte-seeded hydroxyapatite for repair of large articular cartilage defects. A pilot study in the goat. , 1998, Biomaterials.

[82]  B. Ratner,et al.  Development of an esophagus acellular matrix tissue scaffold. , 2006, Tissue engineering.

[83]  U Kneser,et al.  Tissue engineering of bone: the reconstructive surgeon's point of view , 2006, Journal of cellular and molecular medicine.

[84]  Dimitrios P Sokolis,et al.  Biomechanical and histological characteristics of passive esophagus: experimental investigation and comparative constitutive modeling. , 2009, Journal of biomechanics.

[85]  B. Zimmerman,et al.  Effects of gender and age on esophageal biomechanical properties and sensation , 2003, American Journal of Gastroenterology.

[86]  A Haverich,et al.  Acellularized porcine heart valve scaffolds for heart valve tissue engineering and the risk of cross-species transmission of porcine endogenous retrovirus. , 2003, The Journal of thoracic and cardiovascular surgery.

[87]  Kerm Sin Chian,et al.  In vitro cell infiltration and in vivo cell infiltration and vascularization in a fibrous, highly porous poly(D,L-lactide) scaffold fabricated by cryogenic electrospinning technique. , 2009, Journal of biomedical materials research. Part A.

[88]  C. Murphy,et al.  Epithelial contact guidance on well-defined micro- and nanostructured substrates , 2003, Journal of Cell Science.

[89]  Y. Shimizu,et al.  Intrathoracic esophageal replacement in the dog with the use of an artificial esophagus composed of a collagen sponge with a double-layered silicone tube. , 1999, The Journal of thoracic and cardiovascular surgery.

[90]  Masayuki Yamato,et al.  Long-term survival and growth of pulsatile myocardial tissue grafts engineered by the layering of cardiomyocyte sheets. , 2006, Tissue engineering.

[91]  Lucie Germain,et al.  Inosculation of Tissue‐Engineered Capillaries with the Host's Vasculature in a Reconstructed Skin Transplanted on Mice , 2005, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[92]  K. Leong,et al.  The design of scaffolds for use in tissue engineering. Part I. Traditional factors. , 2001, Tissue engineering.

[93]  B. Sellhaus,et al.  In vitro assessment of axonal growth using dorsal root ganglia explants in a novel three-dimensional collagen matrix. , 2007, Tissue engineering.

[94]  M. Kitajima,et al.  A hybrid artificial esophagus using cultured human esophageal epithelial cells. , 1993, ASAIO journal.

[95]  J. West,et al.  Modification of surfaces with cell adhesion peptides alters extracellular matrix deposition. , 1999, Biomaterials.

[96]  S. Badylak,et al.  Reinforcement of esophageal anastomoses with an extracellular matrix scaffold in a canine model. , 2006, The Annals of thoracic surgery.

[97]  Nicola H. Green,et al.  The development and characterization of an organotypic tissue-engineered human esophageal mucosal model. , 2010, Tissue engineering. Part A.

[98]  R. Peto,et al.  Esophageal cancer and body mass index: Results from a prospective study of 220,000 men in China and a meta‐analysis of published studies , 2007, International journal of cancer.

[99]  Jeroen Rouwkema,et al.  Vascularization in tissue engineering. , 2008, Trends in biotechnology.

[100]  Petra Lynen Jansen,et al.  Surgical Mesh as a Scaffold for Tissue Regeneration in the Esophagus , 2004, European Surgical Research.

[101]  J. Peters,et al.  Prevalence and risk factors for ischemia, leak, and stricture of esophageal anastomosis: gastric pull-up versus colon interposition. , 2004, Journal of the American College of Surgeons.

[102]  Tatsuo Nakamura,et al.  The experimental replacement of a cervical esophageal segment with an artificial prosthesis with the use of collagen matrix and a silicone stent. , 1998, The Journal of thoracic and cardiovascular surgery.

[103]  Wei Sun,et al.  Effect of Dielectric Barrier Discharge Plasma on the Attachment and Proliferation of Osteoblasts Cultured over Poly(ε‐caprolactone) Scaffolds , 2008 .

[104]  Buddy D. Ratner,et al.  A paradigm shift: biomaterials that heal , 2007 .

[105]  C. Sawyers,et al.  Visualization of the Interstitial Cells of Cajal (ICC) Network in Mice , 2011, Journal of visualized experiments : JoVE.

[106]  R. Finaly,et al.  The use of collagen-coated vicryl mesh for reconstruction of the canine cervical esophagus , 1998, Pediatric Surgery International.

[107]  Y Ikada,et al.  Experimental studies of a hybrid artificial esophagus combined with autologous mucosal cells. , 1990, ASAIO transactions.

[108]  Tatsuo Nakamura,et al.  Experimental replacement of the thoracic esophagus with a bioabsorbable collagen sponge scaffold supported by a silicone stent in dogs. , 1999, ASAIO journal.

[109]  J. Kerr,et al.  Atlas of Functional Histology , 1999 .

[110]  R. Orlando,et al.  Esophageal submucosal glands: structure and function , 1999, American Journal of Gastroenterology.

[111]  H. M. Morfit,et al.  Long-term end results in bridging esophageal defects in human beings with Teflon prostheses , 1962 .

[112]  H. Köksal,et al.  Colonic interposition vs. gastric pull-up after total esophagectomy , 2004, Journal of Gastrointestinal Surgery.

[113]  Hans Gregersen,et al.  Biomechanics of the Gastrointestinal Tract: New Perspectives in Motility Research and Diagnostics , 2010 .

[114]  K. Schulze,et al.  Matrix Composition in Opossum Esophagus , 2001, Digestive Diseases and Sciences.

[115]  Nobuhiko Yui,et al.  Electrospun PLGA nanofiber scaffolds for articular cartilage reconstruction: mechanical stability, degradation and cellular responses under mechanical stimulation in vitro , 2006, Journal of biomaterials science. Polymer edition.

[116]  Seeram Ramakrishna,et al.  Biomimetic electrospun nanofibers for tissue regeneration , 2006, Biomedical materials.

[117]  M. Chan-Park,et al.  Esophageal epithelium regeneration on fibronectin grafted poly(L-lactide-co-caprolactone) (PLLC) nanofiber scaffold. , 2007, Biomaterials.

[118]  Y. Hirooka,et al.  Evaluation of decellularized esophagus as a scaffold for cultured esophageal epithelial cells. , 2006, Journal of biomedical materials research. Part A.

[119]  Xu Weiqing,et al.  Complication following gastric pull-up reconstruction for advanced hypopharyngeal or cervical esophageal carcinoma: a 20-year review in a Chinese institute. , 2011, American journal of otolaryngology.

[120]  S. Guelcher,et al.  Effect of fiber diameter and alignment of electrospun polyurethane meshes on mesenchymal progenitor cells. , 2009, Tissue engineering. Part A.

[121]  S. Badylak,et al.  Resorbable bioscaffold for esophageal repair in a dog model. , 2000, Journal of pediatric surgery.

[122]  Stephen F Badylak,et al.  The extracellular matrix as a scaffold for tissue reconstruction. , 2002, Seminars in cell & developmental biology.

[123]  M. Bronner,et al.  The esophageal wall. , 2011, Thoracic surgery clinics.

[124]  Eva L Feldman,et al.  Aligned electrospun nanofibers specify the direction of dorsal root ganglia neurite growth. , 2007, Journal of biomedical materials research. Part A.

[125]  Roland Hetzer,et al.  Tissue-engineering bioreactors: a new combined cell-seeding and perfusion system for vascular tissue engineering. , 2002, Tissue engineering.

[126]  K. Chian,et al.  Dependence of alignment direction on magnitude of strain in esophageal smooth muscle cells , 2009, Biotechnology and bioengineering.

[127]  M. Hermida-Prieto,et al.  Lack of Cross-Species Transmission of Porcine Endogenous Retrovirus in Pig-to-Baboon Xenotransplantation with Sustained Depletion of Anti-&agr;Gal Antibodies , 2005, Transplantation.

[128]  M. Höllwarth,et al.  Esophagus tissue engineering: in situ generation of rudimentary tubular vascularized esophageal conduit using the ovine model. , 2010, Journal of pediatric surgery.

[129]  David F Meaney,et al.  Matrices with compliance comparable to that of brain tissue select neuronal over glial growth in mixed cortical cultures. , 2006, Biophysical journal.

[130]  J. Cha,et al.  Time-dependent modulation of alignment and differentiation of smooth muscle cells seeded on a porous substrate undergoing cyclic mechanical strain. , 2006, Artificial organs.

[131]  Dennis E. Discher,et al.  Adhesion-contractile balance in myocyte differentiation , 2004, Journal of Cell Science.

[132]  Xiaosong Gu,et al.  Construction of tissue engineered nerve grafts and their application in peripheral nerve regeneration , 2011, Progress in Neurobiology.

[133]  M. Goernig,et al.  Unsuccessful alloplastic esophageal replacement with porcine small intestinal submucosa. , 2009, Artificial organs.

[134]  Hans Gregersen,et al.  A two-layered mechanical model of the rat esophagus. Experiment and theory , 2004, Biomedical engineering online.

[135]  J. Vacanti,et al.  Tissue engineering: a 21st century solution to surgical reconstruction. , 2001, The Annals of thoracic surgery.

[136]  C. K. Chong,et al.  Perfusion Bioreactors Improve Oxygen Transport and Cell Distribution in Esophageal Smooth Muscle Construct , 2009 .

[137]  Kwangsok Kim,et al.  Control of degradation rate and hydrophilicity in electrospun non-woven poly(D,L-lactide) nanofiber scaffolds for biomedical applications. , 2003, Biomaterials.

[138]  Effect of Basic Fibroblast Growth Factor on Vascularization in Esophagus Tissue Engineering , 2003, The International journal of artificial organs.

[139]  A. Bedirli,et al.  Comparison of free jejunal graft with gastric pull-up reconstruction after resection of hypopharyngeal and cervical esophageal carcinoma. , 2008, Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus.

[140]  C. K. Chong,et al.  Directional, regional, and layer variations of mechanical properties of esophageal tissue and its interpretation using a structure-based constitutive model. , 2006, Journal of biomechanical engineering.

[141]  D. Bezuidenhout,et al.  Effect of Well Defined Dodecahedral Porosity on Inflammation and Angiogenesis , 2002, ASAIO journal.