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Tissue Engineering Scaffolds. Flat sheets of direct-printed titanium hydride ink (http://medtechinsider.com/archives/13873). Some Limitations of Direct Transplantation ( allogenic ) . Availability. Insufficient donor organs (patients waiting for years) Risk of pathogens transmission.
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Tissue Engineering Scaffolds Flat sheets of direct-printed titanium hydride ink (http://medtechinsider.com/archives/13873)
Some Limitations of Direct Transplantation(allogenic) • Availability. Insufficient donor organs (patients waiting for years) • Risk of pathogens transmission. • Host rejection of the organ. • Post- surgery immunosuppressive dependence. • Risk to new organ replacement within days to years after surgery.
Tissue Engineering • “Defined as the interdisciplinary field applying the principles and methods of engineering and life sciences to fundamentally understand and develop biological substitutes to restore, maintain, or improve tissue functions”. (Papenburg) • (Papenburg) • In short, TE attempts to mimic the function of natural tissue
The Scaffold • Biological Tissue: Cells, signaling system, and extracellular matrix (ECM.) • The scaffold is the reproduction of the ECM.
The Extra Cellular Matrix • The extracellular matrix (ECM) is a heterogeneous composition of proteoglycans, proteins, and signaling molecules. • The ECM influences in cell differentiation, proliferation, survival, and migration.
Scaffolds Design Aspects • Criteria based on Material Properties, Surface Characteristics, and 3D Architecture. • Shape and size • Biocompatible: To provoke only an appropriate biological response. • Biodegradable: It should degrade into smaller nontoxic substances.
Scaffolds Design Aspects • Promote cell attachment, spreading and proliferation. • Suitable mechanical strength: Flexible or rigid comparable to In vivo tissue. (Owen)
Scaffolds Design Aspects • Good transport properties: For the cell intake of nutrients and removal of waste (permeability.) • Connectivity: To the vascular system to ensure transport of nutrients. • Suitable surface: improving the tissue organization improves the tissue function (surface topography.)
Scaffolds Design Aspects (papenburg)
Materials (papenburg)
Materials (papenburg)
Fabrication Methods • Emulsion freeze-drying: Emulsion of Polymer – solvent and water is freeze and then solvent and water are removed by freeze-drying. • Foaming: Inert gas (CO2 or N2 ) is used to create porosity via pressure quenching. Often too small pores. • Particle leaching: Inserts particles of sugar, salt or other spheres to be washed out after the polymer has solidify. Creates additional porosity. • Polymer casting (Sachlos)
Sintering: Specially use for hard TE. It uses heat to make powder particles to add each other. • Decellularization: Highly desirable but result in disruption of the architecture and potential loss of surface structure and composition. • Electrospinning http://midwestresearchswine.com/productsservices/midwest-porcine-recovery/perfusion-decellularization/
Experiences • Mouse with a human ear: Seeding chondrocytes from bovine auricular cartilage on a polymer (polyglycolic acid‐polylacticacid) scaffold in the form of a human ear • Tissue engineering airway • Cardiovascular tissue (since 1999), skin and bone.
To work on … • Degradation of synthetic polymers releases acids and may affect cellular function. • Small pH changes in cell culturing can significantly affect the expression of some proteins. • Synthetic polymers don’t have a surface chemistry like the native tissue and it’s not familiar to cells. • The scaffold production techniques can’t precisely control pore size. • In cell culturing, cellular migration is affected by lack of oxygen and nutrients • In decellularization, detergents and enzymes and physical forces disrupt the ECM structure.
References • Crapo, Peter M. Ph.D., Thomas W. Gilbert, Ph.D., and Stephen F. Badylak, D.V.M., Ph.D., M.D., “An overview of tissue and whole organ decellularization processes” – Published online feb 2011 <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084613/?tool=pmcentrez> • Owen, Shawn C., Molly S. Shoichet, “Design of three-dimensional biomimeticscaffolds” – Published online July 2010, <http://www.ecf.toronto.edu/~molly/Binder/Design%20of%20Three-Dimensional%20Biomimetic%20Scaffolds.pdf> • Papenburg, Bernke, “DESIGN STRATEGIES FOR TISSUE ENGINEERING SCAFFOLDS”, 2009-Enschede- The Netherlands, < http://doc.utwente.nl/61561/1/thesis_B_Papenburg.pdf> • Rozario, Tania and Douglas W. DeSimone, “The Extracellular Matrix In Development and Morphogenesis: A Dynamic View”, Published online Oct 2009, < http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854274/?tool=pmcentrez> • Sachlos, E. and J.T. Czernuszka,“MAKING TISSUE ENGINEERING SCAFFOLDS WORK. • REVIEW ON THE APPLICATION OF SOLID FREEFORM FABRICATION • TECHNOLOGY TO THE PRODUCTION OF TISSUE ENGINEERING SCAFFOLDS”, University of Oxford,< http://xhtml.ecmjournal.org/journal/papers/vol005/pdf/v005a03.pdf>