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)

• In short, TE attempts to mimic the function of natural tissue (Papenburg)

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.

(Rozario)

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 polylactic acid) ‐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 biomimetic scaffolds” – 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>