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Overview
Scaffolds Necessity! What to look for in a scaffold? Scaffold materials How are scaffolds fabricated? Advantages and disadvantages of the fabrication methods
Scaffolds
Prevent encroachment of tissues from the immediate vicinity Temporary support structure Substrate for cells to attach, proliferate, migrate and differentiate Delivery vehicle for cells and drugs/growth factors Vascularization, neo-tissue formation and remodeling
Desired Characteristics
Biocompatible Biodegradable Degrade at a rate proportional to the re-growth of new tissue Suitable mechanical properties Desired surface properties Optimum architectural properties Easy and well-controlled fabrication Reproducible production
Material selection
Bio-ceramics Polymers
Synthetic Natural
Polypeptides
Bio-ceramics
Polymers
Polypeptides
EAK16 Biomaterial Called Scientists Best Hope for Growing Nerves - Boston Globe ;June 6, 2000 AEAEAKAKAEAEAKAK-NH2 1g = 50.4 lakh INR http://www.anaspec.com/products/product.asp?id=44278
http://web.mit.edu/lms/www/PDFpapers/Nature%20N&V%206-15-00.pdf
Properties of a Scaffold
Mechanical:
Youngs Shear
http://invsee.asu.edu/srinivas/stress-strain/ssgraph.jpg
Architectural:
Pore size
Oh et al. fabricated cylindrical PCL scaffolds Pore sizes with gradual increase from 88 - 405 mm Chondrocytes, osteoblasts,and broblasts were grown 380405 mm range showed better chondrocyte and osteoblast growth 186200 mm better suited for broblast growth 290310 mm range pore size seemed to be best suited for new bone formation
Pore Interconnectivity:
Lee et al. produced PPF scaffolds with controlled pore architecture Three pore sizes (300,600 and 900 mm) and randomly closed 0%, 10%, 20%, or 30% of the pores Permeability decreased as the number of closed pores increased Murphy et al. improved pore interconnectivity to PLGA scaffolds by partially fusing the salt before creating the polymer matrix
Permeability
Higher the porosity more the permeability Provided, interconnectivity is high too
Fabrication
Gas Foaming
Fiber Bonding
PLLA dissolved in methylene chloride and casted over PGA mesh. Solvent evaporated and construct heated. Once cooled, PLLA is removed by dissolving in methylene chloride again Results in a mesh of PGA fibres joined at the cross-points
Dissolution of polymer in a solvent at a high temperature Liquidliquid or solid-liquid phase separation induced by lowering the solution temperature TIPS produced less changes in dimension, mass, internal architecture and mechanical properties when compared to SCPL
Ultrapure water added to a solution of methylene chloride with PGA Two immiscible layers are homogenised to form a water-in-oil emulsion, which is quenched in liquid nitrogen and freeze-dried to produce the porous structure
Incapability to precisely control pore size, pore geometry, spatial distribution of pores Lacks any long-range channeling micro architecture For gas foaming, it has been reported that only 10-30% of the pores were interconnected (Mooney et al., 1996)
Collection of techniques for manufacturing solid objects by the sequential delivery of energy and/or material to specified points in space to produce that solid Also called layer manufacturing CAD Tissue Engineering
Advantages
Produce scaffolds with customized external shape and predefined and reproducible internal morphology Controlled pore size, porosity and pore distribution Increases the mass transport of oxygen and nutrients throughout the scaffold
Techniques
Fused deposition modeling Laminated object manufacturing Laser engineered net shaping Polyjet matrix Selective laser sintering Stereolithography Three-dimensional printing
Acrylonitrile Butadiene Styrene (ABS) polymer, polycarbonates, polycaprolactone, polyphenylsulfones and waxes
Sheet is adhered to a substrate with a heated roller Laser traces desired dimensions of prototype Laser cross hatches non-part area to facilitate waste removal Platform with completed layer moves down out of the way Fresh sheet of material is rolled into position Platform moves up into position to receive next layer The process is repeated
Uses a high power laser to fuse small particles of plastic, metal, ceramic, or glass powders into a mass representing a desired 3-dimensional object Laser selectively fuses powdered material by scanning cross-sections generated from a 3-D digital description of the part on the surface of a powder bed
Stereolithography
Additive manufacturing process using a vat of liquid UV-curable photopolymer "resin" and a UV laser to build parts a layer at a time
3D printing
Institute of Biomaterials and Biomedical Engineering, University of Toronto LIDAN YOU et al 2008
Hydrogel
Hydrogel? Photopolymerization
Visible or UV light can react with light-sensitive compounds called photoinitiators to form crosslinked hydrogels Eosin Y, PEG diacrylate, triethanolamine Polymerization results in a conformal, crosslinked hydrogel
Characterization of permeability and network structure of interfacially photopolymerized poly(ethylene glycol) diacrylate hydrogels. Biomaterials 19 (1998) 1287-1294
Nanofibers
Electrospinning
References
Nanotechnology and Tissue Engineering The Scaffold Cato T. Laurencin, Lakshmi S. Nair E. Sachlos 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 www.en.wikipedia.com