Scaffolds Examples, Properties and Fabrication Techniques

Dr. Ajay Rajaram

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

Hydroxyapatite Ca10(PO4)6(OH)2 Bioglass Bio-inert Bio-active

Polymers

Polyesters Polyfumarates Polyanhydrides Poly (ortho esters) Polyphosphazenes

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:

Stress Pa or N/m2 Strain Elastic Modulus

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

Conventional Fabrication Techniques Solid Freeform Fabrication (SFF)

Conventional Fabrication Techniques

Solvent-casting particulate-leaching (SCPL)

Chloroform + PLLA + salt

Gas Foaming

PLGA + CO2 High pressure to atm. Pressure

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

Thermally Induced phase separation (TIPS)

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

Emulsion Freeze Drying

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

Creating Macroporous Structures with Sugar Fibers

Limitations of the conventional methods

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)

Solid Freeform Fabrication (SFF)

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

CAD editors for architecture, engineering and construction

Autocad Caddie CATIA CYCAS NX Pro/Engineer QCAD Solid Works

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

Fused deposition modeling

Acrylonitrile Butadiene Styrene (ABS) polymer, polycarbonates, polycaprolactone, polyphenylsulfones and waxes

Laminated object manufacturing

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

Selective laser sintering

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

Molds for Scaffolds

3D Microuidic Approach to Mechanical Stimulation of Osteocyte Processes

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