Structuring of (biodegradable) polymers Flashcards

1
Q

What is the importance of scaffold dimensions?

A
  • Scaffolds need to have a pore structure
  • Pores need to be interconnected
  • Pore size dependent on tissue/cell type:
  • Fibroblast ingrowth occurs with scaffold pore sizes of 5-15 µm, hepatocytes and osteoid cells need pore sizes of 20 µm and 40–100 µm
  • Vascularisation: needs pore sizes of at least 250 µm
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2
Q

What can you make micrometer scale pores?

A

Salt/sugar particles
Effervescent salt
High pressure gas (CO2)
Freeze drying

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3
Q

What is solvent casting and particulate leaching?

A

Mix polymer in solvent (e.g. PLA/chloroform) with salt (NaCl, porogen), cast, vacuum dry, wash out the salt. Overall porosity and connectivity can be controlled by salt size and ratio polymer salt particulates.
- Solid salt/sugar particles in polymer matrix, particles washed out

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4
Q

How can random porous materials be made?

A
  • Solvent casting and particulate leaching
  • Gas foaming
  • Freeze drying
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5
Q

What is gas foaming?

A

Gas (CO2) or gas forming particles (evanescent salt, e.g. CaCO3) in polymer matrix
- Using gas as porogen via using effervescent salt. This technique includes both melt/solvent molding and particulate leaching aspects. Porosities as high as 90% with pore sizes from 200-500 µm are obtained using this technique

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6
Q

What is freeze drying?

A

Solvent (water) polymer mixture which phase separates at low temperature, solvent sublimes

  • High-pressure processing/supercritical fluid technology: applying a gas, e.g. CO2, to dry polymer at high P, forms a single phase polymer/gas solution. High Pressure Gas Foaming
  • The pressure is reduced and results in nucleation of dissolved CO2 and growth of gas cells to generate pores within the polymer matrix.
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7
Q

What are the advantages of Solvent casting and particulate leaching, gas foaming and freeze drying?

A

Experimentally easy techniques.

Can make very porous materials that are interconnected.

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8
Q

What are the disadvantages of Solvent casting and particulate leaching, gas foaming and freeze drying?

A

Poor mechanical integrity, lack of structural stability, morphology and porosity is difficult to control independently

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9
Q

How are fibres made?

A
  • Spinning
  • Knitting and Weaving
  • Electrospinning: non-woven fabrics
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10
Q

What is spinning?

A

Polymer solution coagulates after spinnerette to produce fibres Variants: wet spinning (chemical bath) – dry spinning (solvent evaporation) – melt spinning (solidification) Continuous industrial production of typically 10-100 µm diameter fibres that can be woven Used for Silk-PLA-PCL

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11
Q

What is knitting and weaving?

A

Popular choice for vascular implants

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12
Q

What is electrospinning?

A

Electro-spinning uses an electrical charge to form a mat of fine fibers. When the electrical force at the surface of a polymer solution or polymer melt overcomes the surface tension, a charged jets is ejected

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13
Q

How can user controlled structures be created?

A

Additive Manufacturing techniques

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14
Q

What is Additive Manufacturing?

A

family of fabrication processes developed to make engineering prototypes in minimum lead time based on a CAD model of the item

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15
Q

What are the benefits and disadvantages of Additive Manufacturing?

A

1) Reduced lead times to produce prototype components or to manufacture parts.
2) Increased capability to compute manufacturing properties of components and assemblies.
3) Manufacturing of bespoke parts, e.g. Patient specific implants
4) Possibility of developing a distributed economy (print parts at home/in hospital)

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16
Q

How can Additive Manufacturing save lives?

A

3D printed splint to keep newborn’s airways open

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17
Q

What are examples of additive manufacturing techniques?

A

can produce user controlled scaffolds for tissue engineering via using CADCAM
• Printing techniques: 3D printing an wax printing
• Laser based techniques: stereolithography and selected laser sintering
• Fused deposition modelling and bioplotting techniques

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18
Q

What is 3D printing?

A

Prints material, including printing a chemical binder onto powdered material or directly printing wax

  1. Layer of powder spread on platform
  2. Ink-jet printer head deposits drops of binder on part crosssection
  3. Binder dissolves and joins adjacent powder particles
  4. Table lowered by layer thickness
  5. new layer of powder deposited above previous layer 6. Repeat steps 2-4 till part is built
  6. Shake powder to get part
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19
Q

What are laser based techniques?

A

Including laser-based machines that either photopolymerise liquid monomer or sinter powdered material

20
Q

What is stereolithography?

A
  1. Raw material: photocurable monomer by a laser beam
  2. Part constructed layer-by-layer
  3. Supporting platform → in container at depth.
  4. UV laser solidifies part crosssection
  5. Platform lowered by
  6. Part cross-section computed at current height
  7. Repeat Steps 4, 5
  8. Removed completed part, 8. Break off supporting structures
    (9. Cure the part in oven.)
21
Q

What are some examples of SL scaffolds: bone?

A

PLA Stereolithographic scaffolds for bone tissue engineering

1) UV-lamp/laser focused in liquid photocurable material
2) Material polymerises in focus
3) Via scanning 3D object can be built

22
Q

What are nerve guidance conduits?

A

Produce NGCs in PEG, PLA and PCL via projection µSL
• Mimic the structure of the nerve / axons-Schwann cells
• Contact guidance via grooves (20 µm)

23
Q

What are selective laser sintering?

A
  • Moving laser beam sinters heat-fusable powders in areas corresponding to the CAD geometry model one layer at a time to build the solid part
  • After each layer is completed, a new layer of loose powders is spread across the surface
  • Layer-by-layer, the powders are gradually bonded by the laser beam into a solid mass that forms the 3-D part geometry
  • In areas not sintered, the powders are loose and can be poured out of completed part
24
Q

What are nozzle based systems?

A

3d printing

which process material either thermally or chemically as it passes through a nozzle

25
Q

What is fused deposition modelling?

A

• FDM uses a moving nozzle to extrude a fibre of polymeric material (x- and y-axis control) from which the physical model is built layer-by-layer.
• The model is lowered (z-axis control) and the procedure repeated.
• Although the fibre must also produce external structures to support overhanging or unconnected features that need to be manually removed
- Easily produce different morphologies and densities
- Can layer these for different tissues
- Medical-grade polycaprolactone and tricalcium phosphate with Recombinant human bone morphogenetic protein 7 (rhBMP-7)
- Implanted in critical bone defect in sheep

26
Q

What is bioprinting?

A

Similar to ink jet printer or FDM Print gels that are thermo responsive
Cells are sprayed onto the solidifying thin layer of polymer solution
• Organ printing: Tissue spheroids as building blocks
Scaffold-free vascular tissue engineering using bioprinting

27
Q

What are the advantages and disadvantages of 3D printing?

A

45 µm pore size,
ADV: easy process
DISADV: Pore size dependent on powder, binder can be toxic, lack of mechanical strength

28
Q

What are the advantages and disadvantages of stereolithography?

A

10 µm pore size
Advantages: Highest resolution technique available. Disadvantages: Monomers can be costly. Limited by the development of photopolymerisable liquid monomer material

29
Q

What are the advantages and disadvantages of Selective laser sintering?

A

Achievable pore size: 45–200 µm
Advantages: Good compressive strengths, Wide range of materials, Solvent free
Disadvantages: High processing temperatures, Pore size dependent on the powder particulate size

30
Q

What are the advantages and disadvantages of Fused deposition modelling?

A

Achievable pore size:100–1000 µm,
Advantages: Good compressive strengths, Solvent free
Disadvantages: High processing temperatures, Limited material range, Inconsistent pore opening in x-, y- and zdirections, Requires support structures for irregular shapes

31
Q

Why choose additive manufacturing over other techniques?

A
  • Foams are normally much softer than either soft or hard tissue (E < 0.4 MPa)
  • AM based materials can be built with precise mechanical properties
  • More controllable materials manufacture and better tissue ingrowth
32
Q

Why use electrospinning for 3D objects?

A

provides possibility for patterning 3D object manufacture

33
Q

How are additive techniques combined with electrospinning?

A

Electrospinning on construct and replication of underlying pattern can be tuned by changing height of the collectors Electrostatically governed /field lines curve towards object that sticks out Enables patterned electrospun mats

34
Q

What are electrospun corneal rings?

A
  • Stem cell niches can be replicated within electrospun mats
  • Microfibrous mats with added relief, can be replicated easily
35
Q

Why combine additive mandufacturing with HIPEs?

A

High Internal Phase Emulsions, water droplets surrounded by very thin film of organic material (polymer), cure the polymer and dry remainder→ polyHIPE
Porosity and connectivity can be tuned, can be structured

36
Q

What are polyHIPEs?

A

Can be structured via combining them with stereolithography

37
Q

What are hydrogels?

A

Insoluble network of polymer chains that swell in aqueous solutions
Gels can be qualified by crosslinker: Covalent: covalent junctions Physical: non-covalent junctions

38
Q

What is the structure and swelling behaviour of hydrogels?

A

undergo swelling in analogy to dilution of free polymer chains in solution • ΔGmix= ΔHmix – TΔSmix (generally enthalpically favorable and enthropically unfavorable) • depends on T and pH (charged residues)

39
Q

What is hydrogels dependence on temperature and pH?

A

Hydrogels can have a temperature dependent or pH dependent swelling behaviour
Temperature: hydrogels that collapse at body temp
pH: ionic hydrogels with acidic side groups collapse at low pH

40
Q

What is the temperature response of a hydrogel?

A
  • poly(N-isopropylacrylamide), PEO/PPO block copolymers (pluronics)
  • Materials phase separate from solvent with increasing T (Lower Critical Solution Temperature LCST – Transition temperature)
  • ΔGcol = ΔHcol – TΔScol (collapse ΔH unfavorable/ ΔS favorable)

• poly(N-isopropylacrylamide) PNIPAAM (Lower Critical Solution Temperature): 32ºC • Transmittance: collapsed form opaque • Can be done with a hydrogel in solution and with a surface immobilised hydrogel

41
Q

What is the pH response of a hydrogel?

A
  • pH jump ~5 (pKa COOH)
  • COOH releases H+
  • COO- repel each other
  • H+ recombines with OH- COOneeds counter ions
  • Na+ and OH- diffuse into gel
  • Influx of new ions creates osmotic pressure, drives swelling further
42
Q

What is the used of the ph and temperature response of a hydrogel?

A
  • Injectable hydrogel delivery for tissue engineering

* T and pH dependent drug delivery / drug release

43
Q

How can a PH sensitive hydrogel be used for sensing?

A

Used for pH sensing, could be used for glucose sensing

44
Q

What is a glucose responsive hydrogel?

A
  • A bit more complicated
  • Boronic acid binds to glucose
  • Quencher releases fluorescent tag in hydrogel
45
Q

What is the main advantage of using high pressure gas foaming?

A

The main advantage of this method is that it excludes the use of organic solvents. Since the technique does not include a heating process, it is also useful for incorporation of heat sensitive biomolecules.