BIOMATERIALS AND BIOCOMPATIBILITY
Tissue engineering – scaffolds – cells ....................................................................................................3
Introduction to biomaterials and tissue engineering ...........................................................................3
Papers: scaffolds + vascularisation ...................................................................................................4
Basic tissue engineering approaches – properties of cells ...................................................................6
Biocompatibility ..................................................................................................................................8
Biomaterials ....................................................................................................................................8
Features ..........................................................................................................................................8
Paper: definitions ........................................................................................................................... 11
Ceramic biomaterials ........................................................................................................................ 12
Calcium phosphate ........................................................................................................................ 13
Bioactive glass ............................................................................................................................... 16
Biocomposites ............................................................................................................................... 18
Aluminium and zirconium oxides ..................................................................................................... 19
Production and application ............................................................................................................. 20
Metals as biomaterials ....................................................................................................................... 21
Common properties and processing methods .................................................................................. 21
Members ....................................................................................................................................... 23
Applications ................................................................................................................................... 26
Imaging in biomaterials and tissue engineering .................................................................................... 28
Microscopy .................................................................................................................................... 29
Extracellular matrix and biomaterial staining .................................................................................... 31
Animal models ............................................................................................................................... 33
Natural materials and matrigel ........................................................................................................... 35
Matrigel and EHS extract matrices ................................................................................................... 37
Decellularization ............................................................................................................................... 38
Materials for brain regeneration .......................................................................................................... 40
Testing biomaterials ....................................................................................................................... 41
Considerations .............................................................................................................................. 42
Polymers for biomedical applications ................................................................................................. 43
Types ............................................................................................................................................. 43
Processing ..................................................................................................................................... 44
Properties ...................................................................................................................................... 46
Applications ................................................................................................................................... 48
Tissue engineering of complex structures ............................................................................................ 57
1
, Applications ................................................................................................................................... 59
Risks ............................................................................................................................................. 59
Guest lecture: bio-electronic materials for tissue engineering and electric stimulation of tissue ............. 60
Extracellular matrix ........................................................................................................................ 60
Supramolecular hydrogels .............................................................................................................. 61
2
,TISSUE ENGINEERING – SCAFFOLDS – CELLS
INTRODUCTION TO BIOMATERIALS AND TISSUE ENGINEERING
− Definitions
• Biomaterials = material exploited in contact with living tissues – (micro)organisms
o To supply and replace part of a deficient organ
o Therapeutic or diagnostic functions
o Medicine – biology – chemistry – physics – mathematics – tissue engineering
• Biomedical devices = products of health/software claiming medical purposes
o Diagnosis – control – treatment – prevention of disease
o Diagnosis – control – treatment – compensation of wound/handicap
o Study – placement – modification of anatomy/physiological process
! not primarily pharmacological – immunological – metabolical ➔ medicine
• Tissue engineering
o Same goal as biomaterial – but the deficient organ is replaced by non-degradable
material which stays until it stops working
e.g. active construct: promotes regeneration ➔ replaced by tissue eventually
o Top-down approach = scaffold: bodily tissue repairs and heals next to the structure
bottom-up approach = cells: regenerative capacity in your (stem) cells
! you can combine them (= cell- and engineering components) or scaffold/cell-free
− Scaffolds = biomaterials: metals – organic polymers – ceramics – biopolymers – natural – …
• Characteristics
o 3D
o Supporting function: inverted function with healing of tissue
o Porous – defined mechanical properties
o Numerous applications
o Different production methods – hybrid possible
e.g. scaffold + MSC
- Static culturing: cells grow on scaffold and colonize
- Dynamic culturing: cells exchange and form better populations
• Production
e.g. gas foaming/particles leaching: salt particles of desired pore size mixed in with polymer
gel paste – once the solvent evaporates the polymer is strong – to ‘discard’ of the salt: put in
water and freeze-dry
• Properties
o Porosity: mimic the architecture of native ECM
o Pore size
o Vascularization
3
, o Stiffness: structure deforms under load
- Ashby plot: x-axis = strength – y-axis = young’s modulus
! Anisotropy: not all properties are equal in all directions
- One material subject do different types of stress
e.g. a bone: running – skiing – spinning – …
- Viscoelasticity: time-dependent behaviour
e.g. bouncy ball against the wall – or an egg
- Timescale
e.g. age: metabolism and hormone level changes
- Spatial scale
≈ natural extracellular matrix = ECM
o Produced by cells: dynamic – cell-type specific
o Components
- Basis: water
- Proteins: collagen – fibronectin – elastin
- Sugars: glycosaminoglycans (GAG’s)
- Signalling molecules – growth factors – ions – …
− Tissue condition
e.g. increase in tissue stiffness: healthy ➔ fibrosis ➔ cancer
PAPERS: SCAFFOLDS + VASCULARISATION
SCAFFOLDS
− Skeletal constructs: transmission or generation of mechanical forces
• Loading: 10x body weight
• ECM: anisotropic (tensile + compressive) – non-linear – inhomogeneous – viscoelastic
• Types
o Composite scaffolds
- Fiber reinforcement: mechanical characteristics
- Textile structures: fibre = mechanical strength matrix: supports cells
o 3D woven scaffolds
- Multiple orthogonal directions: non-linearity
o Layered scaffolds
- Depth-dependent structure ≈ cartilage
− Myocardial constructs: maintenance of blood circulation
• Muscle fibres: branched (contraction) – 3D collagen network (strong) – microvasculature
• Types
o Decellularized hearts
- Repopulation + contraction
! stiff
o Synthetic scaffold
- Coronary-derived microvascular network: oxygenation and repopulation
- Accordion-like honeycomb scaffold
4
Tissue engineering – scaffolds – cells ....................................................................................................3
Introduction to biomaterials and tissue engineering ...........................................................................3
Papers: scaffolds + vascularisation ...................................................................................................4
Basic tissue engineering approaches – properties of cells ...................................................................6
Biocompatibility ..................................................................................................................................8
Biomaterials ....................................................................................................................................8
Features ..........................................................................................................................................8
Paper: definitions ........................................................................................................................... 11
Ceramic biomaterials ........................................................................................................................ 12
Calcium phosphate ........................................................................................................................ 13
Bioactive glass ............................................................................................................................... 16
Biocomposites ............................................................................................................................... 18
Aluminium and zirconium oxides ..................................................................................................... 19
Production and application ............................................................................................................. 20
Metals as biomaterials ....................................................................................................................... 21
Common properties and processing methods .................................................................................. 21
Members ....................................................................................................................................... 23
Applications ................................................................................................................................... 26
Imaging in biomaterials and tissue engineering .................................................................................... 28
Microscopy .................................................................................................................................... 29
Extracellular matrix and biomaterial staining .................................................................................... 31
Animal models ............................................................................................................................... 33
Natural materials and matrigel ........................................................................................................... 35
Matrigel and EHS extract matrices ................................................................................................... 37
Decellularization ............................................................................................................................... 38
Materials for brain regeneration .......................................................................................................... 40
Testing biomaterials ....................................................................................................................... 41
Considerations .............................................................................................................................. 42
Polymers for biomedical applications ................................................................................................. 43
Types ............................................................................................................................................. 43
Processing ..................................................................................................................................... 44
Properties ...................................................................................................................................... 46
Applications ................................................................................................................................... 48
Tissue engineering of complex structures ............................................................................................ 57
1
, Applications ................................................................................................................................... 59
Risks ............................................................................................................................................. 59
Guest lecture: bio-electronic materials for tissue engineering and electric stimulation of tissue ............. 60
Extracellular matrix ........................................................................................................................ 60
Supramolecular hydrogels .............................................................................................................. 61
2
,TISSUE ENGINEERING – SCAFFOLDS – CELLS
INTRODUCTION TO BIOMATERIALS AND TISSUE ENGINEERING
− Definitions
• Biomaterials = material exploited in contact with living tissues – (micro)organisms
o To supply and replace part of a deficient organ
o Therapeutic or diagnostic functions
o Medicine – biology – chemistry – physics – mathematics – tissue engineering
• Biomedical devices = products of health/software claiming medical purposes
o Diagnosis – control – treatment – prevention of disease
o Diagnosis – control – treatment – compensation of wound/handicap
o Study – placement – modification of anatomy/physiological process
! not primarily pharmacological – immunological – metabolical ➔ medicine
• Tissue engineering
o Same goal as biomaterial – but the deficient organ is replaced by non-degradable
material which stays until it stops working
e.g. active construct: promotes regeneration ➔ replaced by tissue eventually
o Top-down approach = scaffold: bodily tissue repairs and heals next to the structure
bottom-up approach = cells: regenerative capacity in your (stem) cells
! you can combine them (= cell- and engineering components) or scaffold/cell-free
− Scaffolds = biomaterials: metals – organic polymers – ceramics – biopolymers – natural – …
• Characteristics
o 3D
o Supporting function: inverted function with healing of tissue
o Porous – defined mechanical properties
o Numerous applications
o Different production methods – hybrid possible
e.g. scaffold + MSC
- Static culturing: cells grow on scaffold and colonize
- Dynamic culturing: cells exchange and form better populations
• Production
e.g. gas foaming/particles leaching: salt particles of desired pore size mixed in with polymer
gel paste – once the solvent evaporates the polymer is strong – to ‘discard’ of the salt: put in
water and freeze-dry
• Properties
o Porosity: mimic the architecture of native ECM
o Pore size
o Vascularization
3
, o Stiffness: structure deforms under load
- Ashby plot: x-axis = strength – y-axis = young’s modulus
! Anisotropy: not all properties are equal in all directions
- One material subject do different types of stress
e.g. a bone: running – skiing – spinning – …
- Viscoelasticity: time-dependent behaviour
e.g. bouncy ball against the wall – or an egg
- Timescale
e.g. age: metabolism and hormone level changes
- Spatial scale
≈ natural extracellular matrix = ECM
o Produced by cells: dynamic – cell-type specific
o Components
- Basis: water
- Proteins: collagen – fibronectin – elastin
- Sugars: glycosaminoglycans (GAG’s)
- Signalling molecules – growth factors – ions – …
− Tissue condition
e.g. increase in tissue stiffness: healthy ➔ fibrosis ➔ cancer
PAPERS: SCAFFOLDS + VASCULARISATION
SCAFFOLDS
− Skeletal constructs: transmission or generation of mechanical forces
• Loading: 10x body weight
• ECM: anisotropic (tensile + compressive) – non-linear – inhomogeneous – viscoelastic
• Types
o Composite scaffolds
- Fiber reinforcement: mechanical characteristics
- Textile structures: fibre = mechanical strength matrix: supports cells
o 3D woven scaffolds
- Multiple orthogonal directions: non-linearity
o Layered scaffolds
- Depth-dependent structure ≈ cartilage
− Myocardial constructs: maintenance of blood circulation
• Muscle fibres: branched (contraction) – 3D collagen network (strong) – microvasculature
• Types
o Decellularized hearts
- Repopulation + contraction
! stiff
o Synthetic scaffold
- Coronary-derived microvascular network: oxygenation and repopulation
- Accordion-like honeycomb scaffold
4
