7.Processing of Biomaterials Flashcards
Which properties of biomaterials can we modify?
-surface chemistry
-3D structure
-Composition,texture
-Biophysical properties
Which biological responses can we modulate?
cell-material interactions
tissue ingrowth
match tissue/organs shape
blood interactions
cell adhesion
protein adsorption
corrosion resistance
osteointegration
Caracterisitics of conventional manufacturing
Require common equipment;
* Straightforward, cost-effective, and easy to scale up;
* Limited control over key properties such
as the shape (complex, anatomical), porosity (gradients), pore interconnectivity, etc.;
* Do not allow simultaneous incorporation of biologically relevant signals and cells with high spatial control.
Characteristics of additive manufacturing
- Require specialized equipment;
- High degree of control over key
properties such as the shape (complex,
anatomical), porosity (gradients), pore
interconnectivity, architecture, etc. - Allow simultaneous incorporation of
biologically relevant signals and cells with
high spatial control; - Production of patient-specific implants and
medical devices.
Compression Molding & Injection Molding
- Widely used for polymer processing => heating + mechanical compression
- Molds are used to impart the final shape
- Molds can also be closed and the biomaterial injected
- Thermosets => reaction injection molding
Casting & Extrusion
Casting: liquid biomaterial (metal, polymer, ceramic) is casted into a mold (not heated) => material solidification occurs via a physical (cooling) or chemical (polymerization) process
* Extrusion: shaping process
Solvent-casting/particulate-leaching
- Polymer solution is dissolved with an uniformly distributed particulate porogen;
- Solvent is allowed to evaporate, leaving a matrix with uniformly distributed salt particles;
- The polymer matrix is then immersed in water to allow leaching of the salt particles, forming a highly porous 3D scaffold.
-
Porosity can be adjusted by the porogen concentration, while the pore size
and geometry can be tuned by the size and shape of the porogen; -
Pore interconnectivity depends on the amount, spatial arrangement, and
geometry of the porogen particles => low volume fraction ↑ closed pores; - Scaffolds need to be extensively washed to ensure complete removal of the
solvents and porogen particles.
Compression molding/particulate-leaching
- Applied to create porous scaffolds made of synthetic polymers;
- NaCl particles and gelatin microspheres are typically used as porogen agents;
- Scaffolds with porosities between 50% to 90% and pore sizes from 10 to
1000μmhave been reported.
Gas foaming
- The polymer is saturated with a foaming agent such as carbon dioxide, nitrogen at high pressures;
- The pressure of the foaming agent is decreased, leading to a decrease in the solubility of the gas in the polymer;
- Gas bubbles are formed and grow in the polymer as a result of this thermodynamic instability, leaving a porous structure => limited pore interconnectivity.
Freeze-drying (lyophilization)
- The polymer solution is cooled below its freezing point =>solidification of the solvent molecules;
- The solvent is evaporated via sublimation, leaving a highly porous polymeric structure with interconnected pores.
- The pore size depends on the freezing regime, the polymer concentration, the size of the ice crystals, etc.
- Polymers are usually crosslinked either before or after freeze-drying;
- The process requires extensive optimization of the freeze-drying cycles on the pore size and mechanical properties;
- Lengthy timescales and high energy consumption.
Electrospinning
Electrospinning – nano to micrometer fibers
* Uses high electrical voltage to fabricate fine fibers (~ 20-1000 nm) from a polymer solution (Solution electrospinning);
* Fibers are deposited onto a collector with either a randomor defined alignment.
Characterisitics of nanofibers
Nanofibers:
* High surface area to volume ratio;
* Mimic the native ECM fibers;
* Low density.
Main operation parameters in electrospinning
- Solution (viscosity, concentration, type of solvent);
- Processing (flow rate, distance between needle and collector, voltage supply, type of collector);
- Environmental (temperature and humidity).
Additive manufacturing technologies
“‘Technologies which use a process of joining materials to make objects from in silico 3D model datasets, usually layer upon layer, as opposed to subtractive manufacturing methodologies”
Vat polymerization – Stereolithography
- Produces 3D scaffolds through the selective photo-initiated curing reaction of a liquid photosensitive material;
- The curing reaction is triggered by the incidence of light with an appropriate wavelength (UV, visible), intensity, and duration.
Features: - Photosensitive-materials
- Resolution 30-70 μm
- No support materials
- Cell compatible
Two-photon polymerization (2PP)
- Uses a near-infrared ultrashort-pulsed laser to excite in a confine space molecules (photoinitiators) to a two-photon state => photopolymerization;
- Fabrication of 3D nano/micro-structures without supports.
Fused deposition modeling (FDM)
- Molten thermoplastic polymers are extruded into filaments;
- The material leaves the extrusion nozzle in a liquid state and hardens immediately.
Features: - Thermoplastic polymers, ceramics;
- Printing resolution (~100 μm) depends on the nozzle;
- Support materials are required.
Selective Laser Sintering (SLS)
- A laser beam selectively scans powder material slightly above its melting temperature =>fusion of powder particles=>3D scaffold;
- After solidification, a new layer of powder is laid down and the process is repeated to build the scaffold layer-by-layer.
- Scaffold properties strongly depend on the powder properties (e.g., particle size,
powder morphology) and operational parameters, such as spot diameter, laser
power, scanning speed, and layer thickness; - Heat process – possible degradation and shrinkage effects;
- Powder materials (polymers and ceramics).
Features: - Heat process
- Nozzle-free printing process
- Printing resolution (~50 μm) depends on the powder properties
- No support materials
- Non cell compatible
Selective Laser Melting (SLM)
- Processing of metallic biomaterials to create functional and complex structures;
Melt Electrospinning
- Fibers generally have larger diameters compared to solution electrospinning;
- Absence of solvent;
- Flight path of the melt jet is stable and fiber deposition is reasonably predictable.
Supply zone: forces a molten polymer through a spinneret to a jet initiation point;
High voltage: induces an electrical force on the polymer emerging from the spinneret at the
jet initiation point;
-Molten polymer jet goes towards the collector where it solidifies as an ultrafine filament.
Inkjet Bioprinting
- Dispensing of small drops (typically 1–100 picolitres) of a liquid bioink onto a collector substrate.
- DOD inkjet bioprinting: thermal (vapor bubble formation) or piezoelectric inkjet (mechanical actuation) - mechanism used for droplet formation and ejection.
Extrusion Bioprinting
- Most popular method to fabricate 3D cell-laden constructs for tissue regeneration;
- Cells are usually suspended in hydrogel precursor solutions and subsequently printed onto a platform driven by pressurized air or mechanical forces generated by either a piston or a rotating screw.
Features: - Contact printing
- Nozzle-based
- Low to high viscosity
- Bioink rheology is critical
- Printing resolution > 100 μm
Modes:
-piston
-pneumatic
-screw
hAFSCs
human amniotic fluid–derived stem cells
Multimaterial multinozzle 3D (MM3D) printing
- Ultrarapid multimaterial switching for enhanced complexity and build speed with multinozzle printing;
- Each printhead is connected to multiple syringes, each of which contains a different material, that are actuated by a bank of fast-cycling pneumatic solenoids to enable high-frequency switching
