Chapter 2

Scaffolds for Tissue Engineering

Scaffold (new definition)

• 3D, biocompatible, biodegradable, and porous strucutre

• used for tissue and cell ingrowth

• common raw materials used: biocompatible polymers, peptides, proteins, and hydrogels

Requirements for fabrication of scaffold

1. A suitable macrostructure (to promote cell growth)

2. An open-pore geometry

3. Optimal pore size

4. Suitable surface morphology (the way the scaffold is laid down is important!)

5. A predictable rate of degradation

Conventional Fabrication Techniques of Scaffold

• electrospining, melt moulding, solvent casting and particulate leaching (SCLP), freeze-drying, gas foaming, phase separation

Electrospining

• uses electrostatic forces

• polymers are dissolved in solvent, an ejected from a syringe onto a surface

• advantages: continuous fibers, large surface area, versatile with materials, doesn’t require heat

Melt Moulding

• use of mould

• polymer and porogen particles are mixed, heated, and combined in a mould

• matieral is then taken out, and put into a liquid tank to remove excess porogen

• advantages: controlled porosity, control of the shape

• disadvantages: requires high temperature

Solvent casting and particulate leaching (SCPL)

• a mixture containg polymer and solvent is poured around a porogen

• solvent is evaporated, and porogen is dissolved, leaving the polymer behind

• advantages: controlled porosity and pore size (93%)

• disadvantages: limited membrane thickness, lack of strength, possible residue

Freeze-drying

• polymer, solvent, and water is mixed together and poured into a mould

• it is frozen (using liquid nitrogen) and the solvent and water are removed to leave behind a porous scaffold

• advantages: no need for to dissolve solvent, enables use of water-soluble polymers, control over pore size

• disadvantages: limited thickness, equipment-based technique, skin effect, requires freezing

Gas foaming

• polymer is moulded into a solid disc

• the disc rests in a high pressure carbon dioxide chamber for several days

• gas infiltrates the polymer creating pores

Phase separation

• a biocompatible polymer is dissolved in a solvent

• bioactive molecules are added to said solution

• temperature is reduced and phase separation takes place, solvent is evaporated and porous scaffold is left behind

• disadvantages: lack of control, process dependent

Additive Manufacturing Techniques of Scaffolds

• fused deposition modeling, selective laser sintering, SLA, 2PP, SLM (metal scaffold)

Material extrusion (FDM)

• material is melted (heat) into a semi-liquid state and deposited through a nozzle

• layers are built and the process is repeated

FDM (fused deposition modeling)

• material is melted into a semi-liquid state and deposited through a nozzle

• layers are built and the process is repeated

• disadvantages:

  • only certain types of material can be used

  • the input raw material has to be of a certain size

  • low resolution

SLS (Selective Laser Sintering)

• a laser beam selectively scans the surface of a powder

• the area impacted fuses together, and layer by layer a 3D form appears

• advantages

  • overhanging features can be easily made\

  • control of porosity

  • wide selection of materials

  • design freedom

Stereolithography Apparatus (SLA)

• photopolymerisation

  • a laser beam heats up the surface of a liquid photopolymer resin

  • liquid resin turns in a solid

  • after a layer is produced, a base plate moves downward and the process repeats

2PP (Two-photon Polymerisation)

• uses a focused laser to turn resin into a solid

• 2 sources of energy/lasers

• high resolution

SLM (Selective Laser Melting)

• a laser is aimed onto powdered metal to melt them together

• layer by layer a solid is formed

• metal is MELTED polymers are SINTERED

Tissue/Organ 3D Model Process

Step 1: create design through..

• Medical blueprints

• Segmentation is key! (helps to size it and think more 3D)

Step 2:

• Export it into a STL file and fix the details within the file

Step 3

• Decide pore size and balance

• Are you mimicking the bone? Are you optimizing the permeability?

5 Things a Biodegradable Polymer Scaffold Should be

1. nontoxic

2. able to maintain mechanical integrity

3. control degradation rate

4. nonimmunogenic (does not cause an immune system reaction)

5. not cause infection

Clinical Considerations with Scaffold-Based Tissue Engineering

1. Immune reaction

2. Degradation of Scaffolds in vivo

3. Risk of infection

4. Biofilms

5. Risks of disease transmission by scaffolds

Ways biodegradation can be toxic (Degradation of Scaffolds in vivo)

• scaffold itself is toxic

• metabolized to become toxic (ex: by liver enzymes)

• decomposed by hydrolysis → accumulation of acids

2 Major Sources of Injection

• biofilm