5 - Scaffolds for Biological Tissue Reconstruction Flashcards
Tissue engineering
Interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function
Components of native tissues
- Cells
- ECM
- Vessels (nutrients, O2 supply)
Tissue engineering paradigm
- Cell isolation
- Cell expansion
- 3D scaffold (mechanical stimulus, growth factors, cells)
- Graft transplantation
Hurdles for tissue engineering success
- Technical
- Commercial
- Regulatory
- Ethical
Autologous cells
From patient
Allogeneic cells
From another human
Xenogenic cells
From a different species
Biomaterials
- Used to develop scaffolds or templates for cells to organize and restore structure and function to damaged or dysfunctional tissues.
- Guidance can be achieved through biophysical and biochemical cues that direct cell behaviour, morphology, adhesion, and motility
Biological factors that influence the function and behaviour of cells in the scaffold
- Hormones
- Cytokines
- Growth factors
- Extracellular matrix molecules
- Cell surface molecules
- Nucleic acids
How does a cell interact with its environment
- Chemical signals
- Mechanical signals
Mechanotransduction
Mechanical signals are converted into signal transduction pathways.
Mediators of mechanotransduction
- Surface processes
- Membranes (ion channels)
- Cytoskeleton (microfilaments)
- ECM (collagen)
- Cell ECM adhesions (integrins)
- Nuclei (gene expression)
- Cell-cell adhesions (gap junctions)
What regulates stem cell lineage commitment
Cell shape, Cytoskeletal tension and RhoA
Two categories of tissue engineering approaches
- Transplantation of in vitro grown tissues
- Promotion of tissue regeneration in situ
Transplantation of in vitro grown tissues
Biomaterial/scaffold + cells transplanted leading to tissue regeneration
Promotion of tissue regeneration in situ
Biomaterial/scaffold transplanted, leading to recruitment and reorganisation of host cells and eventually tissue regeneration
Materials in tissue engineering / desirable properties of biomaterials
- Adequate mechanical properties
- Biocompatible
- Biodegradable
- Porous structure
- Promote tissue regeneration/cell attachment
Fabrication process in tissue engineering
- Precise
- Reproducible
- Compatible with cells/ biological signals
- Tailored size/shape
- Cheap
- Quick
Order of kilopascals of organs (weakest to strongest)
- Fat
- Brain
- Heart
- Intestine
- Cartilage
- Bone
Stress equation
Stress = Force / area (kPa)
Natural polymers
- Polypeptides (collagen, gelatine, silk)
- Polysaccharides (Agarose, alginate)
Synthetic polymers
Glycolic acid, lactic acid, polycarbonate
Bioinks
- Generally soft hydrogels
- Cells as mandatory component, optionally combined with materials, and processing with a biofabrication technique
Biomaterial inks
- Generally hard thermoplastic polymers
- Additive manufacturing of biomaterials as inks, and seeing of the scaffolds with cells
Hydrogels
- 3D hydrophilic polymer networks that can absorb large amount of water
- Usually biocompatible & biodegradable
- Resemblance to ECM
- True 3D environment for cells
- Suitable for suspension of cells, drugs and
biologically active materials - Ideal as bioinks
Different bioprinting technologies
- Extrusion based bioprinting
- Droplet based bioprinting
- Laser based bioprinting
Advantages of extrusion based bioprinting
- Mechanical/structural integrity
- High cell viability
- Hydrogel viscosity
Disadvantages of extrusion based bioprinting
- Low resolution
- Low accuracy
Advantages of droplet based bioprinting
- High cell viability
- High gelation speed
Disadvantages of droplet based bioprinting
- Low mechanical/structural integrity
- Low hydrogel viscosity
Advantages of laser based bioprinting
- High resolution
- High accuracy
- High gelation speed
Disadvantages of laser based bioprinting
- Low mechanical/structural integrity
Natural hard tissue
Collagen
Natural soft tissue
- Ligament
- Tendon
- Skin
Collagen
- The most abundant protein in the body by weight
- Main structural protein in the ECM
- Key player in tissue biomechanics
- Acts as a fibrous reinforcement within a
matrix made of GAGs containing the cells & other biological signals
Melt electro writing (MEW)
- A robust method to print high-resolution scaffolds with controlled microarchitectures, interfaces and mechanical properties
- High resolution and accuracy
- Tailorable mechanical properties
- Solvent-free (suited for direct printing of medical-grade polymer)
- Unique optical access enables real time monitoring of process
- Can be used alone or in combination with hydrogels/bioprinting for soft tissue engineering applications.
MEW challenges
Layer bonding and print path
Heart valve replacement
- Mechanical valves
- Bio-prosthetic valves
Mechanical valves
- Durability (~20 years)
- Lifelong anti-coagulation therapy
- Open heart surgery required
- Sudden failure (catastrophic outcome)
Bio-prosthetic valves
- TAVR compatible with minimally invasive
surgery - No anti-coagulation therapy
- Durability (~5 years in younger patients)
- Neither demonstrate ability to grow with patient
Complex requirements of tissue-engineered solution in clinical trials
- Accommodate cell recruitment and
infiltration - Guide tissue formation
- Maintain tissue/organ functionality
Multiple strategies to achieve the complex requirements of tissue engineered solutions
- Advanced biomaterials
- Drug delivery/elution
- Biomimetic scaffolds (Morphological, Mechanical or Both)
Cues that cells respond to
Not only to biochemical cues but also other important tissue properties such as elasticity, geometry, cell contractility… (cell mechano-sensing).
