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PATH3308 > 5 - Scaffolds for Biological Tissue Reconstruction > Flashcards

5 - Scaffolds for Biological Tissue Reconstruction Flashcards

1
Q

Tissue engineering

A

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

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2
Q

Components of native tissues

A
  • Cells
  • ECM
  • Vessels (nutrients, O2 supply)
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3
Q

Tissue engineering paradigm

A
  • Cell isolation
  • Cell expansion
  • 3D scaffold (mechanical stimulus, growth factors, cells)
  • Graft transplantation
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4
Q

Hurdles for tissue engineering success

A
  • Technical
  • Commercial
  • Regulatory
  • Ethical
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5
Q

Autologous cells

A

From patient

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6
Q

Allogeneic cells

A

From another human

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7
Q

Xenogenic cells

A

From a different species

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8
Q

Biomaterials

A
  • 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
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9
Q

Biological factors that influence the function and behaviour of cells in the scaffold

A
  • Hormones
  • Cytokines
  • Growth factors
  • Extracellular matrix molecules
  • Cell surface molecules
  • Nucleic acids
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10
Q

How does a cell interact with its environment

A
  • Chemical signals
  • Mechanical signals
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11
Q

Mechanotransduction

A

Mechanical signals are converted into signal transduction pathways.

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12
Q

Mediators of mechanotransduction

A
  • Surface processes
  • Membranes (ion channels)
  • Cytoskeleton (microfilaments)
  • ECM (collagen)
  • Cell ECM adhesions (integrins)
  • Nuclei (gene expression)
  • Cell-cell adhesions (gap junctions)
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13
Q

What regulates stem cell lineage commitment

A

Cell shape, Cytoskeletal tension and RhoA

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14
Q

Two categories of tissue engineering approaches

A
  • Transplantation of in vitro grown tissues
  • Promotion of tissue regeneration in situ
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15
Q

Transplantation of in vitro grown tissues

A

Biomaterial/scaffold + cells transplanted leading to tissue regeneration

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16
Q

Promotion of tissue regeneration in situ

A

Biomaterial/scaffold transplanted, leading to recruitment and reorganisation of host cells and eventually tissue regeneration

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17
Q

Materials in tissue engineering / desirable properties of biomaterials

A
  • Adequate mechanical properties
  • Biocompatible
  • Biodegradable
  • Porous structure
  • Promote tissue regeneration/cell attachment
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18
Q

Fabrication process in tissue engineering

A
  • Precise
  • Reproducible
  • Compatible with cells/ biological signals
  • Tailored size/shape
  • Cheap
  • Quick
19
Q

Order of kilopascals of organs (weakest to strongest)

A
  • Fat
  • Brain
  • Heart
  • Intestine
  • Cartilage
  • Bone
20
Q

Stress equation

A

Stress = Force / area (kPa)

21
Q

Natural polymers

A
  • Polypeptides (collagen, gelatine, silk)
  • Polysaccharides (Agarose, alginate)
22
Q

Synthetic polymers

A

Glycolic acid, lactic acid, polycarbonate

23
Q

Bioinks

A
  • Generally soft hydrogels
  • Cells as mandatory component, optionally combined with materials, and processing with a biofabrication technique
24
Q

Biomaterial inks

A
  • Generally hard thermoplastic polymers
  • Additive manufacturing of biomaterials as inks, and seeing of the scaffolds with cells
25
Q

Hydrogels

A
  • 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
26
Q

Different bioprinting technologies

A
  • Extrusion based bioprinting
  • Droplet based bioprinting
  • Laser based bioprinting
27
Q

Advantages of extrusion based bioprinting

A
  • Mechanical/structural integrity
  • High cell viability
  • Hydrogel viscosity
28
Q

Disadvantages of extrusion based bioprinting

A
  • Low resolution
  • Low accuracy
29
Q

Advantages of droplet based bioprinting

A
  • High cell viability
  • High gelation speed
30
Q

Disadvantages of droplet based bioprinting

A
  • Low mechanical/structural integrity
  • Low hydrogel viscosity
31
Q

Advantages of laser based bioprinting

A
  • High resolution
  • High accuracy
  • High gelation speed
32
Q

Disadvantages of laser based bioprinting

A
  • Low mechanical/structural integrity
33
Q

Natural hard tissue

A

Collagen

34
Q

Natural soft tissue

A
  • Ligament
  • Tendon
  • Skin
35
Q

Collagen

A
  • 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
36
Q

Melt electro writing (MEW)

A
  • 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.
37
Q

MEW challenges

A

Layer bonding and print path

38
Q

Heart valve replacement

A
  • Mechanical valves
  • Bio-prosthetic valves
39
Q

Mechanical valves

A
  • Durability (~20 years)
  • Lifelong anti-coagulation therapy
  • Open heart surgery required
  • Sudden failure (catastrophic outcome)
40
Q

Bio-prosthetic valves

A
  • TAVR compatible with minimally invasive
    surgery
  • No anti-coagulation therapy
  • Durability (~5 years in younger patients)
  • Neither demonstrate ability to grow with patient
41
Q

Complex requirements of tissue-engineered solution in clinical trials

A
  • Accommodate cell recruitment and
    infiltration
  • Guide tissue formation
  • Maintain tissue/organ functionality
42
Q

Multiple strategies to achieve the complex requirements of tissue engineered solutions

A
  • Advanced biomaterials
  • Drug delivery/elution
  • Biomimetic scaffolds (Morphological, Mechanical or Both)
43
Q

Cues that cells respond to

A

Not only to biochemical cues but also other important tissue properties such as elasticity, geometry, cell contractility… (cell mechano-sensing).

PATH3308 (8 decks)

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