Tissue Engineering - WIP

Question 1

What is Tissue Engineering?

Answer 1

The understanding of mammalian tissues and how to restore, maintain or improve tissue function using biological substituents

Question 2

What is Regenerative Medicine?

Answer 2

The process of creating living, functional tissues to replace or regenerate humans cells, tissues or organs to restore or establish normal function

Question 3

What are the factors to consider in the Biocompatibility of a Scaffold?

Answer 3

Cells must adhere, function normally, proliferate and have no immune or inflammatory response

Question 4

What are the factors to consider in the Biodegradability of a Scaffold?

Answer 4

Scaffolds are not permanent, body cells should replace the implanted scaffold, but it should be able to stay for an extended period of time before cell growth is complete.

By-products of biodegradation should be non-toxic and able to be excreted

Question 5

What are the factors to consider in the Mechanical Properties of a Scaffold?

Answer 5

strong enough for surgical manipulation, have sufficient mechanical integrity to complete re-modelling, match properties of anatomical site

Question 6

What are the factors to consider in the Scaffold Architecture?

Answer 6

Needs an interconnected pore structure with high porosity to enable cellular penetration, diffuse nutrients to cells and matrix, remove waste products of cells and scaffold degradation, and allow vascularisation

Question 7

What are the factors to consider in the Manufacturing Technology of a Scaffold?

Answer 7

Cost effective, can scale-up. Consider how clinician will receive and use the product (e.g. will it require patients own cells?)

Question 8

What are the pros/cons of Natural Polymers as a Scaffold Biomaterial choice?

Answer 8

Biologically active, promotes good cell adhesion and growth, biodegradable

Difficult to fabricate, poor mechanical properties

Question 9

What are the pros/cons of Synthetic Polymers as a Scaffold Biomaterial choice?

Answer 9

Can be fabricated and tailored, good control over degradation

Risk of rejection (low bioactivity), degradation of many polymers may result in cell necrosis

Question 10

What are the pros/cons of Ceramics as a Scaffold Biomaterial choice?

Answer 10

Very compatible with mineral bone (high mechanical stiffness, low elasticity, hard brittle surface), enhances osteoblast differentiation and proliferation

Difficult to shape (brittle), unable to sustain mechanical loading needed for remodelling, degradation is difficult to control

Question 11

Why are Composites often used as Scaffold biomaterials?

Answer 11

Each class of biomaterials have cons.
Ceramics can be used in polymer-based scaffolds ??
Combination synthetic and natural polymer scaffolds increase biological capacity

Question 12

What are Decellularized Matrices and why are they used in Scaffolds?

Answer 12

Decellularized matrices are tissues that have come from a donor or cadaver in which the cells have been lysed to leave the extracellular components undamaged, resulting in a natural extracellular matrix that can be used as a scaffold.

They provide durability, enhanced integration and biocompatibility, and avoid allosensitization (antibodies attack foreign tissue, associated with rejection of transplants)

Question 13

What are Scaffolds in Tissue Engineering?

Answer 13

Tissue Engineering relies extensively on the use of porous 3D scaffolds to provide the appropriate environment for the regeneration of tissues and organs.
These scaffolds act as a template for tissue formation and are typically seeded with cells and occasionally growth factors.

Synthesised tissues are cultured in vitro to be implanted into the scaffold, or regeneration of tissues in the injured site is induced using the body’s own systems.

Question 14

Stem cells

Question 15

What are the levels of Tissue Engineering?

Answer 15

Level 1 – flat tissue: layers of cartilage, muscle, skin

Level 2 – tubular: blood vessels, esophagus, fallopian tubes, intestine, trachea, ureter, urethra

Level 3 – hollow non-tubular: bladder, stomach, vagina

Level 4 – solid organs: heart, kidney, liver, lung

Question 16

What are the current therapies for Skin?

Answer 16

An autologous split-thickness graft - the patient’s own skin in an undamaged site is stretched and then applied over the debrided (dead cells cut away to freshly bleeding tissue) wound area.

Doesn’t work if injury is extensive, allographs can work if immunosuppressive therapy is provided. There are now commercially available dermo-biopolymer composites.

Bioprinting – a printer designed to print skin cells onto burn wounds, scanner determines size/depth of wound and uses ink which includes patient’s skin cells

Question 17

What are the current therapies for Cornea?

Answer 17

Corneal transplantation from cadaver.

Stem cells from different sources have been isolated, expanded in vitro, differentiated and proven to function as corneal cells in vivo

Transparent thin gelatin gel scaffold have been functionalized with heparin to support transfer of cultured human corneal endothelial cells

Question 18

What are the current therapies for Blood Vessels?

Answer 18

Bioreactors (able to reproduce biochemical/biophysical stimuli as in physiological conditions) are predominantly used to develop artificial blood vessels

Tubular biodegradable scaffold uses all synthetic polymers, seeded with the patient’s own endothelial cells from blood sample and placed in bioreactor to acclimatize

Problems with high pressure blood vessels such as aorta as there is higher risk of aneurysm

Question 19

What are the current therapies for the Bladder?

Answer 19

Used of bladder decellularized matrix has alone never been able to achieve full bladder regeneration as muscle layers develop incompletely. It is now being associated with stem cells to improve tissue regeneration.

Scaffold materials are typically decellularized matrices with natural and synthetic polymers. No optimal biomaterial at this date

Question 20

What are the Regulatory and Financial Considerations of Tissue Engineering?

Answer 20

Efficacies of regenerative medicine products vary, but are generally better or comparable to pre-existing products

Medical devices reach the market after 3-7 years of development, but may undergo expedited process if similar to pre-existing devices

Question 21

What are the Clinical Considerations of Tissue Engineering?

Answer 21

There is a requirement in tissue engineering to have at least 2 procedures and delay treatment while construct is being cultured in vitro

There is a prolonged regulatory process before tissue engineering constructs can be approved for use

Long term in vitro tissue engineering may be the only solution in tissues such as cartilage (no ability to regenerate from damage) to prevent eventual joint arthroscopy