Tissue engineering Flashcards
what is tissue engineering
Tissue Engineering is the in vitro development (growth) of tissues or organs to replace or support the function of defective or injured body parts.
why is research limited?
research is currently restricted by the limited mass transport of artificial tissues resulting in lack of blood supply
what is tissue organisation?
Before a tissue can be developed in vitro, first we must understand how tissues are organized. The basic tenant here is that:
“all tissues are comprised of
several levels of structural hierarchy”
what is the purpose of scaffold?
Scaffold: serves as temporary or permanent artificial Extracellular Matrices (ECM) to accommodate cells and support 3D tissue regenerations
what is Extracellular matrix (ECM)
The extracellular matrix (ECM) provides the physical and chemical conditions that enable the development of all biological tissues.
It is a complex nano-to-microscale structure made up of protein fibres and serves as a dynamic substrate that supports tissue repair and regeneration.
Scaffolds should mimic ECM by forming highly branched networks of fibres that span microscopic dimensions.
what is the basic principles of tissue engineering?
cells from a biopsy
monolayer cell culture
expanded cells
culture on 3D polymeric scaffold
generation of a graft
to human
what are the problems with tissue engineering?
The Wound Healing Process
Blood Clotting
- protein activation to form fibrin
- platlets/ red blood cells
- causes blood clot –> thrombosis
Chronic Inflammatory response
- Inflammation – cells degrade/remove material
- Biomaterial is persistent source of irritation – chronic inflammatory
response
-Scar tissue form around material – impede function
Biological tissue environment is an aggressive and hostile medium with respect to foreign materials
Biomaterial design must work with bodies defence mechanism
- what functions
Fight against possible infection – caused by surgery
Immune response – as the body attempt to degrade, remove and repair
Blood clotting – body uses to prevent significant blood loss (wound healing)
what are the Approaches to Biocompatibility
Biocompatibility could arise from total absence of interaction between material and tissue
- Concept is that body ignores material which is passively tolerated rather than actively accepted
- This approach is reasonably successful – especially in the short term
- there is no such thing as true inertness
what is biocompatibilty?
biocompatibility has been redefined by some as ‘the ability of a material to perform with an appropriate host response in a specific application’
what should ideal scaffold for Tissue engineering do?
Act as template for tissue growth in 3D
Mechanical properties similar to the host tissue
Have an interconnected macroporous network for vascularisation, tissue ingrowth and nutrient delivery
Bond to the host tissue without the formation of scar tissue
Resorb at the same rate as the tissue is repaired
Influence the genes in the cells of the tissue to enable efficient cell differentiation and proliferation
Be easily and cheaply produced (must be easily sterilized)
what are the ideal physical properties of porous scaffolds?
-spatial pore orientation and continuity: reconstruction of tissue framework
-sufficient pore volume: tissue expansion
-micropores (10-50 micrometers): cell adhesion, diffusion of oxygen and nutrients, waste clearance
- macropores (100 micrometers): cell infiltration, invasion of blood vessels, building of tissue layers
-mechanical stability
what are the biomaterial scaffolds materials:
A) Synthetic polymers
chitosan, alginate, etc.
Common feature: polysaccharides with polyanions
Highly hydrated along with desirable mechanical properties
Other non-biodegradable, strong and biocompatible scaffold material : Carbon nanotubes
B) natural
collagen, elastin, fibrin, etc.
hydrogels
Still polymeric!
Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen which causes it to polymerize. The polymerized fibrin together with platelets forms a hemostatic plug or clot over a wound site.
C) Synthetic calcium phosphate
ceramics
calcium phosphate based for bone tissue engineering
porous structures
Calcium phosphate ceramics (CPCs) are a class of tunable bioactive materials that have been widely used for bone tissue repair and augmentation
They possess surface properties that support osteoblast adhesion/proliferation (i.e. osteoconduction) and stimulate new bone formation (i.e. osteoinduction)
More significantly, CPCs have been shown to promote bone growth in vivo, and recruit bone marrow stromal cells (BMSCs) to ectopic sites to induce bone formation.
- Elastin is a major protein component of tissues that require elasticity such as arteries, lungs, bladder, skin and elastic ligaments and cartilage. It is composed of soluble tropoelastin protein containing primarily, glycine and valine and modified alanine and proline residues. Tropoelastin is a ~65kDa protein that is highly cross-linked to form an insoluble complex.
How to optimize properties of scaffolds
Comparative SEM images of (a) collagen-GAG (CG) scaffold (b) hydroxyapatite (HA) and (c) composite collagen-HA (CHA) scaffold.
The high porosity of the collagen-GAG scaffold, which promotes improved cell infiltration and vascularization, is evident.
The drawback is that it has poor mechanical properties.
The hydroxyapatite HA scaffold has better mechanical properties but poorer capacity for cell infiltration and vascularization.
By producing a collagen-HA scaffold (c), it is possible to overcome the problems with both materials while retaining their positive attributes.
The high porosity of the CHA scaffold and uniform distribution of HA particles (green dots) can clearly be seen.
