tissue regeneration in dentistry Flashcards
how does a cell know where to go?
why is this important
- Physiological requirementE.g. Response to cyclic AMP
- Situation during embryonic development
- Pathological requirement
- E.g. Wound signals cause cell migration to centre of wound
- determines how efficient tissue regeneration
how does cell move
anterior vs posterior guidance
- ‘frog - leap’
- under chemical gradient
- P13K more at higher concentration of chemical
- goes to end to pull
- PTEN remains at back to push cells forward
- by reactivating myosin
role of ECM under natural conditions
- ECM plays role in storing, displaying and releasing growth factors
- Conduction response to fill void
- Release of material into that space to attract stem cells
- Migration into that area
- Chemotaxis activity
- How efficiently is cell able to release out of ECM - determines efficiency of proliferation and migration into the void
- Conduction response to fill void
- Growth factor release is linked to cell activity
- Cells are exposed to a low dose of growth factor over an extended period of time
important factors for growth factor delivery
why are they important
- prolonged availability of bioactive factors at defect site
- find smart way to anchor set of growth factors onto scaffold
- so stem cells have prolonged access to set of growth factors within the scaffold
- scaffolds must maintain space in which tissue formation can occur
- pore size of the scaffold is important
- carrier scaffold must be biologically acceptable
- biocompatible vs biodegradable
- determines how long the scaffold and growth factors will be available for
- if biodegradable - will release growth factors eventually
why is pore size of scaffold important?
- Determines end product of stem cells based tissue engineering
- Different tissue reactions
- Too large
- Cells wont survive
- growth factors will be too far from each other
- concentration of growth factors will be too low and diluted
- cells cannot access GF well
- Too small
- Cells might run out of oxygen and nutrients
categories of matrix materials
inorganic materials
synthetic polymers
natural polymers
advantages of natural polymers
- natural product
- no later problems
- no unknown factors
- not toxic
disadvantages of natural polymers
- purity is low
- combination with other materials has unknown factors
how is the materials used for scaffolds degraded?
either :
- Based on chemical clocks
- I.e. Programmed via selection of detailed chemical environment around labile bond e.g. ester hydrolysis
- –> material-controlled degradation rate
- Based on bioactivity
- i.e. Degradation proceeds along healing response via cell-derived enzymatic activity
- Using enzyme based activity
- –> cell-controlled degradation rate
advantages of ECM as scaffold in tissue engineering
- well controlled porosity
- offers precise degradation speed
- by controlling speed of chemical
- to expose GF more
- no cytotoxic effects
central nervous system damage repair using hSAF and RGDS
RGDS - good ECM - fibrous scaffold - attracts neural stem cells
Very efficient in promoting central nervous system damage repair
hSAF-RGD conjugates together
combination strategy used in tissue engineering
Combination of
- 3D nano-structure
- fill damage with biomaterials
- Conduction
- Growth factors
- aid with stem cell proliferation and differentiation
- Induction
- Stem cells on surface
- Cell transplantation
example of transfering larger amount of material onto larger pathological site
in regeneration of brain e.g.
- PDMS microchamber array
- Lots of pockets on the material
- Stem cells in each of the pockets
- Stem cells will grow out and form network
- Filling surface
- Form 3d mesh
- Stick it onto the damage
- This was used on the brain
- Leaving the individual pockets of stem cells on the brain
what is osteoconduction?
Ability of material to support bone growth by allowing bone formation on its surface/pores is used where sufficient quantities and margins of bone exist
- Specific material to support bone growth
- Good for small areas
what is osteoinduction
De novo bone formation at soft or hard tissue sites which can be used in biologic reconstruction where normal bone formation is inadequate (critical size defects, osteoporosis)
- For larger areas
- Bioactive factors to promote self regeneration
what is BMP
Bone morphogenic Proteins
Are soluble local acting signalling molecules
roles of BMPs
- controls transcription of selected genes
- triggers signalling via Smad proteins
- act as differentiation factors
- can turn responsive multipotent mesenchymal stem cells into cartilage- or bone-forming cells
- primary function
-
transdifferentiation
- can change phenotype of selected cell types
- e.g. fat and muscle cells into osteoblastic
pathways by which BMP implants lead to bone remodelling
what do BMPs initiate to lead to bone formation
- Mesenchymal cell infiltration
- Chondrogenic differentiation of cells
- Cartilage resorption and bone formation
- Population of the bone with marrow elements
- Normal bone remodelling
what is the significant difference between BMPs and other growth factors
BMPs are differentiation factors
also can cause host to induce formation of its own bone
why is it difficult to repair cartilage bone?
- Is a vascular tissue
- Limited capacity for repair
- Restricted
therefore stem cell based approach should be used
how is stem cell engineering used for cartilage repair
- Cartilage progenitor cells combined with notch 1 expression
- Promotes differentiation into mature cartilage cells
- Continuous proliferation of cartilage progenitor cells
- Combination of bioactive material - notch 1 - with 3d scaffold
- Promotes notch 1 induced cartilage differentiation
in gene therapy, how is non-viral domains used, what is the disadvantage?
gene gun or electroporation is used to inject it directly into the nuclei
only applies to short term
advantages of disadvantages of viral vectors : adenovirus
advantages
- capable of infecting many cell types
- no gene transfer to offspring
- reduced risk fo mutagenesis
- safe
disadvantages
- limited time period of gene expression
advantages of disadvantages of viral vectors : retroviruses, adeno-associated viruses
advantages
- more powerful
disadvantages
- retoviruses are limited to proliferating cells
- can directly integrate into host genome
- significant risk for insertional mutagenesis
- cancer
what should be assessed in risk:benefit assessment
Efficacy
Localised activity
Systemic availability
Immunogenicity
Purity
Biocompatibility
Biodegradability
Specific inherent risks
