tissue regeneration in dentistry Flashcards

1
Q

how does a cell know where to go?

why is this important

A
  • 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
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2
Q

how does cell move

anterior vs posterior guidance

A
  • ‘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
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3
Q

role of ECM under natural conditions

A
  • 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
  • Growth factor release is linked to cell activity
  • Cells are exposed to a low dose of growth factor over an extended period of time
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4
Q

important factors for growth factor delivery

why are they important

A
  • 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
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5
Q

why is pore size of scaffold important?

A
  • 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
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6
Q

categories of matrix materials

A

inorganic materials

synthetic polymers

natural polymers

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7
Q

advantages of natural polymers

A
  • natural product
    • no later problems
    • no unknown factors
    • not toxic
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8
Q

disadvantages of natural polymers

A
  • purity is low
  • combination with other materials has unknown factors
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9
Q

how is the materials used for scaffolds degraded?

A

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
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10
Q

advantages of ECM as scaffold in tissue engineering

A
  • well controlled porosity
  • offers precise degradation speed
    • by controlling speed of chemical
    • to expose GF more
  • no cytotoxic effects
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11
Q

central nervous system damage repair using hSAF and RGDS

A

RGDS - good ECM - fibrous scaffold - attracts neural stem cells

Very efficient in promoting central nervous system damage repair

hSAF-RGD conjugates together

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12
Q

combination strategy used in tissue engineering

A

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
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13
Q

example of transfering larger amount of material onto larger pathological site

in regeneration of brain e.g.

A
  • 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
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14
Q

what is osteoconduction?

A

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
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15
Q

what is osteoinduction

A

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
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16
Q

what is BMP

A

Bone morphogenic Proteins

Are soluble local acting signalling molecules

17
Q

roles of BMPs

A
  • 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
18
Q

pathways by which BMP implants lead to bone remodelling

A
19
Q

what do BMPs initiate to lead to bone formation

A
  1. Mesenchymal cell infiltration
  2. Chondrogenic differentiation of cells
  3. Cartilage resorption and bone formation
  4. Population of the bone with marrow elements
  5. Normal bone remodelling
20
Q

what is the significant difference between BMPs and other growth factors

A

BMPs are differentiation factors

also can cause host to induce formation of its own bone

21
Q

why is it difficult to repair cartilage bone?

A
  • Is a vascular tissue
    • Limited capacity for repair
    • Restricted

therefore stem cell based approach should be used

22
Q

how is stem cell engineering used for cartilage repair

A
  • 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
23
Q

in gene therapy, how is non-viral domains used, what is the disadvantage?

A

gene gun or electroporation is used to inject it directly into the nuclei

only applies to short term

24
Q

advantages of disadvantages of viral vectors : adenovirus

A

advantages

  • capable of infecting many cell types
  • no gene transfer to offspring
  • reduced risk fo mutagenesis
    • safe

disadvantages

  • limited time period of gene expression
25
Q

advantages of disadvantages of viral vectors : retroviruses, adeno-associated viruses

A

advantages

  • more powerful

disadvantages

  • retoviruses are limited to proliferating cells
  • can directly integrate into host genome
    • significant risk for insertional mutagenesis
    • cancer
26
Q

what should be assessed in risk:benefit assessment

A

Efficacy

Localised activity

Systemic availability

Immunogenicity

Purity

Biocompatibility

Biodegradability

Specific inherent risks