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Topic 1 Flashcards

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1
Q

What are autologous cells?

A

patients own cells, problem is that we may not get enough

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2
Q

What are allogenic cells?

A

other human cells, immunogenic

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3
Q

What are xenogenic cells?

A

Animal cells, immunogenic

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4
Q

What are scaffolds?

A

they provide appropriate environments for cells to be able to effectively accomplish their functions
made of biomaterials with well defined biochemical and biophysical cues to effectively regulate cellular behaviours
used to supply drugs, nutrients and bioactive factors that direct tissue growth
should be biocompatible and non toxic

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5
Q

What is the function of signals/biomolecules?

A

to guide and regulate cellular response to regenerate tissue
the mediators of molecular signalling mechanisms and crosslink between the cells and their immediate microenvironment
the temporal and spatial coordination of cellular processes is orchestrated by these signals from the extracellular environment

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6
Q

What are some examples biological factors?

A

hormones, cytokines, growth factors, ECM molecules, cell surface molecules and nucleic acids

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7
Q

What is the 1986 definition of biomaterial?

A

a nonviable material used in a medical device intended to interact with the biological systems
- ‘nonviable’ no longer relevant because biomaterials are used in many applications other than implanted devices including drug delivery

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8
Q

New definition of biomaterial

A

a material designed to take a form which can direct, through interactions with living systems, the course of any therapeutic or diagnostic procedure,
- ‘to take a form’ = processing, considers the current research on biomaterials with engineering properties and structure
- ‘through interactions with living systems’ highlights the importance of the host biomaterial interaction that is dependant on the host response

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9
Q

Definition of biocompatible

A

biologically compatible to host tissue
should not provoke any rejection, inflammation or immune reponses
the ability of a material to interact with the human body without eliciting an adverse local or systemic reaction

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10
Q

What are the basic charactistics of biomaterials

A
  • biocompatible
  • nontoxic
  • nonimmunogenic
  • noncorrosive
  • adequate mechanical strength
  • sterilizable
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11
Q

What are bioinert materials?

A

do not release any toxic consistuents but neither do they elicit a response from the host tissues

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12
Q

What are bioactive materials?

A

elicit a specific biological reponse at the interface of the material, resulting in the formation of a bond between the tissue and the material

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13
Q

What is the first generation of biomaterials?

A
  • bioinert
  • serves as mechanical support, prevent rejection
  • metals (titanium, alloys, stainless steel) and certain synthetic polymers (PEEK) and some ceramics (Alumina)
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14
Q

What is the 2nd generation of biomaterials?

A
  • Bioactive/Bioresorble
  • can stimultae regeneration, form strong biomaterial bone interface
  • synthetic and naturally derived biodegradable polymers (collagen)
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15
Q

What is the 3rd generation of biomaterials?

A
  • Instructive/Multifunctional
  • can moderate cellular behaviour, bioresponse
  • highly porous scaffolds, nanotechnology based strategies
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16
Q

What are the levels of smartmess for biomaterials?

A

1 - Inert
2 - active - release
3 - responsive - sense and respond
4 - autonomous - sense, response, adapt

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17
Q

What are autonomous biomaterials?

A

They can independently adjust their properties and therapeutics in reponse to changes in the surrounding environments and biological processes.
They deliver targeted/precise therapies after receiving a trigger from an appropriate stimulus
interact by sensing, responding and adapting to specific signals
designed to mimic natures complexity by offering the ability to adapt to the microenvironment

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18
Q

Advantages of 1st generation (in case of bone tissue engineering)

A

replacement of damaged bone tissue, mechanical sustain

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19
Q

Disadvantages of 1st generation (in case of bone tissue engineering)

A

no interaction with the surrounding tissues: adverse reactions caused by pure materials

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20
Q

Advantages of 2nd generation (in case of bone tissue engineering)

A

bioactivity or bioresorbaility, binding and interaction with host tissues, porous structures, promotion of bone regeneration

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21
Q

Disadvantages of 2nd generation (in case of bone tissue engineering)

A

no predesigned 3D structure, rarely used in critical size defects repair, lack ni functionalized materials with biological molecules

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22
Q

Advantages of 3rd generation (in case of bone tissue engineering)

A

bioresorbability during new bone formation, complete replacement of bone damage with new formed tissue, enhanced physical stabilisation, improve bone functionality and sealf healing properties

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23
Q

Disadvantages of 3rd generation (in case of bone tissue engineering)

A

lack of antineoplastic drugs

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24
Q

Advantages of 4th generation (in case of bone tissue engineering)

A

smart devices, multifunctionality, combined antitumor and anti-infective effects, release of bioactive molecules, targeted activation of specific molecular pathways and electrophysiology

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25
Disadvantages of 4th generation (in case of bone tissue engineering)
need to further improve fabrication techniques, better control of drug release kinetics, better resemble mechanical and 3D structural features of natural bone.
26
What materials do we tend to use for soft tissue biomaterials?
polymers, sometimes combined with bioceramics depending on environment
27
What materials do we tend to use for soft tissue biomaterials?
metals, ceramics or polymers with high mechanical strength
28
What are metals and metal alloys used for?
medical devices due to mechanical properties. such as joint replacements, spinal devices, stents, dental implants to provide strength and fatigue resistance over a patients life
29
Name some metals and metal alloys used
- stainless steel - cobalt-based alloys - titanium based alloys - Mg = biodegradable orthopedic implants materials need to be apporoved by the FDA
30
Explain the use of titanium alloys and why they are used
- better corrosion resistance - biocompatible - relatively low youngs modulus - inertness - strength to weight ratio - flexibility mirroring bone - protein adsorption aiding osseointegration - low iron release - non-magnetic nature(good for x-rays/MRI)
31
Where in the body are titanium alloys used?
- orthopedic implants - load-bearing due to high strength and resistance to corrosion - dental implants - bone plates/screws - spinal fusion devices
32
What are the three groups of bio ceramics?
1 - biological near inert cermics 2 - bioactive ceramics 3 - bioresorable ceramics
33
What are biological near-inert ceramics?
examples: aluminia and zirconia The formation of nonadherent fibrous capsule is the most common response of tissue to an implant made from these materials. The tissue attemots to reject the implant by essentially creating a barrier around it to prevent biological reactions
34
What are bioactive ceramics?
examples: crystalline hydroxyapatite and calcium phosphate A bond forms across the interface between the implant and the tissue. The interfacial bond prevents motion between the 2 surfaces and mimics the type of interface that forms when tissues under self repair
35
What are bioresorable ceramics?
examples: amorphous hydroxyapatite The implant material is dissolved and absorbed by the surrounding tissues. It is ultimately being completely replaced by the host tissue
36
What are the properties of alumina?
excellent corrosion resistance high wear resistance high mechanical strength however: mediocre fracture toughness example of use: hip implants/dental implants
37
What are the properties of zironia?
high fracture toughness high flexural strength however: strength reduction in time with physiological fluids, unfavourable wear and friction properties exmaple of use: hip joint replacements
38
What are the properties of calcium phosphate and hydroxyapatite?
excellent biocompatibility due to close chemical and crystal resemblance to bone mineral example of use: bone fillers, coatings for implants
39
What are polymers and what do they have control over property wise?
Polymers represent the largest class of biomaterials used for biomedical applications control over: - mechanical - chemical - MAIN - biodegradability - surface properties - processing
40
What are the 2 classes of biodegraable polymers?
- synthetic - made in a lab environment - natural
41
Examples of synthetic polymers
- polyester contains polycaprolactone -low glass transition temperature (good mechanical properties) - polyphosphazene
42
Examples of natural polymers
- polyanhydride - polysaccharide - anti inflammatory properties - poly(glutamic acid)
43
What are scaffolds and their fundemental role?
provide mechanical support, allow prefusion of nutrients and oxygen, transfer biochemical signals that modulate cell behaviour, used to release drugs and growth factors
44
What are we trying to mimic with the use of a scaffold?
the extracellular matrix of the native tissue which ensures that the architecture and functions exhbited by the scaffolds are corresponding similar to the role played by the ECM.
45
What is the extracellular matrix?
a well organized 3D network of molecules with critical structural and functional roles in tissue organisation and remodelling and in the regulation of cellular processes.
46
What is the ECM made up of?
- collagen - proteoglycans - glycosaminoglycans - elastin and elastic fibres - laminas - fibonectin - matricellular proteins
47
Why are micro and nanostructures included in a scaffold?
increase the surface area and roughness of the scaffold. promoting the adhesion of cells (hierarchial structure)
48
What are the 3 different approaches to producing scaffolds?
1 - generate scaffolds from natural or synthetic biomaterials 2 - decellularize the tissue of interest leaving the ECM as the scaffolding materials 3 - stimulate cells to generate their own matrix
49
What are decellularized extracellular matrix scaffolds?
refer to biomaterials formed by human or animal organs/tissues with the removal of immunogenic cellular components mainly consist of ECM such as collagen, elastin, fibornectin, laminin and matericellular proteins
50
What are organ/tissue derived dECM scaffolds?
refer to the scaffolds obtained from specific organs or tissues which possess the natural 3D architecture from the whole organ or tissue. ECM structure and interior architecture is partically maintained mechanical and microenvironment properties are similar to the native ECM
51
What are cell drived dECM scaffolds?
cells are cultured in vitro (outside of the body) they can secrete cell-specific ECM which can be decellularized. The accelular ECM can be recellularized to generate bioengineered grafts for tissue engineering. positives: has right biochemistry negatives: takes longer to obtain right volume of material needed
52
What are the 4 main properties of scaffolds?
1 - structure/morphology eg porosity 2 - mechanical properties 3 - biodegrability 4 - biochemical bahviour, chemical properties
53
What does scaffold stiffness dictate and why?
dictates the adhesion, spreading and fate of cells changing the youngs modulus stiffer surfaces directs stem cells towards osteogenic lineages softer matrix promotes chondrogenic differentiation
54
The role of mechanical properties for a scaffold
effects on cell differentitation, proliferation and death. properties like stiffness and elastic modulus affect tissue growth in vivo. need to replicate the modulus and ductility of a range of native environments.
55
The role of porosity on scaffolds
pores are necessary to allow cells and nutrients to migrate and infiltrate into the bulk of the scaffolds control over cellular infiltration: -transport of nutrients, oxygen and waste products - vascularisation of scaffolds by facilitating angiogenesis - changes in scaffolds mechanical properties
56
The role of biodegradation on scaffolds
limit complications like inflammatory degradation rate should match the rate of tissue regeneration for optimal tissue growth biomaterial degradation results in loss of mechanical stiffness, therefore the newly found tissue should sustain load transfer
57
Definition of biodegradable materials
Break down due to molecular degradation into by-products that can move away from the implanation site but are not necessarily removed from the body
58
Definition of bioresorbable materials
break down due to molecular degradation into by-products that are eliminated through natural pathways with no residual side effects
59
Definition of bioabsorable materials
Do not break down into by-products and they dissolve in body fluids
60
What is hydrophobic behaviour?
water droplet >90 degrees from surface
61
What is hydrophilic behaviour?
water droplet <90 degrees from surface
62
How is cell adhesion affected by the surface of the scaffold?
1 - the cell would sense the environmental cues through cell signalling during contact with surface 2 - with the integrin clustering and binding with ECM, the cells anchored on substrate forming the related focal adhesions 3 - the cell can distinguish whether the underlying substrate is suitable for adhesion and proliferation
63
What are focal adhesions?
large macromolecules that provide physical linkages between the cell and the substrate (also the ECM). through FA's cells can sense the surrounding and transmit cell-generated forces to the outside environment. integrins - provide cell attachment
64
What affects protein absorption?
proteins have hydrophobic and charged domains so electrostatic and hydrophobic interactions could be used in explaining the mechanism of protein absorption Due to hydrophobic interactions, proteins tend to prefer moderate hydrophobic surfaces
65
The role of biochemical properties on scaffolds
biological properties of both the surface and bulk of the scaffold material. affect cell adhesion, cell growth, migration and differentiation as well as tissue morphogenesis and ECM synthesis - charged density of the scaffold surface as well
66
How can biochemical cues be used?
used to activate specific signalling pathways or a set of genes to direct and control cellular responses or can stimulate angiogenesis in vivo.
67
How can we sterilize a scaffold?
The scaffold must be able to withstand sterilization procedures and be properly sterlized to prevent infections without changing its properties like structure/mechanical behaviour - chemical treatment (ethanol) - radiation - plasma - antimicrobial treatment - heat
68
Aspects that affect cell adhesion
- substrate stiffness - chemistry and exposure to bioactive factors - surface roughness - viscosity - topographical activate specific downstream signalling pathways
69
What is the ex-vivo approach for scaffolds?
scaffolds are combined with cells and biomolecules outside of the body to obtain cell-laden tissue constructs for implantation
70
Limits and risks of ex vivo
- Requires a compatible cell source - complex culture conditions - poor homing and engraftment efficacy - expensive - donor site morbidity - immune reaction
71
What is the 'top-down' approach for convential tissue engineering approaches?
cells are expected to attach/proliferate and populate a prefabricated 3D biodegradable scaffold, while simultaneously depositing de novo formed ECM
72
Limitations of 'top down'
not suitable in replicating the natural intricacies and modularity of human tissues/organs eg. no blood vessels in scaffold
73
What is 'in situ' tissue regeneration?
the use of biomaterials that can be loaded with bioactive cues, to guide functional restoration to the site of injury. implanted without cell attachment.
74
Advantages of in situ
- leverages body's innate regeneration potential - improved shelf life and lower cost - fewer regulatory hurdles - scalable and consistent quality
75
limitations of 'in situ'
- ineffective for tissue with limited endogenous progenitor stem cells - difficult to monitor the regeneration process
76
What is 'bottom up' / Modular tissue engineering?
based on the self assembly of multicellular modules and/or cell ECM mimetic biomaterial constructs more suitable for replicating the natural intricacies and modularity of human tissues/organs require the use of living building blocks - cell spheroids, cell sheets or cell laden micro gels
77
What are cell spheroids?
3D aggregation of cells. cells suspended in culture medium are injected into specialized microenvironments, wherein they establish cell-cell interactions and form compacted structures.
78
Potential Issues of spheroids
The larger the spheroid diameter, the greater the likelihood of occuring hypoxia and nutrients depletion in the innermost regions effectiveness of mass and therefore of cell viability depends on the size of the spheroid
79
How does shear stress play a role in spheroid formation?
larger spheroids are exposed to higher shear stress that can cause changes in the cell metabolism, cell lysis and may also affect cellular proliferation.
80
What is in vivo?
studies are performed on whole, living organisms (animals, plants, humans)
81
What is ex vivo?
studies are performed on tissues and organs outside living organisms
82
What is in vitro?
studies are performed will cells or microorganisms outside of their physiological environment
83
What is in silico?
studies are performed on computer or via computer stimulation
84
What are cells?
they are the basic structural, functional and biological unit of all known living organisms about 20 micrometers
85
What is the nucleus?
contains genetic material
86
What is the cytoplasm?
contains organelles devoted to specific biochemical functions
87
What is plasma membrane?
controls the exchange of materials in and out
88
What are the limitations of fluoresence microscopy?
- cannot reuse samples - limited images (need multiple regions)
89
What is the extracellular matrix?
network of macromolecules into which cells are embedded. Provides physical and regulates many cellular processes such as growth , migration and differentiation
90
What is the interstatial ECM?
surrounds the cell
91
What is the pericellular ECM?
in close contact with cells
92
What is the first point of contact between cells and the ECM?
intergrins they connect collagen fibres. connect cell and biomaterial as well
93
What is a tissue?
a group of cells that usually function together to carry out specialized activities
94
What are the 4 main typs of tissue?
1 - Epithelial 2 - connective 3 - muscular 4 - nervous
95
What is epithelial tissue?
covers body surfaces and line hollow organs, body canies, ducts, also forms glands allows the body to interact with both its internal and external environments consists of cells in a continuous sheet in single or multiple layers
96
Examples of epithelial tissue regeneration
1 - blood vessels - tissue engineered vascular grafts - establishment of the endothelial lining 2 - Skin - skin substitutes and dressings for wound healing - re-epithelisation without scarring
97
What is connective tissue?
protect and support the body and its organs bind organs together store energy reserves as fat help provide the body with immunity to disease causing organisms
98
What are the types of connective tissue?
1 - loose connective (adipose tissue- fat) - reduces heat loss and an energy reserve 2 - Dense connective (dense regular - tendons) - provides strong attachment between various structures, withstands tension along long axis of fibres 3 - Bone tissue (Bone) - support, storage, protection
99
Examples of connective tissue regeneration
1 - tendon and ligaments - decellularized and acellular grafts - bioengineered substitutes 2 - Bone implants - bone grafts and composite scaffolds - osteoconductive and osteogenic implants
100
What is muscular tissue?
composed of cells specialized for contraction and generation of force. muscular tissues produce body movements, maintain posture and generate heat. muscular tissues consist of elongated cells called muscular fibres or myocytes
101
Examples of muscular tissue regeneration
1 - cardiac tissue - atrifical and decellularised scaffolds - functional vascularised tissues 2 - artifical muscles - engineered scaffolds - biomimetic and stimuli responsive scaffolds
102
What is nervous tissue?
detects changes in variety of conditions inside and outside the body responds by generating electrical signals called nerve action potentials that activate muscular contractions and glandular secretions.
103
Examples of nervous tissue regeneration
1 - brain and spinal cord implants - cell implants - combination of delivery devices, axon bridges and scaffolds

Biomaterials (4 decks)

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