Tissue Engineering - Lecture 2 Higbee

  1. What are some modern biomaterial sciene successes in Cardiovascular disease, Orthopedic diseases and artificial skin?
    • Cardiovascular disease
    • Valve diseases
    • Dissecting aneurysm
    • Abnormal electrical conduction
    • Vascular stenosis

    • Orthopedic diseases
    • Hip, knee, ankle fractures

    • Artificial skin
    • Burn patients
    • chronic diabetic ulcers/wounds
  2. What are considerations that have to been taken into account for tissue engineering when designing an implant?
    • Structure of natural tissues
    • Interactions with foreign materials
    • Macromolecular structures change shape and size
    • Order packing structures
    • Stresses, strains, forces
    • Inflammation
  3. What are the four categories for artificial biomaterial types?
    • Metals
    • Ceramics
    • Polymers
    • Composites
  4. What are artificial biomaterials used for?
    • Repair
    • Assistance
    • Replacement
  5. What are some of uses of metals?
    Extensive use in orthopedics where load-bearing structures are required.

    • Hips
    • Knees
    • Joints
    • Plates
    • Valves
    • Organs
    • Supports
    • Screws
    • Nails
    • Wires
  6. What is one of main issues with metal implants?
    • Corrosion that leads to the following:
    • Weakening the implant
    • Risks causing damage to tissues
    • Occurs in two ways: Phyiscal erosion by wear, electrochemical corrosion

    • May lead to:
    • Toxicity
    • Mutagenesis
    • Inflammation
    • Carcinogenesis
  7. What are some types of metals used in inplants?
    • Stainless Steel
    • Cobalt-based Alloys
    • Titanium and associated allows
    • NiTi Shape Memory Alloy (exhibits pseudoelasticity)
  8. What are some of the medical applications for metalic implants?
    • Bone Screws - SS, Ti
    • Bone Plates - SS, Co, Ti
    • Intramedullary Pins - SS
    • Hip Joints - SS, Co, Ti
    • Knee Joints - SS, Co
    • Spine Disc Cages - SS, Ti
    • Rods (Scoliosis) - NiTi
    • Dentistry - Au, Ag, Ni
    • Blade Implants - SS, Ti
    • Subperiosteal Implants - Co
    • Arch wires - SS, NiTi
    • Heart Valves - Co, NiTi
    • Vascular Stents - SS, Co, NiTi
    • Cardiac Pacemakers - Ti
  9. What is a ceramic's use in tissue engineering?
    Ceramics include a variety of applications in areas where it is not load-bearing or will not experience impacts.

    • Bioglass
    • Hydroxyapatite
  10. What are types of implant-tissue responses for the following:

    If the material is toxic...
    ... the surrounding tissue dies.
  11. What are types of implant-tissue responses for the following:

    If the material is nontoxic and biologically inactive (nearly inert)...
    ...a fibrous tissue of variable thickness forms.
  12. What are types of implant-tissue responses for the following:

    If the material is nontoxic and biologically active (bioactive)
    ... an interfacial bond forms.
  13. What are types of implant-tissue responses for the following:

    If the material is nontoxic and dissolves...
    ...the surrounding tissue replaces it.
  14. What is bioactivity?
    The ability of an implant's materials to bond to tissues.
  15. Where does TEM examine?
    Cross-section of a material
  16. What does SEM examine?
    Surface properties of a material.
  17. What does IR examine?
    Structural properties of a material
  18. What does XRD examine?
    Structural properties of a material
  19. What does Zeta examine?
    The charge analysis of a material
  20. What are factors influencing bioreactivity?
    • Composition - mimic original tissue
    • Morphology - mimic original tissue
    • Porosity - mimic original tissue
    • Resorption capacity - how fast should this occur if it does?
  21. What are some of the medical uses for ceramics?
    • Scaffold materials including:
    • Bone grafts
    • Drug Delivery Devices
    • Cell encapsulation

    Sockets/sliding surfaces
  22. What are some of the advantages of polymers in tissue engineering?
    • Most diverse group
    • Various mechanical, physical and reactive properties
    • Carbon, hydrogen, oxygen, nitrogen, sulfur and phosphorus
    • Natural and synthetic group of polymers

    Some of the FDA approved materials include collagen, PGA, PLA, PCL, PLGA
  23. What is a composite?
    A composite is the mixture of at least two different categories such as a polymer with a ceramic

    • Allows for hard tissue applications
    • Good integration and ossification
    • Good resorption characteristics
    • Ceramics with PCL or PLGA controls degradation
  24. What are different types of scaffolds?
    • Temporary structures - short term need for drug delivery
    • Smart scaffolds - stimulus response
    • Chemistry patterning - cell influx, migration, adhesion, repair
  25. What is force?
    The amount of energy applied to an object.

    • The change of linear momentum of an object of mass, m.
    • F = ma
  26. What is stress?
    The force over a unit area. MPa = N/m^2
  27. What is strain?
    The relative ratio between the change in length of the original length
  28. What is the ultimate tensile strength?
    "Stress at failure" - from notes.

    However, it is truly the point at which the failure begins and necking occurs.
  29. What is the ultimate strain?
    "The strain at failure" - from notes.

    However, it is truly the point at which the failure begins and necking occurs.
  30. What is the modulus of elasticity?
    "Extent of deformation" - from notes.

    Mathematical expression describing the object's tendency to be deformed elastically.
  31. What is the cell type "primary cell type" referring to?
    A cell that is harvested directly from a living organism.

    Primary cells are cultured cells freshly derived from a living organism. Once in culture they undergo a limited, predetermined number of cell divisions. For this reason, primary cells can be passaged a finite number of times and are considered to be very delicate and sensitive.

    Cell lines, in contrast to primary cells, typically undergo unlimited cell division and have an infinite lifespan. These are in contrast to immortal cell types.
  32. What is the cell type "immortal cell type" referring to?
    An immortalised cell line is population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division.

    This is in contrast to primary cell types which have a limited number of cell divisions.
  33. What are some of the cell - ECM interactions?
    • Adhesion - integrins
    • Migration - cytoskeletal involvement, patterning
    • Dynamic forces - gravity, shear stresses, compression, tension etc

    • Cytokine/Growth factor delivery for modulation of cellular activities:
    • Proliferation
    • Differentiation
    • Migration
    • Adhesion
    • Gene expression
  34. What are the three types of growth factor delivery? Where are the intended targets?
    Endocrine - Target cells located away from the site of synthesis, transported via vasculature

    Paracrine - Target cells are nearby and factors diffuse readily

    Autocrine - Target cells are the synthesis cells
  35. What are endocrine cells?
    Cells that create growth factors that are intended for target cells that are located away from the site of synthesis, transported via vasculature.
  36. What are paracrine cells?
    Cells that create growth factors that are intended for target cells nearby where the factors that may diffue readily
  37. What are autocrine cells?
    Cells the create growth factors that the target cells are the same as the cells synthesizing the factors.
  38. What is vascularization?
    Tissue engineered structures need nutrition and waste removal from the system. Vascularization (or neovascularization) includes the creation of vessels to achieve those functions.

    The minimum distance for diffusion is 200 microns.
  39. What is hypoxia?
    Hypoxia is a condition in which the body as a whole or a general region of the body is deprived of adequate oxygensupply.

    This is the driving force for vascularization leads to increased angiogenesis (production of blood vessels).

    Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole (generalized hypoxia) or a region of the body (tissue hypoxia) is deprived of adequate oxygensupply. Variations in arterial oxygen concentrations can be part of thenormal physiology, for example, during strenuous physical exercise. A mismatch between oxygen supply and its demand at the cellular level may result in a hypoxic condition. Hypoxia in which there is complete deprivation of oxygen supply is referred to as anoxia.
  40. What is angiogenesis? What are some growth factors? What does the process include?
    Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. This includes splitting off of existing vessels.

    • Angiogenic factors include:
    • VEGF
    • FGF
    • PDGF
    • TGF-Beta
    • Angiopoietin

    The process includes vasodilation (widening of vessels) and the proliferation of endothelial cells, pericytes, smooth muscle cells prior to migration.
  41. List three angiogenic factors.
    • VEGF - Angiogenesis
    • FGF
    • PDGF - Mitogen for fibroblasts, granulation tissue, chemotactic
    • TGF-Beta - Stimulates matrix deposition
    • Angiopoietin
  42. How is inflammation brought about by chemical mediators? Is it local?
    It is a local response by chemical mediators.

    • The triple response of Lewis is a superficial scratch.
    • Red scratch mark
    • Red flare around the scratch mark
    • Red swollen area ("wheal") around the flare

    Cutting the autonomic nerve supple prevent the "axon reflex" which led to the discovery of hisamine (chemical in inflammatory response)
  43. What is a leukocyte?
    A white blood cell in the immune response.

    There are some types of white blood cells that have a role in the early stages of inflammation .
  44. What is acute inflammation?
    Early phase

    Response to recent or ongoing injury with the principal feature of dilation and leaking of vessels, and involvement of circulating leukocytes
  45. What is chronic inflammation?
    Late phate

    Response to prolong problems and orchestrated by T-help lymphocytes. It may feature recruitment and activation of T- and B-lymphocytes, macrophages, eosinophils, and or fibroblasts. This process is very complex, as well as acute inflammation.
  46. What are granulomas?
    An organized group of macrophages.

    Granulomas are seen in certain chronic inflammation situations. They are clustors of macrophages that have stuck tightly together, typically to wall something off. Such are called epithelioid cells.

    You will recognize granulomas in tissue sections by their characteristic appearance, or the presence of giant cells.
  47. What is fibrin?
    A fibrous, non-globular protein involved in the clotting of blood.

    Released as fibrinogen from damaged vessels, and activated by the clotting cascades when blood meets tissue juices.

    Fibrin forms the meshwork that controls bleeding and then becomes the framework for fibroblasts and angioblasts that form the scar.

    Until the new scar is complete, the whole meshwork of the immature scar is called granulation tissue.

    When the scar has matured, it contracts.
  48. What is the advantage of vasodilation?
    Leads to greater blood flow to the area of inflammation, resulting redness and heat.
  49. What is vascular permeability's role in the inflammation response?
    Endothelial cells become "leaky" from either direct endothelial cell injury or via chemical mediators. This allows for leukocytes to pass through if necessary.
  50. What is exudation?
    The process in which fluid, proteins, red blood cells, and white blood cells escape from the intravascular space as a result of increased osmotic pressure extravascularly and increased hydrostatic pressure intravascularly.
  51. What is vascular stasis?
    Slowing of the blood in the bloodstream with vasodilation and fluid exudation to allow chemical mediators and inflammatory cells to collect and response to the stimulus.
  52. War is the metaphor for inflammation. Both are necessary evils that are more-or-less sterotyped responses to outside threads.

    There are specialized troops (____________) that include suicide-commandos (____________), long-term siege armies (___________) and many others.

    There are supply routes (______), communications and intelligence (mediators) and a huge array of lethal weapons (inflammatory enzymes).
    • White blood cells
    • Neutrophils - high percentage of these are found in pus
    • Granulomas - organized groups of macrophages
    • blood vessels - modes of transportation
  53. (T/F) Inflammation and infection are the same.

    What are the differences?

    • Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the
    • injurious stimuli and to initiate the healing process. Inflammation is not a synonym for infection, even in cases where inflammation is caused by infection. Although infection is caused by a microorganism, inflammation is one of the responses of the organism to the pathogen.

    An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease. Colloquially, infections are usually considered to be caused by microscopic organisms or microparasites like viruses, prions, bacteria, and viroids, though larger organisms like macroparasites and fungi can also infect.
  54. What are the differences between acute and chronic inflammation?
    Acute inflammation - intial response of the body to farmful stimuli and is achieved by the increased movement of plasma and leukocytes (especially granulocytes) from the blood to the tissue.

    Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells present at the site of inflammation and is characterized by simultaneous destruction and healing of the tissue from the inflammatory process.
  55. What are the most predominat cells in pus from an inflammation reaction?
    Neutrophils are phagocytes, capable of ingesting microorganisms or particles attracted by chemotaxis.

    Neutrophils are recruited to the site of injury within minutes following trauma and are the hallmark of acute inflammation. They are the predominant cell in pus.
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Tissue Engineering - Lecture 2 Higbee
Tissue Engineering - Lecture 2 Higbee