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BIOMATERIALS ENT 311

BIOMATERIALS ENT 311. LECTURE 13 TISSUE ENGINEERING. Prepared by: Nur Farahiyah Binti Mohammad Date: 9 TH October 2008 Email : farahiyah@unimap.edu.my. Teaching Plan. A Tissue Engineering Definition.

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BIOMATERIALS ENT 311

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  1. BIOMATERIALSENT 311 LECTURE 13 TISSUE ENGINEERING Prepared by: Nur Farahiyah Binti Mohammad Date: 9TH October 2008 Email : farahiyah@unimap.edu.my

  2. Teaching Plan

  3. A Tissue Engineering Definition Tissue engineering is the application of principles and methods of engineering, basic sciences and life sciences towards fundamental understanding of structure-function relationships of soft and hard tissues resulting in the development of autogenic substitutes to restore, maintain, or improve tissue and organ functions.

  4. Scope and potential of TE industry • In 2001, TE industry has grown markedly with scientific research and development expenditures exceeding $600M in 2001. • To date, a handful of products have progressed through clinical implementation and regulatory approval.

  5. Scope and potential of TE industry • Tissue-engineered medical products (TEMPs) typically take one of several forms: • Hybrid products of biological components (e.g., cells) with or without nonbiological components (e.g. polymer construct) • Products that induce a specific tissue response (e.g., regeneration) • Biological cells that have been significantly manipulated in vitro (e.g., genetically modified)

  6. Cells as Therapeutic Agents • Blood transfusion • RBC to anaemic patient • Platelet transfused into patients who have blood clotting defect • Bone marrow transplantation • Newer cell based therapies: • Chondrocytes for cartilage repair • Liver and kidney cells grown in extrcorporeal support devices • Encapsulated ß-islet cells for diabetes • Sheets of dermal fibroblast for ulcers and burns • Genetically modified myocytes for treatment of muscular dystrophy

  7. Cells as Therapeutic Agents • Cells can be sourced from a variety donors: • Autologous (donor back to donor) • Allogenic (donor to recipient) • Syngeneic (genetically identical donor: twin) • Xenogenic (cross-species: animal cells)

  8. Objective of TE • Repair, regeneration or replacement of damaged or diseased tissues to their original state and function • To generate natural tissues, in sufficient quantity and of the desired shape that are structurally and functionally equal (if not better) to the tissue it has been “engineered” to replace prior to injury

  9. TE PROCEDURE Cell from patient

  10. Repair and regeneration of damaged or diseased tissues • Requirements: • Recapitulate tissue morphogenesis • Generate adequate cell population/tissue size • Differentiate to/maintain specific phenotype • Phenotype = A particular (mature) functional cellular state • Appropriate 3-D organization (ECM/Scaffolds) • Mechanical/physical integrity • Prevention of immuno-rejection • Vascularisation • DEPENDENT ON QUALITIES OF CELLS (CELL SOURCE) & SCAFFOLD STRUCTURE/COMPOSITION

  11. CELL SOURCES • 1. Mature [non-stem] cells from patient • 2. Stem cells from patient • “Adult” stem cells from patient • Embryonic stem (ES) cells/Embryonic germ (EG) cells

  12. Mature [non-stem] cells • e.g. bone/skin cells • Advantages • Often easily obtained from patient • No need for immuno-suppression • Disadvantages • Poor growth, difficult to get enough cells • Tendency to turn into different, unwanted cell types

  13. STEM CELLS • What are stem cells? • Stem cells are cells that; • can self-renew • Can differentiate to produce at least one type of highly differentiated or “specialised” descendant

  14. STEM CELL POTENCY • Totipotent - can produce all cell types • Pluripotent – can produce many cell types • Multipotent - “specialised” (adult) stem cells capable of forming a restricted number of cell types • Unipotent - can produce only one cell type,

  15. Adult stem cells

  16. ADULT STEM CELLS • Mesenchymals stem cells • multipotent or pluripotent cells isolated from bone marrow stroma • Can differentiate into: • Osteocytes (bone cells) • Chondrocytes (cartilage cells ) • Myoblasts (muscle cells) • Fibroblasts (tendon cells) • Adipocytes (fat cells)

  17. Mesenchymals stem cells

  18. Mesenchymals stem cells

  19. Neuronal stem cells • The cells isolated from the ventricular zone in the human fetal brain can be clonally cultured and then induced to differentiate into the major cell types in neural tissue.

  20. Adult Stem cells • Advantages: • Potential to generate various cell types not just mesodermal lineage • Harvested from donor and implanted back into donor following expansion & differentiation in vitro • potentially “rapid” (~ 1month) • problems of immunocompatibility negated

  21. Adult Stem Cells • Disadvantages • Stem cells may be very sparse (1:100K) • Potential to propagate or transmit harmful mutations/disease? • Numbers & potency diminishes with age

  22. Embryonic stem (ES) cells • These stem cells present in the earliest stages of embryo development. • These cells capable of generating all of the cell types in the fetus and subsequently in the adult.

  23. Embryonic stem (ES) cells

  24. ES cells derived from inner mass cells of pre-implanted blastocyst

  25. Embryonic stem (ES) cells • Embryonic stem cells differentiate into embryonic germ cells and can differentiate into all derivatives of the three primary germ layers: • Ectoderm [outer layer of embryo cells; gives rise to nervous system, eyes, ears, epidermal tissue, etc] • Endoderm [inner layer of embryo cells; gives rise to epithelial linings of the body, covering cavities, passages and most organs] • Mesoderm [middle layer of embryo cells; gives rise to bone, connective tissue, muscle, blood, etc].

  26. Adult or ES cells for tissue repair • Advantages • Rapid growth • Plastic, can form various cell types

  27. ES cells - isolation • ES cells derived from: • mouse (Evans et al. 1981; Martin 1981) • primate (Thomson et al. 1998) • humans (Thomson et al. 1998) • Inner cell mass (ES cells) dissected from blastocyst by “immunosurgery”

  28. Embryonic stem (ES) cells • Advantages: • Potential to generate any cell type in the body • Amenable to genetic manipulation • Introduce beneficial/therapeutic genes • Modulate/control immunotolerance(negates need for immunosuppression)

  29. Embryonic stem (ES) cells • Disadvantages: • Ethical concerns • cloning (therapeutic NOT reproductive) • donors • Stability (mutations /tumours) & transmission of heritable diseases unknown • karoytyping/screening

  30. Morphogenesis • Formation of the structure of an organism or part; differentiation and growth of tissues and organs during development.

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