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Lecture 7

Lecture 7.docx

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Caroline Starrs

Science 1P51 Organ growth Anthony Atala- New organs (documentary) -Age affects organ work Challenges 2-> Cells (used to engineer organs with printer after growth and reproduction outside body) 3 -> Blood supply chemicals 4 -> Biomaterials (bridge gap to help regenerate tissue) Luke M. Received an engineered bladder - 16 surgery’s - Kidney failure at 10 - Bladder replacement saved his life - One of the first 10 to receive this surgery Hydrogel-> network of polymers - Scaffolding - Keep things together - Insoluble - Delivery mechanism Collagen -> most cosmetic collagen from cows (99.9%) O’Brien – stops blood from bleeding out - Invisible MHDS- multi-head disposition system - Allows hybrid scaffolds to be made - Technique Alginate- used as thickener in dairy products - Part of list of raw materials Gelatin- also used in producing skin and other tissues Electrospinning- like spinning silk - Uses electric field to create very fine fibres PCL- Polycaprolactone - Resistant to water and oil - Polymer 1 - Used in making scaffolds - Breaks down easily (easily excreted) - Like polyester Chondrocytes- cartilage cells GAGs - glycosaminoglycans - Carbohydrates - Breaks down into more energy units Young modulus- measure stiffness of material Cartilage is hard bearing without tensile strength it is useless Research goals -> trying to make it more effective in vivo Methods – printer construction - Obtain materials (from animals) - 4 categories to look at… o Mechanical properties o Cell survival o Formation of extra cellular matrix Tests of viability – test life of cells - Test cell to see if working together - Test to see if blood bearing - Young’s modulus - UTS Still worse off than human cartilage Tissue engineering -the application of engineering and genetics toward the development of biological substitutes to restore, maintain or improve functions of human tissue Physiologists, clinicians, bioengineers, MEMs engineers, CAD/CAMers, Polymer chemists, material, scientists, biologists, imaging physicist -investing + maintaining biofunctionality -Stem Cells –have a unique ability to renew themselves and give rise to the more specialized cell types. They remain undifferentiated until protein initiates change. Examples…  Bone Marrow Transplants - First model where stem cells were used - Used to treat leukemia - Haematopoietic stem cell extracted -> stem cells multiplied in cell culture transplanted into patient - Transfusions 2 Cellular processes (*required) - Cell replication - Cell Differentiation - Cell mortality - Cell apoptosis - Cell adhesion (skin) ECM – Extra Cellular matrix - Mechanical and Biological support environment - Bioreactors - Possible procedure o + stimulatory factors o Cytokines o Cell interactions/density o Oxygen concentrations etc. - Cultured cells -> scaffolds -> implantation What is engineered? - Skin (most successful) - Pancreas cells - Bone - Cartilage (relatively successful) - Veins - Bladder (successful transplants) - Heart tissue (permanent cells)- always in 60 Cells - Human tissue 1- 3 X 10 cells/ml 9 - Typical organ 100- 500 ml Skin - Connective tissue - Dermis - Epidermis - Most are bilayered constructs Cloning New Skin Collagen- cells from donor Clone from stem cells Autologous - one from own body (cells)- preferred Sources of stem cells - Embryonic (slightly problematic) - Gut lining - Fat (liposuction) - Skin - Bone marrow Skin 3 - Source of stem cells o Source from circumcised male babies (2 foreskin could make 250, 000 sq yards of skin) (placed in growth media) - Extract the stem cells - Culture for 3 weeks Bone history M Urist 1965 BMPs Bone morphogenetic proteins Clinic trials- not extremely successful but still successful -similar to humans (morphogenetic proteins) J Folkman 1972 Various scaffolds Porous Ability to mold - Need to add BMPs, growth factors, nutrients, osteoblasts “cook” in bio-reactor Cell -> skin Culture for 3 weeks Day 0 – dermal cells spread over matrix of collagen. This will form the lower layer of skin Day 6- epidermal cells spread over the outer layer of skin Day 10-20 structure is exposed to give triggering development of the strength Integra - Most well known design of skin engineering - Consists of 2 layers - Bottom layer of collagen filters that create the basis of a scaffold for the dermal cells - Top players of protective film Bone -need to add BMPs, growth factors, nutrients, osteoblasts (cells that change to bone cells) “cook” in bioreactors - Earliest successful example of creating bone - Dr. C. Vacancies coral thumb scaffold prior to transplantation - Appeared to integrate with existing cells Cartilage Tissues from patient cells - Culture - Replant - Repair small tears - Chondrocytes (cartilage cells) - Adapted well to peoples own tissues - Build collagen scaffold - Seed with cartilage cells - Add growth factors and nutrients - Australian artist- Stelarc has an engineered ear implanted in his arm 2007 4 Sean McCormick - born with Poland & syndrome, biodegradable scaffold (Vacanti brothers) - Molded to shape - “Cooked” - Reimplanted (at age 16) - Integrated remarkably well, implant growth eventually matched normal cell growth Cornea University of Ottawa- May Griffith - Corneal blindness, clinical trials in pigs 100% successful - Human trials 2010 - 10 patients- 6 successful (no scarring or clouding) - Long term monitoring to check for change Heart tissue Codocytes Repair heart tissue - Animal model (mice/rats) - Induced heart attack - Scar tissue - Injected stem cells - Little to no success o Missing proteins? o Missing nutrients? Human stem cell -> heart transfer -Dimitri Bonnville – nail shot to the heart Bone marrow stem cells- cells harvested- injected into his heart cell harvested - Survival but on constant medication - Parents believed themselves coerced o Sued everyone involved Bladder Grew from fetal cell Successfully in clinical trials in lambs Growing New Organs -New-organs Growth factors Owners/donor cells -scaffolds of biodegradable polymers (plastic) -structure transplanted to woun
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