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Tissue Engineering Hottest job for 21 st Century

Learn about the field of tissue engineering and regenerative medicine, including biomaterials, forecasts of the aging population, and FDA-approved products. Explore the roadblocks and principles of tissue engineering, as well as the ultimate vision for regenerative medicine.

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Tissue Engineering Hottest job for 21 st Century

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  1. Five hottest jobs for the next millennium will be bioengineering/biomedical related. Tissue Engineering Hottest job for 21st Century

  2. If Humans Were Built to Last Larger ears Bones that lose minerals after age 30 Shorter limbs and stature Forward-tilting upper torso Fallible spinal disks Muscles that lose mass and tone Curved neck with enlarged vertebrae Thicker disks Extra muscles and fat Leg veins prone to varicosity Leg veins with more check valves Joints that wear Thicker bones Knee able to bend backward Larger hamstrings and tendons Alternative Design Current Design Adapted from Olshansky, Carnes, Butler, Sci Am 2001 Mar PhilCampbell, Carnegie Mellon

  3. Replacing diseased or injured tissues with tissue constructs designed and fabricated for the specific needs of each individual patient. A material intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or function in the body. What is Tissue Engineering/ Regenerative Medicine? What are Biomaterials?

  4. Forecasts of the American Population Aged 85 Years and Over Oxford Textbook of Geriatric Medicine 2000

  5. Medical costs (1996 US dollars per capita) USA $3898 United Kingdom $1317 Turkey $232 US Medicare expenditures for last year of life is double for aged 65 to 69 years compared to 90+ years. (excluding nursing home costs) 1987-1995 Hip replacements among women rose from 143/100,000 to 1444/100,000 Oxford Textbook of Geriatric Medicine 2000

  6. FDA approved products Infuse Bone Graft Bone morphogenetic protein-7, Osteogenic peptide-1 Regranex Carticel Transcyte Intergra Dermal Regeneration Template Dermagraft Apligraft Ortec

  7. Apligraft

  8. Adult Stem Cells Example Bone marrow-derived mesenchymal stem cells

  9. Adult Stem Cells Example Bone marrow-derived mesenchymal stem cells

  10. Tissue Engineering Roadblocks  Inadequate understanding of the basic biology of regenerative processes  Lack of adequate biomimetic materials to act as scaffolds for either induction of regeneration in vivo, or to build bioartificial tissues in vitro  Inadequate cell sources for transplantation or building bioartificial tissues  Problem of immunosuppressive regimens introduced by allogeneic and xenogeneic cells.  Bioethical issues associated with the use of fetal and embryonic stem cells as sources

  11. Principles of Tissue Engineering Cells ECM Defect Regeneration Blood Supply Hormones PhilCampbell, Carnegie Mellon

  12. Endocrinology Applied to Tissue Engineering: A Quick History -Hormonal-based tissue engineering has been around for thousands of years Castration as a means to control behavior and tissue quality in domesticated animals -Systemically targeted (purified) protein hormone therapies – mid 1900s. -Systemically targeted (recombinant) protein hormone therapies (insulin) – 1980s -Locally targeted (recombinant) protein hormone therapies (PDGF-BB, BMP-2, BMP-7) – late 1990s to present PhilCampbell, Carnegie Mellon

  13. An Ultimate Vision for Regenerative Medicine: Complete Tissue Regeneration Spinal Cord Upper and Lower Jaw Retina and Lens Tail Heart Limb The Newt Adapted from Brockes From Dr. Susan Bryant, Univ. of Calif., Irvine Phil Campbell, Carnegie Mellon

  14. What controls biological pattern formation associated with morphogenesis- • Cells to Tissues to Organism? • How can patterns emerge from an initial structureless system? • How do developing parts of an organism become different? • How can different genetic information be activated at different spatial positions? • This requires cell-to-cell communication and feedback. • Cell-cell communication via secreted molecules: hormones • “Morphogen” gradients provide directional cues for cell recruitment and the interaction of those gradients provide the cues for organization. PhilCampbell, Carnegie Mellon

  15. 3D Inkjet Printing Tr: Thrombin Fg: Fibrinogen GF: Growth factor Co-jetting and local mixing of bio-inks Lee Weiss, Carnegie Mellon

  16. Fibrin/Growth Factor Printer Lee Weiss, Carnegie Mellon

  17. Gradient of VEGF or FGF-2 Direction of cell migration (up from the dura) Example of a Biologically-Inspired, Engineered Design With Solid-Phase Spatial Patterning Critical size defect Calvarium Fibrin scaffold bone bone brain dura (Coronal view) Why fibrin: • Provisional extracellular matrix in wound healing • Binds numerous growth factors of interest, i.e., the-solid-phase • Supports cell attachment and migration • Degrades in register with new tissue formation • FDA approved Lee Weiss, Carnegie Mellon

  18. In Situ Printing Lee Weiss, Carnegie Mellon

  19. Conclusions • Our approach is to develop toolsets to understand the biology…. control the biology…. translate that control into cost effective, clinically relevant therapies. • As important as developing the bioprinter is developing the bioimaging and biological response toolsets. • The most critical roadblock to overcome remains our inadequate understanding of the basic biology…what do we print? PhilCampbell, Carnegie Mellon

  20. No One Discipline Can Tackle the Problem Alone Lee Weiss, Carnegie Mellon

  21. Alternatives to Traditional Grafts/Implants • Harvested tissues from cloned transgenic animals • Human cloning • Gene therapy • Fetal stem cells …… but all have significant technical, ethical, political, and religious issues • Our approach is to understand how the body naturally heals itself and then provide the minimal set of cues needed to restore the body’s healing capacity. Lee Weiss, Carnegie Mellon

  22. Guided Tissue Repair If needed, harvest cells from patient. Growth factors Cells Biomimetic extracellular matrix Implant Culture Lee Weiss, Carnegie Mellon

  23. Guided Tissue Repair If needed, harvest cells from patient. Growth factors Cells Biomimetic extracellular matrix Implant Culture Lee Weiss, Carnegie Mellon

  24. Guided Tissue Repair If needed, harvest cells from patient. Growth factors Cells Biomimetic extracellular matrix Implant Culture Lee Weiss, Carnegie Mellon

  25. Bone regeneration Design Parameter r1 r2 There are no ‘one-design fits all’ silver bullets… • In addition to custom geometry, key factors are: • Development (adolescent, adult, geriatric) • Wound site • Alcohol • Smoker • Diabetic Libraries of surrogate models. Lee Weiss, Carnegie Mellon

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