Tissue engineering and Regeneration
- 1. Tissue Engineering and Regeneration- Past, Present and Future Moderator Presenter Prof. V. K. Shukla Katyayani K. Choubey Prof Alexander Seifalian Dr Michelle Griffin
- 2. Introduction • Tissue engineering (TE)- “an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ” (Langer &Vacanti, 1993) • Regenerative medicine- “the process of replacing or regenerating human cells, tissues or organs to restore or establish normal function” (Mason & Dunnill, 2008)
- 3. Tissue Engineering Vs Regenerative Medicine Manufacturing body parts ex vivo, by seeding cells on or into a supporting scaffold Replace / regenerate human cells, tissues, or organs - restore or establish normal function Three pillars- scaffolds, cells, growth factors Cell-based therapies, immunomodulation, gene therapy, nanomedicine, and TE itself Tissue Engineering and Regenerative Medicine (TERM) Similar Objectives
- 4. Tissue Engineering and Regenerative Medicine (TERM) • Multidisciplinary • Collaboration required TERM Biochemistry Genetics Molecular Biology Bioengineering Biomaterial sciences Surgery Organ Transplant ation Mathematics Immunology Physiology Physics Veterinary Medicine Cell Biology Chemistry Internal Medicine
- 5. Why the need? • Supply of donor organs cannot keep with demand- better organs • Cure of the disease • No rejection • Repair of organs, tissues, bones
- 6. Role • Repair or replacement of injured or diseased - cartilage, skin, pancreatic islets, bladder, intestine, heart tissue, arteries, larynx and bronchus • To test therapeutic drugs for efficacy and toxicity.
- 7. Past
- 8. History Early Days • 1930s: Carrel and Lindbergh develop the perfusion pump Tissue Engineering Days • 1981: First tissue-engineered product, a living, autologous human skin epithelium, implanted in burn patients • 1997: The Harvard mouse Regenerative Medicine Days • 1998: Human embryonic stem cells • 2000s: Bladder, vessels , urethra , heart, trachea 1st mammal cloned from adult cell Auriculosauras
- 9. Basic Steps
- 12. Cells Somatic Cells Stem cells Mature differentiated cell Undifferentiated cells • Embryonic stem cells • Fetal stem cells • Adult or somatic stem cells • iPSCs Autologus / Allogenic / Xenogenic/Syngenic Totipotent Pluripotent Multipotent Unipotent Primary/ Secondary
- 13. Adult or somatic stem cells • Stem cells in different tissues • Multipotent • Commonly used- > Haematopoeitic stem cells > Neural stem cells > Endothelial progenitor stem cells > Mesenchymal/ stromal stem cells TERM Haematological malignancies
- 14. Mesenchymal stem and stromal cells • Source- Marrow, adipose tissue, umbilical cord • Potent trophic & anti - inflammatory properties Surface markers CD105 CD73 CD90 CD34 CD45
- 15. Embryonic stem cells • Inner cell mass of early human blastocyst (day 4-5 of IVF) • Totipotent Ethical issues Allogenic Rejection Autologus Nuclear transfer to oocyte stem cells
- 16. Fetal stem cells • Source- Blood , bone marrow, and the tissues of aborted fetus • Pluripotent • Ethical issues • Used in- PD, Diabetes, spinal cord injury
- 17. Induced pluripotent stem cells (iPSCs) • Specialised adult cells Reprogrammed (genetic manipulation) • Pluripotent ~Embryonic stem cells Embryonic- like iPSCS
- 18. Characteristics of cells in TERM
- 20. Journey of Cells Stem cells to specialized tissue cells Stem Cells Endoderm/Ectoderm/ Mesoderm Cytokines Specialised tissues Confirm Purity Mechanical Stress Growth factors Chemicals
- 21. Scaffolds
- 22. Scaffolds - Role • Present a surface/structure resembles the extracellular matrix (ECM) • Surfaces- maximize favorable biological responses (cell-matrix interaction, Protein-matrix interaction)
- 23. What do we want in Scaffolds? • Biocompatible, non-immunogenic and biodegradable • Structural architecture and surface properties for cell adhesion and growth, • 3D porous - large surface cell-scaffold interaction and for cell migration • Temporary mechanical support • Degradation rate matched with regeneration ra
- 24. Scaffolds classification Absorbable Non Absorable Synthetic Polymer •P.L.A. P.G.A Natural Minerals Anorganic Bone Natural Polymers •Collagen •Fibrin •Chitosan Synthetic Polymers •Polytetra flouroethylene Synthetic Ceremics •Calcium Phosphate
- 27. Designing of Scaffolds Solvent Casting & Particulate Leaching (SCPL) Gas Foaming CAD/ CAM- 3D printing Textile technologies Nanofiber self-assembly Detergent
- 28. Growth Factors • Inhibition/stimulation of differentiation, proliferation, adhesion, migration. • Secretion and activation of other growth factors. • Concentration dependent effect. Bone morphogenetic proteins (BMPS), Insulin-like growth factors (IGFS), Transforming growth factor-β (TGF-β), Fibroblastic growth factors (FGFS), Platelet-derived growth factor (PDGF).
- 29. Bioreactors • A device that uses mechanical means to influence biological processes (Darling & Athanasiou, 2003) • Control the culture media conditions temperature, pH, oxygen ratio, osmolality and nutrients • Facilitate more advanced tissue regeneration in vitro. • Uniform cell seeding, and facilitate the mass transfer between the culture and the cells.
- 30. Skin expanding bioreactor Mitchell et al
- 31. Spinner flask Rotating Wall Bioreactor Flow perfusion bioreactors
- 33. Applications Tissue Conditions treated Skin Burns and skin defects after excision or trauma Cardiac muscle Heart failure Heart valves Congenital and acquired valvular heart disease Cartilage Degenerative and traumatic joint disorders Trachea and bronchus Congenital and acquired stenosis and resection for malignancy Bladder Congenital bladder malformation and cystectomy Anal/bladder sphincter Incontinence Pancreatic islets Insulin-dependent diabetes Large blood vessels Atheromatous, aneurysmal and traumatic arterial disease Oesophagus Benign stenosis, and resection for malignancy Small intestine Intestinal failure after surgical resection for Crohn’s disease, cancer or ischaemia
- 35. Before After LaViv Injection and effects Carticel Injection Celution Machine
- 36. Skin • Role in plastic surgey and dermatology • Auto/allografts Product Indications Alloderm Burns and full-thickness injuries Apligraf Venous and diabetic ulcers Dermagraft Diabetic ulcers, epidermolysis bullosa Epicel Deep partial- and full-thickness burns, congenital nevi Integra Dermal Regeneration Template Deep partial- and full-thickness burns OrCel Split-thickness donor sites, epidermolysis bullosa
- 38. Vessels Autologus vessel graft- for arteriovenous fistula 1st clinical application - pulmonary artery reconstructed in Tokyo
- 39. Heart and Valves Tissue engineered heart valves - replacement of diseased ones 3 D printing of heart
- 40. Cartilages and Bones The tissue-engineered cartilage sutured between distracted cricoid plates. Completed ear structure printed Integrated Tissue- Organ Printing System 1st autologous tracheal transplant on allogenic scaffold
- 41. Organs Urinary Bladder from autologous cells
- 42. Genito-urinary Tissue Engineered vaginal scaffold Urethra from autologous cells Institute for Regenerative Medicine at Wake Forest University
- 43. Kidney - Construction of engineered bladder Scaffold seeded with cells Engineered bladder anastamosed to native bladder with running 4–0 polyglycolic sutures Implant covered with fibrin glue and omentum A Atala et al, 2006 Cystoplasty in Neurogenic bladder
- 44. Cornea Tissue engineered Cornea from autologous keratinocytes
- 45. Newer Technologies Computer Aided Tissue Classification Computer Aided Added Modelling Computer Aided Tissue Engineering Computer Aided Tissue Implantation
- 46. Nanotechnology in TERM • Nanostructured scaffolds ~Tissue microenvironment • An extracellular matrix-like architecture can be fabricated by nanopatterning • Properties incorporation of nanomaterials such as carbon nanotubes, nanowires, and nanoparticles.
- 47. 4D-Bioprint • Fourth D- Time • Developing “smart” biomaterial Dynamic changes of structure • self-adaptability, • self-sensing, • shape-memory, responsiveness, multifunctionally, • self-repair, and decision making. Shape memory polymers (SMPs)
- 48. Challenges • Ethics • Quality control of materials • The fundamental understanding of tissue differentiation mechanisms • Meet the increasing demand
- 50. Ethics • Role of cell bank- Privacy of donor • Cloning humans • Embryo use • Animal experiments • Playing God!
- 51. Pros Cons
- 52. Market Orthopaedics > Skin > CTVS > Rest
- 53. Semi living doll Meet the Meat- A clean meat Bullet proof skin
- 55. Conclusion • At early phase of development. • We are gradually living the dream. • Lot more to explore and translate in to clinical fields.
- 56. Thank you…
Editor's Notes
- #39: coronary and peripheral bypass surgeries Bio printed BV. he first clinical use of a tissueengineered blood vessel for high pressure arterial revascularization
- #40: avoiding the limitations faced with currently available bioprosthetic and mechanical heart valves
- #43: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome.