Prof : Heba M Saad Eldien Manager Of Tissue Culture And Molecular Biology center Deputy director Of Genetic and metabolic disorders Lab Professor Of Histology And Cell Biology Faculty Of Medicine Director of Quality Assurance unit –Faculty of medicine Application Of Nanotechnology In Tissue Engineering

Agenda The Goal Of Tissue Engineering The Goal Of Tissue Engineering Advantages Of Nanomaterials In Stem Cell Engineering Advantages Of Nanomaterials In Stem Cell Engineering Cell Therapy And Tissue Therapy Cell Therapy And Tissue Therapy What Are The Potential Benefits Of Regenerative Medicine/HumanTissue Engineering What Are The Potential Benefits Of Regenerative Medicine/HumanTissue Engineering Tissue Engineering,Challenges And Future Directions Tissue Engineering,Challenges And Future Directions Translating Regenerative Therapies To The Clinic Translating Regenerative Therapies To The Clinic

The Goal Of Tissue Engineering : developing functional substitutes for damaged tissues by assemble functional constructs that restore, or improve damaged tissues or whole organs. Artificial skin and cartilage are examples of engineered tissues that have been approved by the FDA.

Tissue engineering components: cells, In- vitro culture systems

Two main benefits 1.Medical applications, 2.Non-therapeutic applications include using tissues as: Tissue chips that can be used to test the toxicity of an experimental medication.

Problem :Organ transplantation is limited by the number of available donors and high process cost, rejection of organs,leaving thousands of people each year on the transplant waiting lists.Many die before an organ donor becomes available.

TherapyTissueCellular

Types of stem cells Embryonic stem cells Adult stem cells Stem cells from somatic cell nuclear transfer Called Genetic “reprogramming” for generation of iPS cells Amniotic fluid and placental stem cells

The efficiency of injected stem cells in some cases as damaged myocardium or cirrhotic liver could possibly be hindered by : Mechanical trauma due to the injection low survival in the hostile environment. Cell mortality due to the injection approaches 90% The efficiency of injected stem cells in some cases as damaged myocardium or cirrhotic liver could possibly be hindered by : Mechanical trauma due to the injection low survival in the hostile environment. Cell mortality due to the injection approaches 90%

Goal of Tissue Engineering and Regenerative Medicine An ultimate goal will be to build human tissue engineered organs on three dimensional scaffolds. Multidisciplinary collaboration between medicine, biology, biochemistry, materials,engineering sciences and immunology Goal of Tissue Engineering and Regenerative Medicine An ultimate goal will be to build human tissue engineered organs on three dimensional scaffolds. Multidisciplinary collaboration between medicine, biology, biochemistry, materials,engineering sciences and immunology

The concept of tissue engineering Our lab collaborate with other labs that: Develop and uses nanotechnological tools Design of advanced nanocomposite scaffolds that can better mimic the extracellular matrix.

Intracellular drug carriers to control stem cell differentiation Biosensors to monitor intracellular levels of relevant biomolecules/enzymes in the stem cell Intracellular delivery of DNA, RNA interference molecules, proteins, peptides, genes and growth factors Nanomaterials Have Unique Advantages In Controlling Stem Cell Function And In Tissue Regeneration

Transfection using nanoparticles encapsulated with plasmid DNA encoding differentiation to hepatic, ondotogenic or osteogenic differentiation. Thus targeting stem cells by nanoparticles and release payload in the cytoplasm, followed by activation of signaling cascades, are likely to be the focus of future research

Cells are implanted or 'seeded' into an artificial structure capable of supporting three-dimensional tissue formation. These structures, typically called scaffolds:three-dimensionalscaffolds Allow cell attachment and migration Deliver and retain cells and biochemical factors Enable diffusion of vital cell nutrients and expressed products Modify the behaviour of the cell phase

18 The ideal matrices should thus consist of a two- or a three- dimensional structure that should favor not only cells’ attachment and growth but also their further organization and possibly differentiation. Carbon nanotube biocompatible biocompatible biodegradationbiodegradation

SyntheticPLA - polylactic acid polyglycolic acid (PGA)PLApolyglycolic acid

Natural materialsfibrin, and polysaccharide like chitosan or glycosaminoglycansfibrinchitosanglycosaminoglycans

Another form of scaffold is decellularised tissue extracts whereby the remaining cellular remnants/extracellular matrices act as the scaffold

Bioreactors Bioreactors are dynamic cell culture systems Generate larger volumes of cells when compared with conventional static-culture techniques. The flow of tissue culture medium and their mixing within bioreactors Enhance the mass transfer of nutrients, gases, and metabolites Thus regulate the size and structure of the tissue being generated

25 Growth factors Platelet-derived growth factor and basic fibroblast growth factor are essential for wound healing and tissue generation, including angiogenesis. Two ways to incorporate growth factors in TE: direct blending or coating on the scaffold(drug delivery system) addition to the cell culture medium during the development of the cell/scaffold construct. The second approach is extremely important for stem cell TE.

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What are the potential benefits of regenerative medicine/human tissue engineering? 1- Human tissue engineered skin and tissue engineered cartilage are the first to be used for the treatment of chronic wounds and burns, and joint degeneration 2- Other regenerative techniques are being developed to repair bone, the cornea, the bladder and several other common medical conditions. What are the potential benefits of regenerative medicine/human tissue engineering? 1- Human tissue engineered skin and tissue engineered cartilage are the first to be used for the treatment of chronic wounds and burns, and joint degeneration 2- Other regenerative techniques are being developed to repair bone, the cornea, the bladder and several other common medical conditions.

Current Research Are Treatments such as Nerve regeneration for conditions like parkinson’s disease or alzheimer’s disease, Pancreatic islet cells for Transplantation into the liver for diabetes treatment, Regeneration of damaged Heart tissue.

Challenges And Future Directions In Regenerative Medicine: Translating Regenerative Therapies To The Clinic Formation of a vasculature to support oxygen and nutrient transport within the growing tissue. Through the formation of a microfluidic network within the tissue engineering scaffold;.

some large sized organs contain extremely complex internal structures, simple cell seeding techniques may not be sufficient for thus delivery of oxygen and nutrients to each part of the organ will be a challenge, functional vascular network is required Also successful connection with the nervous system important for the functionality of neo-organs, The controlled release of neurotrophic factors.

In the heart, the main three targets for tissue engineering are valves, coronary grafts and myocardium. In the heart, the main three targets for tissue engineering are valves, coronary grafts and myocardium. 32

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A clinical study of patients with hypospadias and urethral stricture disease. Decellularized cadaveric bladder submucosa was used as an onlay matrix for urethral repair in patients with stricture disease and hypospadias. Outcome Patent, functional neo-urethras were noted in these patients with up to a 7-year follow-up.

Current research interests: Microfluidics -based tissue engineering. Recreating stem cell niches Nanotechnological strategies for engineering thick cardiac tissue and hepatic tissue (( microfluidics bioreactors for tissue engineering)) Engineering a 3D neuronal network for spinal cord and brain regeneration. Fabrication of Nanoelectronics/engineered tissue hybrids. Developing smart delivery systems that recruit stem cells to defected organs.

Students (Msc, Phd) And Post-docs From Biology, Chemistry, Physics And Engineering.

macroporous, flexible and free-standing nanowire nanoelectronic scaffolds (nanoES), and their hybrids with synthetic or natural biomaterials. 3D macroporous nanoES mimic the structure of natural tissue scaffold

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