Surface Engineered And Drug Releasing Pre-fabricated Scaffolds For Tissue Engineering

1. Advanced drug delivery system PE-820 Presented By Sunil Kumar Jena Surface Engineered And Drug Releasing Pre-fabricated Scaffolds For Tissue Engineering

2. Contents Introduction Materials Scaffold fabrication Surface engineered scaffolds Scaffold for growth factor release Injectable matrices Tissue Engineering

3. Introduction • Tissue engineering was firstly coined in the mid of 1980s. • In 1993, Langer and Vacanti defined TE as: “An interdisciplinary field that apply the principles of engineering and life sciences towards the development of biological substitutes that restore, maintain or improve tissue function or a whole organ” ChiaraGualandi, Porous polymeric bioresorable scaffolds for tissue engineering, 2011; 1-10 Tissue Engineering

4. ChiaraGualandi, Porous polymeric bioresorable scaffolds for tissue engineering, 2011; 1-10 Tissue Engineering

5. Three general strategies have been utilized in the creation of new tissue using scaffolds: • The replacement of only those isolated cells or cell substitutes needed for function (Conductive approach); • Production and delivery of tissue-induced substances such as growth factors and signal molecules (Inductive approach) • Cells placed on or within a scaffold made from synthetic materials such as polyethylene glycol or natural materials such as hyaluronic acid (cell seeding approach) Tissue Engineering

6. M.N. Collins, C. Birkinshaw / Carbohydrate Polymers 92 (2013) 1262–279 Tissue Engineering

7. Scaffolds • It is a temporary supporting structure for growing cells and tissues. • It is also called synthetic extracellular matrix (ECM) and plays a critical role in supporting cells. These cells then undergo proliferation, migration, and differentiation in three dimensions, which leads to the formation of a specific tissue with appropriate functions as would be found in the human body. Tissue Engineering

8. An ideal polymeric scaffold requires several structural and chemical features: • A three-dimensional architecture with a desired volume, shape, and mechanical strength • A highly porous and well inter-connected open pore structure to allow high cell seeding density and tissue in-growth • Chemical compositions such that its surface and degradation products are biocompatible causing minimal immune or inflammatory responses, and • Their degradation rate finely tuned in a pattern that it provides sufficient support until the full regrowth of impaired tissues. Tissue Engineering

9. Materials Materials Fibrin Collagen Gelatin Chitosan Alginate Hyaluronic acid • Poly(α-hydroxyester)s • PLA • PGA • PolyanhydridesPolyorthoesters Tissue Engineering Tissue Engineering 9

10. Scaffold Fabrication Tissue Engineering

11. Phase Separation • Non solvent induced phase separation • Chemically induced phase separation and • Thermally induced phase separation (TIPS) • In the TIPS process a relatively new approach for preparing porous membranes, the temperature of a polymer solution is decreased to induce phase separation. After the solvent is removed by extraction, evaporation, or sublimation, the polymer in the polymer-rich phase solidifies into the skeleton, the space occupied by the solvent becomes porous. Tissue Engineering

12. V. Beachley, X. Wen / Progress in Polymer Science 35 (2010) 868–892

13. Solid freeform fabrication (SFF) & Bioprinting Bio-printing is a variant of 3D printing and can be defined as computer-aided, automatic, layer-by-layer deposition, transfer, and patterning of biologically relevant materials.  It is also known by other names such as “computer aided tissue engineering” and “biofabrication”.  In simpler words, bioprinting involves printing devices that deposit biological material. Tissue Engineering

14. Organ printing is a variant of bio-printing aiming at producing 3D organs. The 3D- Bioprinter was listed among the TIME magazine’s 50 best inventions of 2010. Most of the 3D printers use a modified version of inkjet printers to deposit dots of “bio ink” (cell suspension with 10 to 30 thousand cells per drop) that coalesce to form layers of organ interrupted by layers of biopaper (hydrogel mimicking the microenvironment of tissue) which is water-soluble. Tissue Engineering

15. http://blogs.dolcera.com/blog/2011/08/17/need-an-organ-print-it/roadmap-to-bioprinting/http://blogs.dolcera.com/blog/2011/08/17/need-an-organ-print-it/roadmap-to-bioprinting/

16. Freeze Drying The material in hydrogel form, is frozen and the water content of the solution forms dense pockets, or nuclei of ice, throughout the polymer. These nuclei act as the porogen and are removed by sublimination under vacuum (<100 mTorr) leaving behind a porous sponge network. • Solvent Casting/Particulate leaching D. Zhang et al. / Polymer 53 (2012) 2935-2941 Tissue Engineering

17. Gas forming/Particulate leaching H.J. Chung, T.G. Park / Advanced Drug Delivery Reviews 59 (2007) 249–262 Tissue Engineering

18. Electrospinning Tissue Engineering Wei Ji et al., Pharm Res (2011) 28:1259–1272

19. Surface Engineered Scaffolds Surface characteristics such as hydrophilicity/hydrophobicity arising from chemical composition may not be satisfactory for inducing selective cell adhesion, migration, and proliferation. The surface engineered scaffolds were capable of enhanced cell adhesion and growth, or sustained release of growth factors, thereby providing a chance to facilitate the tissue regeneration process. The surface of a scaffold can be functionalized either by physical adsorption or chemical modification. Tissue Engineering

20. Substances including poly(L-lysine), collagen, and cell adhesive proteins such as fibronectin, laminin, or vitronectin have been adsorbed onto the surface of a polymeric matrix to promote cell attachment. Naturally derived macromolecules such as collagen, gelatin, heparin, hyaluronic acid, short peptide sequences originating from cell adhesive proteins such as the arginine–glycine– aspartic acid (RGD) or YIGSR, and sugar moieties such as galactose or lactose, have been grafted onto polymer surfaces to modulate cell–matrix interactions Tissue Engineering

21. H.J. Chung, T.G. Park / Advanced Drug Delivery Reviews 59 (2007) 249–262

22. Scaffolds for growth factor release Polymeric scaffolds can be designed to function more actively in tissue remodeling and regeneration by incorporating growth factors. Growth factors can be incorporated into the scaffold matrix either by bulk encapsulation, specific or non-specific surface adsorption, and adding microspheres encapsulating them. • Angiogenesis • Therapeutic angiogenesis is crucial in treating ischemic heart diseases, wound repair, and tissue regeneration. • In tissue engineering, the formation of blood vessels is essential for the survival of a growing tissue or organ, for it provides facile transport of oxygen and nutrients. Tissue Engineering

23. Various angiogenic growth factors, such as vascular endothelial growth factor (VEGF), acidic or basic fibroblast growth factor (aFGF, bFGF), angiopoietin, and platelet-derived growth factor (PDGF). To achieve sustained release of angiogenic growth factors from the scaffold, heparin immobilized scaffolds were prepared. • Bone and cartilage regeneration Members of the transforming growth factor-β(TGF-β) superfamily, platelet-derived growth factor (PDGF), and insulin-like growth factor (IGF). Among the TGF-β superfamily, TGF-β1 is the most well known factor involved in chondrogenic differentiation. Tissue Engineering

24. Chitosan scaffolds containing TGF-βencapsu-latedchitosan microspheres were developed for in vitro culture of chondrocytes. The presence of TGF-βwithin the scaffold enhanced cell proliferation, and stimulated production of GAG and collagen type II, leading to better cartilage formation. • Wound repair Wound dressing materials usually comprise of an inner gel or scaffold layer that directly contacts the wound site, and an outer elastic covering layer that fixes the device to the patients’ tissue. A variety of growth factors including epidermal growth factor (EGF), FGFs, TGF-β, and PDGF have been utilized for promoting the healing process. EGF, a potent mitogen for epithelial cells, is the most widely used therapeutic agent for skin regeneration. Tissue Engineering

25. H.J. Chung, T.G. Park / Advanced Drug Delivery Reviews 59 (2007) 249–262 Tissue Engineering

26. Liver regeneration Growth factors known to promote survival and proliferation of hepatocytes include EGF and hepatocyte growth factor (HGF). Hepatocyte culture has often been associated with angiogenesis. • Neural tissue engineering Neurotrophic factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), glial growth factor (GGF), and FGFs have been used to promote proliferation and migration of neural cells. Tissue Engineering

27. Injectable Matrices In-situ formed injectable scaffold materials can be administered using a syringe needle. For instance, injectablehydrogels can be combined with the desired cells and growth factors in a solution state prior to injection, but after injection, it immediately becomes a temporal gel depot at the tissue defect site while the tissue regenerates. Typically, temperature-sensitive sol–gel transition hydrogels and photo-crosslinkablehydrogels have been popularly used for cell and growth factor delivery. Tissue Engineering

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