Material science-1

1. INTRODUCTION 1.1 Material science2 1.2 Stem cells 2 2. SCOPE & OBJECTIVE 2.1 Organ transplantation Vs Stem cells3 2.2 Development of Artificial stem cells3 2.3 Role of scaffolds4 3. LITERATURE SURVEY 3.1 Material science involved in stem cells5 3.2 Types of scaffolds5 3.2.1 Classification based on nature of application5 3.2.2 Classification based on type of origin.6-7 3.3 Functions and mechanical features of scaffolds.8 3.4 Natural Vs Synthetic scaffolds9-10 3.5 Common synthetic scaffolds10 3.5.1 Polygycolic acid (PGA).11 3.5.2 Polylactic acid (PLA)12-13 3.5.3 Polylactic co-glycolic acid ( PLGA )14-16 3.6 Degradation of polymers 17-19 3.7 Tailoring of scaffolds.20 3.7.1 Inject able scaffolds for tissue engineering20 3.7.2 Development of fabrication technologies for porous scaffolds21-23 3.7.3 Custom scaffold production24 3.7.4 Plasma modification of scaffold surfaces24 4. CURRENT RESEARCH25 5. CONCLUSIONS26 6. REFERENCES27-30 7. NOMENCLATURE31  1. INTRODUCTION 1.1 Material science: Material science or material engineering field is inherently multidisciplinary, encompassing mechanical, chemical, biomedical engineering and physics and chemistry. It involves investigating the relationships that exist between the synthesis and processing (shaping, treating conditioning etc), structure (subatomic, atomic, microscopic, macroscopic) and properties (microscopic or bulk response to external stimuli, i.e., force vs. deformation: strength, ductility etc)of materials on the basis of structure-property relationships, design or engineering the structure of a material to produce pre-determined properties. It involves the characterization of the physical and chemical properties of solid materials which include metals and alloys, ceramics, polymers, semiconductors, and composites for the purpose of using, changing, or enhancing inherent properties to create or improve end products. 1.2 Stem Cells: Stem cells are type of biological cells found in multicellular organisms. There are two broad types of stem cells: Embryonic stem cells (ESCs) : Obtained from the inner cell mass of embryo. Pluripotent – they can differentiate to become almost every type of cell in the body. Adult stem cells: Are isolated from various tissues including bone marrow, adipose tissue, skeletal muscle, placenta etc. Multipotent – they can differentiate to become only the types of cells in the tissue they come from. Can self-renew many times. 2. SCOPE & OBJECTIVE 2.1 Organ transplantation Vs Stem cells: In case of diseases such as acute liver failure or bone cancer, which leads to tissue impairment, cannot be treated with a particular drug. Though, tissue/organ transplantation provides an alternative way to restore the health of patients it is severely limited by crucial donor shortage and possible immune rejection. Patients who undergo organ transplants require loads of toxic drugs to suppress their immune systems; otherwise their body might reject the organ. In this light, stem cells have attracted much attention due to their unique capabilities of self-renewal in an undifferentiated state for prolonged time and this tissue technology could regenerate patients’ tissues or organs that are biocompatible, biofunctional, bioresorbable, immunologically compatible and easily available. As a result of this Stem cells have found applications in treatment of diseases and disorders of every organ of the human body From Alzheimer’s to arthritis, blindness, burns, cancer, diabetes, heart disease, liver disorders, multiple sclerosis, Parkinson’s, spinal cord injury, stroke etc 2.2 Development of Artificial stem cells: As a result of growing applications of stem cells in the treatment of various diseases, stem cells are cultivated under laboratory conditions which include reconstructing the extracellular matrix that imitates the natural environment of the cells, incorporate growth factors, into said extracellular matrix structures. Figure 1 depicts the following steps in formation of organ: Stem cells are first extracted from bone marrow, adipose tissue (lipid cells), blood etc of human body. The cells are allowed to expand in number in an appropriately prepared culture medium They are then, seeded along with suitable growth factors onto an appropriate SCAFFOLD made of polymeric material which acts as a matrix. This is then placed in culture medium which after appropriate time forms an engineered tissue which can be re-implanted to repair or replace the damaged tissue. Figure 1: Concepts of tissue engineering 2.3 Role of scaffolds: A bio-scaffold can be broadly termed as a structure used to substitute an organ either permanently or temporarily to restore functionality. They are defined as constructs, which are used as a temporary support structure allowing the tissues/cells to adhere, proliferate and differentiate to form a healthy bone/tissue for restoring the functionality. Act as shape and guidance template for in vitro and in vivo tissue development Permit 3D immobilization and maintain differentiation and incorporation of biofactors. 3. Literature survey 3.1 Material science involved in stem cells: Scaffolds provide cell culture medium, a three-dimensional biocompatible frame structure that can imitate the native extracellular matrix as natural environment around cells. Thus, scaffold matrices can be utilized to fill the tissue void, to provide structural support and to deliver growth factors and cells that have the ability to form tissues within the body upon transplantation. 3.2 Types of scaffolds: 3.2.1 Classification can be made based on the nature of application.(Prasad k. et al., 2009) Temporary A temporary scaffold provides the necessary support and assistance in cell/tissue growth until the tissue/cell regains original shape and strength; these types of scaffolds are useful especially in case of young patients where the growth rates of tissues are higher and the use of an artificial organ to restore functionality is not desired. Most of the works on scaffolding has been done on temporary scaffolds owing to the immediate advantages of the materials used and the ease of processing. Permanent In case of older patients, temporary scaffolds fail to meet the requirements in most cases. These include poor mechanical strength, mismatch between the growth rate of tissues and the degradation rate of the said scaffold. Thus the older patients need to have a stronger scaffold, which can either be permanent or have a very low degradation rate. Classification based on type of origin: Both natural and synthetic polymers have been used in tissue engineering applications as mentioned in the literature (Willerth et al., 2008). Natural scaffolds Natural polymers are derived from a variety of sources including fish scales, rat tails, crab shells and from parts of human body itself. Table 1: List of natural biomaterial Type of material Protein based scaffold Material Application Collagen Bone, Cartilage, Heart, Ligament, Nerve, Vasculature. Fibrin Cartilage, Nerve, Vasculature Silk Bone, Cartilage, Liver Polysaccharide based scaffold Agarose Cartilage, Heart, Nerve An alternative to using natural matrices is to synthesize polymer matrices for use as tissue engineering scaffolds. Artificial or synthetic scaffolds: Table 2: List of synthetic biomaterials (Willerth et al., 2008) Type of material Material Application Polymer based biomaterials PLA (Polylactic acid) Adipose, Bone, Cartilage, Muscle, Nerve. PEG (Polyethylene glycol) Adipose, Bone, Cartilage, Liver, Heart, Nerve. Ceramic based biomaterials - Bone, cartilage. Metals and alloys Stainless steel , Cu-Cr and Ti alloy Joint prostheses, dentistry and cardio-vascular applications. 3.3 Functions and mechanical features of scaffolds: Table 3: Functions of stem cells (Atala et al., 1958) Functions of scaffolds in engineered tissues Required Architectural, biological, and mechanical features of scaffolds. Provides structural support for exogenously applied cells to attach, grow, migrate and differentiate Biomaterials with binding sites for cells; porous structure with interconnectivity for cell migration and for nutrients diffusion; Provides the shape and mechanical stability to the tissue defect and gives the rigidity and stiffness to the engineered tissues. Biomaterials with sufficient mechanical properties filling up the void space of the defect. Interacts with cells actively to facilitate activities such as proliferation and differentiation Biological cues such as cell-adhesive binding sites; Physical cues such as surface topography. Serves as delivery vehicle and reservoir for exogenously applied growth-stimulating factors. Microstructures and other matrix factors retaining bioactive agents in scaffold. Provides a void volume for vascularization and new tissue formation during remodeling. Porous microstructures, matrix design with controllable degradation 3.4 Natural Vs Synthetic scaffolds Advantage of natural scaffolds: Superb biocompatibility. Cells can attach and grow with excellent viability. Disadvantage of natural scaffolds: Natural materials have limited physical and mechanical stability which cannot be tailored. Not suitable for some load-bearing applications. Poor resistance. Naturally derived scaffolds must be isolated from plants animals or human tissues and are typically expensive and suffer from large batch to bath variations. Advantage of synthetic scaffolds: Better controlled physical and mechanical properties and can be used to tailor for both soft and hard tissues. Controllability of porosity, 3-d structure and mechanical properties. The ability to tailor scaffolds with specific degradation rate. The bioresorption or disintegration of these materials after they have fulfilled their functions minimizes chronic foreign body response and leads to completely natural tissue. Disadvantage of synthetic scaffolds: Biocompatibility becomes the major issue because cells may have difficulties in attachment and growth on these materials. lack of sites for cell adhesion potential for toxic byproducts after degradation Many natural polymers have charged functional groups and present less ionic affinity to therapeutic biomolecules such as growth factors. Taking in to account the disadvantages associated with natural biomaterials, synthetic biomaterials provide an alternative to natural materials to serve as scaffolds for the stem cell culture formation. The advantage of shaping a synthetic material allows for production of scaffolds that conform to specifications of the injury or transplantation site. The ability to tailor scaffolds with specific degradation rate is one advantage of synthetic scaffolds over natural biomaterials and these properties can also affect the release rate of drugs incorporated into such scaffolds. In order to take care of disadvantages many processes modifying the surface and bulk properties have been developed to improve their biocompatibility Examples include, surface laser engineering and coating with natural biomaterials such as collagen. Thus synthetic scaffolds prove to be perfect alternative. 3.5 Common synthetic scaffolds: Typical modulus values of the most of the ceramic and metallic implants used lies above 70 GPa. This results in stress shielding effect on bones and tissues which otherwise is useful in keeping the tissue/bone functional. Moreover rejection by the host tissue especially when toxic ions (in the alloy such as Vanadium in Ti alloy) are eluted causes discomfort in patients necessitating operations to be performed. Polymers have modulus within the range of 0.001-0.1 GPa and have been used in medicine for long whose application ranges from artificial implants. FDA approved aliphatic polyester which include Polygycolic acid (PGA) and Polylactic acid (PLA) and PLA, PGA copolymer which is Polylactic co-glycolic acid (PLGA) are by far most commonly used synthetic polymers for stem cell cultivation as, they fulfill the criteria of biocompatibility, processability and controlled degradation. Polygycolic acid (PGA): It is a biodegradable, thermoplastic polymer and the simplest linear, aliphatic polyester. Obtained by, polycondensation of glycolic acid or ring-opening polymerization of glycolide. As mentioned in literature (Atala et al., 1958). Table 4: Properties of Polygycolic acid Properties Value Structure Shape Braided and monofilament sutures and meshes Trade name Dexon Nature Hydrophilic Tensile strength 550-700MPa Young’s modulus 4GPa Glass transition temperature 35-40 °C Melting point 225-230°C Crystallinity 45-55% Solubility in water and organic solvents Insoluble Knot strength 450MPa Solubility in fluorinated solvents soluble Advantages of PGA: Good mechanical properties. It induces cartilage repair and degrades completely. No negative effects of its degradation components could be observed. Disadvantages: Due to its hydrophilic nature on account of hydrolysis, PGA tends to lose its mechanical strength rapidly, typically over a period of two to four weeks of post-implantation. The high rate of degradation, acidic degradation products and low solubility however, limit the biomedical applications for PGA. Owing to its hydrolytic instability PGA are less widely used as compared to PLA and PLGA. Polylactic acid (PLA): They are obtained from polymerization of lactic acid produced from renewable resources such as starch. Because Lactic acid (2-hydroxy propionic acid) is a chiral molecule it exists as 2 optically active configurations, the L (+) and D (−) stereo isomers their polymerization results in the formation of l-PLA or PLA or PLLA and d-PLA respectively and the polymerization of racemic (D, L)-lactide yields dl-PLA. d- PLA and l-PLA are crystalline while dl-PLA is amorphous in nature. l- PLA is employed much more often than d-PLA since the hydrolysis of PLA yields L-lactic acid which is naturally occurring stereoisomer of lactic acid also L-PLA is more frequently used in because it possesses high mechanical strength. . Table 5: Properties of Poly (L-lactic acid) Properties of PLLA Value Structure Trade name Dacron,Dexon Nature Hydrophobic Crystallinity ~ 37 % Glass transition temperature 60-65°C Young’s modulus 4.8GPa Melting point 175°C Solubility in organic solvents Soluble Hydrophobicity: The presence of an extra methyl group poly (L-lactic acid) (PLA) or poly (D-lactic acid) d-PLA makes them more hydrophobic than PGA and soluble in organic solvents. Due to the presence of methyl group PLA is less liable to hydrolysis. In addition, the ester bond in PLA is less liable to hydrolysis due to steric hinderance of the methyl group .Therefore PLA degrades much more slowly than PGA and has higher solubility in organic solvents. Advantages: They are biodegradable and compostable, and they have very low or no toxicity. High mechanical performance and Good tensile strength. High hydrolytic stability. Poly (L-lactic acid) is a slow-degrading polymer compared to PGA has good tensile strength, low extension and a high modulus and hence, has been considered an ideal biomaterial for load bearing applications, such as orthopedic fixation. Polylactic co-glycolic acid ( PLGA ): Poly (lactic-co-glycolic acid) (PLGA) is a copolymer that consists of monomers of glycolic acid and lactic acid connected by ester bonds. Table 6: Properties of Polylactic co-glycolic (PLGA) Properties Value Structure Trade name Vicryl and Polyglactin 910 Shape nonwoven felt, fibres with diameter ~ 17 µm Nature Amorphous Melting point 200-250°C Glass Transition temperature 37-55°C Factors affecting copolymer crystallinity and hydrophobicity: The ratio of lactide to glycolide monomer units in copolymer. The stereoregularity of monomer affect polymer chain packing in the copolymer. Randomness of lactide and glycolide decrease the ability of chains to crystallize. Low molecular weight polymers degrade faster than high molecular weight polymers, especially when the end group are free acid rather than capped with ester or other groups. Advantages of PLGA: PLGA Seems to be promising, mechanically stable, biologically compatible and bio re-absorbable scaffold which may offer effective biomechanical and biochemical properties for cell based tissue repair. In the presence of cells, PLGA scaffolds degrade in the monomers, which are natural metabolites. Scaffold design Inner Scaffold seeded with stem cells Outer Scaffold Outer layer of scaffold generated by means of phase separation. Surgical insertion of the implant into the spinal cord Figure 2: Schematic of PLGA scaffolds designed to mimic the spinal cord (Willerth et al., 2008) Table 7: Comparison of crystallinity and thermal properties of PGA, PLA and PLGA % Crystallinity Tm (°C) T g (°C) PGA 46-45 225 36 90:10 PGLA 40 210 37 50:50 PGLA 0 None 55 PLA 37 185 57 Table 8: Structural variables used to control biodegradable polymer properties. (Atala et al.,1958) VARIABLES EFFECTS EXAMPLES Incorporation of both natural and / or non-natural monomers May reduce /eliminate immunologic response Non immunologic PGA and PLA (Vs collagen) Incorporation of liable groups in polymer chain. Controls kinetics of biodegradation. Hydrolyzable ester bond in PGA. Incorporation of functional group in side chains Controls chemical and physical properties of polymer. Hydrophilic, hydrophobic and amphiphilic polyphosphazenes Incorporation of chiral centers in polymer chains. Control physical and mechanical properties of polymers. Semi-Crystalline I-PLA and amorphous dl-PLA. Possibility of utilizing multiple monomers. Control properties of polymers Glycolic and lactic acid in PLGA. Use of natural compounds as monomers. Biocompatible breakdown products. Lactic acid in PLA Use of different polymer architectures. Control of mechanical and physical properties of polymers exhibits. Branched polymers lower viscosity than linear ones. 3.6 Degradation of polymers: The scaffold material eventually degrades by hydrolysis (i.e., non-enzymatically) during which the polymers undergo random chain scission of ester bonds into acidic monomers which diffuses out of the polymer bulk into water, which can be removed from the body by normal metabolic pathways thus, leaving only normal healthy tissue. Characteristics of degradation: It is necessary that, the degradation products should be biocompatible, non-toxic, and transportable out of the body. Degradation rates of polymers and mechanical properties can be altered via co- and graft-polymerization techniques, and by processing conditions. High molecular weight degradation times are of the order of two to three years make which is unsuitable for short term implants. Degradation mechanism: (Atala et al., 2012) The degradation process is erosive and appears to take place in two steps during which the polymer is converted back to its monomer Water diffuses into the amorphous (non-crystalline) regions of the polymer matrix, cleaving the ester bonds. After the amorphous regions have been eroded, it leaves the crystalline portion of the polymer susceptible to hydrolytic attack. Upon collapse of the crystalline regions the polymer chain dissolves. Degradation of PGA: Loss of mechanical strength of PGA is faster when the polymer is incubated at a temperature higher than its Tg. This indicates that the glassy state protects PGA from hydrolysis since all short term chain motions are frozen. Degradation of PLA: Due to the steric hindrance of the methyl group the ester bond of L-PLA is less liable to hydrolysis hence it degrades much more slowly than PGA. Hydrolysis of the ester groups forms L-lactic acid which is harmless as it is a normal human metabolic byproduct, which is broken down into water and carbon dioxide via the citric acid cycle in the body. D l-PLA is amorphous in nature unlike L-PLA which crystalline therefore; dl-PLA gets easily degraded as compared to PLA. Degradation of PLGA: The degradation of PLGA is via random hydrolysis of the ester bonds. Due to morphological changes which result in an increase in the rates of hydration and hydrolysis, copolymers tend to degrade more rapidly than PLA and PGA. The degradation of a block co-polymer such as PLGA is affected by the ratio of hydrophilic poly glycolic acid (PGA) to hydrophobic poly lactic acid (PLA).Amorphous 50:50 PLGA (50% lactic acid, 50% glycolic acid) degrades faster than other co-polymer ratios, which are semi-crystalline. Disadvantages associated with degradation: The molecular weight decreases as monomer releases from the samples as shown in figure 3.2. This mechanism of degradation may be undesirable in certain applications. The relatively rapid release of large quantities of acid (lactic or glycolic) may lead to local acidosis if large mass of these polymers is present in a concentrated form. Furthermore, their degradation products being relatively strong acids cause inflammation and structural instability in scaffolds. High molecular weight degradation times are of the order of two to three years make which it unsuitable for short term implants. Factors affecting degradation of scaffolds: It is also found that enzymatic action may partially contribute to biodegradation. The chemical compositions and the ratio of monomers in case of copolymers strongly influence the degradation characteristics of copolymer. Since degradation is induced by hydrolysis a crystalline and hydrophobic structure disfavors dissociation and degradation. Figure 3: Change of molecular weight scaffolds fabricated from 50/50 PLGA, and release of Glycolic acid (GA), l-lactic acid (l-LA) and d-lactic acid (d-LA) which it was placed in an environment of 37°C found in literature (Gombotz et al.,1995). Degradation properties are dependent on several other factors, such as molecular weight, sample size and shape. Those factors can be used to predict and control the degradation of scaffolds. Large surface area (low mass to volume ratio) speeds up the diffusion of water molecules in the bulk of polymers when placed in an aqueous environmentthus increasing the rate of degardation. Tailoring of scaffolds: 3.7.1 Inject able scaffolds for tissue engineering (Howard et.al) Scaffold in the form of microparticles are delivered by syringe and can be used as an injectable by incorporating temperature and moisture sensitive or adherent systems. Suciati et al.,(2006) mentions that such microparticles are produced using droplet formation of solvents or by spraying. Furthermore, live cells could be incorporated into this system such that scaffolds could be injected containing evenly distributed cells. The range of applications can be increased with the incorporation of various drugs and surface modifications. The dynamics of this scaffold type allows injection at room temperature and solidification at body temperature allowing for a non-invasive delivery system for treatment of non-union bone defects. For example, a scaffold developed for orthopaedic use called ‘Injectabone’ formed via the use of two types of PLGA microparticles. Type 1 is a temperature-sensitive PLGA/polyethylene glycol (PEG) composite that acts as an adhesive for the type II PLGA particles. The dynamics of this scaffold type was such that it allowed injection at room temperature and solidification at body temperature. Development of fabrication technologies for porous scaffolds (Howard et.al) The creation of porosity in three-dimensional (3D) structures of scaffolds plays a critical role in cell proliferation, migration, and differentiation into the specific tissue while secreting extracellular matrix components. These pores are used to transfer nutrients and oxygen and remove wastes produced from the cells. The physical properties of scaffolds such as porosity and pore interconnectivity can improve mass transfer and have a great impact on the cell adhesion and penetration into the scaffolds to form a new tissue. Typical pore size may vary from 5µm to 200µm depending on the application as published in the literature (Brahatheeswaran et al., 2011). Several techniques have been developed to fabricate porous scaffolds, including particulate leaching, fiber bonding (unwoven meshes), gas foaming and phase separation. Particulate leaching: It is mentioned in the literature by Benjamin J L., (2004) that when porogen such as salt (NaCl) is introduced into the polymer which is dissolved in a solvent at room temperature and then subsequently removed by suitable solvent (particulate leaching); the leaching of salt from a polymer composite forms pores within scaffolds, and the pore sizes are dependent on the size and amount of salt crystals. An average pore size of 100µm is obtained. Phase separation: The phase-separation technique is based on demixing of a homogeneous polymer-solvent solution into a polymer-rich phase and a polymer-poor phase. Solvent is removed by freeze drying, leaving behind the polymer as foam. Chen et al., (2002), has reported that the liquid-liquid phase separation leads to isotropic polymer forms with highly interconnected pores and the solid-liquid phase separation results in anisotropic foams with a sheet like morphology. Figure 4: Phase separation method of fabricating porous scaffold Gas foaming: The gas-foaming technique uses high-pressure CO2 gas processing for generation of pores it serves as an alternative to eliminate the use of organic solvents. But the pores created in this method are non-uniform, limiting cell seeding and migration. Supercritical carbon dioxide processing of polymers: Kanczler et al. (2007) found that Supercritical CO2 forms a phase between liquid and gas that is able to penetrate many polymers and plasticize them. Figure 5: Phase diagram for the point at which CO2 becomes supercritical and can be used to melt polymers at ambient temperatures to produce porous scaffolds. Evaporation results in solidification of the polymer and can be controlled to fuse separate bubble nucleation points, providing a reticulated and interconnected scaffold with a high strength to weight ratio (Fig. 6). The structures produced are architecturally very strong and are able to easily incorporate otherwise sensitive peptide drugs. The use of CO2 needs careful control of the supercritical foaming process for correct formation of interconnected chamber structures and the use of this process requires quality control of the scaffolds produced. Figure 6: Supercritical CO2 produced poly lactic acid foamed porous block (5 mm) viewed using (A) X-ray micro-computed tomography in section and (B) reconstructed Custom scaffold production: These include development of custom matrices either tailored for purpose, or for the individual patient. In this case, scaffolds are produced for individuals via custom three-dimensional (3D) printing using a laser stereo lithography technique. Which allows the scaffold to be built layer by layer, and the pore size and spacing are controlled by the pattern derived from computed 3D information derived from patient scans or from computer simulations as mentioned in (Antonov et al.,2004).In this process layers of particles are selectively sintered using a directed laser; these fused particles are further layered and sintered until several to several hundred layers have been bonded together, producing a custom 3D scaffold. The advantage of 3D printing is the control of pore size and distribution and the disadvantage is that the fiber diameter limits the pore sizes and configurations possible. Currently, construction is limited to a 150µm fiber diameter. Plasma modification of scaffold surfaces: This includes modification of the surface chemistry of scaffolds with deposition of charged gas plasma polymerization, in order to guide the cells to specific locations and prevent cell build up and thus manipulate the regions to which cells will adhere and grow. Deposition of plasma polymerized allyl amine (ppAm) allows stronger cell adherence to coated surfaces; conversely, deposition of plasma polymerized hexane (ppHex) strongly repels cell adhesion (Barry et al., 2006). By using the deposition of ppHex surface over a ppAm core, cells can be moved from the non-adherent surface layer to the more adherent inner core, thus allowing some redress of the typical cell attachment primarily to the surface of scaffolds.  4. CURRENT RESEARCH Formation of human ear using PLGA scaffold: Cao et al., were the first to apply Polyglycolic acid-Polylactic acid to form a polymer template in the shape of a human ear and seeded chondrocytes into the construct. New tissue-engineered cartilage grew for 12 weeks after implantation under the dorsal skin. The Polyglycolic acid-Polylactic acid construct degraded gradually following transplantation, but the cartilage was formed and confirmed by morphological and histological analysis .The technique is particularly useful for plastic and reconstructive surgery. Formation of human bladder using hybridized PLGA and collagen: For this, Atala's team sliced a postage-stamp-sized fragment of bladder tissue from each patient and encouraging the cells to proliferate. They spread a layer of muscle cells on the outside of a bladder-shaped, biodegradable mould of synthetic PLGA polymer and collagen, and added a separate layer of bladder urothelial cells on the inside. The organ part grew in a soup of nutrients for several weeks before the team sewed it to the patient's bladder. However the rate of degradation of scaffold is increased on account of hybridization with collagen. 5. Conclusions Biodegradable synthetic polymers show tremendous potential as matrices for stem cells to engineer new tissues. Polylactic acid (PLA), Polyglycolic acid (PGA) and copolymer of PLA and PGA are by far the most commonly used synthetic polymers as matrices for stem cells in order to form organ. These matrices provide mechanical support and maintain shape and integrity of scaffolds in aggressive environments of the body and guides the organization, growth, and differentiation of cells in tissue engineered constructs, the biomaterial scaffold should be able to provide not only a physical support for the cells but also the chemical and biological cues needed in forming functional tissues. The advantage of using polymers is that they can be tailored to have desired properties and structure. The bioresorption or disintegration after they have fulfilled their function minimizes the chronic foreign body response and leads to the formation of completely natural tissue. References: Agrawal C.M., McKinney J.S., Lanctot D., Athanasiou K.A., E!ects of fuid flow on the in vitro degradation kinetics of biodegradable scaffolds for tissue engineering”, Biomaterials ,21 ,2443-2452,2002. Altman G.H., Horan R.L., Lu H.H., Moreau., J. Martin., I. Richmond J.C and Kaplan D.L Silk matrix for tissue engineered anterior cruciate ligaments”, Biomaterials, 23, 4131–4141 (2002). Antonov E.N., Bagratashvili V.N., Whitaker M.J., Barry J.J., Shakesheff K.M., Konovalov A.N., Popov V.K. and Howdle S.M., Three-Dimensional Bioactive and Biodegradable Scaffolds Fabricated by Surface-Selective Laser Sintering”, Advanced Material, 17(3), 327-330 (2004). Atala A. and David J M ., “Synthetic biodegradable polymer scaffolds, pp.1-253,1958. Barry J.J.A., Howard D., Shakesheff K.M., Howdle S.M. and Alexander M.R,,Using a core-sheath distribution of chemistry through tissue engineering scaffolds to control cell ingress”,Advanced Materials,18, 1–6 (2006). Benoit D.S and Anseth K.S., Heparin functionalized PEG gels that modulate protein adsorption for hMSC adhesion and differentiation, Acta biomaterialia”, 1, 461–470 (2005). Benjamin j. lawrence. , “Composite scaffolds of natural and synthetic polymers for bladder tissue engineering”, master of science Thesis, Oklahoma state university, 2004. Bhang S.H., Lim J.S., Choi., C.Y., Kwon Y.K and Kim B.S., The behavior of neural stem cells on biodegradable synthetic polymers, Journal of biomaterials science”, 18, 223–239,(2007). Brahatheeswaran D., Yasuhiko Y., Toru M., and Sakthi .D, Polymeric Scaffolds in Tissue Engineering Application”, International Journal of Polymer Science, 1-19 (2011). Chen.G.,Takashi U., Tetsuya.T., and Macromol, Scaffold Design for Tissue Engineering“ Molecular Biocience,2, 67-77 (2002). Chunyan Zhao., Aaron Tan., Giorgia Pastorin., Han Kiat Ho., Nanomaterial scaffolds for stem cell proliferation and differentiation in tissue engineering”, Biotechnology Advances ,31 ,654–668, 2013. Flynn L., Prestwich G.D., Semple J.L and Woodhouse K.A., Adipose tissue engineering with naturally derived scaffolds and adipose-derived stem cells”, Biomaterials, 28, 3834–3842,(2007) . Freed L.E., Marquis J.C., Nohria A., Emmanual J., Mikos A.G. and Langer R., Neocartilage formation in vitro and in vivo using cells cultured on synthetic biodegradable polymers”,J Biomed Mater, 27(1),11-23 (1993). Gombotz W.R and Pettit D.K., Biodegradable polymers for protein and peptide drug delivery”, Bioconjugate Chem ,6 ,332-351,(1995). Gunatillake PA., And Adhikari R., Biodegradable synthetic polymers for tissue Engineering”, Eur Cell Material ,5,1-16 , 2003. Hamilton L., France RM., and Shakesheff KM., Development of an injectable scaffold for application in regenerative medicine to deliver stem cells and growth factors”, J Pharm Pharmacol,58, 52–53 (2006). Howard. D, Lee. D . B,  Shakesheff. M. K and Roberts. J. S Tissue engineering: strategies, stem cells and scaffolds”, Journal of Anatomy, 213, 66–72 (2008). Kanczler J.M., Barry J, Ginty P., Howdle S.M., Shakesheff K.M., and Oreffo R.O.,Supercritical carbon dioxide generated vascular endothelial growth factor encapsulated poly(DL-lactic acid) scaffolds induce angiogenesis in vitro”, Biochem Biophys Res Commun, 352(1), 135-41 (2007). Ke Cheng., Yinzhi La.i, William S.K., Three-dimensional polymer scaffolds for high throughput cell-based assay systems”,Biomaterials 29, 2802–2812,2008. Kuo Y., Chen C W, Inverted colloidal crystal scaffolds with induced pluripotent stem cells for nerve tissue engineering”,Colloids and Surfaces B: Biointerfaces 102 ,789– 794.2013. Lampe J K., Sarah C. H., Building stem cell niches from the molecule up through engineered peptide Materials”, Neuroscience Letters, 519,138– 146,2012. Lichte P., Pape H.C., Pufe T., Kobbe P., Fischer H., Scaffolds for bone healing: Concepts, materials and evidence”, Injury, Int. J. Care Injured ,42 , ,569–573.2011. Mitchell.B.S “An introduction to materials engineering and science for chemical and materials engineers, John Wiley & Sons, Inc., Hoboken, New Jersey,76,1962. Prasad K., Yarlagadda., Chandrasekharan., Margam., Shyan., And John Yong Ming, Recent advances and Current developments in tissue scaffolding” , Bio-Medical Materials and Engineering, 15(3),159-177 (2005). Reed A.M., and Gliding D.K., Biodegardable polymer for use in surgery polyglycolic/Polylactic homo and copolymers: 2. Invito degradation”, Polymer, 22,494-498 (1981). Rowlands A.S., Lim S.A., Martin D., Cooper-White J.J., Polyurethane/poly(lactic-co-glycolic) acid composite scaffolds fabricated by thermally induced phase separation”, Biomaterials ,28 ,2109–2121,2007. Schugens Ch., Maquet V., Grandfils Ch., Jerome R., Teyssie Ph., Polymer ,37, 1027,1996. Susan L., Casey K. Chan., Ramakrishna S., Stem cells and biomimetic materials strategies for tissue engineering”, Materials Science and Engineering , 28 ,1189–1202,2008. Suciati T., Howard D., Barry J., Everitt N M., Shakesheff K.M., and Rose F.R, Zonal release of proteins within tissue engineering scaffolds,” J Material Science, 17(11),1049-56 (2006). Vincenzo G ., Filippo C., Paola T ., Foggia M., Ciapetti G., Desire`e M., Concezio F., Baldini N., Ambrosio L., Polylactic acid fibre-reinforced polycaprolactone scaffolds for bone tissue engineering”,Biomaterials, 29 ,3662–3670,2008. Willerth.M.S and Sakiyama-Elbert.E.S “Stem book, National center for biotechnology information, USA, 2-11, 2008. Nomenclature: ESCs-Embryonic stem cells PLA- Polylactic acid PGA-Polyglycolic acid PLGA-Polylactic-co-glycolic acid Tm-Melting point T g-Glass transition temperature PEG-polyethylene glycol ppHex - plasma polymerized allyl amine ppAm - plasma polymerized allyl amine Introduction Scope & Objective Literature Survey Conclusion Current Research Conclusion Nomenclature INDEX _____________________________________________________________________________________ 1