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Online Available online. More options. Find it at other libraries via WorldCat Limited preview. Contributor IGI Global, publisher. Information Resources Management Association, editor. Bibliography Includes bibliographical references and index. Contents Volume I. Section 1. Fundamental concepts and theories. Chapter 1. Cross-cultural psychology of play and early childhood education ; Chapter 2.

Where are we if our batteries die? Integrating play therapy and mental health consultation ; Chapter 4. Play-based literacy instruction: interactive learning in a kindergarten classroom ; Chapter 5. Parental investment in early childhood: a Tunisian regional comparisons study ; Chapter 6. Current trends and perspectives in the K Canadian blended and online classroom ; Chapter 7.

Hidden curriculum determinants in pre school institutions: implicit cognition in action Section 2. Development and design methodologies. Chapter 8. Constructing a multidimensional socioeconomic index and the validation of it with early child developmental outcomes ; Chapter 9. Early childhood play with reclaimed resources: potential benefits for young children ; Chapter Play and speech therapy in schools: toward a model of interprofessional collaborative practice ; Chapter The impact of trauma on brain development: a neurodevelopmentally appropriate model for play therapists ; Chapter Art therapy: a social work perspective ; Chapter Eye-tracking as a research methodology in educational context: a spanning framework ; Chapter Using theory-based research in supporting creative learning environment for young children ; Chapter Constructivism in education: interpretations and criticisms from science education ; Chapter Dynamics of culture and curriculum design: preparing culturally responsive teacher candidates ; Chapter An analysis of mobile applications for early childhood students with bilateral hearing loss ; Chapter Toward a participatory view of early literacies in second language contexts: a reflection on research from Colombia ; Chapter Do-it-our-way or do-it-yourself?

Resilience and psychomotricity: strategies of action in preschool education ; Chapter Metacognition and metacognitive skills: intellectual skills development technology ; Chapter Using brain-based instruction to optimize early childhood English language education ; Chapter Young children and narrative meaning-making to promote arts and technology ; Chapter Early experiences with family involvement: strategies for success and practices that make a difference Volume II.

Chapter Social-emotional learning and students' transition from kindergarten to primary school in Italy Section 3. Tools and technologies. Using new technologies to engage and support English language learners in mathematics classrooms ; Chapter Mathematics gaming in early childhood: describing teacher moves for effective and appropriate implementation ; Chapter Development of linguistic abilities in bilingual education through musical stories ; Chapter The use of eye-tracking in spatial thinking research ; Chapter Parents and technology: integration of web-based resources to improve the health and well-being of children ; Chapter Eye tracking and spoken language comprehension ; Chapter Dynamic electronic textbooks: a new learning experience ; Chapter Child development associate CDA credential: a competency-based framework for workforce development ; Chapter Teaching history of mathematics through digital stories: a technology integration model ; Chapter Active learning strategies in technology integrated K classrooms ; Chapter Kinesthetic gaming, cognition, and learning: implications for P education ; Chapter Tracking children's interactions with traditional text and computer-based early literacy media ; Chapter The appropriateness of scratch and app inventor as educational environments for teaching introductory programming in primary and secondary education ; Chapter Comparing the effectiveness of using tablet computers for teaching addition and subtraction ; Chapter The effects of interactive multimedia ipad e-books on preschoolers' literacy ; Chapter Emerging use of tablets in K environments: issues and implications in K schools ; Chapter Computational thinking and young children: understanding the potential of tangible and graphical interfaces ; Chapter Robotics in early childhood education: a case study for the best practices Section 4.

Utilization and applications. In order to replicate the natural bones, scaffolds are engineered to be bioactive or bioresorbable to enhance tissue growth.

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Scaffolds are often porous that supports mechanically. There are various criteria such as biocompatibility, mechanical properties, pore size and bioresorbability that have to be considered as requirements of an ideal scaffold. Different classes of materials are used for fabrication of scaffolds such as polymers, bioglass, composite and metals.

Significant progress was achieved in terms of scaffolds for mechanical support with better osteogenesis and angiogenesis. Various material fabrication methodologies enable the possibility to fabricate scaffolds with complex design [ 17 ] to ensure mechanical integrity and scaffold interconnectivity. The objective of this chapter is to review the different fabrication methodologies and the recent advances in the fabrication of biomimetic and bioactive scaffolds are presented with a case study and the possible improvements envisaged are discussed. Human body being a complex and sensitive biological system requires the scaffold materials with diverse and challenging characteristics.

Scaffold must combine structural, material, bioactivation, signaling molecules, cells and biological requirements satisfied for different applications. Human bone [ 18 ] is classified as the long bones femur and tibia , short bones vertebrae and metacarpal bone , flat bones and the spongious bone [ 19 ]. The structural property of the corresponding bones is strongly interdependent on the mechanical property [ 20 ]. The spongy bones act as a host to soft tissues, cartilage, and meniscus and prevent the stress concentration.

The fibrous tissue surrounding the bones is ligaments, which are highly organized fiber tissue composed of collagens, elastin, proteoglycan, water and cells. The mineral inorganic part will be assisting in compression and shear and the collagen matrix provides tensile strength. In the current state of art, it can be observed that the mechanical integrity of the synthetic scaffolds is inadequate. Polymers have yielded results close to the cancellous bone properties.

Bimodal architectures [ 22 ] matching the natural bone is yet in progress. Scaffolds should provide sufficient strength [ 23 ] for cell ingrowth in in vitro conditions and integrate completely under in vivo conditions. In order to fabricate the biomimetic materials various systems [ 24 ] such as polysaccharides, proteins, nanocomposites based on calcium phosphates CaPs e. The polymers [ 25 ] employed usually assist in structural integrity and promotes cell adhesion.

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Whereas, CaPs are biocompatible, osteoconductive and biodegradable with limitations on mechanical strength that forbids the load-bearing applications. Ionic co-substitutions in calcium phosphates are also used that can influence the structure, microstructure, crystallinity and dissolution rate.


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The substitution of these aforesaid ions have significant role in causing alterations to bone resorption, bone formation, solubility, structure and morphological changes and enhanced surface microstructure. There are also Calcium phosphate based cements [ 28 ] that can be used as injectable pastes in the defect bone site for cell delivery and is an upsurging topic of research.

Nanocomposites [ 29 ] consisting the component of polymer and nanosized CaPs improves the tissue bonding, cell adhesion and cell differentiation. Designing of the 3D scaffold [ 30 ] should stimulate the adhesion, proliferation and differentiation mechanisms in addition to the structural complexity of natural bones. The synthetic bone should also enable vascularization to enable biointegration with transport and support of signaling molecules, passage of nutrients and blood vessels.

Hence the critical aspects such as highly porous interconnected microstructure and degree of porosity for uniform cell distribution, proliferation and migration in vitro. Critical pore sizes [ 31 ] are necessary to adjudge their function, because when the pore size is small the cell adherence can block the pores and matrix formation of the scaffold. It was reported that the tangent elastic modulus of natural bones decreases with the increase in porosity such as in porous tantalum [ 32 ]. Equally the pore shape, size and orientation are important in adjudging the mechanical properties of the scaffolds.

Variation of the mechanical properties [ 33 ] of the scaffold with two different pore structures was reported earlier. It was observed that the mechanical properties of the scaffold with spherical pore structure have higher elastic modulus in comparison to the scaffold with cylindrical pore [ 34 ]. Similar alteration in the mechanical properties was also reported in the case of polycaprolactone [ 35 ].

From the aforesaid it can be concluded that the mechanical properties of the fabricated scaffold can be altered by the variation of the pore shape. Similar influence was reported on the pore size, where an increase in the pore size reduces the mechanical properties. The orientation of the pores also significantly altered the mechanical properties of the scaffold irrespective of the matrix of the material chosen ranging from metals to polymers. When the pore geometry was parallel or aligned in the same direction, the mechanical strength of these scaffolds were high.

The mechanical stability of the multiscale porosity can be interesting in terms of crack propagation. This multiscale porosity can be achieved by combining two or three scaffold fabrication methods. Materials for fabrication of scaffolds [ 36 ] are selected based on their degradability, chemical and physical properties. Animal and plant based materials such as starch, alginate, chitosan, hyaluronic acid, gelatin, collagen, fibrin, silk, etc.

Due to the disease transmission and purification, synthetic biomaterials are attracting the interest of the researchers. Synthetic organic and inorganic materials such as HAp, CaPs, glass, polyesters are actively studied for usage as scaffold material.


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Autograft bone scaffold [ 37 ] was considered to the gold standard for bone repair defect. Lack of donors and possible disease infection are few of the major disadvantages of autograft scaffolds. Bone allograft [ 38 ] was considered as an alternative to the autograft, but still the transmission of diseases, inflammatory reactions and rejection by the recipient body is prevalent. Hence artificial scaffolds have been proposed as an alternative to the autograft and allograft scaffolds. Usage of metallic implants [ 39 ] dates back to Currently synthetic bone implants made of metals, ceramics, composites and glasses are employed for bone regeneration and bone reconstruction.

There are several issues such as poor strength of the polymer scaffolds, poor ion release of ions from the metallic scaffolds, brittleness of the ceramics and difficulty in controlling degradation rate of the composite scaffold to be addressed. Langer and Vacanti [ 40 ] were the pioneers of the tissue engineering concept in early nineties. They introduced the concept of introducing the bone marrow cells, different growth factors, gene and drug delivery in to the artificial bone scaffolds. Further investigations by various researchers enabled the possibility of improving the biocompatibility by changes in the topology, nanostructure, chemistry and structural aspects of the scaffolds.

Metallic biomaterials are especially preferred for their usage in load-bearing applications due to their good mechanical properties.

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The porous metallic scaffolds [ 41 ] based on the stainless steel, titanium and magnesium are used to eliminate stress shielding and reduce the stiffness to match the natural bone. Interconnected porous metallic scaffolds [ 42 ] were fabricated by combining the various rapid prototype techniques such as solvent leaching and 3D printing was reported in the fabrication of Ti scaffolds.

Other fabrication techniques such as powder metallurgy, sintering and rapid prototyping to modulate the scaffold design. The mechanical properties of the Ti scaffolds can be used to mimic the human cancellous bone due to its structural flexibility. The elasticity and other vital properties such as deformation force, stress and strain can be modified by alloying with a suitable metal.

NiTi alloys were reported to exhibit good in vivo compatibility than pure Ti porous scaffolds [ 43 ]. The porous metallic scaffold assisted in rapid formation of new bone tissues for load-bearing conditions. Bioactive glasses [ 44 ] were reported to have good osteoconductivity, controlled biodegradability, cell delivery capabilities and inducing osteogenic gene expression for formation of bone minerals and capability for drug delivery.

In order to improve the mechanical properties of the bioactive glasses, modification of structure and composition is achieved during bioglass scaffold fabrication. Biomorphic and mesoporous bioactive scaffolds [ 45 ] were shown to have better mechanical properties than in comparison to the classical bioactive glasses.

The inorganic component phase in the bioactive glass scaffold is important in addition to the structural design of these bioactive glass scaffolds. Biopolymers and its derived composites are also used for fabrication of scaffold for tissue engineering applications. However their poor mechanical strength makes it difficult to use them in load bearing applications.

Biopolymer based composites and hybrids for bone scaffold applications [ 46 ] with required strength are prepared by varying the volume fraction of polymer in the composites. In order to replicate the biomimetic conditions, surface modifications are also carried out. Controlled release of biological molecules is also a key function that the scaffolds play. Porous biomimetic scaffolds [ 48 ] with their 3D structure is advantageous for 1 better cell biomaterial interactions, cell adhesion and growth 2 interconnected porosity for angiogenesis and transport of nutrients, regulatory factors for cell survival, proliferation and differentiation 3 Sufficient structural integration with good tensile strength and elasticity 4 Control degradation and minimal toxicity in vivo.

Nanocomposites of CaPs and natural polymers such as collagen and gelatin are well known for tissue engineering. Techniques such as foam replica method [ 49 ], freeze casting [ 50 ], freeze drying [ 51 ], phase separation [ 52 ], gas foaming [ 53 ], rapid prototyping [ 54 ] and electrospinning [ 55 ] are employed for fabrication. The challenge of nanocomposite scaffolds lies in the ensuring the retention of chemical phases and retaining the porous structure without disturbing their porous structure. A combination of different method of fabrications such as freeze casting and electrospinning are used for fabrication of scaffolds.

Other polymers such as poly lactic co-glycolic acid PLGA , Sodium dodecyl sulfate SDS , cellulose, poly glycolic acid PGA , poly ethylene glycol and poly l-lactic acid PLA are also used for fabricating the nanocomposites due to their excellent biodegradability and biocompatibility. Collagen of type I, the predominantly available protein in mammals can be readily obtained from animal tissues and from human tissues.


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This extracellular matrix protein collagen can be reconstituted in a different morphology into fibrillary matrix by changing the pH and temperature of precursors. Due to the lack of mechanical strength in collagen for in vivo applications, several strategies are employed such as crosslinking with hydrogels [ 56 ] or compression so that it can sustain or resist cell-induced contraction.

Inherent characteristics of collagen such as dipole moment and alignment under strong magnetic field [ 57 ] were demonstrated to induce cell migration and allow preferential growth of neurites along the alignment of the fibril direction. Collagens can hold several cellular receptors that can variate the cell behavior and their biological function can be induced by combining with growth factors for example, vascular endothelial growth factor VEGF to improve cardiac function was observed.

Fibrin [ 58 ] is a specialized protein network clinically available from autologous sources such as human blood plasma.

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In the presence of thrombin protease, fibrin matrix is formed spontaneously by polymerization of fibrinogen. Cell migration in fibrin is dependent on the cell-associated proteolytic activity from plasmin and MMPs due to their small diameter. This indeed assists in strong fibril-fibril interaction and the natural network formation and stabilization through covalent bond stabilization. As fibrin matrices are poorly active for most of the cell types, functionalization with ECM peptides or growth factors is necessary.

The controlled release of the growth factors and hormones can be efficiently done by covalent bonding of biomolecules. Hyaluronan or Hyaluronic acid [ 60 ] is a structural protein that is noncovalently attached to the protein core and entwine ECM. Due to their strong anionic nature, these polymers absorb water and hence providing the compressive strength to the ECM.

Various chemical hyaluronic acid derivatives have been prepared by controlling the functional group and the type of covalent bond. It is possible to create a wide range of materials with diverse properties. Hyaluronic acid [ 61 ] is used for various applications for dermal wound healing, chondrocyte transplantation for tissue repair and for incorporation of other functional biomolecules for improved fibroblast proliferation and wound healing.

Other self-assembling polypeptides are also used to form nanofibrillar matrices in situ. Self-assembled peptide hydrogels [ 62 ] are used as a tool for developing 3D cell culture plates. To have properties similar to natural ECM, it is necessary to have facilities for cell seeding, adhesion, proliferation, differentiation and new tissue generation. Essential characteristics such as biodegradability and mechanical properties are important to be studied.

The biodegradation of the scaffold should be in coherence with the rate of the formation of the new tissue formation that it supports initially to act as a scaffold material to serve as a template. Elastomeric properties of scaffolds [ 63 ] are studied to improve their applications in tissue engineering applications. Tensile modulus and strength are critical parameters necessary for tendons and ligaments. Natural fibrous protein from silk worm cocoon is a material with excellent tensile and mechanical strength [ 65 ].

Silk fibroins have hydrophobic and hydrophilic blocks which forms crystals through hydrophobic interactions and hydrogen bonding resulting in the improved tensile strength. Spider silk fibroin polymers [ 66 ] are used for genetic engineering due to their excellent mechanical and cell adhering capacity.

As extracellular proteins have a fibrous structure with diameters in the nanometer or sub-micrometer scales, various advanced material shaping techniques were developed. Techniques such as electrospinning, self-assembly and phase separation are a few worthy-to-mention. Electro-spinning technique were used to produce nanofibers, but the disadvantage of this technique is to fabricate the complex 3D scaffold structure or to produce intricate pore structures. Various cells were reported to proliferate, differentiate and attach on these electro-spun nanofibers [ 67 ].

Phase separation arises when homogeneous multicomponent system tends to be unstable resulting in multiphase system due to the system free energy. This technique is employed in generating porous structures as tissue engineering scaffolds. The huge disadvantage of this technique is the lack of interconnected porosity and the lack of control over 3D shapes.

Biological effects of nanofibrous scaffold [ 68 ] were found to adsorb more human serum proteins in comparison to the scaffolds of smooth pore wall morphology. The cell adhesion proteins were comparatively well detected than the conventional scaffolds.

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Hydroxyapatite being the major inorganic compound used in most of the composite scaffolds, it provides good osteoconductivity. In the presence of the composite structures with polymers hydroxyapatite provides structure and design flexibility. Further it assists in improving the protein adsorption capacity, microstructure favoring the bone tissue regeneration and diminishing the cell death. These nanocomposites mimic the features similar to the natural bone with improved mechanical properties.

However regarding the biodegradation rate of stoichiometric HAp are less efficient than the partially carbonated apatite. The surface of scaffolds affect cellular response and in turn also the tissue regeneration [ 69 ]. Composites of scaffold materials with organic and inorganic components were designed for mechanical and physiological requirements in tissue engineering. However the brittle nature of ceramics and low mechanical strength inhibits their usage in clinical applications.

Composite structure of HAp with porous polymers alongside their pore size, shape and morphology has improved the mechanical strength for tissue engineering applications. With the recent advances in the biodegradable polymers [ 70 ], glass and ceramics, it is possible to cater degradation kinetics and resorption in vivo after stimulating cellular responses at the molecular level.

It is expected that the new generation of scaffolds can perfectly mimic the natural bone in terms of mechanical and structural aspects. With the advances in the manufacturing techniques such as selective laser sintering and rapid prototyping should be helpful in bone tissue engineering applications.

These techniques are widely used in the fabrication of temporomandibular joints [ 71 ], craniofacial [ 72 ] or periodontal structures [ 73 ]. The fabrication methodology allows the flexibility of the combination of different materials for increasing mechanical strength. The current state-of-art, however, does not allow to exactly replicate the natural architecture of the extracellular matrix or the natural bone.

There is a continuous demand for the improvement and functioning of the scaffold fabrication. Here we will discuss few of the fabrication techniques such as solvent casting, particulate leaching electrospinning, gas foaming, phase separation, fiber meshing and bonding, self-assembly, rapid prototyping, melt molding, lamination and freeze drying. A nineteenth century technology, which was initially used for production of thin films, is currently employed for diverse applications ranging from optical applications, photographical film base flexible printed circuits and high temperature resistive films.

Solvent casting [ 74 ] are generally produced by evaporation of the solvent in order to form the scaffolds. In order to successfully employ the solvent casting, it is necessary that the polymer used should be soluble in a volatile solvent or in water. A stable solution with an adequate solid content and viscosity should be formed.

Formation of homogeneous film after removing from cast support must be possible. The main disadvantage of this technique is the denaturation of the protein caused due to the solvent if toxic and influence of the organic material on the solvent. To remove the toxicity of the solvent left over in the scaffold, they are usually dried by vacuum process and dried completely. To make it time efficient, other techniques such as particulate leaching were combined for the fabrication of scaffolds.

Being one of the popular techniques in the fabrication of scaffolds for tissue engineering [ 75 ] is relatively a technique of ease. Usage of porogens such as salt, sugar and wax is common to produce the pore channels by this technique. Mixture of porogen of the desired size is mixed with the material, then after leaching the porogen, the pores are left behind in the matrix.

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The control of the pore size is possible by choosing the required size and shape of the porogen. Gas foaming process uses the utilization of high pressure gases for the fabrication of highly porous scaffolds [ 53 ]. When the gas is injected the gas bubble starts to create the phase separation.

A three dimensional porous structure can be obtained by using the gas foaming technique. But the control over the interconnectivity is highly lagging behind in this technique, though is advantageous in terms as a solvent free technique. The porosity will be frequently absent on the external surface. This technique involves quenching of the polymers which can cause two phases of polymers to separate as polymer rich and polymer poor phases [ 76 ]. The polymer poor phase will cause the porous structure network to be formed.

The control of the porous microstructure is possible with the help of parameters such as polymer concentration, quenching rate and temperature, solvent concentration, solvent type and dispersion of the solute molecules. The solvent can be removed by extraction, evaporation and sublimation after integrating the bioactive molecules in the scaffold. Nanofibers can be prepared by liquid-liquid phase separation to replicate the architecture similar to type I collagen molecules and other extracellular matrix architectures for 3D cell culture environment.

As these experiments are carried out at low temperatures, the incorporation of bioactive molecules is feasible. The phase separation methodology can be used in conjunction with other techniques that can control the porous architecture and also with other rapid prototyping techniques for tissue engineering applications. When the porogen is leached out and then the scaffold is formed.