An introduction to biomaterials second edition pdf

Over the past decades, compelling studies have suggested that sol-gel-derived scaffolds are important as drug delivery systems to treat diseases Habraken, Wolke, and Jansen Synthesis of biomaterials using the sol-gel process involves three main steps: 1.

In general, hydrolysis and condensation reactions occur simultane- ously once the hydrolysis reaction is initiated. These condensation reactions produce high- molecular-weight molecules that continually combine to form an infinite-molecular- weight network characterized by a gel point Munk Condensation: As soon as the alkoxide becomes hydrolyzed, two reversible condensation reactions can occur.

The first condensation reaction forms an alcohol and the second con- densation reaction forms water Figure Complete hydrolysis of the alkoxide is not necessary for condensation reactions to occur; this has been demonstrated by several dif- ferent studies Artaki, Zerda, and Jonas ; Artaki, Zerda, and Jonas ; Brinker ; Chen, Tsuchiya, and Mackenzie ; Colby, Osaka, and Mackenzie ; Colby, Osaka, and Mackenzie ; Kawaguchi et al. The reverse reactions of con- densation are known as alcoholysis and hydrolysis.

These reactions result in the cleavage of a Si- 0 - Si bond through a nucleophilic attack by alcohol or water. Drying: Drying parameters control the final properties of the bioactive material in regen- erative medicine. A high rate of drying usually results in nanoparticles that can be used for various applications in the biomedical field. Controlled low rates of drying can result in three-dimensional 3D scaffolds with various porosity characteristics.

High-density materials with superior optical and mechanical properties can be produced by employing a bulky R group in the alkoxide and a slow rate of drying. For example, sol-gel chemistry has been used to synthesize porous bioactive structures that are osteoconductive, with Si-substituted HA. The biomaterial improvements were due to the finite control of composition and structural morphology Borros et al.

This outcome has a profound potential for controlling porosity and pore-size range and distribution for precision fabrication of structural templates and scaffolds. Despite the promise for sol-gel methodologies in producing drug delivery systems, the goal of synthesizing a biomechanically compatible bone implant for regenerative therapy has not yet been realized. Remarkably, recent reports on sol-gel-derived star glass show promising results.

A composite is made from more than one material in which the bond between the components is on a level higher than the atomic level. The molecular precursors consist of a core atom and a linear segment, or a ring from which two or more flexible arms originate Figure The arms terminate in trialkoxy- silyl or tri polyftuoroalkoxy silyl groups, which are then used to construct the inorganic portion of the network via one of several sol-gel alternatives.

The gel is then converted into glass by room temperature evaporation of the liquids entrapped in the pores of the gel. Figure The methodology is relatively simple and efficient in producing a high yield of the desired biomaterial.

Star glass materials have an amorphous structure that lacks a long-range atomic order. The physicochemical properties of star glass can be engineered by modifying the chemistry and processing techniques used. Addition of other ingredients such as Ca to induce bioactivity properties can be achieved using calcium alkoxide. Various bioactive star glass formulations Table From Sharp, K. J Mater Chem 15 Ehrenfried, and L.

Biomaterials 27 7 From M. Manzano, D. Arcos, M. Rodriguez Delgado, E. Ruiz, F. Gil, and M. Chem Mater 18 24 The later sol-gel bioactive glasses were prepared by adding TEOS, a Si02 source, to calcium methoxyethoxide in the appropriate stoi- chiometric amounts.

A key advantage of star glass materials is the ability to tailor processing parameters, such as gelation chemistry and duration, to engineer physicochemical properties of the material includ- ing strength, toughness, and chemical reactivity.

Parameters that control the gelation chemistry include silane structure and functionality, the molar ratio of gelation agent to silane, pH, and type of solvent. The star reacts faster in acid media and water without a catalyst.

The toughness of star glass counteracts one of the most significant and difficult limitations of bioactive calcium phosphate ceramics and bioactive glasses. Moreover, in comparison with conventional sol-gel glass star glasses have significantly higher levels of impact resistance. Therefore, producing tough bioactive star glass has great therapeutic potential for new therapy strategies in orthopedic and maxillofacial surgeries.

The modulus of elasticity, as discussed in Section Although the moduli of conventional silica gel glasses are higher than those of star glasses, the latter show substantially greater fracture toughness and tensile strength over the former.

Remarkably, star glasses show no evidence of plastic deformation during or after compression cycling. J Mater Chem 15 36 The reason why star glasses have superior toughness over traditional bioactive glass is the incorporation of the organic matrix.

When subjected to mechanical loading, the flexibility of the organic chains allows them to slide over each other. The mobility of the molecules of the organic component of star glass is controlled by their length, functional groups, and percentage. The mechanical properties of star glass can be engineered by controlling the parameters of the sol- gel process, including rate of gelation, porosity of the dried glasses, percolation threshold for gel formation, and the relative tendency for intra- versus intermolecular structures.

Mechanical properties were determined by indentation techniques. Compressive strength values were obtained by means of a metal testing solution MTS nanoindenter. Around indentations were carried out on the star gel disks 15 mm in diameter and 3 mm in thickness. The MTS nanoin- denter system records material displacement as a function of the applied load to calculate the compres- sive strength of a material. Fracture toughness Kc values were determined by means of a Matzuzawa microhardness tester with Vickers and Knoop indenters.

It can be seen that the maximum value is for the conventional sol-gel glass 90Si:l0Ca , whereas star gels are softer.

These results are in agreement with the calculated Young's modulus Figure The Young's modulus is a material constant that measures the degree of deformation when a material is subjected to stress. Material deformation is mainly dependent on strength of the atomic 0.

Values represent the average of multiple tests with the corresponding standard deviations. Vallet- Regi. Biologically Active Glasses bond, atomic packing density in the crystal, structural defects, and intermolecular spaces. In the case of conventional sol-gel glasses, chemical bonds undergo very little deformation under a mechanical load, mainly due to their high bond energy that leads to rigidity and, consequently, very small deformations.

The addition of the organic component results in a decrease in average bond stiffness, which is produced by this new, more flexible, and more geometrical configuration. In this case, the elastic deformation is higher under the same mechanical load. Bone implant materials that have a similar modulus of elasticity to bone do not cause stress-shielding problems. By calculating the compressive maximum strength values, one can observe the same trend for Young's modulus and hardness Figure It should be noted that these values approximate the true values, as the sample shapes were not normalized.

The configuration influence in SGB-2Ca is clearly observed, where the strain at maximum strength deformation is higher compared with those of the other samples. This fact can be explained by the chemical bond's deformability in SGB-2Ca. It can be observed that the fracture deformation values were around 0. This means there is no energy absorption before breaking and the frac- ture can be considered fragile. The mechanism of material fracture includes crack initiation, propagation, and failure.

The occurrence of microcracks on the surface of the material is almost unavoidable. Preexisting cracks are detrimental to fracture strength because an applied stress may be amplified at the tip of a surface crack. Therefore, cracks are called stress raisers. For brittle materials, for example, ceramics and glasses, the rigidity of the atomic bond concentrates the stress energy at the crack tip; once the stress reaches critical value, crack propagation is extremely rapid and is accompanied by energy release.

As a result, once crack propagation starts, it continues spontaneously without an increase in the magnitude of applied stress.

Stress concentration factor is simply a measure of the degree to which an external stress is amplified at the tip of a crack. The magnitude of this amplification depends on crack orientation and geometry. In ductile materials, the crack's tip or propagation point is deformed and not sharp; hence crack propagation is slow, resulting in delayed fracture.

The fracture toughness, Kc, measures the resistance of a material to brittle fracture when a crack is present. When the material is thick and the crack dimensions are small, the Kc value is known as plain strain fracture toughness, K 1c Brittle materials for which no appreciable plastic deformation occurs in front of an advancing crack tip have low K1c values and are vulnerable to catastrophic fail- ure.

Fracture toughness values of star gels are significantly higher than those of conventional sol-gel glasses Figure The flexible structure of star gels allows local molecular rotation and deformations, resulting in energy consumption and better toughness compared with conventional sol-gel glasses.

The fracture toughness of star glass can be engineered by tailoring the composition of the material Figure This structural difference between SGA-Ca and SGB-2Ca is not as important with respect to the rest of the mechanical parameters, such as hardness, Young's modulus, and compressive strength, since these properties are not as sensitive to the differences among structural chains. Preliminary fatigue testing carried out by means of cyclic loading with a nanoindenter indicates that bone, which is normally subjected to cyclic stresses, undergoes fatigue failure.

Under a MPa stress force, a human femur undergoes cycles to fracture. Star gels resisted more than cycles, whereas the conventional sol-gel glass 90Si:l0Ca resisted only around 30 cycles.

From these results, star gels are expected to exhibit good long-term fatigue behavior. This is an essential perfor- mance attribute for exploiting star gel glasses in bone tissue engineering. Biomaterials that do not bond to bone do not form either a surface amorphous calcium phosphate or an HA layer when immersed in SBF.

The SBF is an acellular protein-free tris buffer with ionic concentrations and pH similar to those of human plasma. On the other hand, SGB-Ca and control star gels without Ca were not bioactive; they did not show the formation of a calcium phosphate surface layer.

The explanation rests on the network connectivity of the different star gels. These results indicate that the star gel's molar ratio of Ca:Si must be around 9 or lower for the star gel to be bioactive. Before soaking, the micrograph shows the smooth surface characteristic of a nonporous and homogeneous gel. After 7 days, SEM micrograph reveals the deposition of a new phase that partially covers the star gel surface.

The SEM analyses at higher magnifications reveal that the deposited phase is made of rounded submicrometer crystals. The micrograph of the star gel after 17 days shows the monolith surface fully covered by layers of aggregates of needle-shaped crystallites, which are typical of carbonated H A.

Note: More precisely, the mineralized matrix of bone is actually composed of a carbonated HA. The structural homogeneity of SGA-Ca and the formation of a nanocrystalline apatite phase on the surface have been further demonstrated by high-resolution transmission electron microscopy HRTEM.

Figures The images show a structure "typical" for amor- phous material, and the ED pattern suggests a broad diffuse scattering, which is indicative of the amorphous nature of the material. These results confirm the amorphous structure of bioactive star gels.

The images were collected from the surface of the star gels. For this purpose, some particles were gently scratched from the surface monoliths.

Transmission electron microscopy TEM images show crystalline domains, where ori- ented planes can be easily distinguished Figure The EDX spectra collected from these areas show elemental chemical compositions that correspond to those expected for an apatite-like phase, that is, a phase containing Ca and P as main components. Moreover, the ED patterns correspond to a typical polycrystalline material Figure The interplanar spacing of the rings observed corresponds to the , , and reflections of an apatite-like phase.

The EDX spectra clearly show the evolution of the inorganic chemical composition on the surface, from silicon and calcium oxide to a calcium phosphate. Contemporary orthopedic implant materials do not adequately match the complex and dynamic biomechanical properties of bone. For example, bioactive ceramics are brittle with a high modulus of elasticity. Images c and d are magnifications of images a and b , respectively.

The insets in a and b are the electron diffraction patterns that were acquired during the observations. Energy-dispersive X-ray spectra before soaking bottom-left and after soaking for 3 weeks in SBF bottom-right confirm the surface evolution during the bioactive process. Star glass is unique in that it can be engineered with bioactivity and mechanical properties that are compatible with bone. Consequently, it remains uncertain whether this class of new biomaterials will fulfill the current unmet needs in this field.

In addition, star glasses in general do not show significant surface area by nitrogen adsorption isotherm measurements. The apparent lack of open porosity has been confirmed by comparison of bulk density and skeletal density using helium He pycnometry.

The two densities were identical, indicating the inability of He to penetrate into the interior of the solid. The reason for the lack of measurable porosity is related to the flexibility of the network, which leads to pore collapse on dry- ing Sharp It is not known if this pore collapse is reversible.

Star glass biomaterials must be engineered with a biomimetic morphological structure, mimicking that of bone. The biomimetic architecture must be a 3-D template for osteoconduction and must include an interconnected net- work of macropores. Star gel material technology may provide compelling new regenerative opportunities for twenty- first century tissue engineering of orthopedic therapeutics. However, at this time their potential must first be validated using standardized in vitro and in vivo systems refer to Chapters 8 and 9 before star gel glasses can find suitable roles to play in this field.

Cheng, W. Freeman, and M. Porous silicon in drug delivery devices and materials. Adv Drug Deliv Rev 60 11 Artaki, I. Zerda, and J. Solvent effects on hydrolysis stage of the sol-gel process. Mater Lett 3 12 Solvent effects on the condensation stage of the sol-gel process. J Non Cryst Solids 81 3 Borros, S. Semino, E. Genove, D. Gasset, E.

All aspects of biomaterials science are thoroughly addressed, from tissue engineering to cochlear prostheses and drug delivery systems. Over 80 contributors from academia, government and industry detail the principles of cell biology, immunology, and pathology. Focus within pertains to the clinical uses of biomaterials as components in implants, devices, and artificial organs.

This reference also touches upon their uses in biotechnology as well as the characterization of the physical, chemical, biochemical and surface properties of these materials. Provides comprehensive coverage of principles and applications of all classes of biomaterials Integrates concepts of biomaterials science and biological interactions with clinical science and societal issues including law, regulation, and ethics Discusses successes and failures of biomaterials applications in clinical medicine and the future directions of the field Cover the broad spectrum of biomaterial compositions including polymers, metals, ceramics, glasses, carbons, natural materials, and composites Endorsed by the Society for Biomaterials Author : Buddy D.

Author : J. This activity has led to biomaterials based medical devices like a plethora, which are now commercially available. Scope of biomaterials, this is an especially exciting time. On the one hand, they have the opportunity to meet and learn from some of the stalwarts and pioneers of the field such as Sam Hulbert, one of the founders of the Society for Biomaterials SFB.

Most of these individuals are still active in research and teaching. The authors C. Mauli Agrawal of this Introduction to Biomaterials book have been privileged to interact and learn from them in various forums, and students today have the same opportunities. On the other hand, with the current availability of sophisticated processing and characterization technologies, present-day students also have the tools to take the field to unprecedented new levels of innovation.

This Introduction to Biomaterials by C. Mauli Agrawal's book has been written as an introduction to biomaterials for college students.

It is best suited for students who have already taken an introductory course in biology. We have felt the need for a textbook that caters to all students interested in biomaterials and does not assume that every student intends to become a biomaterials scientist.