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ScienceWeek
MATERIALS SCIENCE: ON NEW BIOMATERIALS
The following points are made by D.G. Anderson et al (Science 2004 305:1923):
1) More than 2000 years ago, the Romans, Chinese, and Aztecs used biomaterials such as gold for dentistry. Yet it is only with the development of synthetic polymer systems in the past few decades that biomaterials have begun to find broad applications in modern medicine (1). A new wave of advances in cell biology, chemistry, and materials science is enabling the production of a new generation of smart biomaterials.
2( Minute nanofibers of various structures and chemistries are formed through simple self-association and organization of peptides and proteins (2). Several bioactive extracellular protein domains have been identified that can be incorporated as small peptides into nanofibers through simple modification of the peptide amino acid sequence. Nanofibers can be designed to present these peptide sequences at high density. Three-dimensional (3D) macroscopic gel-like solids can also present high densities of such bioactive peptides.
3) Applying molecular self-assembly, Silva et al(3) report a new 3D material capable of directing the differentiation of neural progenitor cells to a specific lineage without the help of growth factors.. Stem and progenitor cells have the ability to differentiate into derivative tissues and have great potential for tissue repair or replacement. Typically, differentiation is controlled by soluble compounds such as growth factors. Silva et al(3) synthesized self-assembling peptide amphiphiles that present the pentapeptide epitope isoleucine-lysine-valine-alanine-valine (IKVAV).
4) IKVAV is an amino acid sequence found in laminin, which promotes neurite adhesion, sprouting, and growth. These peptide amphiphiles self-assemble in aqueous media to form nanofibers with diameters of 5 to 8 nm and lengths several orders of magnitude higher. Macroscopically, these intermeshed fibers form highly hydrated 3D gels that are able to direct the rapid differentiation of encapsulated neural progenitors into neurons while discouraging the production of astrocytes. The inhibition of astrocyte proliferation may prevent glial scar formation, which inhibits the regeneration and elongation of axons after central nervous system trauma.
5) Although the discovery of specific bioactive peptides has enabled the rational design of materials with the ability to control cell behavior, it is often unclear which chemical properties are necessary to provide this control. A high-throughput synthesis and screening platform for the testing of polymer-cell interactions can accelerate the discovery of such materials (4). Researchers have screened a library of polymers synthesized in nanoliter volumes for their effects on human embryonic stem (hES) cell growth and differentiation. There were numerous unexpected interactions: Some materials supported high levels of hES cell differentiation into epithelial-like cells, and others supported hES cell growth only in the absence of certain growth factors. Future studies combining rationally designed combinatorial libraries of biomaterials and high-throughput screening methods should allow the identification of new methods to control cellular behavior in tissue-engineered constructs.(5)
References (abridged):
1. R. Langer, D. A. Tirrell, Nature 428, 487 (2004)
2. S. Zhang, Nature Biotechnol. 21, 1171 (2003)
3. G. A. Silva et al., Science 303, 1352 (2004)
4. D. G. Anderson et al., Nature Biotechnol. 22, 863 (2004)
5. M. P. Lutolf et al., Nature Biotechnol. 21, 513 (2003)
Science http://www.sciencemag.org
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Related Material:
CHEMICAL ENGINEERING: ON DESIGNING BIOMATERIALS
The following points are made by R. Langer and D.A. Tirrell (Nature 2004 428:487):
1) Biomaterials have been defined as substances other than foods or drugs contained in therapeutic or diagnostic systems(1) and in some cases have been described as materials composed of biologically derived components (for example, amino acids) irrespective of their application.
2) Throughout history, biomaterials have played an important role in the treatment of disease and the improvement of health care. Early biomaterials include metals such as gold that were used in dentistry over 2000 years ago. Other early examples of biomaterials include wooden teeth and glass eyes(2). However, with the advent of synthetic polymers at the end of the nineteenth century, these materials became increasingly used in health care. For example, polymethylmethacrylate, PMMA, was used in dentistry in the 1930s(1) and cellulose acetate was used in dialysis tubing(2) in the 1940s. Dacron was used to make vascular grafts; polyether-urethanes, the materials used in ladies' girdles, were used in artificial hearts; and PMMA and stainless steel were used in total hip replacements(1,2). Naturally occurring materials such as collagen have also been used as biomaterials(3).
3) However, in nearly every case, these materials were adopted from other areas of science and technology without substantial redesign for medical use. Although these materials helped usher in new medical treatments, critical problems in biocompatibility, mechanical properties, degradation, and numerous other areas remain. To this end, researchers are creating new materials including those with improved biocompatibility, stealth properties, responsiveness (smart materials), specificity, and other critical properties. Modern biomaterials science is characterized by a growing emphasis on identification of specific design parameters that are critical to performance, and by a growing appreciation of the need to integrate biomaterials design with new insights emerging from studies of cell-matrix interactions, cellular signalling processes, and developmental and systems biology.
4) Biomaterials are already having an enormous effect on medicine. Controlled drug delivery systems that largely involve polymers(4) are used by tens of millions of people annually(5). Recent examples are polymer-coated stents, which have been approved both in Europe and the US. Hundreds of thousands of lives are expected to be saved each year. In addition, various controlled release systems for proteins, such as human growth hormone, as well as molecules decorated with polyethylene glycol (PEG), such as pegylated interferon(4,5), have recently been approved by regulatory authorities, and are demonstrating how biomaterials can be used to positively affect the safety, pharmacokinetics, and duration of release of important new drugs.
5) Another area where biomaterials have recently had an impact is in tissue engineering. By combining polymers with mammalian cells, it is now possible to make skin for patients who have burns or skin ulcers, and various other polymer/cell combinations are in clinical trials, including corneas, cartilage, bone and liver. Biomaterials have also had a major impact as the central components of dental implants, sutures, and numerous medical devices(2).
References (abridged):
1. Peppas, N. A. & Langer, R. New challenges in biomaterials. Science 263, 1715-1720 (1994)
2. Ratner, B. D., Hoffman, A. S., Schoen, J. F. & Lemons, J. E. Biomaterials Science, an Introduction to Materials in Medicine 1-8 (Academic, San Diego, 1996)
3. Bell, E., Ivarsson, B. & Merrill, C. Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc. Natl Acad. Sci. USA 76, 1274-1278 (1979)
4. Langer, R. Drug delivery and targeting. Nature 392(Suppl.), 5-10 (1998)
5. Langer, R. Where a pill won't reach. Sci. Am. 288, 50-57 (2003)
Nature http://www.nature.com/nature
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MATERIALS SCIENCE: ON SYNTHETIC SEASHELLS
The following points are made by Michael Rubner (Nature 2003 424:28):
1) For a materials scientist, cross-sectional images of the complex microstructures of naturally occurring hard materials such as bones and sea shells are awe-inspiring. Over many millions of years, nature has devised schemes to combine seemingly incompatible building-blocks -- "soft" organic proteins and "hard" inorganic particles of calcium carbonate -- in a manner that produces composite materials with the unusual combination of high strength, hardness and toughness. Imagine, however, that you could build such a structure as a mason would, one layer at a time, from the bottom up. This has recently been achieved by Tang et al(1) by using a molecular-level processing scheme known as layer-by-layer assembly(2,3).
2) Flexible soft materials that can undergo energy-absorbing molecular rearrangements during deformation are tough, but also very compliant. In contrast, rigid hard materials are stiff but often also very brittle, and they have little ability to absorb energy, so their toughness is low. To be strong, hard, and tough, a material must be able to absorb a large amount of energy during mechanical deformation and also maintain high stiffness. In bone or shell, this desirable combination of properties is made possible by one key attribute -- a bricks-and-mortar-like structure, made up of strongly interacting, nanometer-size building-blocks. The "hard" bricks and "soft" mortar are complementary in their response to stress and strain.
3) So far, attempts to mimic these structures with synthetic building-blocks have failed to produce a material with similarly impressive mechanical properties, because most conventional processing techniques simply do not offer the nanoscale level of control needed to create a highly regular bricks- and-mortar-type arrangement. Nature has no such difficulty with nanoengineering: it can assemble, in a regular manner, building-blocks of the right dimensions that interact strongly enough at their interfaces to allow the transfer of deformation energy between the rigid bricks and the softer mortar. Reproducing these elements synthetically is a challenge.
4) But this is exactly what Tang et al(1) have achieved, through the alternating sequential deposition of negatively charged, nanometer-thick clay platelets (the bricks) and a positively charged polymer (the mortar). The primary driving force for this adsorption-based assembly, which is carried out entirely from dilute aqueous solutions of the materials, is electrostatic: the positively charged polymer chains are attracted to the negatively charged clay platelets, and vice versa. By assembling the clay platelets (in this case, a material called montmorillonite) and polymer chains one deposition step at a time, the authors are able to create a bricks-and-mortar-type arrangement that mimics the natural structure of nacre, the material known as mother-of-pearl.
References (abridged):
1. Tang, Z., Kotov, N. A., Magonov, S. & Ozturk, B. Nature Mater. 2, 413-418 (2003)
2. Decher, G., Hong, J. D. & Schmitt, J. Thin Solid Films 210, 831-835 (1992)
3. Decher, G. Science 277, 1232-1237 (1997)
4. Mamedov, A. A. et al. Nature Mater. 1, 190-194 (2002)
5. Joly, S. et al. Langmuir 16, 1354-1359 (2000)
Nature http://www.nature.com/nature
ScienceWeek http://scienceweek.com
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