Racionalizando el diseo de materiales polimricos Polymers remain the most versatile class of biomaterials, being extensively applied in medicine

and biotechnology, as well as in the food and cosmetics industries. Polymers used as biomaterials can be synthesized to have appropriate chemical, physical, interfacial and biomimetic characteristics, which permit various specific applications. Compared with other types of biomaterial, such as metals and ceramics, polymers offer the advantage that they can be prepared in different compositions with a wide variety of structures and properties. Current research and development is focused on tissue engineering, for which such materials are considered to have a particularly significant potential. After more than three decades of development, in which numerous polymers have been used to replace body parts or to help to restore vital functions, clinical success is still relatively rare. Recent approaches in macromolecular biomaterials technology combine the efforts of scientists in various fields to obtain polymers with well-defined structures with specific chemical, physicochemical, mechanical and biological properties. Another trend in biomaterial development is macromolecular engineering, which involves the evaluation of versatile optimized routes for new low-cost, tailor-made commercial polymeric structures

Existing polymeric biomaterials Polymers used as biomaterials can be naturally occurring, synthetic or a combination of both. Naturally derived polymers are abundant and usually biodegradable. Their principal disadvantage lies in the development of reproducible production methods, because their structural complexity often renders modification and purification difficult. Synthetic polymers are available in a wide variety of compositions with readily adjusted properties. Processing, copolymerization and blending provide simultaneous means of optimizing a polymers mechanical characteristics and its diffusive and biological properties. The primary difficulty is the general lack of biocompatibility of the majority of synthetic materials, Synthetic polymers are therefore often associated with inflammatory reactions, which limit their use to solid, unmoving, impermeable devices.

Biocompatibility Polymer biocompatibility refers to the reaction of polymers with blood and tissues, depending on the site and purpose of use. A response in the host organism is generally unfavourable unless vascularization is required to support living cells. A material may be biocompatible in one application but bioincompatible in another.

Because the surface of the material is in immediate contact with the biological medium, the interfacial characteristics are often significant for impermeable solid devices. In such cases, the surface structure governs the biological response. This is initially determined by cell and protein interactions. The distribution of functional groups on the biomaterials surface, and hence the macromolecular microstructure, is one of the key factors determining the interactions with the surrounding medium. The physical properties (durability, permeability) and degradability may also influence the biocompatibility. The material should not be toxic to any biological components and should be stable. Polymers used as matrices in tissue engineering, in artificial organs and in implants often have to imitate the properties of the tissues in natural organs.

Biomaterials in which bulk properties dominate The bulk morphology of the material must also be considered, because it determines many of the physical properties of the biomaterial. Mechanical strength, density, elasticity, ageing and creep resistance play an important role in the selection of polymers for matrices in tissue engineering. Polymer coatings are also generally soft. It therefore follows that certain requirements have to be met by developing suitable bulk materials. The bulk morphology also determines the permeability of the material (permeation rate) to gases or aqueous substances. Careful design of the structural and interfacial properties of the matrix, and its micromorphology and pore size are particularly important for biomaterials used as cellgrowth scaffolds, in artificial organs and as supports for immobilized biomolecules. In addition to other general requirements, properties such as durability, elasticity, tensile strength, the shapememory effect and adhesion should be considered when selecting polymer compositions for use as sutures and long-term skin substitutes. The selection of polymers for matrices or carriers in controlled-delivery devices requires the consideration of characteristics such as molecular weight, adhesion and solubility, depending on the type of system to be prepared, its action and the target site in the body. In some cases, polymeric materials for drug delivery must satisfy additional requirements, such as environmental responsiveness. The choice of a material for a specific application is mainly based on its physicochemical, interfacial and biomimetic properties, although traditional mechanical properties such as impact strength, elasticity and permeability are also essential for specific applications. Indeed, the choice of the polymer is primarily governed by the end use of the biomaterial and involves selection not only on the basis of physical and chemical properties but also on extensive biochemical characterization followed by specific preclinical testing of the chosen material. Tissue-engineering matrices

This often limits versatility in designing devices with well-defined properties. Synthetic polymers have become more attractive owing to the potential for controlling their properties by tailoring their molecular structure. The use of chemically engineered synthetic polymers enables very precise manipulation of the physical characteristics and mechanical properties of the materials, porosity and degradation times. Biodegradable polymeric systems, which are completely bioresorbable in the body, are particularly attractive in tissue engineering3. One of their main advantages is that they eliminate the need for surgical removal of a polymer matrix. Surface-bioerodible biomaterials are hydrophobic and are used to maintain long-term stability. The choice of material depends strongly on the required service life. As degradation affects the materials properties and results in changes in strength and fatigue life, it must be optimized for durable devices.

Biodegradable polymers The use of biodegradable synthetic polymers as biomaterials is particularly attractive because their mechanical and physical properties can readily be adjusted by varying the preparation techniques and molecular structure. Biodegradable polymers containing hydrolysable groups in their chains, which are susceptible to biodegradation to low molecular weight, nontoxic products, have also been considered for controlled drug delivery systems. Indeed, this appears to be their most widely investigated practical application. Fibres and porous sponges are widely used in surgery, although they are not permanent implants and their blood-contact time is limited. They are preferred in plastic surgery for replacing various tissue defects. Surface characteristics As the surface can control the device performance, the interfacial properties should be addressed from the outset. The surface load and energy should then be considered, because they regulate the fluidmaterial interactions within the host. In general, a high charge Odensity is required to reduce protein adsorption and thus to promote thromboresistance of the surface. Various approaches have been used to increase the surface load, including the introduction of polar groups, the creation of negatively charged interfaces and hydrogel coatings; hydrogel coatings enhance the surface hydrophilicity and can render the surface resistant to protein adsorption. The interface composition and morphology should be designed to modulate or suppress specific interactions. There are numerous applications where polymer materials interact with biological components such as cells, tissues and extracellular fluids. These interactions are dependent on the nature and morphology of the surface. If they are to be avoided, the surface should be smooth.

Bulk properties To rationalize a material for a certain application, bulk properties such as permeability, diffusional characteristics and the degradation rate must be considered. This last becomes increasingly important for long-term applications (permanent implants). Permeability to water-soluble substances and bodyfluid components must be considered when designing medical devices. Water-repellent devices are preferable where long-term mechanical resistance is required, owing to the influence of fluid absorption. Well-defined mass-transport properties and molecular weight cut-off of gels, microcapsules and hollow fibres are required in devices for the immunoisolation of cells and bioartificial organs, as well as for drug delivery and ocular applications.

Biomaterial design: techniques for macromolecular engineering The optimization of properties following materials selection for a specific application is the remaining key factor to be considered. The ability to tailor the macromolecular chemistry and material morphology to satisfy a given set of physicochemical and biological criteria determines the ultimate success of a biomaterial. Responsive systems also require further development. To date, most polymers have been engineered to satisfy the main criteria for biomedical applications and exhibit a non-specific biological reaction. Future needs include optimization of engineering and design processes, which should permit biomaterials with precise bulk and surface architectures to show precise biological recognition and specific bioreactions in vivo. Biocompatibility is one of the main criteria for the selection of a particular biomaterial and so improving the host organisms tolerance for the polymer, depending on the intended application, must be the primary consideration in macromolecular design. The biocompatibility of a polymer depends on the specific adsorption of proteins to the polymer surface and the subsequent cellular interactions. The first contact is between the surface of the polymer and the organism (blood and other tissues) and results in a foreign-body reaction.