Inert biomaterials

Biomaterials with Low Thrombogenicity. Poly(ethylene oxide) exhibits extraordinary inertness toward most proteins and biological macromolecules. The polymer is therefore used in bulk and surface modification of biomaterials to develop antithrombogenic surfaces for blood contacting materials. Such modified surfaces result in reduced concentrations of ceU adhesion and protein adsorption when compared to the nonmodifted surfaces. 

Abstract In this paper the synthesis, properties and applications of poly(organophos-phazenes) have been highlighted. Five different classes of macromolecules have been described, i.e. phosphazene fluoroelastomers, aryloxy-substituted polymeric flame-retardants, alkoxy-substituted phosphazene electric conductors, biomaterials and photo-inert and/or photo-active phosphazene derivatives. Perspectives of future developments in this field are briefly discussed. 

Polymers used in medicine fall into two main categories those that are sufficiently inert to fulfill a long-term structural function as biomaterials or membranes, and those that are sufficiently hydrolytically unstable to function as bioeradible materials, either in the form of sutures or as absorbable matrices for the controlled release of drugs. For the synthetic organic polymers widely used in biomedicine this often translates to a distinction between polymers that have a completely hydrocarbon backbone and those that have sites in the backbone that are hydrolytically sensitive. Ester, anhydride, amide, or urethane linkages in the backbone usually serve this function. 

Aryloxyphosphazene polymers, such as compound 1 or its mixed-substituent analogs, are also hydrophobic (contact angles in the region of 100°). These too show promise as inert biomaterials on the basis of preliminary in vivo tissue compatibility tests (13). 

Biomaterials cover a broad range of properties from those that are designed to be inert to those that are intended to elicit a particular set of biological responses. In the latter category are materials with surfaces tailored to retard blood clotting, or surfaces that bear covalently bound bioactive agents such as enzymes or antigens. 

Successful applications of materials in medicine have been experienced in the area of joint replacements, particularly artificial hips. As a joint replacement, an artificial hip must provide structural support as well as smooth functioning. Furthermore, the biomaterial used for such an orthopedic application must be inert, have long-term mechanical and biostability, exhibit biocompatibility with nearby tissue, and have comparable mechanical strength to the attached bone to minimize stress. Modem artificial hips are complex devices to ensure these features. 

Biomaterials are inert substances that are used in contact with living tissue, resulting in an interface between living and non-living substances [45,46], Biocompatibility of this interface is achieved by using such biomaterials for encapsulation in the construction of sensor devices. 

When biomaterials were inert it was simple to think of biomaterials in terms of the absence of inflammation or the absence of thrombi. Now, with... 

Silk fibers or monolayers of silk proteins have a number of potential biomedical applications. Biocompatibility tests have been carried out with scaffolds of fibers or solubilized silk proteins from the silkworm Bombyx mori (for review see Ref. [38]). Some biocompatibility problems have been reported, but this was probably due to contamination with residual sericin. More recent studies with well-defined silkworm silk fibers and films suggest that the core fibroin fibers show in vivo and in vivo biocompatibility that is comparable to other biomaterials, such as polyactic acid and collagen. Altmann et al. [39] showed that a silk-fiber matrix obtained from properly processed natural silkworm fibers is a suitable material for the attachment, expansion and differentiation of adult human progenitor bone marrow stromal cells. Also, the direct inflammatory potential of silkworm silk was studied using an in vitro system [40]. The authors claimed that their silk fibers were mostly immunologically inert in short and long term culture with murine macrophage cells. 

Many biomaterials are composites. Bone and skin are relatively light compared to metals. Composite structures can approach the densities of bone and skin and offer the necessary inertness and strength to act as body-part substitutes. 

Siloxanes are the most extensively used synthetic biomaterial due to several reasons such as flexibility, chemical and biological inertness, low capacity to bring about blood clotting, overall low degree of biological toxicity, and good stability within biological environments. 

Elastomers of this type are usually cross-linked during fabrication, and often contain fillers such as carbon black or iron oxide to reduce the compliance of the elastomer (i.e. to provide a greater resistance to deformation). Such materials are depicted in Figure 3.1. They are used in technology because of their flexibility and elasticity at low temperatures (-60 °C), their resistance to hydrocarbon solvents, oils, and hydraulic fluids, and their fire resistance.145 For these reasons, they are utilized in aerospace and advanced automotive applications. Some interest exists in their development as inert biomaterials, mainly because of their surface hydrophobicity and consequent biocompatibility. 

Photoswitchable antigen/antibody (substrate/ receptor) complexes 1. Reversible immunosensors 2. Patterning of surfaces with biomaterials using antigen/antibody-biomaterial conjugates (Design of biosensor arrays, biochips) 1. Immobilization of systems on electronic transducers (electrodes, piezoelectric crystals, FET) or the assembly of biomaterials on inert supports by non-covalent interactions (eg. glass, polymers)... 

Based on their behavior in living tissue, polymeric biomaterials can be divided into two groups biostable and biodegradable. Biostable polymers are used when permanent aids are needed, e.g., as prostheses [13]. Biostable polymers, typically polyethylene and poly(methyl methacrylate), should be physiologically inert in tissue conditions and maintain their mechanical properties for decades [11]. 

Gold, and more recently iridium, has been considered ideal biomaterials for stents. It is liiglily radio-opaque (it shows clearly in X-ray type analysis) and it is considered inert (corrosion should not be expected of the surface due to its noble characteristics.) Indeed, a gold electrodeposited stainless steel stent made it through clinical trials and it was actually approved for clinical use. " It was, nonetheless, a failure because its rate of restenosis was higher than stents already on tlie market When the production process for the stent was reviewed, it turned out that proper heat treating of the plated surface was not performed. Early animal da-... 

Another area of great interest in biomaterials research has been that of immobilization of reaction centers on an inert substrate to create reaction specific cites. One group (36) has been interested in stabilization of chloroplasts for use in solar energy development (Figure 11). Various hydrophillic and hydrophobic monomers were mixed with isolated chloroplasts in a specific buffer solution (Figure 12). The mixture was cooled to below -24C and irradiated with a Co-60 source to 1 MRad. After irradiation, residual monomer and chloroplast were washed leaving the immobilized product stored in a buffer solution. 

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