Hydrophilic polymeric biomaterials

The objective of this chapter is to review degradable materials, including polymers, and the resulting delivery systems fabricated from them that are usefid for the delivery of proteins and peptides. Owing to the diverse nature of the subject area, we have chosen to divide the chapter into sections on hydrophobic synthetic polymers, hydrophilic polymeric biomaterials, and hydrophobic nonpolymeric biomaterials. Each section seeks to briefly highlight ftie chemist and characteristics of the polymer or matrix and provide recent examples of their use in the delivery of proteins. 

HYDROPHILIC POLYMERIC BIOMATERIALS AND HYDROPHOBIC NONPOLYMERIC BIOMATERIALS... 

Lopour P et al. (1990) Silicone rubber-hydrogel composites as polymeric biomaterials. II Hydrophilicity, permeability to water-soluble low-molecular-weight compounds. Biomaterials 11 (6) 397—402... 

Hydrophilic coatings have also been popular because of their low interfacial tension in biological environments [Hoffman, 1981]. Hydrogels as well as various combinations of hydrophilic and hydrophobic monomers have been studied on the premise that there will be an optimum polar-dispersion force ratio which could be matched on the surfaces of the most passivating proteins. The passive surface may induce less clot formation. Polyethylene oxide coated surfaces have been found to resist protein adsorption and cell adhesion and have therefore been proposed as potential blood compatible coatings [Lee et al., 1990a]. General physical and chemical methods to modify the surfaces of polymeric biomaterials are listed in Table 40.7 [Ratner et al., 1996]. 

Hydrophobicity of biomedical polymers influences the biocompatibility depending on the particular application such as tissue engineering, blood contacting devices, and dental implants [35]. Polymers are dynamic structures and can switch their surface functional groups depending on the environment. For example, polymeric biomaterials need to have a hydrophilic smface for most of the applications, so that the cell-adhesive proteins present in the serum will be adsorb and promote cell adhesion and proliferation. This is achieved by snrface treatment procedures such as... 

In another variation, dense gas CO can be used to induce porosity in polymeric biomaterials. As dense gas CO generally has a low solubility in hydrophilic polymers, various attempts have been made to improve the ability of dense gas to diffuse into hydrogel precursor solutions and produce porosity in hydrogel matrices, such as COj-water emulsion templating or the use of cosolvent systems [69]. With this technique, it is difficult to control pore size and ensure pore interconnectivity. 

Surface modification with hydrophilic polymers, such as poly(ethylene oxide) (PEO), has been beneficial in improving the blo( compatibility of polymeric biomaterials. Surface-bound PEO is expected to prevent plasma protein adsoiption, platelet adhesion, and bacterial adhesion by the steric repulsion mechanism. PEO-rich surfaces have been prepared either by physical adsorption, or by covalent grafting to the surface. Physically adsorbed PEO homopolymers and copolymers are not very effective since they can be easily displaced from the surface by plasma proteins and cells. Covalent grafting, on the other hand, provides a permanent layer of PEO on the surface. Various methods of PEO grafting to the surface and their effect on plasma protein adsorption, platelet adhesion, and bacterial adhesion is discussed. 

Marchant RE, Johnson SD, Schneider BH, Agger MP, Anderson JM. A hydrophilic plasma polymerized film composite with potential application as an interface for biomaterials. Journal of Biomedical Materials Research 1990, 24, 1521-1537. 

Because of the instability of the anhydride bond in the presence of water, special properties are required for stable polyanhydride devices. A critical element in the development of polyanhydride biomaterials is controlling hydrolysis within a polymeric device. To obtain implants where hydrolysis is confined to the surface of the polymer, hydrophobic monomers can be polymerized via anhydride linkages to produce a polymer that resists water penetration, yet degrades into low molecular weight oligomers at the poly-mer/water interface. By modulating the relative hydrophobicity of the matrix, which can be achieved by appropriate selection of monomers, the rate of degradation can then be adjusted. For example, copolymers of sebacic acid, a hydrophilic monomer, with carboxyphenoxypropane, a hydrophobic monomer, yield ... 

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