Development of Artificial Salivas

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Abstract
Salivary research is at a critical crossroads regarding the clinical application of basic knowledge. Studies by numerous salivary researchers over the last 5 years using advanced technologies (e.g., protein chemistry, molecular biology, and biophysics) have demonstrated that the structural requirements for salivary function are quite complex. Nevertheless, several patterns or principles have evolved. First, the majority if not all salivary molecules are multifunctional. Second, the conformation of a molecule is an important factor in biological activity. Third, many molecules have overlapping functions (e.g., mucins and amylase interact with viridans streptococci; statherin and proline-rich proteins are involved in mineralization). Thus, saliva has "built-in" compensatory or redundant properties. Nevertheless, it must be determined which molecule is more potent or effective with respect to a particular function. Fourth, salivary molecules may be "amphifunctional". In other words, the different functions of a single molecule may be protective or potentially harmful depending on the intraoral site of action. Examples of amphifunctional molecules are amylase and statherin. Fifth, functional relationships may exist between different salivary components. The principles mentioned above can provide experimental strategies for the design and synthesis of a first generation of salivary substitutes that can be topically applied to oral surfaces. These molecules should be used to combat microbial mediated diseases and occlusal disharmony in subjects with normal salivary flow as well as those with xerostomia. In general, these substitutes should be long-lasting, biocompatible, biodegradable, and provide specific protective qualities that can be targeted to selected intraoral sites. Subsequent research endeavors will focus on the design and subsequent engineering of a second generation of artificial salivas comprised of molecules with enhanced as well as multiple functions. Examples of these strategies are provided.