The invention relates to the development of compositions and methods for increasing the amount of collagen cross-linking in a mammalian tissue. A typical composition as described herein includes at least one cross-linking agent such as a bioflavonoid compound (e.g., proanthocyanidin), a grape seed extract, a Casein Phosphopeptide-amorphous Calcium Phosphate, or an iridoid compound (e.g., genipin) in an amount effective for increasing collagen cross-linking in the mammalian tissue in a pharmaceutically acceptable carrier. A typical method for increasing the amount of collagen cross-linking in dentin in a mammalian tooth includes the steps of preparing the surface of the tooth to be treated; and applying a composition including at least one of: a bioflavonoid compound, a grape seed extract, a Casein Phosphopeptide-amorphous Calcium Phosphate, and an iridoid compound in a pharmaceutically acceptable carrier to the tooth surface for a time period of 0.0001 hours to about 4 hours. In some embodiments, two or more cross-linking agents are included in the compositions described herein. The compositions and methods as described herein are particularly useful for applying to dentin in a mammalian tooth requiring a restorative procedure for improving the mechanical properties of restoration interfaces to withstand degradation over time. Compositions containing one of the collagen cross-linking agents as described herein were applied to dentin collagen and resulted in a significant improvement in ultimate tensile strength indicating the value of these compositions in restorative dentistry. The compositions and methods described herein will also find use in preventive dentistry applications, and can be applied to sound dentin, caries-affected dentin, and dentin that is impaired, weak, or degraded in any way.

 
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