For many years, operative dentistry has been using regenerative approaches to treat dental disease. The use of calcium hydroxide to stimulate reparative or reactionary dentin is clearly an example of such a therapeutic strategy. The advent of tissue engineering is allowing dentistry to move forward in the use of regeneration as an underlying principle for the treatment of dental disease. Tissue engineering is a multi-disciplinary science that brings together biology, engineering and clinical sciences with developing new tissues and organs. It is based on fundamental principles that involve the identification of appropriate cells, the development of conducive scaffolds and an understanding of the morphogenic signals required to induce cells to regenerate the tissues that were lost. This review is focused on the presentation and discussion of existing literature that covers the engineering of enamel, dentin and pulp, as well on the engineering of entire teeth. There are clearly major road-blocks to overcome before such strategies move to the clinic and are used regularly to treat patients. However, existing evidence strongly suggests that the engineering of new dental structures to replace tissues lost during the process of caries or trauma will have a place in the future of operative dentistry.

Tooth regeneration in operative dentistry.

For many years, operative dentistry has been using regenerative approaches to treat dental disease. The use of calcium hydroxide to stimulate reparative or reactionary dentin is clearly an example of such a therapeutic strategy. The advent of tissue engineering is allowing dentistry to move forward in the use of regeneration as an underlying principle for the treatment of dental disease. Tissue engineering is a multi-disciplinary science that brings together biology, engineering and clinical sciences with developing new tissues and organs. It is based on fundamental principles that involve the identification of appropriate cells, the development of conducive scaffolds and an understanding of the morphogenic signals required to induce cells to regenerate the tissues that were lost. This review is focused on the presentation and discussion of existing literature that covers the engineering of enamel, dentin and pulp, as well on the engineering of entire teeth. There are clearly major roadblocks to ...

Buonocore Memorial Lecture

Amelogenesis imperfecta (AI) is a collective term for a number of conditions with abnormal enamel formation. Many cases are inherited, either as an X-linked, autosomal dominant or autosomal recessive trait. Several classifications have evolved since 1945, based primarily on phenotype with the mode of inheritance being used in some systems as a secondary factor in allocating a case into a particular category. The benefits and shortcomings of these systems are reviewed. As we move into an era of establishing the molecular basis of AI we propose a robust mechanism for classification and cataloguing of the disorder which parallels systems used in medical genetics. This system is applicable to individuals and families irrespective of current or future knowledge of the molecular defect involved. We argue that this system is of more benefit to these individuals and families than previous classifications.

Amelogenesis imperfecta: a classification and catalogue for the 21st century.

Dental enamel is the epithelial-derived hard tissue covering the crowns of teeth. It is the most highly mineralized and hardest tissue in the body. Dental enamel is acellular and has no physiological means of repair outside of the protective and remineralization potential provided by saliva. Enamel is comprised of highly organized hydroxyapatite crystals that form in a defined extracellular space, the contents of which are supplied and regulated by ameloblasts. The entire process is under genetic instruction. The genetic control of amelogenesis is poorly understood, but requires the activities of multiple components that are uniquely important for dental enamel formation. Amelogenesis imperfecta (AI) is a collective designation for the variety of inherited conditions displaying isolated enamel malformations, but the designation is also used to indicate the presence of an enamel phenotype in syndromes. Recently, genetic studies have demonstrated the importance of genes encoding enamel matrix proteins in the etiology of isolated AI. Here we review the essential elements of dental enamel formation and the results of genetic analyses that have identified disease-causing mutations in genes encoding enamel matrix proteins. In addition, we provide a fresh perspective on the roles matrix proteins play in catalyzing the biomineralization of dental enamel.

Enamel formation and amelogenesis imperfecta.

Dental enamel is the hardest and most mineralized tissue in extinct and extant vertebrate species and provides maximum durability that allows teeth to function as weapons and/or tools as well as for food processing. Enamel development and mineralization is an intricate process tightly regulated by cells of the enamel organ called ameloblasts. These heavily polarized cells form a monolayer around the developing enamel tissue and move as a single forming front in specified directions as they lay down a proteinaceous matrix that serves as a template for crystal growth. Ameloblasts maintain intercellular connections creating a semi-permeable barrier that at one end (basal/proximal) receives nutrients and ions from blood vessels, and at the opposite end (secretory/apical/distal) forms extracellular crystals within specified pH conditions. In this unique environment, ameloblasts orchestrate crystal growth via multiple cellular activities including modulating the transport of minerals and ions, pH regulation, proteolysis, and endocytosis. In many vertebrates, the bulk of the enamel tissue volume is first formed and subsequently mineralized by these same cells as they retransform their morphology and function. Cell death by apoptosis and regression are the fates of many ameloblasts following enamel maturation, and what cells remain of the enamel organ are shed during tooth eruption, or are incorporated into the tooth’s epithelial attachment to the oral gingiva. In this review, we examine key aspects of dental enamel formation, from its developmental genesis to the ever-increasing wealth of data on the mechanisms mediating ionic transport, as well as the clinical outcomes resulting from abnormal ameloblast function.

Dental enamel formation and implications for oral health and disease.

Dental enamel formation is a remarkable example of a biomineralization process. The exact mechanisms involved in this process remain partly obscure. Some of the genes encoding specific enamel proteins have been indicated as candidate genes for amelogenesis imperfecta. Mutational analyses within studied families have supported this hypothesis. Mutations in the amelogenin gene (AMELX) cause X-linked amelogenesis imperfecta, while mutations in the enamelin gene (ENAM) cause autosomal-inherited forms of amelogenesis imperfecta. Recent reports involve kallikrein-4 (KLK4), MMP-20, and DLX3 genes in the etiologies of some cases. This paper focuses mainly on the candidate genes involved in amelogenesis imperfecta and the proteins derived from them, and reviews current knowledge on their structure, localization within the tissue, and correlation with the various types of this disorder.

Genes and Related Proteins Involved in Amelogenesis Imperfecta

HER2/neu gene amplification is being evaluated by fluorescent in situ hybridization (FISH). In order to avoid interobserver variations in the assessment of HER2/neu status, an integrated FISH image analysis system is developed to automate the classification of FISH images from breast carcinomas. Using a two-stage algorithm, for nuclei and dot detection, and combining results from multiple images taken from a slice for overall case classification, FISH signals ratio per cell nucleus were measured and cases were classified as positive or negative. The system consists of functions for red spot detection, green spot detection, nuclei segmentation and FISH signal ratio. Therefore, it provides the capability to manually correct the resulted images after the analysis.

M.-E. Garefalaki

Papers

Genes and Related Proteins Involved in Amelogenesis Imperfecta

Fish Image Analysis System for Breast Cancer Studies