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      Epigenetic therapeutics in dental pulp treatment: Hopes, challenges and concerns for the development of next-generation biomaterials

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          Abstract

          This opinion-led review paper highlights the need for novel translational research in vital-pulp-treatment (VPT), but also discusses the challenges in translating evidence to clinics. Traditional dentistry is expensive, invasive and relies on an outmoded mechanical understanding of dental disease, rather than employing a biological perspective that harnesses cell activity and the regenerative-capacity. Recent research has focussed on developing minimally-invasive biologically-based ‘fillings’ that preserve the dental pulp; research that is shifting the paradigm from expensive high-technology dentistry, with high failure rates, to smart restorations targeted at biological processes. Current VPTs promote repair by recruiting odontoblast-like cells in a material-dependent process. Therefore, exciting opportunities exist for development of next-generation biomaterials targeted at regenerative processes in the dentin-pulp complex. This article analyses recent research using pharmacological-inhibitors to therapeutically-target histone-deacetylase (HDAC) enzymes in dental-pulp-cells (DPCs) that stimulate pro-regenerative effects with limited loss of viability. Consequently, HDAC-inhibitors have the potential to enhance biomaterial-driven tissue responses at low concentration by influencing the cellular processes with minimal side-effects, providing an opportunity to develop a topically-placed, inexpensive bio-inductive pulp-capping material. Despite positive results, clinical translation of these innovations requires enterprise to counteract regulatory obstacles, dental-industry priorities and to develop strong academic/industry partnerships. The aim of this opinion-led review paper is to discuss the potential role of therapeutically-targeting epigenetic modifications as part of a topical VPT strategy in the treatment of the damaged dental pulp, while considering the next steps, material considerations, challenges and future for the clinical development of epigenetic therapeutics or other ‘smart’ restorations in VPT.

          Highlights

          • Illustrates the need for next-generation targeted vital pulp biomaterials to improve tissue response and treatment outcome.

          • Provides evidence supporting the use of HDACi as a bioactive component to pulp capping materials to stimulate repair..

          • Discusses the implications of recent legislation on the development of ‘smart’ dental restorations that contact pulp tissue.

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          Most cited references313

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          Oral diseases: a global public health challenge

          Oral diseases are among the most prevalent diseases globally and have serious health and economic burdens, greatly reducing quality of life for those affected. The most prevalent and consequential oral diseases globally are dental caries (tooth decay), periodontal disease, tooth loss, and cancers of the lips and oral cavity. In this first of two papers in a Series on oral health, we describe the scope of the global oral disease epidemic, its origins in terms of social and commercial determinants, and its costs in terms of population wellbeing and societal impact. Although oral diseases are largely preventable, they persist with high prevalence, reflecting widespread social and economic inequalities and inadequate funding for prevention and treatment, particularly in low-income and middle-income countries (LMICs). As with most non-communicable diseases (NCDs), oral conditions are chronic and strongly socially patterned. Children living in poverty, socially marginalised groups, and older people are the most affected by oral diseases, and have poor access to dental care. In many LMICs, oral diseases remain largely untreated because the treatment costs exceed available resources. The personal consequences of chronic untreated oral diseases are often severe and can include unremitting pain, sepsis, reduced quality of life, lost school days, disruption to family life, and decreased work productivity. The costs of treating oral diseases impose large economic burdens to families and health-care systems. Oral diseases are undoubtedly a global public health problem, with particular concern over their rising prevalence in many LMICs linked to wider social, economic, and commercial changes. By describing the extent and consequences of oral diseases, their social and commercial determinants, and their ongoing neglect in global health policy, we aim to highlight the urgent need to address oral diseases among other NCDs as a global health priority.
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            The molecular hallmarks of epigenetic control.

            Over the past 20 years, breakthrough discoveries of chromatin-modifying enzymes and associated mechanisms that alter chromatin in response to physiological or pathological signals have transformed our knowledge of epigenetics from a collection of curious biological phenomena to a functionally dissected research field. Here, we provide a personal perspective on the development of epigenetics, from its historical origins to what we define as 'the modern era of epigenetic research'. We primarily highlight key molecular mechanisms of and conceptual advances in epigenetic control that have changed our understanding of normal and perturbed development.
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              Biomedical Applications of Biodegradable Polymers.

              Utilization of polymers as biomaterials has greatly impacted the advancement of modern medicine. Specifically, polymeric biomaterials that are biodegradable provide the significant advantage of being able to be broken down and removed after they have served their function. Applications are wide ranging with degradable polymers being used clinically as surgical sutures and implants. In order to fit functional demand, materials with desired physical, chemical, biological, biomechanical and degradation properties must be selected. Fortunately, a wide range of natural and synthetic degradable polymers has been investigated for biomedical applications with novel materials constantly being developed to meet new challenges. This review summarizes the most recent advances in the field over the past 4 years, specifically highlighting new and interesting discoveries in tissue engineering and drug delivery applications.
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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                14 May 2023
                September 2023
                14 May 2023
                : 27
                : 574-593
                Affiliations
                [a ]Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin, University of Dublin, Lincoln Place, Dublin, Ireland
                [b ]Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ, USA
                Author notes
                []Corresponding author. hduncan@ 123456tcd.ie
                Article
                S2452-199X(23)00131-7
                10.1016/j.bioactmat.2023.04.013
                10199232
                37213443
                9b565e1a-08d9-4048-92e1-9a015f7bf126
                © 2023 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 14 March 2023
                : 11 April 2023
                : 11 April 2023
                Categories
                Article

                epigenetics,vital pulp treatment,histone deacetylase inhibitors,regenerative endodontics,pulp capping

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