Molecular Basis beyond Interrelated Bone Resorption/Regeneration in Periodontal Diseases: A Concise Review.

Periodontitis is the sixth most common chronic inflammatory disease, destroying the tissues supporting the teeth. There are three distinct stages in periodontitis: infection, inflammation, and tissue destruction, where each stage has its own characteristics and hence its line of treatment. Illuminating the underlying mechanisms of alveolar bone loss is vital in the treatment of periodontitis to allow for subsequent reconstruction of the periodontium. Bone cells, including osteoclasts, osteoblasts, and bone marrow stromal cells, classically were thought to control bone destruction in periodontitis. Lately, osteocytes were found to assist in inflammation-related bone remodeling besides being able to initiate physiological bone remodeling. Furthermore, mesenchymal stem cells (MSCs) either transplanted or homed exhibit highly immunosuppressive properties, such as preventing monocytes/hematopoietic precursor differentiation and downregulating excessive release of inflammatory cytokines. In the early stages of bone regeneration, an acute inflammatory response is critical for the recruitment of MSCs, controlling their migration, and their differentiation. Later during bone remodeling, the interaction and balance between proinflammatory and anti-inflammatory cytokines could regulate MSC properties, resulting in either bone formation or bone resorption. This narrative review elaborates on the important interactions between inflammatory stimuli during periodontal diseases, bone cells, MSCs, and subsequent bone regeneration or bone resorption. Understanding these concepts will open up new possibilities for promoting bone regeneration and hindering bone loss caused by periodontal diseases.

Polymeric Nanocomposite Hydrogel Scaffolds in Craniofacial Bone Regeneration: A Comprehensive Review.

Nanocomposite biomaterials combine a biopolymeric matrix structure with nanoscale fillers. These bioactive and easily resorbable nanocomposites have been broadly divided into three groups, namely natural, synthetic or composite, based on the polymeric origin. Preparing such nanocomposite structures in the form of hydrogels can create a three-dimensional natural hydrophilic atmosphere pivotal for cell survival and new tissue formation. Thus, hydrogel-based cell distribution and drug administration have evolved as possible options for bone tissue engineering and regeneration. In this context, nanogels or nanohydrogels, created by cross-linking three-dimensional polymer networks, either physically or chemically, with high biocompatibility and mechanical properties were introduced as promising drug delivery systems. The present review highlights the potential of hydrogels and nanopolymers in the field of craniofacial tissue engineering and bone regeneration.

Nutrition Profile for Countries of the Eastern Mediterranean Region with Different Income Levels: An Analytical Review.

The World Health Organization's (WHO) Eastern Mediterranean Region (EMR) is suffering from a double burden of malnutrition in which undernutrition coexists with rising rates of overweight and obesity. Although the countries of the EMR vary greatly in terms of income level, living conditions and health challenges, the nutrition status is often discussed only by using either regional or country-specific estimates. This analytical review studies the nutrition situation of the EMR during the past 20 years by dividing the region into four groups based on their income level-the low-income group (Afghanistan, Somalia, Sudan, Syria, and Yemen), the lower-middle-income group (Djibouti, Egypt, Iran, Morocco, Pakistan, Palestine, and Tunisia), the upper-middle-income group (Iraq, Jordan, Lebanon, and Libya) and the high-income group (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and United Arab Emirates)-and by comparing and describing the estimates of the most important nutrition indicators, including stunting, wasting, overweight, obesity, anaemia, and early initiation and exclusive breastfeeding. The findings reveal that the trends of stunting and wasting were decreasing in all EMR income groups, while the percentages of overweight and obesity predominantly increased in all age groups across the income groups, with the only exception in the low-income group where a decreasing trend among children under five years existed. The income level was directly associated with the prevalence rates of overweight and obesity among other age groups except children under five, while an inverse association was observed regarding stunting and anaemia. Upper-middle-income country group showed the highest prevalence rate of overweight among children under five. Most countries of the EMR revealed below-desired rates of early initiation and exclusive breastfeeding. Changes in dietary patterns, nutrition transition, global and local crises, and nutrition policies are among the major explanatory factors for the findings. The scarcity of updated data remains a challenge in the region. Countries need support in filling the data gaps and implementing recommended policies and programmes to address the double burden of malnutrition.

The effect of unhealthy dietary habits on the incidence of dental caries and overweight/obesity among Egyptian school children (A cross-sectional study).

Background: Obesity and dental caries are public health problems in Egypt. Factors such as unhealthy diet, poor oral hygiene, and physical inactivity can play a major role in both problems. This study was carried out to illuminate the mutual unhealthy dietary risk factors associated with the incidence of both health conditions. Methods: Between 1 October 2020 and 1 July 2021, 369 Egyptian children (5-10 years) were examined. Dental status was assessed using decayed, missing/extracted, and filled tooth indices (dmft, deft, and DMFT) for deciduous, mixed, and permanent dentitions, respectively. Moreover, the lifestyle, food habits, and body mass index (BMI) were recorded. Results: A total of 342 (93.7%) of the included subjects suffered from caries, and only 27(7.3%) were caries-free. Based on BMI percentiles, 247 (66.9%) of the youngsters were overweight/obese, while 122 (33.1%) had normal weight. The mean dmft was 6.9 (±4.6), deft 4.2 (±3.3), and DMFT 0.1 (±1.7). In the primary dentition, a significant positive correlation was detected between dmft and BMI, legumes, sweetened milk and juice, soft drinks, and desserts, while a significant negative correlation was detected between dmft/deft, meat/poultry/fish, fresh fruits, and vegetables. A significant positive correlation was detected between deft and BMI, sweetened milk and juice, ice cream, candies, and crackers. In the permanent dentition, a significant positive correlation was detected between age, soft drinks, sweetened juice, desserts, and DMFT, while a significant negative correlation was detected with fresh fruits and vegetables. BMI was significantly negatively correlated with a healthy lifestyle, meat/poultry/fish consumption, and fresh fruits and vegetables while positively correlated with legumes, ice cream, soft drinks, granulated sugars, desserts, fast food, and caffeinated drinks. Conclusion: Overweight/obesity was positively correlated with primary dentition dental caries. Desserts (sweetened snacks) and soft drinks could be the common risk factors associated with high caries and overweight/obesity incidence among Egyptian school children; conversely, consumption of fruits and vegetables could hinder both health conditions. Moreover, sweetened juices were associated with primary and permanent dental caries.

Unhealthy Dietary Habits and Obesity: The Major Risk Factors Beyond Non-Communicable Diseases in the Eastern Mediterranean Region.

There are 22 countries in the Eastern Mediterranean Region (EMR) expanding from Morocco in the west to Pakistan and Afghanistan in the east, containing a population of 725,721 million in 2020. In the previous 30 years, the illness burden in the EMR has transmitted from communicable diseases to non-communicable diseases such as diabetes, cardiovascular diseases, and cancer. In 2019, cardiovascular mortality in the EMR was mostly attributed to ischemic heart disease, the first reason for mortality in 19 countries in the region. Stroke was the second reason for death in nine countries followed by diabetes, which was ranked as the second reason for death in two countries. The prominent nutrition-related NCDs risk factors in EMR include obesity, hypertension, high fasting plasma glucose, and upregulated unhealthy diet consumption. Most of the EMR population are unaware of their NCDs risk factor status. These risk factors, even if treated, are often poorly controlled, therefore, inhibiting their existence by changing the lifestyle to proper dietary habits and sufficient physical activity is mandatory. In this review, the epidemiology and nutrition-related risk factors of NCDs in the EMR will be discussed and illustrated, aiming to scale up action and support decision-makers in implementing cost effective strategies to address obesity and NCDs prevention and management in the region.

Effect of Polymeric Matrix Stiffness on Osteogenic Differentiation of Mesenchymal Stem/Progenitor Cells: Concise Review.

Mesenchymal stem/progenitor cells (MSCs) have a multi-differentiation potential into specialized cell types, with remarkable regenerative and therapeutic results. Several factors could trigger the differentiation of MSCs into specific lineages, among them the biophysical and chemical characteristics of the extracellular matrix (ECM), including its stiffness, composition, topography, and mechanical properties. MSCs can sense and assess the stiffness of extracellular substrates through the process of mechanotransduction. Through this process, the extracellular matrix can govern and direct MSCs' lineage commitment through complex intracellular pathways. Hence, various biomimetic natural and synthetic polymeric matrices of tunable stiffness were developed and further investigated to mimic the MSCs' native tissues. Customizing scaffold materials to mimic cells' natural environment is of utmost importance during the process of tissue engineering. This review aims to highlight the regulatory role of matrix stiffness in directing the osteogenic differentiation of MSCs, addressing how MSCs sense and respond to their ECM, in addition to listing different polymeric biomaterials and methods used to alter their stiffness to dictate MSCs' differentiation towards the osteogenic lineage.

Hydrogels and Dentin-Pulp Complex Regeneration: From the Benchtop to Clinical Translation.

Dentin-pulp complex is a term which refers to the dental pulp (DP) surrounded by dentin along its peripheries. Dentin and dental pulp are highly specialized tissues, which can be affected by various insults, primarily by dental caries. Regeneration of the dentin-pulp complex is of paramount importance to regain tooth vitality. The regenerative endodontic procedure (REP) is a relatively current approach, which aims to regenerate the dentin-pulp complex through stimulating the differentiation of resident or transplanted stem/progenitor cells. Hydrogel-based scaffolds are a unique category of three dimensional polymeric networks with high water content. They are hydrophilic, biocompatible, with tunable degradation patterns and mechanical properties, in addition to the ability to be loaded with various bioactive molecules. Furthermore, hydrogels have a considerable degree of flexibility and elasticity, mimicking the cell extracellular matrix (ECM), particularly that of the DP. The current review presents how for dentin-pulp complex regeneration, the application of injectable hydrogels combined with stem/progenitor cells could represent a promising approach. According to the source of the polymeric chain forming the hydrogel, they can be classified into natural, synthetic or hybrid hydrogels, combining natural and synthetic ones. Natural polymers are bioactive, highly biocompatible, and biodegradable by naturally occurring enzymes or via hydrolysis. On the other hand, synthetic polymers offer tunable mechanical properties, thermostability and durability as compared to natural hydrogels. Hybrid hydrogels combine the benefits of synthetic and natural polymers. Hydrogels can be biofunctionalized with cell-binding sequences as arginine-glycine-aspartic acid (RGD), can be used for local delivery of bioactive molecules and cellularized with stem cells for dentin-pulp regeneration. Formulating a hydrogel scaffold material fulfilling the required criteria in regenerative endodontics is still an area of active research, which shows promising potential for replacing conventional endodontic treatments in the near future.

Induced Pluripotent Stem Cells in Dental and Nondental Tissue Regeneration: A Review of an Unexploited Potential.

Cell-based therapies currently represent the state of art for tissue regenerative treatment approaches for various diseases and disorders. Induced pluripotent stem cells (iPSCs), reprogrammed from adult somatic cells, using vectors carrying definite transcription factors, have manifested a breakthrough in regenerative medicine, relying on their pluripotent nature and ease of generation in large amounts from various dental and nondental tissues. In addition to their potential applications in regenerative medicine and dentistry, iPSCs can also be used in disease modeling and drug testing for personalized medicine. The current review discusses various techniques for the production of iPSC-derived osteogenic and odontogenic progenitors, the therapeutic applications of iPSCs, and their regenerative potential in vivo and in vitro. Through the present review, we aim to explore the potential applications of iPSCs in dental and nondental tissue regeneration and to highlight different protocols used for the generation of different tissues and cell lines from iPSCs.

Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications.

Regenerative medicine literature has proposed mesenchymal stem/progenitor cell- (MSC-) mediated therapeutic approaches for their great potential in managing various diseases and tissue defects. Dental MSCs represent promising alternatives to nondental MSCs, owing to their ease of harvesting with minimally invasive procedures. Their mechanism of action has been attributed to their cell-to-cell contacts as well as to the paracrine effect of their secreted factors, namely, secretome. In this context, dental MSC-derived secretome/conditioned medium could represent a unique cell-free regenerative and therapeutic approach, with fascinating advantages over parent cells. This article reviews the application of different populations of dental MSC secretome/conditioned medium in in vitro and in vivo animal models, highlights their significant implementation in treating different tissue' diseases, and clarifies the significant bioactive molecules involved in their regenerative potential. The analysis of these recent studies clearly indicate that dental MSCs' secretome/conditioned medium could be effective in treating neural injuries, for dental tissue regeneration, in repairing bone defects, and in managing cardiovascular diseases, diabetes mellitus, hepatic regeneration, and skin injuries, through regulating anti-inflammatory, antiapoptotic, angiogenic, osteogenic, and neurogenic mediators.

Mesenchymal Stem/Progenitor Cells: The Prospect of Human Clinical Translation.

Mesenchymal stem/progenitor cells (MSCs) are key players in regenerative medicine, relying principally on their differentiation/regeneration potential, immunomodulatory properties, paracrine effects, and potent homing ability with minimal if any ethical concerns. Even though multiple preclinical and clinical studies have demonstrated remarkable properties for MSCs, the clinical applicability of MSC-based therapies is still questionable. Several challenges exist that critically hinder a successful clinical translation of MSC-based therapies, including but not limited to heterogeneity of their populations, variability in their quality and quantity, donor-related factors, discrepancies in protocols for isolation, in vitro expansion and premodification, and variability in methods of cell delivery, dosing, and cell homing. Alterations of MSC viability, proliferation, properties, and/or function are also affected by various drugs and chemicals. Moreover, significant safety concerns exist due to possible teratogenic/neoplastic potential and transmission of infectious diseases. Through the current review, we aim to highlight the major challenges facing MSCs' human clinical translation and shed light on the undergoing strategies to overcome them.

The prevalence of dental caries among Egyptian children and adolescences and its association with age, socioeconomic status, dietary habits and other risk factors. A cross-sectional study.

Background: Dental caries is a chronic, multifactorial disease, with limited data available for the Egyptian population. The aim of this study is to assess the prevalence of dental caries among Egyptian children and adolescents in correlation with age, gender, body mass index, socioeconomic status, parental education, biological risk factors and dietary habits. Methods: A total number of 369 Egyptian children and adolescents (age ranges from 3-18 years) were examined over the period from 15 th November 2017 to 13 th January 2018. Socio-demographic data, oral hygiene measures and dietary habits for children were recorded. Dental status was analyzed using decayed, missing and filled tooth index (dmft) for deciduous dentition and (DMFT) index for permanent dentition. For mixed dentition (deft) index was used, d (decayed tooth indicated for filling), e (decayed tooth indicated for extraction) and f (filled tooth). Results: 74% of the children had dental caries with mean dmft: 3.23±4.07; deft: 4.21±3.21; DMFT: 1.04±1.56. In primary dentition, dmft of the children was positively correlated with age, beans, candies, crackers, chocolates and inversely correlated with gender, socio-economic status (SES), parental education, brushing frequency of the parent, brushing frequency of the parent to the child teeth, brushing frequency of the child and consumption of eggs, fruits/vegetables, milk and milk products. In mixed dentition, deft was positively correlated with candies, crackers, citric juices, while negatively correlated with age, SES, parental education, brushing frequency of the parent to the child, brushing frequency of the child, fruits/vegetables. In permanent dentition, DMFT in children was positively correlated with age and chocolates while not correlated with any of the remaining risk factors. Conclusion: The present study clarifies the significant risk factors associated with dental caries amongst Egyptian children. This will help in planning strategies to prevent and treat such disease.

The potential impact of age, gender, body mass index, socioeconomic status and dietary habits on the prevalence of dental caries among Egyptian adults: a cross-sectional study.

Background: Dental caries is a major public health problem and the most widespread chronic disease to affect individuals throughout their lifetime. Little information exists about the prevalence of dental caries among Egyptian adults. Therefore, this study investigated the dental caries experience among Egyptian adults in correlation with different risk factors. Methods: A total of 359 Egyptian adults (age range, 18-74 years) were examined over a period of 3 months, starting on the 15 th of November 2017 until the 13 th of January 2018. Socio-demographic data, brushing frequency, body mass index (BMI) and eating habits were recorded and collected using a questionnaire. Dental examination was performed using the Decayed, Missing and Filled tooth (DMFT) index. Results: In total, 86.63% of participants had dental caries experience. Of the participants, 60.45%, 48.47% and 55.43% had at least one decayed, missing and filled tooth, respectively. The mean number of decayed, missing, filled or DMFT for the whole sample were 2.4±3.6, 1.98±3.99, 1.79±2.45, 6.09±5.7, respectively. Decayed teeth were inversely correlated with socio-economic status (SES), education level, brushing frequency and milk consumption and positively correlated with grains, junk food and soda drinks consumption. Missing teeth were inversely correlated with SES, education level and brushing frequency, while positively correlated with age, BMI and caffeinated drink consumption. Conversely, filled teeth were positively correlated with age, BMI, SES and education level, while negatively correlated with grains and sugars in drinks. Conclusion: The present study clarifies that age, BMI, SES, education level and brushing frequency are risk factors significantly associated with dental caries prevalence amongst Egyptian adults. Egyptian adults' dietary habits might lead to obesity, which indirectly causes dental caries rather than directly as in children.

The occurrence of periodontal diseases and its correlation with different risk factors among a convenient sample of adult Egyptian population: a cross-sectional study.

Background: Even though extensive studies on the prevalence of periodontal diseases in various populations worldwide have been carried out, data for the Egyptian population is limited.  The present study was carried out to evaluate the occurrence and the severity of periodontal disease and its correlation with different risk factors. Methods: Periodontal examination was performed on 343 adults attending the outpatient clinics of the Faculty of Dentistry, Cairo University, as well as three private clinics. Socio-demographic data, brushing frequency, body mass index (BMI) and dietary habits were recorded using a questionnaire. Results: It was found that 58.9% of participants had calculus deposits. The occurrence of periodontitis was 89.8%, where 70.8% of participants had stage I and 15.2% had stage II, while only 4.4% and 2.05% suffered from stage III and stage IV, respectively. Calculus was positively correlated with age, grains, and sugar in drinks and negatively correlated with socioeconomic status, education level, brushing frequency and milk. Calculus was not correlated with gender and BMI. Periodontitis was positively correlated with age, carbohydrates other than bread, grains, and crackers, as well as caffeinated drinks, while negatively correlated with gender, socioeconomic status, brushing frequency. Periodontitis was not correlated with BMI or education level. Conclusion: The present study clarifies that age, brushing frequency, carbohydrates and caffeinated drinks consumption are significant factors influencing the occurrence and the severity of periodontal diseases.

Biomimetic remineralization of acid etched enamel using agarose hydrogel model.

Background: Minimally invasive dentistry aims to prevent progression of caries and treats non-cavitated lesions through non-invasive approaches to preserve the integrity of tooth structure. The aim of this research was to investigate the possible biomimetic effect of agarose hydrogel in remineralizing a human demineralized enamel model. Methods: Mandibular third molars were distributed into three groups (G1, G2 and G3) according to the follow up time (2, 4 and 6 days respectively). Caries like lesion was prepared by applying 37% phosphoric acid gel for 1 minute and then remineralization was performed through applying agarose hydrogel on the demineralized surfaces. The specimens were placed in phosphate solution at 37˚C for 2, 4 & 6 days. Scanning electron microscope (SEM), surface microhardness (SMH) and surface roughness analysis (SR) were performed to assess the regenerated tissue. Results: SEM revealed mineral depositions on the demineralized enamel surface that increased in density by time resulting in a relatively smooth surface in G3. SR and SMH analysis revealed significant differences between the remineralized enamel surfaces of different groups (p< 0.00001) with the highest SR in G1 and the highest SMH in G3. Conclusions: Agarose hydrogel application is a promising approach to treat early carious lesion. Further studies are needed to clarify the stability of agarose hydrogels in clinical application.

The ability of H1 or H2 receptor antagonists or their combination in counteracting the glucocorticoid-induced alveolar bone loss in rats.

BACKGROUND: The aim of the present study was to compare between three possible osteoporotic treatments in prevention of glucocorticoid-induced alveolar bone loss. METHODS: Fifty adult female Wistar rats with an average weight 150-200 g were randomized into five groups: group I (control) was intraperitoneally injected with saline. The other experimental groups (II & III, IV & V) were intraperitoneally injected with 200 µg/100 g body weight dexamethasone. The experimental groups III, IV and V received intraperitoneal injection of 10 mg/kg/day pheniramine maleate (H1 receptor antagonist), ranitidine hydrochloride (H2 receptor antagonist) and concomitant doses of both H1 & H2 receptor antagonists respectively. After 30 days, the rats have been sacrificed. The mandibles were examined histologically, histochemically and histomorphometrically. The bone mineral density was measured using dual-energy X-ray absorptiometry (DEXA). RESULTS: Histopathologically the glucocorticoid group showed wide medullary cavities with wide osteocytic lacunae. These marrow cavities were reduced in the prophylactic groups (III, IV) but increased in group V. Bone histomorphometric analysis revealed improvement in static bone parameters in groups III and IV and deterioration in group V in comparison to group II. The DEXA revealed significant reduction in the bone mineral density in all experimental groups compared to the control group. CONCLUSIONS: In a rat model, the administration of H1 or H2 receptor antagonists separately could minimize the alveolar bone loss caused by the administration of glucocorticoids while concomitant administration of both H1 and H2 receptor antagonists deteriorated the bone condition.