Improved Neurodevelopmental Outcomes at 5.5 Years of Age in Children Who Received Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula Through 12 Months: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the neurodevelopmental outcomes at 5.5 years of age in children who were previously randomized to cow milk-based infant formula (control) or similar formula (milk fat globule membrane + lactoferrin) with added sources of bovine milk fat globule membrane and bovine lactoferrin through 12 months of age. DESIGN: Children who completed study feeding were invited to participate in follow-up assessments: cognitive development across multiple domains (primary outcome; Wechsler Preschool & Primary Scale of Intelligence, 4th Edition), inhibitory control/rule learning (Stroop Task), flexibility/rule learning (Dimensional Change Card Sort), and behavior/emotion (Child Behavior Checklist). RESULTS: Of 292 eligible participants (control: 148, milk fat globule membrane + lactoferrin: 144), 116 enrolled and completed assessments (control: 59, milk fat globule membrane + LF: 57). There were no group demographic differences except family income (milk fat globule membrane + lactoferrin significantly higher). Wechsler Preschool & Primary Scale of Intelligence, 4th Edition composite scores (mean ± standard error) for Visual Spatial (100.6 ± 1.7 vs 95.3 ± 1.7; P = .027), Processing Speed (107.1 ± 1.4 vs 100.0 ± 1.4; P < .001), and Full-Scale IQ (98.7 ± 1.4 vs 93.5 ± 1.5; P = .012) were significantly higher for milk fat globule membrane + lactoferrin versus control, even after controlling for demographic/socioeconomic factors. Stroop Task scores were significantly higher in milk fat globule membrane + lactoferrin versus control (P < .001). Higher Dimensional Change Card Sort scores (P = .013) in the border phase (most complex/challenging) were detected, and more children passed the border phase (32% vs 12%; P = .039) for milk fat globule membrane versus control. No group differences in Child Behavior Checklist score were detected. CONCLUSIONS: Children who received infant formula to 12 months of age with added bovine milk fat globule membrane and bovine lactoferrin versus standard formula demonstrated improved cognitive outcomes in multiple domains at 5.5 years of age, including measures of intelligence and executive function. TRIAL REGISTRATION: Clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT04442477.

DHA Supplementation During Pregnancy Enhances Maternal Vagally Mediated Cardiac Autonomic Control in Humans.

BACKGROUND: DHA is an essential omega-3 (ω-3; n-3) fatty acid that has well-established benefits for the fetus. DHA also has the potential to influence the health of the mother, but this area is understudied. OBJECTIVES: The objective of this secondary analysis was to determine if DHA was related to maternal heart rate (HR) and heart rate variability (HRV) metrics in a large cohort of pregnant women. METHODS: In the parent trial (1R01HD086001) eligible participants (≥18 y old, English speaking, carrying a singleton pregnancy, 12-20 wk of gestation) were randomly assigned to consume 200 mg/d or 800 mg/d DHA for the duration of their pregnancy (n = 300). Weight, blood pressure, and magnetocardiograms (MCGs) were collected at 32 wk and 36 wk of gestation (n = 221). Measures of HR and HRV in time-, frequency-, and nonlinear-domains were determined from the isolated maternal MCG. Treatment group and timepoint were examined as predictors in association with HR and HRV metrics using random-intercept mixed-effects ANOVA unadjusted and adjusted models accounting for weight and dietary DHA intake. RESULTS: Women receiving the higher dose of DHA (800 mg/d) during pregnancy had lower HR, lower sympathetic index, higher vagally mediated HRV indices, and greater HRV complexity when compared with the women who received the lower dose (200 mg/d; all P < 0.05). All the dose relations remained significant even after controlling for the effect of time, maternal weight, and dietary DHA intake. CONCLUSIONS: DHA supplementation increases vagal tone in pregnant women. Longitudinal studies examining the potential link between DHA, enhanced vagal tone, and reported reduction in early preterm birth are warranted.

Pneumothorax in Intubated Patients With COVID-19: A Case Series.

Pneumothorax is a rare complication among mechanically ventilated patients since low tidal volumes are used nowadays instead of traditional high tidal volumes, but the incidence is slightly higher in patients with high positive end-expiratory pressure (PEEP). Herein we describe a case series of nine patients who were on mechanical ventilation due to acute respiratory distress syndrome (ARDS) secondary to coronavirus disease 2019 (COVID-19) and developed pneumothorax in due course. A retrospective analysis was done on COVID-19 intubated patients from March 2020 to June 2020 in a community hospital in Central New Jersey, which was one of the early hit states in the United States at the beginning of the pandemic. Outcomes were studied. The demographics of patients like age, gender, and body mass index (BMI); risk factors like smoking, comorbidities especially chronic lung disease, and the treatment they received were compared. We compared the total number of days on the ventilator, the highest PEEP they received, and the ventilator day when pneumothorax developed. All the patients who developed pneumothorax had a chest tube inserted to treat it. The mortality was noted to be 100% indicating that pneumothorax is a life-threatening complication of COVID-19 and COVID-19 by itself is a risk factor for pneumothorax likely due to a change in lung mechanics. There is a need for large-scale studies to confirm that these outcomes are related to COVID-19.

Maternal Docosahexaenoic Acid Exposure Needed to Achieve Maternal-Newborn EQ.

Achieving maternal docosahexaenoic acid (DHA) status equal to or greater than the infant's DHA status at delivery is known as maternal-newborn DHA equilibrium (EQ) and is thought to be important for optimizing newborn DHA status throughout infancy. The objective of this study was to determine the daily DHA intake during pregnancy most likely to result in EQ. The participants (n = 1145) were from two randomized control trials of DHA supplementation in pregnancy. DHA intake was estimated using an abbreviated food frequency questionnaire. Total DHA exposure during pregnancy was calculated as a weighted average of the estimated DHA intake throughout pregnancy and the randomized DHA dose (200, 800, 1000 mg). Red blood cell DHA was measured from maternal and cord blood plasma at delivery and EQ status was calculated. The DHA intake required to achieve EQ was estimated by regression. In terms of DHA exposure, the point estimate and 95% confidence interval to achieve EQ was 643 (583, 735) mg of DHA/day. The results of our trial suggest an intake of 650 mg of DHA/day is necessary to increase the potential for EQ at delivery. The clinical benefits of achieving EQ deserves continued study.

Highly targeted electrochemical disruption of microbes with minimal disruption to pulp cells.

INTRODUCTION: Pulpitis results from the infiltration of mixed populations of bacteria which trigger inflammation in the dental pulp, causing significant disruption to these tissues. Clinically, pulpitis frequently leads to devitalization or extraction, as disinfection of the dental pulp while maintaining its vitality is extremely difficult. Here we describe the use of an electrocatalytic titanium dioxide (TiO2)-based apparatus adapted from water purification technology, which can efficiently deliver anti-microbial oxidants (e.g., hydroxyl radicals) when low voltages are applied. As these oxidants are also potentially harmful to pulp cells, oxidant exposure protocols that disrupt oral bacteria, yet are innocuous to dental pulp cells must be established. METHODS: Stem cells from Human Exfoliated Deciduous teeth (SHEDs) and mixed salivary bacteria were exposed to apparatus generated oxidants for time points of 15, 100 or 300 s. SHED apoptosis, necrosis, and vitality post exposure were analyzed by florescent marker staining and flow cytometry. Destruction of mixed salivary bacteria was analyzed by post exposure counts of adherent bacterial cells. RESULTS: When applied to SHEDs the apparatus generated oxidants do not significantly induce apoptosis or necrosis at any exposure time. SHED cell vitality is not decreased with apparatus exposure. Exposure to apparatus generated oxidants destroys mixed salivary bacteria, with significant destruction seen at 15 s and maximal destruction achieved at 100 s. CONCLUSIONS: This technology has the potential to be useful in the disinfection of deep lesions and pulp tissues, efficiently producing oxidants which eliminate bacteria but do not harm native pulp cells after relatively brief exposures. CLINICAL SIGNIFICANCE: Incomplete disinfection of inflamed dental pulp is a significant cause of pulp destruction, leading to devitalization or extraction. Novel technology which enhances the disinfection of the pulp may provide clinicians with treatments options that preserve pulp vitality and tooth structure.

An Investigation of the Relationship Between Dietary Patterns in Early Pregnancy and Maternal/Infant Health Outcomes in a Chinese Cohort.

Background: Studies assessing links between maternal diet and pregnancy outcomes have focused predominantly on individual nutrients or foods. However, nutrients are typically consumed in combinations of foods or beverages (i.e., dietary patterns). Taking into account the diet as a whole appreciates that nutrient absorption and metabolism are influenced by other nutrients and the food matrix. Objective: The aim of this study was to investigate the relationship between dietary pattern consumption in early pregnancy and pregnancy/infant outcomes, including gestational diabetes mellitus, gestational weight gain, preeclampsia, placental weight, gestational age at delivery, small-for-gestational-age, large-for-gestational-age, macrosomia, measures of infant body composition, and scores on two main indices of the Bayley Scales of Infant Development [Mental Development Index (MDI) and the Psychomotor Development Index (PDI)] at 12 months. Design: Our study included 1,437 participants from a mother-infant cohort in Chongqing, China. Maternal diet was assessed using a 96-item food frequency questionnaire at 11-14 weeks gestation. Dietary patterns were constructed using principal component analysis. Multivariate regressions were performed to assess associations between maternal dietary pattern scores and pregnancy and infant outcomes, adjusting for confounders. Results: Two dietary patterns were derived: a pattern high in pasta, sweetened beverages, and oils and condiments (PSO-based dietary pattern) and a pattern high in fish, poultry, and vegetables (FPV-based dietary pattern). Higher scores on the PSO-based dietary pattern were associated with lower infant standardized scores on the PDI of the Bayley Scales of Infant Development, ß (95% confidence interval) = -1.276 (-2.392, -0.160); lower placental weight, ß (95% CI) = -6.413 (-12.352g, -0.473); and higher infant's tricep skinfold thickness at 6 weeks of age. ß (95% CI) = 0.279 (0.033, 0.526). Higher scores on the FPV-based dietary pattern were associated with higher gestational weight gain between visit 1 (11-14 week's gestation) and 3 (32-34 week's gestation). ß (95% CI) = 25.612 (13.255, 37.969). No significant associations were observed between dietary pattern scores and the remaining pregnancy/infant outcomes investigated or MDI scores on the Bayley Scales of Infant Development. This was the first study to investigate the association between dietary patterns in early pregnancy and infant neurocognition in a Chinese cohort.

Dental Pulp Stem Cell Heterogeneity: Finding Superior Quality "Needles" in a Dental Pulpal "Haystack" for Regenerative Medicine-Based Applications.

Human dental pulp stem/stromal cells (hDPSCs) derived from the permanent secondary dentition are recognised to possess certain advantageous traits, which support their potential use as a viable source of mesenchymal stem/stromal cells (MSCs) for regenerative medicine-based applications. However, the well-established heterogeneous nature of hDPSC subpopulations, coupled with their limited numbers within dental pulp tissues, has impeded our understanding of hDPSC biology and the translation of sufficient quantities of these cells from laboratory research, through successful therapy development and clinical applications. This article reviews our current understanding of hDPSC biology and the evidence underpinning the molecular basis of their heterogeneity, which may be exploited to distinguish individual subpopulations with specific or superior characteristics for regenerative medicine applications. Pertinent unanswered questions which still remain, regarding the developmental origins, hierarchical organisation, and stem cell niche locations of hDPSC subpopulations and their roles in hDPSC heterogeneity and functions, will further be explored. Ultimately, a greater understanding of how key features, such as specific cell surface, senescence and other relevant genes, and protein and metabolic markers, delineate between hDPSC subpopulations with contrasting stemness, proliferative, multipotency, immunomodulatory, anti-inflammatory, and other relevant properties is required. Such knowledge advancements will undoubtedly lead to the development of novel screening, isolation, and purification strategies, permitting the routine and effective identification, enrichment, and expansion of more desirable hDPSC subpopulations for regenerative medicine-based applications. Furthermore, such innovative measures could lead to improved cell expansion, manufacture, and banking procedures, thereby supporting the translational development of hDPSC-based therapies in the future.

Prenatal docosahexaenoic acid supplementation has long-term effects on childhood behavioral and brain responses during performance on an inhibitory task.

Introduction: Offsprings from a prenatal docosahexaenoic acid (DHA) supplementation trial, in which pregnant women were assigned to placebo or 600mg DHA/day, were followed to determine the effect of prenatal DHA supplementation on the behavior and brain function at 5.5 years (n=81 placebo, n=86 supplemented).Methods: Event-related potentials (ERP) were recorded during a visual task requiring a button press (Go) to frequent target stimuli and response inhibition to the rare stimuli (No-Go). Univariate ANOVAs were used to test differences between group and sex for behavioral measures. ERP differences were tested using a three-way mixed-design multivariate analysis of variance (MANOVA).Results: There was a significant sex × group interaction for hit rate and errors of omission; there was no difference between males and females in the placebo group, but DHA males outperformed DHA females. Males overall and the placebo group made more errors requiring response inhibition; DHA females were significantly better than placebo females and DHA males. ERP P2 amplitude was larger in the DHA group. A significant N2 amplitude condition effect was observed in females and DHA group males, but not in placebo group males.Discussion: Prenatal DHA supplementation improved inhibitory performance overall, especially for females in the DHA group, possibly accounting for their conservative behavior during Go trials. Development of brain regions responsible for visual processing may be sensitive to maternal DHA status, evidenced by greater P2 amplitude. Males may benefit more from maternal DHA supplementation, indicated by the N2 condition effect seen only in males in the DHA group.

Prenatal docosahexaenoic acid effect on maternal-infant DHA-equilibrium and fetal neurodevelopment: a randomized clinical trial.

INTRODUCTION: Maternal-infant equilibrium occurs when cord blood docosahexaenoic acid (DHA) is less than or equal to maternal DHA at delivery. Equilibrium may be an indicator of sufficient DHA for optimal fetal and infant neurodevelopment. The purpose of this study was to test the effect of maternal DHA supplementation on equilibrium status and fetal neurodevelopment. METHODS: Women enrolled between 12 and 20 weeks gestation and were randomized to 200 or 800 mg DHA/day until delivery. Maternal red blood cell (RBC) phospholipids were measured at enrollment, 32 weeks, delivery, and in cord blood at delivery. Fetal neurodevelopment was measured at 32 and 36 weeks gestation. Intent-to-treat analyses were conducted to test differences in equilibrium status by group. Fetal outcomes were assessed by equilibrium status and group. RESULTS: Three hundred women enrolled and 262 maternal-infant dyads provided blood samples at delivery. No maternal-infant dyads with maternal RBC-DHA ≤ 6.96% at delivery achieved equilibrium. The incidence of equilibrium was significantly higher in the 800 mg group. There was no effect of maternal group or equilibrium status on fetal neurodevelopment. CONCLUSION: The significance of maternal-infant DHA equilibrium remains unknown. Ongoing research will test the effect of treatment group, equilibrium, and nutrient status on infant behavior and brain function. IMPACT: Pregnant women who received a higher dose of docosahexaenoic acid (DHA) were more likely to achieve maternal-infant DHA equilibrium at delivery. Equilibrium status had no effect on fetal neurodevelopment in this sample. While DHA is crucial for early life neurodevelopment, the significance of achieving maternal-infant equilibrium above the lower threshold is uncertain. There is a lower threshold of maternal DHA status where maternal-infant DHA equilibrium never occurs. The lack of equilibrium associated with low maternal DHA status may indicate insufficient maternal status for optimal placental transfer.

A Clinical Overview of Acute and Chronic Pancreatitis: The Medical and Surgical Management.

An inflammatory process involving the pancreas, known as pancreatitis, can be categorized as either acute or chronic and may present in one of many ways. The clinical manifestations of acute pancreatitis are generally limited to epigastric or right upper quadrant pain, while manifestations of chronic pancreatitis are broader and may include abdominal pain in tandem with signs and symptoms of pancreatic endocrine and exocrine insufficiency. An understanding of the initial insult, proper classification, and prognosis are all factors that are of paramount importance as it pertains to managing patients who are afflicted with this disease. Our review delves into the depths of pancreatitis by exploring the embryology and anatomy of the pancreas, the pathophysiology and etiology of acute and chronic pancreatitis, and the medical and surgical management of acute and chronic pancreatitis.

Life-Threatening Retroperitoneal Hematoma in a Patient with COVID-19.

COVID-19 is a respiratory illness that affects the human body in many different ways. The disease carries both thrombotic and hemorrhagic complications, especially in those patients who are anticoagulated to prevent the thromboembolic manifestations. In this report, we discuss a case of retroperitoneal hemorrhage in a patient treated with therapeutic anticoagulation which ultimately led to the patient's death. The literature highlights the importance of anticoagulation because it reduces mortality in patients hospitalized with COVID-19. Although, more recent studies suggest that patients treated with therapeutic anticoagulation are at a higher risk of hemorrhage and increased mortality. Therefore, our case stresses the importance of active monitoring of these patients to detect any suspected case of hemorrhage early to reduce mortality. Overall, more research should be conducted to determine the optimal dosing of anticoagulation that balances safety and efficacy.

Postpartum Respiratory Distress Due to Hypertension-Related Pulmonary Edema.

We present the case of a 35-year-old female who presented to the emergency department (ED) shortly after undergoing a cesarean section with dyspnea. Her vitals on admission revealed hypertension, tachypnea, bradycardia, and suboptimal oxygen saturation. Physical examination was remarkable for crackles in the lower lung fields. Laboratory results revealed elevated lactate dehydrogenase (LDH), pro-B-type natriuretic peptide (pro-BNP), and D-dimer levels. A CT angiogram showed no pulmonary emboli, and an echocardiogram revealed a normal ejection fraction and no diastolic dysfunction. A chest X-ray was significant for pulmonary edema and vascular congestion. The patient was diagnosed with respiratory distress due to pulmonary edema that was secondary to hypertension. This unusual case report seeks to highlight the idea that elevated blood pressure in postpartum women should warrant careful monitoring, as its consequential manifestations may be lethal. Additionally, pulmonary edema secondary to hypertension should be considered as a differential in either postpartum or peripartum women who present with respiratory symptoms and elevated blood pressure.

Associations of early pregnancy BMI with adverse pregnancy outcomes and infant neurocognitive development.

The prevalence of overweight and obesity amongst reproductive women has been increasing worldwide. Our aim was to compare pregnancy outcomes and infant neurocognitive development by different BMI classifications and investigate whether early pregnancy BMI was associated with risks of adverse outcomes in a Southwest Chinese population. We analysed data from 1273 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) randomized controlled trial in Chongqing, China. Maternal BMI was classified as underweight, normal weight and overweight/obese according to the Chinese, WHO Asian, and WHO European standards. For the adverse pregnancy outcomes, after adjustment for potential confounders, an underweight BMI was associated with increased risk of small for gestational age (SGA) babies, and an overweight/obese BMI was associated with increased risk of maternal gestational diabetes mellitus (GDM), caesarean section (C-section), macrosomia and large for gestational age (LGA) babies. For infant neurocognitive development, 1017 mothers and their children participated; no significant differences were seen in the Mental Development Index (MDI) or the Psychomotor Development Index (PDI) between the three BMI groups. Our findings demonstrate that abnormal early pregnancy BMI were associated with increased risks of adverse pregnancy outcomes in Chinese women, while early pregnancy BMI had no significant influence on the infant neurocognitive development at 12 months of age.

Innovative Molecular and Cellular Therapeutics in Cleft Palate Tissue Engineering.

Clefts of the lip and/or palate are the most prevalent orofacial birth defects occurring in about 1:700 live human births worldwide. Early postnatal surgical interventions are extensive and staged to bring about optimal growth and fusion of palatal shelves. Severe cleft defects pose a challenge to correct with surgery alone, resulting in complications and sequelae requiring life-long, multidisciplinary care. Advances made in materials science innovation, including scaffold-based delivery systems for precision tissue engineering, now offer new avenues for stimulating bone formation at the site of surgical correction for palatal clefts. In this study, we review the present scientific literature on key developmental events that can go awry in palate development and the common surgical practices and challenges faced in correcting cleft defects. How key osteoinductive pathways implicated in palatogenesis inform the design and optimization of constructs for cleft palate correction is discussed within the context of translation to humans. Finally, we highlight new osteogenic agents and innovative delivery systems with the potential to be adopted in engineering-based therapeutic approaches for the correction of palatal defects. Impact statement Tissue-engineered scaffolds supplemented with osteogenic growth factors have attractive, largely unexplored possibilities to modulate molecular signaling networks relevant to driving palatogenesis in the context of congenital anomalies (e.g., cleft palate). Constructs that address this need may obviate current use of autologous bone grafts, thereby avoiding donor-site morbidity and other regenerative challenges in patients afflicted with palatal clefts. Combinations of biomaterials and drug delivery of diverse regenerative cues and biologics are currently transforming strategies exploited by engineers, scientists, and clinicians for palatal cleft repair.

DHA supplementation in infants born preterm and the effect on attention at 18 months' corrected age: follow-up of a subset of the N3RO randomised controlled trial.

Infants born preterm miss out on the peak period of in utero DHA accretion to the brain during the last trimester of pregnancy which is hypothesised to contribute to the increased prevalence of neurodevelopmental deficits in this population. This study aimed to determine whether DHA supplementation in infants born preterm improves attention at 18 months' corrected age. This is a follow-up of a subset of infants who participated in the N3RO randomised controlled trial. Infants were randomised to receive an enteral emulsion of high-dose DHA (60 mg/kg per d) or no DHA (soya oil - control) from within the first days of birth until 36 weeks' post-menstrual age. The assessment of attention involved three tasks requiring the child to maintain attention on toy/s in either the presence or absence of competition or a distractor. The primary outcome was the child's latency of distractibility when attention was focused on a toy. The primary outcome was available for seventy-three of the 120 infants that were eligible to participate. There was no evidence of a difference between groups in the latency of distractibility (adjusted mean difference: 0·08 s, 95 % CI -0·81, 0·97; P = 0·86). Enteral DHA supplementation did not result in improved attention in infants born preterm at 18 months' corrected age.

Developmental effects on sleep-wake patterns in infants receiving a cow's milk-based infant formula with an added prebiotic blend: a Randomized Controlled Trial.

BACKGROUND: Few studies have evaluated nutritive effects of prebiotics on infant behavior state, physiology, or metabolic status. METHODS: In this double-blind randomized study, infants (n = 161) received cow's milk-based infant formula (Control) or similar formula with an added prebiotic blend (polydextrose and galactooligosaccharides [PDX/GOS]) from 14-35 to 112 days of age. Infant wake behavior (crying/fussing, awake/content) and 24-h sleep-wake actograms were analyzed (Baseline, Days 70 and 112). Salivary cortisol was immunoassayed (Days 70 and 112). In a subset, exploratory stool 16S ribosomal RNA-sequencing was analyzed (Baseline, Day 112). RESULTS: One hundred and thirty-one infants completed the study. Average duration of crying/fussing episodes was similar at Baseline, significantly shorter for PDX/GOS vs. Control at Day 70, and the trajectory continued at Day 112. Latency to first and second nap was significantly longer for PDX/GOS vs. Control at Day 112. Cortisol awakening response was demonstrated at Days 70 and 112. Significant stool microbiome beta-diversity and individual taxa abundance differences were observed in the PDX/GOS group. CONCLUSIONS: Results indicate faster consolidation of daytime waking state in infants receiving prebiotics and support home-based actigraphy to assess early sleep-wake patterns. A prebiotic effect on wake organization is consistent with influence on the gut-brain axis and warrants further investigation. IMPACT: Few studies have evaluated nutritive effects of prebiotics on infant behavior state, cortisol awakening response, sleep-wake entrainment, and gut microbiome. Faster consolidation of daytime waking state was demonstrated in infants receiving a prebiotic blend in infant formula through ~4 months of age. Shorter episodes of crying were demonstrated at ~2 months of age (time point corresponding to age/developmental range associated with peak crying) in infants receiving formula with added prebiotics. Results support home-based actigraphy as a suitable method to assess early sleep-wake patterns. Prebiotic effect on wake organization is consistent with influence on the gut-brain axis and warrants further investigation.

Modeling Hypoxia Induced Factors to Treat Pulpal Inflammation and Drive Regeneration.

INTRODUCTION: The ability to resolve pulpal inflammation to achieve predictable regeneration of the dentin-pulp complex has remained elusive and presents a challenge for clinicians and researchers. Although the dentin-pulp complex can react naturally to injury by forming a bridge of reparative dentin that protects the pulp from further damage, this process is significantly impaired if inflammation persists. Because the secretion of inflammatory cytokines by injured pulpal cells causes significant pain and discomfort to patients, it is critical to resolve pulpal inflammation in a timely manner so as to create a microenvironment conducive for pulpal healing and reparative dentin formation. The emergent field of regenerative endodontics has encouraged the development and application of biologically driven therapies that take advantage of the intrinsic healing capacities of host cells within dental pulp and the periapical complex. METHODS: These studies were designed to test the hypothesis that exposure to hypoxic conditions can modulate the production of inflammatory cytokines/factors by mesenchymal cells in vitro. A multi-domain peptide hydrogel system that is highly conducive for the growth and differentiation of tooth-derived stem cells was used for these studies. Stem cells from human exfoliated deciduous teeth (SHEDs) were first cultured within 3-dimensional hydrogel constructs and then challenged with hypoxic stresses via addition of H2O2. RESULTS: MDP constructs were successfully generated, challenged with H2O2, decellularized and lyophilized, forming a potential biomaterial containing hypoxia induced repair molecules. The ability of cell-derived factors to convert the phenotype of lipopolysaccharide-primed macrophages from a proinflammatory to a pro-resolving state was examined in the presence of the lyophilized SHED cell constructs. CONCLUSIONS: Our data suggest that hypoxia induced SHED cell products can be captured within the hydrogel system and may be useful in the resolution of pulpal inflammation to create a favorable microenvironment for regeneration of the dentin-pulp complex.

Synthesis and characterization of novel calcium phosphate glass-derived cements for vital pulp therapy.

Evaluation of the physicochemical behavior and setting reactions of a novel inorganic pulp capping cement which makes use of the unique corrosion properties of sodium metasilicate (NaSi) glass. NaSi and calcium phosphate (CaP) glass powders were synthesized through a melt-quench method. Cements were created by mixing various amounts of the glasses with deionized water at a powder-to-liquid ratio of 2.5 g mL-1. Working and setting times were measured using the indentation standard ISO 9917-1. Sealing ability was tested by placing set samples of each composition in methylene blue dye solution for 24 h. Set samples were also submerged in phosphate buffered saline and incubated at 37 °C for one week. X-ray diffraction was used to identify mature crystalline phases after incubation. Infrared spectroscopy and scanning electron microscopy were used to characterize cements before and after setting and after incubation. Working and setting times measured in the ranges of 2-5 and 10-25 min, respectively. Working and setting time generally decrease with increased NaSi concentration. Cements with compositions of 25 and 33 wt% NaSi were found to resist the infiltration of dye and maintain their shape. Compositions outside this range absorbed dye and collapsed. Infrared spectroscopy provided insight into the setting mechanism of these cements. After one week in vitro, cements were found to contain crystalline phases matching chemically stable, bioactive phases. The combination of NaSi and CaP glasses has favorable setting behavior, sealing ability, and mature phases for pulp capping while relying on a relatively simple, inorganic composition.