Self-Assembly of an Organized Cementum-Periodontal Ligament-Like Complex Using Scaffold-Free Tissue Engineering

A major challenge in regenerating periodontal tissues is emulating its complex structure containing both mineralized and soft tissues. In this study, scaffold-free tissue constructs engineered using periodontal ligament cells (PDLCs), which contain a population of adult stem/progenitor cells, self-assembled into an organized multi-tissue structure comprising a mineralized cementum-like core enclosed within a periodontal ligament (PDL)-like tissue. Scaffold-free engineered constructs were formed by culturing human PDLCs to form a cell sheet on six-well dishes containing two minutien pins placed 7 mm apart. The cell sheet was contracted by the cells to roll into the pins forming a cylindrical construct anchored on either end by the pins. These tissues were approximately 1 mm in diameter and 7 mm long and contained only the cells and their endogenous matrix. These scaffold-free engineered constructs exhibited two structurally distinct tissues, one in the center of the construct and another on the periphery. The center tissue was mineralized and expressed alkaline phosphatase and bone sialoprotein, similar to cementum. The peripheral tissue was not calcified and expressed periodontal ligament-associated protein-1 and periostin, which is characteristic of the periodontal ligament. This tissue organization was seen after in vitro culture and maintained in vivo following subcutaneous implantation in immunocompromised mice. These data demonstrate that scaffold-free tissue engineering facilitates PDLCs to self-assemble into an organized cementum-PDL-like complex. These engineered tissues could be used as implantable grafts to regenerate damaged periodontal tissues or as model systems to study PDLC biology and mechanisms driving organized tissue assembly within the periodontium

Scaffoldless tissue engineering: a model to study tissue formation and a device for tissue regeneration

Traditional tissue engineering methods involve the combination of cells, growth factors and a scaffold to regenerate 3D tissues for therapeutic purposes. Naturally, cells utilize their endogenous matrix as a scaffold to form 3D structures. The goals of this thesis were to study scaffoldless 3D constructs as a model of tissue formation and as a device for dental and bone regenerative therapies. Scaffoldless 3D constructs were first used as a model that showed that calcium phosphates are osteoinductive and alter 3D spatial differentiation patterns of dental pulp cells through modulations of connexin 43 expression. Scaffoldless 3D constructs were next used as a model system that showed tissues formed from an isolated population of dental pulp pericyte stem cells regenerated structurally and molecularly different 3D tissues than the total population of dental pulp cells. These studies emphasize the importance of scaffold and cell selection for regenerative therapies. Scaffoldless 3D dental pulp cell tissues were then used as a device that regenerated pulp-like tissue in the root canals of human tooth root segments. Dental pulp cells delivered into the root canals with calcium phosphate particles as a delivery system formed a mixture of dentin and pulp-like tissues. These two cell delivery systems show promise for various endodontic therapies. Finally, scaffoldless bone marrow stromal cell sheets were wrapped around calcium phosphate cements to create a structurally and molecularly relevant periosteum-like tissue that will aid in bone regeneration. These studies show the significance of using engineered tissues generated and organized entirely by the cells themselves and emphasize that scaffoldless engineered tissues are powerful tools for dental and bone research and regeneration

Towards Efficient Semantically Enriched Complex Event Processing and Pattern Matching

International audienceManagement and recognition of event patterns is becoming thoroughly ingrained in many application areas of Semantically enabled Complex Event Processing (SCEP). However, the reliance of state-of-the-art technologies on relational and RDF triple model without having the notion of time has severe limitations. This restricts the system to employ temporal reasoning at RDF level and use historical events to predict new situations. Additionally, the semantics of traditional query languages makes it quite challenging to implement distributed event processing. In our vision, SCEP needs to consider RDF as a first class citizen and should implement parallel and distributed processing to deal with large amount of data streams. In this paper, we discuss various challenges and limitations of state-of-the-art technologies and propose a possible solution to extend RDF data model for stream processing and pattern matching. Furthermore, we describe a high-level query design that enables efficient parallel and distributedpattern matching through query rewriting

4D corneal tissue engineering: achieving time-dependent tissue self-curvature through localized control of cell actuators

While tissue engineering is widely used to construct complex tridimensional biocompatible structures, researchers are now attempting to extend the technique into the fourth dimension. Such fourth dimension consists in the transformation of 3D materials over time, namely, by changing their shape, composition, and/or function when subjected to specific external stimuli. Herein, producing a 4D biomaterial with an internal mechanism of stimulus, using contractile cells as bio‐actuators to change tissue shape and structure, is explored. Specifically, producing cornea‐shaped, curved stromal tissue equivalents via the controlled, cell‐driven curving of collagen‐based hydrogels. This is achieved by modulating the activity of the bio‐actuators in delimited regions of the gels using a contraction‐inhibiting peptide amphiphile. The self‐curved constructs are then characterized in terms of cell and collagen fibril reorganization, gel stiffness, cell phenotype, and the ability to sustain the growth of a corneal epithelium in vitro. Overall, the results show that the structural and mechanical properties of self‐curved gels acquired through a 4D engineering method are more similar to those of the native tissue, and represent a significant improvement over planar 3D scaffolds. In this perspective, the study demonstrates the great potential of cell bio‐actuators for 4D tissue engineering applications

Personalized therapy for mycophenolate:Consensus report by the international association of therapeutic drug monitoring and clinical toxicology

When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted.</p

ARIA 2016 : Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.Peer reviewe

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection