In Situ Remodeling Overrules Bioinspired Scaffold Architecture of Supramolecular Elastomeric Tissue-Engineered Heart Valves.

In situ tissue engineering that uses resorbable synthetic heart valve scaffolds is an affordable and practical approach for heart valve replacement; therefore, it is attractive for clinical use. This study showed no consistent collagen organization in the predefined direction of electrospun scaffolds made from a resorbable supramolecular elastomer with random or circumferentially aligned fibers, after 12 months of implantation in sheep. These unexpected findings and the observed intervalvular variability highlight the need for a mechanistic understanding of the long-term in situ remodeling processes in large animal models to improve predictability of outcome toward robust and safe clinical application.

Macrophage-Driven Biomaterial Degradation Depends on Scaffold Microarchitecture.

tissue engineering is a technology in which non-cellular biomaterial scaffolds are implanted in order to induce local regeneration of replaced or damaged tissues. Degradable synthetic electrospun scaffolds are a versatile and promising class of biomaterials for various tissue engineering applications, such as cardiovascular replacements. Functional tissue regeneration depends on the balance between endogenous neo-tissue formation and scaffold degradation.

Morphology and mechanisms of a novel absorbable polymeric conduit in the pulmonary circulation of sheep.

Background: Right ventricular outflow tract (RVOT) conduits used in children with congenital heart disease often degenerate rapidly or develop other complications, and they do not grow with the patient. This leads to multiple surgeries until adult-sized conduits can be implanted. We report experimental in vivo experience with an entirely synthetic absorbable graft, designed to be replaced by tissue in-vivo by host cells, in a process termed Endogenous Tissue Restoration (ETR), and to grow commensurate with somatic growth.

A novel restorative pulmonary valved conduit in a chronic sheep model: Mid-term hemodynamic function and histologic assessment.

Objective: To evaluate the safety and the short-term function of a novel pulmonary valved conduit (Xeltis Pulmonary Valved Conduit; XPV) up to 12 months in a sheep model.

Methods: XPV and Hancock bioprosthetic valved conduits (H, used as control) were implanted in adult sheep in the pulmonary artery position. Animals were killed at 2 months (n = 6 XPV), 6 months (n = 6 XPV and n = 3 H), and 12 months (n = 6 XPV) and examined histologically.

Midterm performance of a novel restorative pulmonary valved conduit: preclinical results.

Aims: The Xeltis bioabsorbable pulmonary valved conduit (XPV), designed to guide functional restoration of patients' own tissue, is potentially more durable than current pulmonary bioprosthetic valves/valved conduits. The aim of this study was to assess the haemodynamic performance of the novel XPV implanted in an ovine model.

Methods And Results: The XPV was surgically implanted in adult sheep under general anaesthesia and cardiopulmonary bypass (XPV group, n=20).

In situ heart valve tissue engineering using a bioresorbable elastomeric implant - From material design to 12 months follow-up in sheep.

The creation of a living heart valve is a much-wanted alternative for current valve prostheses that suffer from limited durability and thromboembolic complications. Current strategies to create such valves, however, require the use of cells for in vitro culture, or decellularized human- or animal-derived donor tissue for in situ engineering. Here, we propose and demonstrate proof-of-concept of in situ heart valve tissue engineering using a synthetic approach, in which a cell-free, slow degrading elastomeric valvular implant is populated by endogenous cells to form new valvular tissue inside the heart.

The economic burden of injury: Health care and productivity costs of injuries in the Netherlands.

Background: Detailed information on health care costs and productivity costs for the whole spectrum of injuries is lacking. We measured the total costs of injuries by external-cause, injury groupings, age and sex.

Method: Injury patients visiting an Emergency Department in the Netherlands were included.

Superior Tissue Evolution in Slow-Degrading Scaffolds for Valvular Tissue Engineering.

Synthetic polymers are widely used to fabricate porous scaffolds for the regeneration of cardiovascular tissues. To ensure mechanical integrity, a balance between the rate of scaffold absorption and tissue formation is of high importance. A higher rate of tissue formation is expected in fast-degrading materials than in slow-degrading materials.

Mutations in Known Monogenic High Bone Mass Loci Only Explain a Small Proportion of High Bone Mass Cases.

High bone mass (HBM) can be an incidental clinical finding; however, monogenic HBM disorders (eg, LRP5 or SOST mutations) are rare. We aimed to determine to what extent HBM is explained by mutations in known HBM genes. A total of 258 unrelated HBM cases were identified from a review of 335,115 DXA scans from 13 UK centers.

Hydrolytic and oxidative degradation of electrospun supramolecular biomaterials: In vitro degradation pathways.

The emerging field of in situ tissue engineering (TE) of load bearing tissues places high demands on the implanted scaffolds, as these scaffolds should provide mechanical stability immediately upon implantation. The new class of synthetic supramolecular biomaterial polymers, which contain non-covalent interactions between the polymer chains, thereby forming complex 3D structures by self assembly. Here, we have aimed to map the degradation characteristics of promising (supramolecular) materials, by using a combination of in vitro tests.

Burden of road traffic injuries: Disability-adjusted life years in relation to hospitalization and the maximum abbreviated injury scale.

Background: The consequences of non-fatal road traffic injuries (RTI) are increasingly adopted by policy makers as an indicator of traffic safety. However, it is not agreed upon which level of severity should be used as cut-off point for assessing road safety performance. Internationally, within road safety, injury severity is assessed by means of the maximum abbreviated injury scale (MAIS).

Degree of scaffold degradation influences collagen (re)orientation in engineered tissues.

Tissue engineering provides a promising tool for creating load-bearing cardiovascular tissues. Ideally, the neotissue produced by cells possesses native strength and anisotropy. By providing contact-guiding cues with microfibers, scaffold directionality can guide tissue organization.

CD8+ T cells produce the chemokine CXCL10 in response to CD27/CD70 costimulation to promote generation of the CD8+ effector T cell pool.

Various cell types can produce the chemokine CXCL10 in response to IFN-γ stimulation. CXCL10 is generally viewed as a proinflammatory chemokine that promotes recruitment of CD8÷ and Th1-type CD4÷ effector T cells to infected or inflamed nonlymphoid tissues. We show that CXCL10 plays a role during CD8÷ T cell priming in the mouse.

Poly-ε-caprolactone scaffold and reduced in vitro cell culture: beneficial effect on compaction and improved valvular tissue formation.

Tissue-engineered heart valves (TEHVs), based on polyglycolic acid (PGA) scaffolds coated with poly-4-hydroxybutyrate (P4HB), have shown promising in vivo results in terms of tissue formation. However, a major drawback of these TEHVs is compaction and retraction of the leaflets, causing regurgitation. To overcome this problem, the aim of this study was to investigate: (a) the use of the slowly degrading poly-ε-caprolactone (PCL) scaffold for prolonged mechanical integrity; and (b) the use of lower passage cells for enhanced tissue formation.

Burden of injury in childhood and adolescence in 8 European countries.

Background: Injury is the major cause of death and suffering among children and adolescents, but awareness of the problem and political commitment for preventive actions remain unacceptably low. We have assessed variation in the burden of injuries in childhood and adolescence in eight European countries.

Methods: Hospital, emergency department, and mortality databases of injury patients aged 0-24 years were analyzed for Austria, Denmark, Ireland, Latvia, Netherlands, Norway, Slovenia and the United Kingdom (England, Wales).

Can promotion of initiated cells be explained by excess replacement of radiation-inactivated neighbor cells?

Recently, the observed promotion in the clonal expansion of a two-stage cancer model was attributed to a small excess replacement probability for the initiated cells. The proposed mechanism of excess replacement was evaluated for single intermediate cells surrounded by normal cells. This paper investigates this mechanism further using the same biological parameters.

Analysis of epidemiological cohort data on smoking effects and lung cancer with a multi-stage cancer model.

A stochastic two-stage cancer model is used to analyse the relation between lung cancer and cigarette smoking. The model contains the main rate-limiting stages of carcinogenesis, which include initiation, promotion (clonal expansion of initiated cells), malignant transformation and a lag time for tumour formation. Various data sets were used to test the model.

Laryngeal oedema in neonatal apnoea and bradycardia syndrome (a pilot study).

Purpose: Some preterm infants in general good health continue to present recurrent apnoeas, bradycardias and desaturations (ABD) despite usual treatments. These events may lead to transitory brain hypoxia and to further neurological injury. The purpose of this study has been to evaluate the role of laryngeal oedema in this symptomatology and to assess corticoid treatment.

Two-mutation models for bone cancer due to radium, strontium and plutonium.

Data from beagle experiments and radium dial painters were used to derive two-mutation carcinogenesis models for bone cancer induced by the bone-seeking radionuclides radium, strontium and plutonium. For all data, the model fits indicate that at low doses both mutation rates depend linearly and equally strongly on dose rate. For the high-LET alpha-particle emitters, a cell killing term reduces the second mutation rate at high dose rates.

Radon-induced lung cancer in French and Czech miner cohorts described with a two-mutation cancer model.

A two-mutation carcinogenesis model with clonal expansion of pre-malignant cells is used to describe lung cancer mortality data from studies on French and Czech miners with relatively low exposures to radon. The aim was to derive radon-induced lung cancer risk estimates applicable to different populations using a model description consistent with both cellular dose-response relationships, and previous model analyses of animal and human epidemiological data. The significantly different baseline lung cancer risks for the two cohorts that include the effects from the unknown smoking habits, are described with different background model parameters.

A contribution to the linear no-threshold discussion.

The paper approaches the linear no-threshold (LNT) hypothesis, currently used as the basis for recommendations in radiological protection, from the point of view of the radiation mechanism. All considerations of the validity of the LNT hypothesis based on experiment or epidemiology are dismissed because of the impossibility of deriving statistically significant data at very low doses. Instead, the LNT hypothesis is assessed from a consideration of the mechanism of radiation action.

The implications of re-analysing radiation-induced leukaemia in atomic bomb survivors: risks for acute and chronic exposures are different.

Implications of risk estimates, as required for practical radiation protection purposes, were explored through a preliminary re-analysis of leukaemia in the Japanese atomic bomb survivors using a biologically based cancer model. The calculations for the risks posed for contracting leukaemia pointed to important differences between low-dose-rate ('chronic') and high-dose-rate ('acute') exposures. For example, the risks caused by long-term ('chronic') exposures are calculated to be substantially lower than those for 'acute' exposures.

The overrated role of 'promotion' in mechanistic modelling of radiation carcinogenesis.

It is argued that the 'cellular' dose-response relationships of model parameters cannot be determined from mechanistic model fits to experimental or epidemiologic cancer data. Baseline population cancer incidence data show conclusions about intermediate cell kinetics to be especially questionable. Here we recommend that mechanistic models should be applied solely in one direction: by starting from known cellular dose-response relationships the models aim at providing a biologically motivated consistent description of the development of radiation-induced cancer for different exposures, which is very important for low-dose risk estimation.