Novel collagen- based biomaterials for bone regeneration

Bone is primarily made of type I collagen, which is a highly abundant natural protein. Collagen can be crosslinked through several methods including chemical agents, physical heating and UV radiation. The result is enhanced physical characteristics such as thermal stability, resistance to proteolytic breakdown, mechanical strength and increased overall biocompatibility. However, with these methods there are drawbacks; including toxicity of residual cross-linking agents, or difficulties with scaling. In recent years, collagen has been cross-linked by a safer, efficient and more practical means by using enzymes as biological catalysts. We demonstrate that crosslinking native collagen with both tissue transglutaminase (TG2) and microbial transglutaminase (mTG- from Streptoverticillium mobaraense) leads to an increase in the proliferation of human osteoblasts (HOB) and an increase in integrins on their cell surface compared to culture on native collagen. These integrins include αV, α5, β1 and β3 which are all important for the ability of HOBs to mature and differentiate. In addition to this, the HOBs were shown to mineralise at a faster rate than on native collagen. Moreover, it was demonstrated that integrin expression and mineralisation rates are further increased in HOBs on crosslinked collagen by incorporating 45S5 bioglass particles. Investigations here show distinct differences between the micro-structure of the scaffolds and the mean pore size between fibrils in native and crosslinked collagen. These results suggest that the crosslinked collagen changes the behaviour of HOBs when seeded, such that through the Wnt canonical pathway there is an overall increased drive towards mineralisation and deposition of collagen by the HOBs. This work shows that crosslinked collagen scaffolds with 45S5 bioglass have the potential to be used as biomaterials for bone regeneration and may eventually replace allografts and titanium plates

Layered approach to persistency modeling in object-oriented environment.

Object persistence is a fundamental feature of any object-oriented environment. Several programming language specifications do not include or discuss any method of providing persistence for objects. Several schemes have been developed for adding persistence in several different programming languages. Some of them require persistent objects to be allocated and treated differently than non-persistent objects, while some others require the programmer to provide vital parts of the persistence mechanism. It is desirable to make the persistence feature transparent, but the nature of object oriented programming makes it difficult. This thesis proposes an approach to build a persistency layer in an object oriented programming language based, in part, on work by Ambler. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis2002 .C468. Source: Masters Abstracts International, Volume: 41-04, page: 1102. Adviser: R. D. Kent. Thesis (M.Sc.)--University of Windsor (Canada), 2002

Hypoxic Preconditioning as a Strategy to Maintain the Regenerative Potential of Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are non-hematopoietic cells with high proliferative potential and multi-lineage differentiation capacity. MSCs are promising therapeutic candidates for cell-based therapies, and hundreds of clinical trials have been registered using these cells. Potential of stem cells is compromised with the factors such as disease condition and age of donor. Therefore, taking the cells from such patients for autologous use may compromise the benefits of cell-based therapies. It is therefore required to enhance the potential of these cells before use in stem cell-based therapies. Optimization of culture conditions is preferred strategies to enhance the regenerative potential of cells before use. This chapter briefly overviews the benefits of hypoxic preconditioning of stem cells to enhance the regenerative potential of cells in terms of their survival, proliferation, and differentiation

The Significance of Cell-related Challenges in the Clinical Application of Tissue Engineering.

Tissue engineering is increasingly being recognized as a new approach that could alleviate the burden of tissue damage currently managed with transplants or synthetic devices. Making this novel approach available in the future for patients who would potentially benefit is largely dependent on understanding and addressing all those factors that impede the translation of this technology to the clinic. Cell-associated factors in particular raise many challenges, including those related to cell sources, up- and downstream techniques, preservation, and the creation of in vitro microenvironments that enable cells to grow and function as far as possible as they would in vivo. This paper highlights the main confounding issues associated with cells in tissue engineering and how these issues may hinder the advancement of therapeutic tissue engineering. This article is protected by copyright. All rights reserved

Variation in treatment of acute childhood wheeze in emergency departments of the United Kingdom and Ireland: An international survey of clinician practice

© 2015, BMJ Publishing Group. All rights reserved. Objective: National clinical guidelines for childhood wheeze exist, yet despite being one of the most common reasons for childhood emergency department (ED) attendance, signi ficant variation in practice occurs in other settings. We, therefore, evaluated practice variations of ED clinicians in the UK and Ireland. Design: Two-stage survey undertaken in March 2013. Stage one examined department practice and stage two assessed ED consultant practice in acute childhood wheeze. Questions interrogated pharmacological and other management strategies, including inhaled and intravenous therapies. Setting and participants: Member departments of Paediatric Emergency Research in the United Kingdom and Ireland and ED consultants treating children with acute wheeze. Results: 30 EDs and 183 (81%) clinicians responded. 29 (97%) EDs had wheeze guidelines and 12 (40%) had care pathways. Variation existed between clinicians in dose, timing and frequency of inhaled bronchodilators across severities. When escalating to intravenous bronchodilators, 99 (54%) preferred salbutamol first line, 52 (28%) magnesium sulfate (MgSO4) and 27 (15%) aminophylline. 87 (48%) administered intravenous bronchodilators sequentially and 30 (16%) concurrently, with others basing approach on case severity. 146 (80%) continued inhaled therapy after commencing intravenous bronchodilators. Of 170 who used intravenous salbutamol, 146 (86%) gave rapid boluses, 21 (12%) a longer loading dose and 164 (97%) an ongoing infusion, each with a range of doses and durations. Of 173 who used intravenous MgSO4, all used a bolus only. 41 (24%) used non-invasive ventilation. Conclusions: Signi ficant variation in ED consultant management of childhood wheeze exists despite the presence of national guidance. This reflects the lack of evidence in key areas of childhood wheeze and emphasises the need for further robust multicentre research studies

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus