A comparative in vivo evaluation of bioactive glasses and bioactive glass-based composites for bone tissue repair

In this work a set of novel materials for bone tissue regeneration have been tested in vivo in an animal model. In fact, despite many studies have been devoted to amorphous 45S5 Bioglass®, there is lack in the literature of works aimed to study the in vivo performance of heat-treated – and thus partially crystallized – 45S5. As widely reported, crystallization limits the bioactivity of 45S5 and is the main reason that prevents a broader use of this material. Thus, in the present work, a recently developed bioactive glass (BG_Ca/Mix) is tested, since previous investigations demonstrated that BG_Ca/Mix is particularly promising by virtue of both its high bioactivity and lower tendency to crystallize with respect to 45S5. BG_Ca/Mix sintered powders and two composites, which contain BG_Ca/Mix and an increasing percentage (20 wt% or 70 wt%) of hydroxyapatite (HA), were considered. As a term of comparison, 45S5 sintered powders were also studied. The samples were implanted in rabbits' femurs and harvested after 8 weeks. The histological analysis demonstrated that BG_Ca/Mix has an osteoconductive ability slightly higher than that of 45S5 glass-ceramics, followed by that of the composites, which may represent the starting point for obtaining systems with degradation rate tailored for a given clinical application. Moreover, the 45S5 samples were locally cracked, probably because of a non-uniform dissolution in the physiological environment. On the contrary such cracks, which could lead to implant instability and unsuitable mechanical performance, were not observed in BG_Ca/Mix

Sol-gel derived bioactive glasses with low tendency to crystallize: synthesis, post-sintering bioactivity and possible application for the production of porous scaffolds.

A new sol-gel (SG) method is proposed to produce special bioactive glasses (BG_Ca family) characterized by a low tendency to devitrify. These formulations, derived from 45S5 Bioglass®, are characterized by a high content of CaO (45.6 mol%) and by a partial or complete substitution of sodium oxide with potassium oxide (total amount of alkaline oxides: 4.6 mol%), which increases the crystallization temperature up to 900°C. In this way, it is possible to produce them by SG preserving their amorphous nature, in spite of the calcination at 850°C. The sintering behavior of the obtained SG powders is thoroughly investigated and the properties of the sintered bodies are compared to those of the melt-derived (M) counterparts. Furthermore, the SG glass powders are successfully used to produce scaffolds by means of a modified replication technique based on the combined use of polyurethane sponges and polyethylene particles. Finally, in the view of a potential application for bone tissue engineering, the cytotoxicity of the produced materials is evaluated in vitro

Inflammatory Responses and Barrier Function of Endothelial Cells Derived from Human Induced Pluripotent Stem Cells

Several studies have reported endothelial cell (EC) derivation from human induced pluripotent stem cells (hiPSCs). However, few have explored their functional properties in depth with respect to line-to-line and batch-to-batch variability and how they relate to primary ECs. We therefore carried out accurate characterization of hiPSC-derived ECs (hiPSC-ECs) from multiple (non-integrating) hiPSC lines and compared them with primary ECs in various functional assays, which included barrier function using real-time impedance spectroscopy with an integrated assay of electric wound healing, endothelia-leukocyte interaction under physiological flow to mimic inflammation and angiogenic responses in in vitro and in vivo assays. Overall, we found many similarities but also some important differences between hiPSC-derived and primary ECs. Assessment of vasculogenic responses in vivo showed little difference between primary ECs and hiPSC-ECs with regard to functional blood vessel formation, which may be important in future regenerative medicine applications requiring vascularization. In this article, Orlova and colleagues show that hiPSC-ECs have similar features to primary ECs but also show some differences. hiPSC-ECs exhibited higher barrier function, lower expression of pro-inflammatory adhesive receptors, and more stringent stromal cell requirements. Importantly, healthy control CD31+ hiPSC-ECs showed high consistency between different batches and lines, forming a good basis for disease modeling applications

Bone regeneration by novel bioactive glasses containing strontium and/or magnesium: A preliminary in-vivo study

In this work, a set of novel bioactive glasses have been tested in vivo in an animal model. The new compositions, characterized by an exceptional thermal stability and high in vitro bioactivity, contain strontium and/or magnesium, whose biological benefits are well documented in the literature. To simulate a long-term implant and to study the effect of the complete dissolution of glasses, samples were implanted in the mid-shaft of rabbits' femur and analyzed 60 days after the surgery; such samples were in undersized powder form. The statistical significance with respect to the type of bioactive glass was analyzed by Kruskal-Wallis test. The results show high levels of bone remodeling, several new bone formations containing granules of calcium phosphate (sometimes with amounts of strontium and/or magnesium), and the absence of adverse effects on bone processes due to the almost complete glass dissolution. In vivo results confirming the cell culture outcomes of a previous study highlighted that these novel bioglasses had osteostimulative effect without adverse skeletal reaction, thus indicating possible beneficial effects on bone formation processes. The presence of strontium in the glasses seems to be particularly interesting

Oxidant and Carbonyl Stress-Related Apoptosis in End-Stage Kidney Disease: Impact of Membrane Flux

Apoptosis is a highly regulated process which mostly affects cell-mediated immunity. In this open-label, randomized, prospective clinical study, we determined the impact in 10 hemodialysis patients treated with high-, medium-, and low-flux membranes on spontaneous or plasma-induced apoptosis, on monocytes, as well as on oxidant and carbonyl stress. High- and medium-flux membranes significantly reduced patients' plasma-dependent proapoptotic activity on U937 monocytic cell lines. Patients who had the highest levels of plasma-induced proapoptotic activity exhibited the highest plasma levels of advanced oxidation protein products (AOPPs) and carbonyls. Plasma carbonyl residues but not AOPPs were significantly lowered. Finally, a significant correlation could be drawn between the extent of plasma-induced proapoptotic activity and both plasma carbonyl and AOPP levels

Applying participatory processes to address conflicts over the conservation of large carnivores: understanding conditions for successful management

Social conflicts over large carnivores are becoming more frequent following the general recovery of large carnivores in human shaped landscapes in Europe. To manage conflicts over large carnivores a detailed knowledge is necessary on the social, economic, cultural but also interpersonal dimensions of the conflicts. This can be achieved through a participatory engagement of all stakeholders within a procedure tailored to local contexts. We looked at conditions necessary for implementing the above approach in areas of intense large carnivores-human conflict across Europe (bear and wolves), and where traditional management conflict policies do not appear to be successful, as often based on urgent responses to emergency situations. We focussed on four areas in Europe where we interviewed stakeholders to characterize the conflicts and assess the potential for mitigation interventions through participatory processes. We focused on four key aspects related to social conflicts: (a) perception of the current situation and relationship with other stakeholders; (b) availability and accessibility of information and communication; (c) economic, ecological and social impacts; and (d) promotion of coexistence and participatory processes. We show that (lack of) trust between stakeholders and the relevant authorities as well as the lack of genuine communication among stakeholders were the key features that characterized social conflicts related to large carnivores. With specific reference to large carnivores, the lack or inaccessibility of reliable information was reported in all cases by all stakeholders, as well as the need for proactive and inclusive policies developed and implemented by the relevant authorities. A consistent message was that support and engagement from relevant management institutions was pivotal for effective management of conflicts over large carnivores. Our findings highlight the importance for conflict mitigation of a deeper and mutual understanding of issues prior to the implementation of participatory processes

OXavidin for Tissue Targeting Biotinylated Therapeutics

Avidin is a glycoprotein from hen egg white that binds biotin with very high affinity. Here we describe OXavidin, a product containing aldehyde groups, obtained by ligand-assisted sugar oxidation of avidin by sodium periodate. OXavidin chemically reacts with cellular and tissue proteins through Schiff's base formation thus residing in tissues for weeks while preserving the biotin binding capacity. The long tissue residence of OXavidin as well as that of OXavidin/biotinylated agent complex occurs in normal and neoplastic tissues and immunohistochemistry shows a strong and homogenous stromal localization. Once localized in tissue/tumor, OXavidin becomes an “artificial receptor” for intravenous injected biotin allowing tumor targeting with biotinylated therapeutics like radioisotopes or toxins. Moreover, present data also suggest that OXavidin might be useful for the homing of biotinylated cells. Overall, OXavidin exhibits a remarkable potential for many different therapeutic applications

LIVESTOCK GUARDING DOGS TODAY: POSSIBLE SOLUTIONS TO PERCEIVED LIMITATIONS

Exchanging experience and finding solutions to problems facing the use of livestock guarding dogs (LGDs) in modern societies were among the goals of a meeting organized in Portugal from 20th to 21st October 2015 within the scope of the LIFE MedWolf Project (www.medwolf.eu). The meeting was attended by 16 specialists from around Europe (Portugal, Spain, France, Switzerland, Italy, Croatia, Slovakia and Bulgaria), as well as from Australia and the USA. In this article we outline constraints on the use of LGDs identified during the meeting and summarize the main solutions proposed. We have grouped the issues into 10 main topics ranging from a lack of quality dogs to personal, social, cultural, economic, time, management, technical, legal and political constraints. Guidelines on the proper raising and caring of LGDs are not the focus of this article, since a great deal of information is already available, including on specific solutions to common problems

Managing wolf impacts on sheep husbandry: a collaborative implementation and assessment of damage prevention measures in an agricultural landscape

Wolves in Europe are expanding their range and significantly impacting farming livelihoods and landscapes. Damage prevention measures such as livestock guarding dogs and night-time enclosures have proven successful in mitigating losses. However, they are often implemented as top-down measures without a proper understanding of the farming dynamics they are meant to alter, making them unappealing and difficult to implement for farmers. Semi-extensive, small scale livestock farming systems are particularly vulnerable and diverse, requiring specific care and catered support when addressing issues related to wildlife management. In these contexts, it is crucial to employ adaptive management approaches that enable solutions to be collaboratively designed at the grassroots level. Here we propose a method for centring the experiences and knowledge of local farmers to co-produce damage prevention practices that better address their needs. We developed this approach in the course of the LIFE MEDWOLF project, which was implemented in the province of Grosseto, Italy, between 2012 and 2017. The project brought together local authorities, environmental associations, farming unions and individual farmers to develop tailor-made damage prevention measures and assess their technical and economic impact, through a stepwise process. Collaboration with 86 local farmers resulted in >50 modifications to the original project plan, and an overall 50% reduction of preyed livestock in farms that participated in the project. Our findings highlight the benefits of collaboratively designing, implementing, and monitoring damage prevention measures with farmers. Based on these results, we reflect on the importance of integrating local and scientific knowledge, on the implications this has had on stakeholder relations, and on the challenges that we faced in upscaling this management approach