Beyond Animal Testing Index: Benchmarking tool for a world beyond animal testing.

While the original definition of replacement focuses on the replacement of the use of animals in science, a more contemporary definition focuses on accelerating the development and use of predictive and robust models, based on the latest science and technologies, to address scientific questions without the use of animals. The transition to animal free innovation is on the political agenda in and outside the European Union. The Beyond Animal Testing Index (BATI) is a benchmarking instrument designed to provide insight into the activities and contributions of research institutes to the transition to animal free innovation.

Animal studies for the evaluation of in situ tissue-engineered vascular grafts - a systematic review, evidence map, and meta-analysis.

Vascular in situ tissue engineering (TE) is an approach that uses bioresorbable grafts to induce endogenous regeneration of damaged blood vessels. The evaluation of newly developed in situ TE vascular grafts heavily relies on animal experiments. However, no standard for in vivo models or study design has been defined, hampering inter-study comparisons and translational efficiency.

A health-based recommended occupational exposure limit for nitrous oxide using experimental animal data based on a systematic review and dose-response analysis.

Background: Nitrous oxide (NO) is a common inhalation anaesthetic used in medical, paramedical, and veterinary practice. Since the mid 1950's, concerns have been raised regarding occupational exposure to NO, leading to many epidemiological and experimental animal studies. Previous evaluations resulted in the classification of NO as a possible risk factor for adverse reproductive health outcomes based on animal data.

A systematic review and meta-analyses on animal models used in bone adhesive research.

Currently, steel implants are used for osteosynthesis of (comminuted) fractures and intra-articular bone defects. These osteosyntheses can sometimes be complicated procedures and can have several drawbacks including stress shielding of the bone. A bone glue might be a safe and effective alternative to current materials.

Welfare Impact of Carbon Dioxide Euthanasia on Laboratory Mice and Rats: A Systematic Review.

There has been increased concern about the suitability of CO as a method for euthanasia of laboratory mice and rats, including the potential discomfort, pain or distress that animals may experience prior to loss of consciousness; time to loss of consciousness; best methods for use of CO; and the availability of better alternatives. These discussions have been useful in providing new information, but have resulted in significant confusion regarding the acceptability of CO for rodent euthanasia. In some cases, researchers and veterinarians have become uncertain as to which techniques to recommend or use for euthanasia of laboratory mice and rats.

How Can Systematic Reviews Teach Us More about the Implementation of the 3Rs and Animal Welfare?

This paper describes the introduction of the systematic review methodology in animal-based research and the added value of this methodology in relation to the 3Rs and beyond. The 3Rs refer to Replacement, Reduction, and Refinement of animal studies. A systematic review (SR) is defined as a literature review focused on a single question that tries to identify, appraise, select, and synthesise all high-quality research evidence relevant to that question.

Topical Host-Modulating Therapy for Periodontal Regeneration: A Systematic Review and Meta-Analysis.

Over the past decades, locally delivered host-modulating pharmacological agents have been extensively investigated to treat periodontitis. Although a small category of agents has been tested in clinical trials, most of them were reported in the animal experiments. This systematic review evaluates the efficacy of local application of currently available host-modulating agents, with or without mechanical removal of plaque, in animal models with periodontitis or periodontal defect.

Establishing a health-based recommended occupational exposure limit for nitrous oxide using experimental animal data - A systematic review protocol.

Nitrous oxide (N O) is widely used as inhalation analgesic and anaesthetic in medical, paramedical, and veterinary practice. Previous evaluations resulted in classification of N O as a possible risk factor for adverse reproductive health outcomes based on evidence from animal data. Available human data were considered inadequate, partly due to the possibility that other risk factors, such as co-exposures to other inhalation anaesthetics may have contributed to the adverse outcomes.

The evidence for the physiological effects of lactate on the cerebral microcirculation: a systematic review.

Lactate's role in the brain is understood as a contributor to brain energy metabolism, but it may also regulate the cerebral microcirculation. The purpose of this systematic review was to evaluate evidence of lactate as a physiological effector within the normal cerebral microcirculation in reports ranging from in vitro experiments to in vivo studies in animals and humans. Following pre-registration of a review protocol, we systematically searched the PubMed, EMBASE, and Cochrane databases for literature covering themes of 'lactate', 'the brain', and 'microcirculation'.

Current insights into extracorporeal perfusion of free tissue flaps and extremities: a systematic review and data synthesis.

Background: Extracorporeal perfusion is a promising new technique for prolonged preservation of free flaps and extremities; however, uncertainties on perfusion settings and efficacy still exist. No overview of literature is currently available. This review systematically appraised available evidence comparing extracorporeal perfusion to static storage.

Assisted delivery of antisense therapeutics in animal models of heritable neurodegenerative and neuromuscular disorders: a systematic review and meta-analysis.

Antisense oligonucleotide (AON)-based therapies hold promise for a range of neurodegenerative and neuromuscular diseases and have shown benefit in animal models and patients. Success in the clinic is nevertheless still limited, due to unfavourable biodistribution and poor cellular uptake of AONs. Extensive research is currently being conducted into the formulation of AONs to improve delivery, but thus far there is no consensus on which of those strategies will be the most effective.

Diabetes Mellitus and Bone Regeneration: A Systematic Review and Meta-Analysis of Animal Studies.

Background: The regeneration of bone defects resulting from trauma, resection of tumors, infection, or congenital disease is a challenge, and bone grafts are utilized in a wide array of clinical settings to augment bone repair and regeneration. Diabetes mellitus (DM) is a chronic metabolic disease, which affects 8.3% of the world population, summing ∼387 million individuals.

Anti-tumor effects of metformin in animal models of hepatocellular carcinoma: a systematic review and meta-analysis.

Background: Several studies have reported that metformin can reduce the risk of hepatocellular carcinoma (HCC) in diabetes patients. However, the direct anti-HCC effects of metformin have hardly been studied in patients, but have been extensively investigated in animal models of HCC. We therefore performed a systematic review and meta-analysis of animal studies evaluating the effects of metformin on HCC.

Systematic reviews of animal studies; missing link in translational research?

Background: The methodological quality of animal studies is an important factor hampering the translation of results from animal studies to a clinical setting. Systematic reviews of animal studies may provide a suitable method to assess and thereby improve their methodological quality.

Objectives: The aims of this study were: 1) to evaluate the risk of bias assessment in animal-based systematic reviews, and 2) to study the internal validity of the primary animal studies included in these systematic reviews.

Assessing the application of the 3Rs: a survey among animal welfare officers in The Netherlands.

Implementation of the 3Rs (Replacement, Refinement and Reduction) in animal studies is a legal requirement in many countries. In The Netherlands, animal welfare officers (AWOs) are appointed to monitor the welfare of laboratory animals. As part of this task, AWOs give advice to researchers and can therefore have an influential role in implementing 3R methods in research.

Outcomes of a Dutch workshop on improvements for the 3Rs in daily practice.

This article describes the outcome of a workshop that was held to generate new ideas to improve the use of the 3R principles in science. The participants of the workshop represented Dutch researchers, Animal Welfare Officers, and members of Animal Ethics Committees from various affiliations, including academia, industry, contract research organizations, and knowledge centers in the Netherlands. The workshop resulted in six diverse consensus statements, which are presented and discussed in this article.

Assessing the search for information on Three Rs methods, and their subsequent implementation: a national survey among scientists in the Netherlands.

A local survey conducted among scientists into the current practice of searching for information on Three Rs (i.e. Replacement, Reduction and Refinement) methods has highlighted the gap between the statutory requirement to apply Three Rs methods and the lack of criteria to search for them.