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A systematic review of animal models used to study nerve regeneration in tissue-engineered scaffolds.

ABSTRACT: Research on biomaterial nerve scaffolds has been carried out for 50 years. Only three materials (collagen, polycaprolactone and polyglycollic acid) have progressed to clinical use. Pre-clinical animal models are critical for testing nerve scaffolds prior to implementation in clinical practice. We have conducted a systematic review of 416 reports in which animal models were used for evaluation of nerve regeneration into synthetic conduits. A valid animal model of nerve regeneration requires it to reproduce the specific processes that take place in regeneration after human peripheral nerve injury. No distinct animal species meets all the requirements for an ideal animal model. Certain models are well suited for understanding regenerative neurobiology while others are better for pre-clinical evaluation of efficacy. The review identified that more than 70 synthetic materials were tested in eight species using 17 different nerves. Nerve gaps ranged from 1 to 90 mm. More than 20 types of assessment methodology were used with no standardization of methods between any of the publications. The review emphasizes the urgent need for standardization or rationalization of animal models and evaluation methods for studying nerve repair.

SUBMITTER: Angius D

PROVIDER: S-EPMC3472515 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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A systematic review of animal models used to study nerve regeneration in tissue-engineered scaffolds.

Angius Diana D Wang Huan H Spinner Robert J RJ Gutierrez-Cotto Yearim Y Yaszemski Michael J MJ Windebank Anthony J AJ

Biomaterials 20120811 32

Research on biomaterial nerve scaffolds has been carried out for 50 years. Only three materials (collagen, polycaprolactone and polyglycollic acid) have progressed to clinical use. Pre-clinical animal models are critical for testing nerve scaffolds prior to implementation in clinical practice. We have conducted a systematic review of 416 reports in which animal models were used for evaluation of nerve regeneration into synthetic conduits. A valid animal model of nerve regeneration requires it to ...[more]

PMID: 22889485

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Project description:ObjectivePeripheral nerve repair is required after traumatic injury. This common condition represents a major public health problem worldwide. Recovery after nerve repair depends on several factors, including the severity of the injury, the nerve involved, and the surgeon's technical skills. Despite the precise microsurgical repair of nerve lesions, adequate functional recovery is not always achieved and, therefore, the regeneration process and surgical techniques are still being studied. Pre-clinical animal models are essential for this research and, for this reason, the focus of the present systematic review (according to the PRISMA statement) was to analyze the different animal models used in pre-clinical peripheral nerve repair studies.Data sourcesOriginal articles, published in English from 2000 to 2018, were collected using the Web of Science, Scopus, and PubMed databases.Data selectionOnly preclinical trials on direct nerve repair were included in this review. The articles were evaluated by the first two authors, in accordance with predefined data fields.Outcome measuresThe primary outcomes included functional motor abilities, daily activity and regeneration rate. Secondary outcomes included coaptation technique and animal model.ResultsThis review yielded 267 articles, of which, after completion of the screening, 49 studies were analyzed. There were 1425 animals in those 49 studies, being rats, mice, guinea pigs, rabbits, cats and dogs the different pre-clinical models. The nerves used were classified into three groups: head and neck (11), forelimb (8) and hindlimb (30). The techniques used to perform the coaptation were: microsuture (46), glue (12), laser (8) and mechanical (2). The follow-up examinations were histology (43), electrophysiological analysis (24) and behavioral observation (22).ConclusionThe most widely used animal model in the study of peripheral nerve repair is the rat. Other animal models are also used but the cost-benefit of the rat model provides several strengths over the others. Suture techniques are currently the first option for nerve repair, but the use of glues, lasers and bioengineering materials is increasing. Hence, further research in this field is required to improve clinical practice.

Project description:Tissue engineering and regenerative medicine (TERM) approaches may provide alternatives for gastrointestinal tissue in urinary diversion. To continue to clinically translatable studies, TERM alternatives need to be evaluated in (large) controlled and standardized animal studies. Here, we investigated all evidence for the efficacy of tissue engineered constructs in animal models for urinary diversion. Studies investigating this subject were identified through a systematic search of three different databases (PubMed, Embase and Web of Science). From each study, animal characteristics, study characteristics and experimental outcomes for meta-analyses were tabulated. Furthermore, the reporting of items vital for study replication was assessed. The retrieved studies (8 in total) showed extreme heterogeneity in study design, including animal models, biomaterials and type of urinary diversion. All studies were feasibility studies, indicating the novelty of this field. None of the studies included appropriate control groups, i.e. a comparison with the classical treatment using GI tissue. The meta-analysis showed a trend towards successful experimentation in larger animals although no specific animal species could be identified as the most suitable model. Larger animals appear to allow a better translation to the human situation, with respect to anatomy and surgical approaches. It was unclear whether the use of cells benefits the formation of a neo urinary conduit. The reporting of the methodology and data according to standardized guidelines was insufficient and should be improved to increase the value of such publications. In conclusion, animal models in the field of TERM for urinary diversion have probably been chosen for reasons other than their predictive value. Controlled and comparative long term animal studies, with adequate methodological reporting are needed to proceed to clinical translatable studies. This will aid in good quality research with the reduction in the use of animals and an increase in empirical evidence of biomedical research.

Project description: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. Despite numerous animal studies on bone adhesives, no such material is clinically applied yet. We have conducted a systematic review to summarize the evidence in experimental animal models used in research on bone adhesive materials for trauma and orthopedic surgery. Additionally, we analysed the efficacy of the different bone adhesives for different experimental designs. A heterogeneity in experimental parameters including animal species, defect types, and control measurements resulted in a wide variety in experimental models. In addition, no standard outcome measurements could be identified. Meta-analysis on bone regeneration between adhesive treatment and nonadhesive treatment showed a high heterogeneity and no statistically significant overall effect (M: -0.71, 95% confidence interval [CI]: -1.63-0.21, p = 0.13). Besides, currently there is not enough evidence to draw conclusions based on the effectiveness of the individual types of adhesives or experimental models. A positive statistically significant effect was found for the adhesive treatment in comparison with conventional osteosynthesis materials (M: 2.49, 95% CI: 1.20-3.79, p = 0.0002). To enhance progression in bone adhesive research and provide valuable evidence for clinical application, more standard experimental parameters and a higher reporting quality in animal studies are needed. Statement of Clinical Significance: Current materials restoring anatomical alignments of bones have several drawbacks. A (biodegradable) adhesive for fixating bone defects can be a treatment breakthrough. Although numerous bone adhesives have been researched, most seemed to fail at the preclinical stage. An overview in this field is missing. This systematic review highlights the relevant parameters for design of experimental bone adhesive studies. It demonstrates evidence regarding benefit of bone adhesives but also that the quality of reporting and the risk of bias in studies need to be improved. The results will aid in designing better quality animal studies for bone adhesive research with higher translational value.

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A systematic review of animal models used to study nerve regeneration in tissue-engineered scaffolds.

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A systematic review of animal models used to study nerve regeneration in tissue-engineered scaffolds.

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