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基于生物材料的方法作为缺血性中风治疗手段的潜力:临床前研究的系统评价和荟萃分析

The Potential of Biomaterial-Based Approaches as Therapies for Ischemic Stroke: A Systematic Review and Meta-Analysis of Pre-clinical Studies.

作者信息

Bolan Faye, Louca Irene, Heal Calvin, Cunningham Catriona J

机构信息

Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, United Kingdom.

Faculty of Biology, Medicine and Health, Centre for Biostatistics, Academic Health Sciences Centre, University of Manchester, Manchester, United Kingdom.

出版信息

Front Neurol. 2019 Aug 27;10:924. doi: 10.3389/fneur.2019.00924. eCollection 2019.

Abstract

In recent years pre-clinical stroke research has shown increased interest in the development of biomaterial-based therapies to promote tissue repair and functional recovery. Such strategies utilize biomaterials as structural support for tissue regeneration or as delivery vehicles for therapeutic agents. While a range of biomaterials have been tested in stroke models, currently no overview is available for evaluating the benefit of these approaches. We therefore performed a systematic review and meta-analysis of studies investigating the use of biomaterials for the treatment of stroke in experimental animal models. Studies were identified by searching electronic databases (PubMed, Web of Science) and reference lists of relevant review articles. Studies reporting lesion volume and/or neurological score were included. Standardized mean difference (SMD) and 95% confidence intervals were calculated using DerSimonian and Laird random effects. Study quality and risk of bias was assessed using the CAMARADES checklist. Publication bias was visualized by funnel plots followed by trim and fill analysis of missing publications. A total of 66 publications were included in the systematic review, of which 44 (86 comparisons) were assessed in the meta-analysis. Overall, biomaterial-based interventions improved both lesion volume (SMD: -2.98, 95% CI: -3.48, -2.48) and neurological score (SMD: -2.3, 95% CI: -2.85, -1.76). The median score on the CAMARADES checklist was 5.5/10 (IQR 4.25-6). Funnel plots of lesion volume and neurological score data revealed pronounced asymmetry and publication bias. Additionally, trim and fill analysis estimated 19 "missing" studies for the lesion volume outcome adjusting the effect size to -1.91 (95% CI: -2.44, -1.38). Biomaterials including scaffolds and particles exerted a positive effect on histological and neurological outcomes in pre-clinical stroke models. However, heterogeneity in the field, publication bias and study quality scores which may be another source of bias call for standardization of outcome measures and improved study reporting.

摘要

近年来,临床前中风研究对开发基于生物材料的疗法以促进组织修复和功能恢复表现出越来越浓厚的兴趣。此类策略将生物材料用作组织再生的结构支撑或治疗剂的递送载体。虽然一系列生物材料已在中风模型中进行了测试,但目前尚无用于评估这些方法益处的综述。因此,我们对研究生物材料在实验动物模型中治疗中风的应用的研究进行了系统评价和荟萃分析。通过搜索电子数据库(PubMed、科学网)和相关综述文章的参考文献列表来识别研究。纳入报告病变体积和/或神经学评分的研究。使用DerSimonian和Laird随机效应计算标准化平均差(SMD)和95%置信区间。使用CAMARADES清单评估研究质量和偏倚风险。通过漏斗图可视化发表偏倚,随后对缺失的出版物进行修剪和填充分析。系统评价共纳入66篇出版物,其中44篇(86项比较)在荟萃分析中进行了评估。总体而言,基于生物材料的干预措施改善了病变体积(SMD:-2.98,95%置信区间:-3.48,-2.48)和神经学评分(SMD:-2.3,95%置信区间:-2.85,-1.76)。CAMARADES清单的中位数评分为5.5/10(四分位间距4.25 - 6)。病变体积和神经学评分数据的漏斗图显示出明显的不对称性和发表偏倚。此外,修剪和填充分析估计病变体积结果有19项“缺失”研究,将效应大小调整为-1.91(95%置信区间:-2.44,-1.38)。包括支架和颗粒在内的生物材料在临床前中风模型中对组织学和神经学结果产生了积极影响。然而,该领域的异质性、发表偏倚以及可能是另一种偏倚来源的研究质量评分要求对结果测量进行标准化并改进研究报告。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2305/6718570/88d33d77d66b/fneur-10-00924-g0001.jpg

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