Effectiveness of biomaterial-based combination strategies for spinal cord repair – a systematic review and meta-analysis of preclinical literature
Alba Guijarro-Belmar, Anna Varone, Martin Rugema Baltzer, Saurav Kataria, Ezgi Tanriver-Ayder, Ralf Watzlawick, Emily S. Sena, Catriona Cunningham, Ann M. Rajnicek, Malcolm Macleod, Wenlong Huang, Gillian L. Currie, Sarah McCann
Abstract
Abstract Study design Systematic review and meta-analysis of preclinical literature. Objectives To assess the effects of biomaterial-based combination (BMC) strategies for the treatment of Spinal Cord Injury (SCI), the effects of individual biomaterials in the context of BMC strategies, and the factors influencing their efficacy. To assess the effects of different preclinical testing paradigms in BMC strategies. Methods We performed a systematic literature search of Embase, Web of Science and PubMed. All controlled preclinical studies describing an in vivo or in vitro model of SCI that tested a biomaterial in combination with at least one other regenerative strategy (cells, drugs, or both) were included. Two review authors conducted the study selection independently, extracted study characteristics independently and assessed study quality using a modified CAMARADES checklist. Effect size measures were combined using random-effects models and heterogeneity was explored using meta-regression with tau 2 , I 2 and R 2 statistics. We tested for small-study effects using funnel plot–based methods. Results 134 publications were included, testing over 100 different BMC strategies. Overall, treatment with BMC therapies improved locomotor recovery by 25.3% (95% CI, 20.3–30.3; n = 102) and in vivo axonal regeneration by 1.6 SD (95% CI 1.2–2 SD; n = 117) in comparison with injury only controls. Conclusion BMC strategies improve locomotor outcomes after experimental SCI. Our comprehensive study highlights gaps in current knowledge and provides a foundation for the design of future experiments.