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 tau2, I2 and R2 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 1.6SD (95% CI 1.2-2SD; 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.
This work was supported by the Institute of Medical Sciences of the University of Aberdeen, International Spinal Research Trust, Scottish Rugby Union, RS McDonald Charitable Trust and The European Union’s Horizon 2020 research and innovation programme (Marie Skłodowska-Curie grant agreement no. 702213).
Data Availability StatementThe statistical analysis code and datasets analysed during this study are openly available from the Open Science Framework at https://osf.io/bgw73/.
The online version contains supplementary material
available at https://doi.org/10.1038/s41393-022-00811-z.
- FUNCTIONAL RECOVERY
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Guijarro Belmar, A. (Creator), Tanriver-Ayder, E. (Creator), Sena, E. (Creator), Macleod, M. R. (Creator), Currie, G. (Creator), McCann, S. K. (Creator) & Bhattacharya, S. (Data Manager), University of Aberdeen, 19 Feb 2022