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 Sena, Catriona Cunningham, Ann Rajnicek, Malcolm R. Macleod, Wenlong Huang* (Corresponding Author), Gillian L Currie, Sarah K. McCann

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)


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 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.

Original languageEnglish
Pages (from-to)1041-1049
Number of pages9
JournalSpinal Cord
Issue number12
Early online date23 May 2022
Publication statusPublished - 1 Dec 2022

Bibliographical note

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 Statement

The statistical analysis code and datasets analysed during this study are openly available from the Open Science Framework at https://osf.io/bgw73/.

Supplementary information
The online version contains supplementary material
available at https://doi.org/10.1038/s41393-022-00811-z.




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