Effectiveness of biomaterial-based combination strategies for spinal cord repair - a systematic review and meta-analysis of preclinical literature.

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 1.6 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.

Lithium chloride prevents interleukin-1ß induced cartilage degradation and loss of mechanical properties.

Osteoarthritis is a chronic degenerative disease that affects the articular cartilage. Recent studies have demonstrated that lithium chloride exhibits significant efficacy as a chondroprotective agent, blocking cartilage degradation in response to inflammatory cytokines. However, conflicting literature suggests lithium may affect the physicochemical properties of articular cartilage and thus long-term exposure may negatively affect the mechanical functionality of this tissue. This study aims to investigate the effect of lithium chloride on the biomechanical properties of healthy and interleukin-1ß treated cartilage in vitro and examines the consequences of long-term exposure to lithium on cartilage health in vivo. Bovine cartilage explants were treated with lithium chloride for 12 days. Chondrocyte viability, matrix catabolism and the biomechanical properties of bovine cartilage explants were not significantly altered following treatment. Consistent with these findings, long term-exposure (9 months) to dietary lithium did not induce osteoarthritis in rats, as determined by histological staining. Moreover, lithium chloride did not induce the expression of catabolic enzymes in human articular chondrocytes. In an inflammatory model of cartilage destruction, lithium chloride blocked interleukin-1ß signaling in the form of nitric oxide and prostaglandin E2 release and prevented matrix catabolism such that the loss of mechanical integrity observed with interleukin-1ß alone was inhibited. This study provides further support for lithium chloride as a novel compound for the treatment of osteoarthritis.