Table 3.
Pre-clinical combinatorial approaches for SCI repair: biomaterials and small molecules
| Models | Molecules + Biomaterials | Outcomes | References |
|---|---|---|---|
| Mice/Contusion T9-10 | Shh + PLGA microspheres | Sprouting of nerve fibers, the proliferation of oligodendrocytes, the decrease of gliosis, and behavioral recovery after SCI. | Lowry et al., 2012 |
| Rat/Compression T2 | FGF2 + PLGA nanoparticles | Achieved higher blood vessel density in the dorsal horns, due to either greater angiogenesis near the epicenter of the injury or vasoprotection acutely after spinal cord injury. | Kang et al., 2013 |
| Rat/Compression T1-2 | NT-3 + PLGA nanoparticles | Significant axon growth with no effect on the astroglial response to injury and functional recovery in comparison with vehicle and injury controls. | Elliott Donaghue et al., 2015 |
| Rat/Contusion T9 | VEGF, angiopoietin-1 (Ang-1), and bFGF + PLGA microspheres | Stimulates neoangiogenesis and neurogenesis, accelerating recovery of neurologic function. | Yu et al., 2016 |
| Rat/Compression T9 | NGF + GNLs | Enhanced the neuroprotection effect in SCI rats compared with NGF alone. This combination has higher monodispersity, half-life, and stability. | Zhu et al., 2016 |
| Rat/Transection T9 | NT-3 + poly(propylene fumarate)-collagen scaffold | Improves the inhibitory microenvironment, facilitates axonal and neuronal regeneration, survival of various types of functional neurons, and remyelination and synapse formation of regenerated axons. | Chen et al., 2018 |
| Rat/Transection T9-10 | Exosomes derived from hMSCs + Peptide-modified adhesive hydrogel | Significant nerve recovery and urinary tissue preservation by effectively mitigating inflammation and oxidation. | Li et al., 2020 |
| Rat/Transection T2 | BDNF + hydrogel - HA and MC | Enhancing axonal growth and promoting neural stem cell formation. | Khaing et al., 2016 |
| Rat/Compression T9 | HGF + gelatin-FA hydrogel | HGF combined with gelatin-FA hydrogel promoted endogenous repair and recovery more effectively than HGF with hydrogel. | Yamane et al., 2018 |
For all the combinations of biomaterials and small molecules mentioned above, approximately 78% reported functional and histological recovery and 22% showed histological recovery with no functional improvements. BDNF: Brain-derived neurotrophic factor; bFGF: basic fibroblast growth factor; FA: furfurylamine; FGF2: fibroblast growth factor-2; GNLs: gelatin nanostructured lipid carriers; HA: hyaluronic acid; HGF: hepatocyte growth factor; hMSCs: human placenta amniotic membrane mesenchymal stem cell; MC: methylcellulose; NGF: nerve growth factor; NT-3: neurotrophin-3; PLGA: poly(lactide-co-glycolide; Shh: sonic hedgehog; VEGF: vascular endothelial growth factor.