TABLE 1.
Selected scaffold‐based approaches with immunomodulation features after spinal cord injury
| Scaffold material | Drug | Cell | Model | Results based on immune response | References |
|---|---|---|---|---|---|
| Natural materials | |||||
| Fragmented chitosan hydrogel suspension (Chitosan–FPHS) | – | – | In vitro mouse monocytes, Rat T8–T9 hemisection |
Polarized macrophage polarization towards anti‐inflammatory phenotypes with decreasing degree of acetylation (DA) and increasing chitosan concentration; Decreased M1 macrophages with low DA chitosan‐FPHS implant in vivo |
217 |
| Chitosan–FPHS | – | – | Rat T8–T9 hemisection | Increased levels of M2 marker protein CD206 and Arg1 | 218 |
| Porcine brain‐derived decellularized extracellular matrix | – | – | In vitro rat macrophages, Rat T9 contusion |
Increased Arg1+ M2 macrophages and IL‐10 expression; Decreased CD86+ macrophages and increased Arg1+ M2 macrophages in vivo |
219 |
| Injectable optimized acellular nerve graft | – | – | Rat C4–C5 contusion | Increased the number of CD206+ M2 macrophages and expressions of CD206, arginase‐1 and IL‐10 | 220 |
| Methacrylated high molecular weight HA | – | – | Rat T7–T8 hemisection |
Decreased ED1+ macrophages; Limited astrocyte activation and CSPG deposition |
221 |
| Acetylated dextran microspheres | – | – | Rat T10 contusion |
Reduced GFAP+ astrocytes and CD68+ microglia; Reduced neuron death by sequestering glutamate and calcium ions |
222 |
| Synthetic/hybrid materials | |||||
| Imidazole‐polyorganophosphazenes (I‐5) hydrogel | – | – | Rat T10 contusion |
Decreased Iba1+ cells; Hydrogel interacted with macrophages and activated macrophage‐mediated wound healing responses |
223 |
| Hyaluronan/poly(ethylene glycol) diacrylate (HA/PEGDA) | – | – | Rat T9–T10 hemisection | Decreased Iba1+ cells and reactive astrocytes | 224 |
| Hyaluronan/methyl cellulose (HA/MC) | – | – | Rat T7 post‐traumatic syringomyelia (compression followed by subarachnoid injection of kaolin) | Decreased CSPG deposition and IL‐1α cytokine level but did not decrease neutrophil or macrophage/microglial activation | 225 |
| Graphene oxide | – | – | Rat C6 hemisection | Decreased ED1+ and Iba1+ cells with the presence of M2 macrophages | 226 |
| Poly(hydroxybutyrate‐co‐hydroxyvalerate)/polylactic acid/collagen (PHBV/PLA/Col) membrane duraplasty | – | – | Rat T10 contusion |
Decreased the expression of NLRP3, ASC, cleaved‐caspase‐1, IL‐1β, TNF‐α, and CD86 but increased the expression of CD206; Reduced the infiltration of CD86+ macrophages to the lesion site |
227 |
| PCL‐HA nanofiber‐hydrogel composite | – | – | Rat T9 contusion | Polarized Infiltrated macrophages towards M2 phenotype; M2 macrophages congregated in nanofiber‐rich areas | 228 |
| Aligned PEG tubes in fibrin | – | – | Mouse T9–T10 hemisection |
No difference in number of CD45+ leukocytes, Arg1+ M2 macrophages, Lyg6+ neutrophils, CD4+ T cells; Increased CD11c+dendritic cells, F4/80+ macrophages |
229 |
Note: The phenotypes of macrophages and microglia are presented as reported by the respective studies. In these studies, M1 typically refers to the pro‐inflammatory phenotypes whereas M2 typically refers to the anti‐inflammatory phenotypes.