Table 7.
CNPs in regenerative medicine: literature summary.
| Nanomaterial | Synthesis Method | Morphology | Size (nm) | Model | Dosage | Route of Administration | Markers | Effects | Ref. | |
|---|---|---|---|---|---|---|---|---|---|---|
| Powder | Hydrodynamic Radius | |||||||||
| CNPs | Hydrothermal | Cubic | 19.5 | 33.7 | Sprague-Dawley-rat-derived primary cortical neurons treated with H2O2 | 1–4000 μg/mL for 24 h | NA | ↓ iNOS | ↑ neuronal cell survival ↓ oxidative stress |
[96] |
| Sprague-Dawley rats exposed to contusion injury at T9 level as in vivo model for spinal cord injury (SCI) | 0.5–4 mg/mL | Lesion cavity injection | ↓ ED1+ cells ↓ iNOS ↓ Nr-f2, COX-2 ↓ TNF-α, IL-1β, IL-6 ↑ IL-10 ↓ p53, caspase 3 |
↓ lesion cavity ↓ inflammation ↓ oxidative stress ↑ locomotor functions ↓ apoptosis ↑ axonal regeneration |
||||||
| BSA-incubated-CNP-based hydrogel (CNPs-Gel) |
BSA-incubation method |
Spherical | ND | 4.97 ± 1.39 | Sprague-Dawley rats exposed to injury at T10 level as in vivo model for spinal cord injury (SCI) | 3–6 mM | Implantation of NSC-loaded CNP gel into the lesion | ↓ ROS, 4-HNE ↓ CD68+ cells ↓ iNOS ↑ Arg-1 ↑ p-FAK, p-PI3K, p-AKT1 ↓ GFAP ↑ MAP-2 ↑ NF+ and MBP+ cells |
↑ motor function ↓ cavity area ↓ oxidative stress ↓ inflammation M2 polarization ↓ glial cell activation ↑ neuron and axonal regeneration |
[98] |
| BV2 microglial cell and neuronal stem cells (NSCs) treated with H2O2 | ND | NA | ↓ ROS ↓ TNF-α, iNOS, IL-6 ↑ IL-10, TGF-β, Arg-1 ↑ p-FAK, p-PI3K, p-AKT1 |
↑ cell survival ↓ oxidative stress ↓ inflammation M2 polarization |
||||||
| CNPs | Wet chemical | Spherical | 5 | 35 | RAW 264.7 murine macrophages and human bone mesenchymal stem cells (BMSC) treated with LPS | 1, 10, or 20 μg/mL | NA | ↓ iNOS ↓ IL-6, IL-1β, TNF-α ↑ IL-10, TGF-β |
↓ inflammation ↑ osteogenic differentiation |
[99] |
| CNPs incorporated hydroxyapatite coating | Plasma spraying | ND | ND | ND | Rat bone mesenchymal stem cells and RAW264.7 macrophages |
10–30 wt% | NA | ↑ ALP, OCN, Runx-2 ↑ BMP2, BMPR1, BMPR2, Smad1, Smad5, and Smad8 ↓ TNF-α, IL-6 ↓ CCR7 and CD11c ↑ CD163, CD206 ↑ IL-1rα, IL-10, TGF-β |
↑ cell proliferation M2 polarization ↑ osteogenic differentiation ↓ inflammation |
[100] |
| Immobilized CNPs on titanium-based biomaterial | Deposition by magnetron sputtering and vacuum annealing | ND | ND | ND | Rat bone marrow mesenchymal stem cells (BMSCs), RAW264.7 murine macrophages |
Elemental concentration: 3.57–7.58% | NA | ↑ ALP, Col-I, OCN, OPN, Runx-2 ↑ IL-10 ↓ TNF-α |
↑ cell proliferation ↑ osteogenic differentiation M2 polarization |
[101] |
| Sprague-Dawley rats | Femoral bone implantation | Femoral bone implantation | ||||||||
| CNP-modified titanium disks (CNPs@TiO2) |
Hydrothermal | Nanorods | 9.6 ± 1.2 Length: 50–600 |
ND | Gram-positive bacteria S. sanguinis and Gram-negative bacteria F. nucleatum | 0.1 M | NA | ↓ bacterial growth | [103] | |
| Cubic | 57.2 ± 17.5 | ND | RAW 264.7 murine macrophages treated with LPS | NA | ↓ ROS ↓ TNF-α, IL-1β, IL-6 ↓ nuclear NF-κB (NF-κB/p65) |
↓ oxidative stress ↓ inflammation |
||||
| Octahedral | 29.1 ± 11.7 | ND | Wistar rats | Subcutaneous implantation | ↓ TNF-α, IL-1β, IL-6 | ↓ immune cell infiltration ↓ inflammation |
||||
| CNPs | NA | spherical | 5 | 10 | RAW 264.7 cells | 2–50 μg/mL | NA | ↓ MAPK NFkB pathway ↓ IL-1β ↓ TNF-α ↓ iNOS ↓ Nrf2, HO-1 ↓ ROS |
↓ oxidative stress ↓ inflammation |
[104] |
| Male Sprague-Dawley rats treated with LPS as in vivo model of gingival inflammation | 10 μL; 2 mg/mL | Gingival injection | ↓ ROS | ↓ destruction of periodontal tissues | ||||||
CNPs: cerium oxide nanoparticles; iNOS: nitric oxide synthases; Nr-f2: nuclear factor erythroid 2-related factor 2; COX: cyclooxygenase; TNF-α: tumor necrosis factor alpha; IL: interleukin; BSA: bovine serum albumin; M: macrophages; ROS: reactive oxygen species; 4-HNE: 4-hydroxynonenal; Arg-1: arginase 1; p-FAK: phosphorylated-focal adhesion kinase; p-PI3K: phosphorylated-phosphatidylinositol 3-kinase; p-AKT1: phosphorylated-protein kinase B; GFAP: glial fibrillary acidic protein; MAP2: microtubule-associated protein 2; NF: neurofilament protein; MBP: myelin basic protein; LPS: lipopolysaccharide; ALP: alkaline phosphate; OCN: osteocalcin; Runx-2: runt-related transcription factor 2; BMP2: bone morphogenetic protein 2; BMPR: bone morphogenetic protein receptor; Smad: suppressor of mothers against decapentaplegic; CCR7: C-C chemokine receptor type 7; Col-I: collagen type I; OPN: osteopontin; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; HO-1: hemeoxygenase-1; ND: not determined; NA: not applicable. Colored areas highlight in vivo experiments.