Table 3.
Summary of composite materials containing nanocarbons developed for bone healing and regeneration.
| Matrix | Filler | Tested Cells | In Vitro | In Vivo | Ref. |
|---|---|---|---|---|---|
| Poly-(l-lactic acid) | Carbon nanotubes | Human osteosarcoma MG63 osteoblast cells | Cell morphology, viability, proliferation | - | [127] |
| Poly(l-lactic acid) | Graphene nanoribbons, nano-hydroxyapatite | - | Allium cepa test, hemolysis | Female Wistar Rats: surgical defects in tibias, comet assay, bone regeneration | [128] |
| Collagen | Carbon nanotubes, hydroxyapatite | Rat bone mesenchymal stem cells | Cell morphology, viability, proliferation, BMP-2 level, insulin-like growth factor 1 receptor | Female SD rats: X-ray, mason staining and toxicology experiments | [129] |
| Arginine-glycine-aspartic acid/BMP-2 peptides, poly-(l-lactic acid) | Carbon nanotubes with carboxyl and amino groups | Mouse preosteoblast cells MC3T3-E1 | Cell adhesion, proliferation, differentiation, mineralization | - | [130] |
| Oligo(poly(ethylene glycol)fumarate), poly(ethylene glycol)acrylate | Carbon nanotubes, black phosphorus | MC3T3 preosteoblast cells | Cell adhesion, proliferation, osteogenic differentiation, electric stimulation enhanced osteogenesis | - | [131] |
| - | Multi-walled carbon nanotubes, nano- hydroxyapatite | Human adipose-derived mesenchymal stem cells | Cell adhesion, attachment, strength, proliferation, osteogenic differentiation, RT-PCR, DNA, ALP assay, total protein analyses | New Zealand white rabbits: dorsal musculature, histological examinations, collagen-I immunostaining analysis, bone-mineral content, macrophage infiltration | [132] |
| Polycaprolactone | Multi-walled carbon nanotubes | UMR-106 cells | Mitochondrial activity of osteoblasts, MTT assay | Male Wistar rats: immunohistochemistry, extraction of bone proteins | [133] |
| Polycaprolactone | Multi-walled carbon nanotubes, nano-hydroxyapatite | Human adipose-derived stromal/stem cells | Cell proliferation, osteogenic differentiation, mineralization, Alamar blue assay, ALP assay, amount of collagen and osteocalcin, Alizarin red S staining | - | [134] |
| Polycaprolactone | Multi-walled carbon nanotubes, eggshell | Bone marrow mesenchymal stem cells | Adhesion and proliferation of osteoblasts | - | [135] |
| Polyion complex (sodium p-styrenesulfonate, 3-(methacryloylamino)propyl-trimethylammonium chloride) | Multi-walled carbon nanotubes | Rat bone marrow-derived mesenchymal stem cells | Biocompatibility, osteogenic differentiation, viability and morphology, Alizarin red S staining, gene expression analysis | SD rats: calvarial defect, micro-CT, histological and immunological staining | [136] |
| - | Nitrogen-doped multiwalled carbon nanotubes, cellulose, nano-hydroxyapatite | SPF Spragu–Dawley rats mesenchymal stem cells | Cellular attachment, proliferation, viability, mineralization, ALP assay, osteogenic gene expressions | Distal femoral condyle critical size defect in rabbit, bone regeneration and micro-CT analysis, histological analysis | [138] |
| Chitosan | Graphene oxide | Human adipose derived stromal/stem cells | Cell viability, proliferation, MTT, cytotoxicity, Live/Dead® assays, distribution and morphology, osteogenic differentiation | Mouse models with a calvaria bone defect, Osx osteogenic marker evaluation | [139] |
| - | Hydroxyapatite, hydrophilic graphene | Mouse preosteoblast cells MC3T3-E1 | MTS assay, cell adhesion, proliferation | - | [140] |
| Carrageenan, acrylic acid | Graphene, hydroxyapatite | Mouse preosteoblast cells MC3T3-E1 | Cell viability and proliferation using neutral red dye assay | - | [103] |
| Poly-ε-caprolactone | Graphene | Mouse preosteoblast cells MC3T3-E1 | Cell adhesion and growth behaviors, MTT assay, ALP assay | - | [141] |
| Polyether ether ketone | Graphene nanosheets | Bone marrow mesenchymal stem cells | Antibacterial screening, cytocompatibility, bone regeneration, Live/Dead® assays, MTT assay, tumor inhibition | Laser treatment on a nude mouse, P/G10 and P/G10-HA tumor growth inhibition | [142] |
| Polyether ether ketone | Graphene oxide | Bone marrow stromal stem cells | Cell adhesion, cytotoxicity | - | [143] |
| Polyether ether ketone | Graphene oxide, nano-hydroxyapatite | Mouse preosteoblast cells MC3T3-E1 | Cell morphology, proliferation | - | [144] |
| - | Graphene oxide, nano-hydroxyapatite | Mouse preosteoblast cells MC3T3-E1, stem cells derived from human dental pulp | Bioactivity assay, cytotoxicity analysis, MTT assay | - | [145] |
| Chitosan | Graphene oxide, nano-hydroxyapatite | Mouse preosteoblast cells MC3T3-E1 | Degradation behavior, biomineralization study, Live/Dead® assays | SD rats: histological assessment, bone specific proteins, osteogenesis gene expression | [146] |
| Spermine based polyurethane-urea | Graphene oxide, 2D rod-like nano-hydroxyapatite, | MG63 osteoblast cells | Cell viability and proliferation, RT-PCR, cell osteogenesis induction, antibacterial study | Mature male SD rats: tibial model, histological assessment | [147] |
| Shape-memory polyurethane | Isocyanate modified graphene oxide | - | - | - | [148] |
| - | Graphene nanoribbons, nano-hydroxyapatite | - | - | Wistar rats: histological, biochemical, and radiographic analyses | [149] |
| Chitosan, quaternized chitosan | Graphene oxide, strontium-substituted hydroxyapatite | Bone marrow stromal cells | Antibacterial test, cytocompatibility using CCK-8 assay, ALP activity | Male SD rats | [150] |
| Collagen | Strontium-graphene oxide | Human adipose-derived stem cells, human umbilical vein endothelial cell | Cytotoxicity assay, viability, morphology, adhesion, osteogenic differentiation, RT-PCR, western blot, angiogenic effects | Male rats: micro-CT analysis, micro-CT angiography, calvarial undecalcified sections, calvarial decalcified sections | [151] |
| Collagen-I | Graphene oxide | Rat bone marrow mesenchymal stem cells | Bioactivity, biodegradation, cytocompatibility | Male Wistar rats: biodegradation; male SD rats: craniofacial bone defect study | [152] |
| Poly(lactic-co-glycolic acid), β-tricalcium phosphate | Graphene oxide, BMP-2 | Rat bone marrow-derived mesenchymal stem cell | Peptide release and scaffold degradation, cell viability, adhesion, morphology, osteogenic differentiation | Male Wistar rats: micro-CT and histological evaluation | [153] |
| Silk fibroin | Graphene oxide, BMP-2 | Bone marrow mesenchymal stem cells | Degradation, cell proliferation, adhesion, Live/Dead® assays, osteogenic differentiation, RT-PCR | Male SD rats: calvarial bone defect implantation, micro-CT measurement, histological evaluation | [154] |
| Silk fibroin, hydroxyapatite | Polyethylenimine functionalized graphene oxide, miR-214 inhibitor | Mouse preosteoblast cells MC3T3-E1, bone marrow mesenchymal stem cells | Cytotoxicity, CCK-8 assay, osteoblast cell proliferation and differentiation, degradation | Calvarial bone-defect model in rats, micro-CT, implantation subcutaneously on back of nude mice | [155] |
| Alginate, gelatin | Graphene oxide, human mesenchymal stem cells-laden | Human mesenchymal stem cells | Live/Dead® assays, cell morphology, DNA content, ALP activity, osteogenic-related gene expression, micro-CT, histology staining | - | [156] |
| - | Graphene oxide, mesoporous bioactive glasses | Rat bone marrow mesenchymal stem cells | Cells proliferation, adhesion, ALP assay, immunofluorescence evaluation, Alizarin red S staining, OCN immunofluorescence assay, osteogenic-related gene expression | Male SD rats: cranial bone defect model, micro-CT, microfil perfusion in bone defect, sequential fluorescent labeling in bone defect, newly bone formation and mineralization analysis, immunohistochemical analysis | [157] |
| - | Fe3O4/graphene oxide, α-tricalcium, phosphate/calcium sulfate, hydroxypropyl methylcellulose | Rat bone marrow derived mesenchymal stem cells | Antitumor effect of hyperthermia, cell viability via CCK-8 assay, Live/Dead® assays proliferation and osteogenic activity | Nude mice, antitumor efficiency, osteogenesis, | [158] |
| - | Reduced graphene oxide, nano-hydroxyapatite | Rat bone marrow mesenchymal stem cells | Cell morphology, adhesion, proliferation, Alizarin red S staining, ALP assay, osteopontin expression | Male SD rats: segmental diaphyseal bone defect on, micro-CT, histological changes, bone volume fraction, trabecular thickness and separation | [47] |
| - | Reduced graphene oxide, zinc-doped hydroxyapatite | Mesenchymal stem cell | Osteogenic differentiation, Alizarin red S staining, osteogenic marker expression, runt-related transcription factor 2, ALP assay, levels of collagen-1, BMP-2, osteocalcin, osteopontin, antimicrobial activity | Rats and mice, a rat femur osteotomy model, micro-CT, calcein evaluation, angiogenesis | [159] |
| Shape memory polyurethane | Reduced graphene oxide, hydroxyapatite, arginyl-glycyl-aspartic acid | Rabbit bone mesenchymal stem cells | Adhesion | - | [160] |
| Gelatin | Reduced graphene oxide, methyl vanillate | Bone marrow stromal cells | ALP assay, Alizarin red S staining, immunofluorescence staining, gene expression, endocytosis of bone marrow stromal cells, osteogenic effect | - | [161] |
| Polyvinyl alcohol | Carbon nanoparticles nano-demineralized bone | MG63 osteoblast cells | Biomineralization, antimicrobial screening, cell viability via MTT assay | - | [162] |
| Ascorbic acid, polyethylenimine | Carbon dots, miR-2861, | Bone marrow stromal cells | ALP assay, Alizarin red S staining, RT-PCR, fluorescent images, cytotoxicity | Male Wistar rats: intra-tibial injection for bone formation and calvarial bone defect for bone repair on fluorescent images and cytotoxicity, osteogenic effects, bone regeneration, biocompatibility | [163] |
| Gelatin, hydroxyapatite | Zinc-passivated carbon dots | Rat bone marrow stromal cells | Cytotoxicity and proliferation via MTS assay, intracellular ROS detection, ALP assay, Alizarin red S staining | Male SD rats: calvarial bone defect, radiographic and histological analysis | [164] |
| Silk fibroin | Carbon nanocages, BMP-2 | Rat bone marrow mesenchymal stem cells | ALP assay, cell adhesion, cytotoxicity, RT-PCR | Rats, micro-CT, volume percentage of new bone formation | [165] |
| - | Carbon nanofiber, gold nanoparticles | MG63 osteoblast cells | MTT and lactate dehydrogenase toxicity assays, cell attachment, morphology | - | [166] |
| Polyether ether ketone | Carbon nanotubes and fibers hydroxyapatite | Rat bone marrow and raw cell culture | Cytotoxicity and cell viability, MTT assay, ALP assay, telomerase repeated amplification protocol assay | - | [167] |