Table 3.
Summary of the 3D printed delivery systems for bone regeneration covered in this review
| Category | Sub-category | Materials (Scaffold)1 | Materials (Delivery matrix)2 | Delivery matrix loading | Therapeutic | Evaluation | Reference |
|---|---|---|---|---|---|---|---|
| Organic Systems | Polymer-based systems | Alginate | Alginate | Chemical linkage | BFP-1 |
In vitro: hADSCs; NIH3T3; In vivo: calvarial bone defects of rabbits |
[129] |
| PCL-TCP | dry collagen | loading | Human recombinant BMP-2 | In vivo: calvarial bone defects of rats | [130] | ||
| PCL; PLGA | Collagen/gelatin | Printing | Human recombinant BMP-2 | In vivo: rabbit radius segmental defect model | [131] | ||
| HA-PLGA | PEG | Direct printing | BMP-2 |
In vitro: osteoblasts; In vivo: calvarial bone defects of SD rats |
[132] | ||
| PCL | PLGA microsphere | Direct printing | CTGF, TGF-β |
In vitro: MSCs In vivo: temporomandibular joint disc in rabbits |
[133] | ||
| PPF/DEF | PLGA microspheres | Direct printing | BMP-2 |
In vitro: pre-osteoblasts In vivo: rat cranial bone defect |
[134] | ||
| PCL/graphene | graphene | Direct printing | P1-latex | In vitro: hADSCs | [135] | ||
| PLGA | Poly (dopamine) | coating | BMP-2, Ponericin G1 | In vitro: pre-osteoblasts | [136] | ||
| PCL/PLGA | Heparin-dopamine | coating | BMP-2 |
In vitro: osteoblast-like cells (MG-63 cells) In vivo: rat femur bone defect |
[137] | ||
| Bioprinting | Alginate | Gelatin microparticles; Alginate | Encapsulation; printing | Human recombinant BMP-2 |
In vitro: goat multipotent stromal cells; In vivo: Subcutaneous implantation |
[138] | |
| Alginate; Alginate-sulfate | Alginate; Alginate-sulfate | Direct printing | BMP-2 | In vitro: MC3T3-E1 osteoblasts; | [139] | ||
| MeHA | MeHA | Direct printing | BMP-2 | N.A. | [140] | ||
| Inorganic systems | CaP-based systems | HA | Chitosan microspheres | Coating | Human recombinant BMP-2 |
In vitro: hMSCs In vivo: ectopic bone formation model |
[141] |
| calcium phosphate cement with mesoporous silica | N.A. | Infiltration | Human recombinant BMP-2 |
In vitro: HUVECs and hBMSCs In vivo: rabbit femoral defect model |
[142] | ||
| CDHA | CDHA | Printing | Quercetin | N.A. | [143] | ||
| P-CPC | P-CPC | N.A. | N.A. | In vitro: hMSCs | [144] | ||
| Titanium-based systems | Titanium | Gelatin | Infiltration | BMP-2 and FGF-2 | In vivo: critical femoral bone defects of rats | [145] | |
| CaP modified Ti6Al4V | N.A. | Coating | BMP-2 | In vivo: calvarial bone defects of rabbits | [146] | ||
| Hybrid Systems | N.A. | PEG:PEGDA with nHA | PLGA | Printing | TGF-β1 | In vitro: hMSC | [147] |
| PCL/PLGA/β-TCP | Collagen | Printing | Human recombinant BMP-2 | In vivo: rabbit calvarial defect model | [148] | ||
| CPC | alginate-gellan gum | Printing | VEGF |
In vitro: endothelial cell, HUVECs and MSCs In vivo: segmental bone defect in the rat femur |
[149, 150] | ||
| Polylactic acid | Gold NPs/GelMA | Infiltration | BMP-2 | In vitro: ADSCs | [151] | ||
| PCL | Alginate; gelatin | Printing | VEGF |
In vitro: DPSCs; In vivo: ectopic bone formation model |
[152] | ||
| PCL | Collagen | Printing | BMP-2 | ||||
| GelMA | GelMA | Printing | VEGF | In vitro: HUVECs and hMSCs | [64] |
materials for scaffold fabrications.
materials of drug-loaded vehicles.
PCL: poly(ε-caprolactone), TCP: tricalcium phosphate, PLGA: poly(lactic-co-glycolic acid), HA: hydroxyapatite, PEG: polyethylene glycol, PPF: poly (propylene fumarate), DEF: diethyl fumarate, MeHA: methacrylated hyaluronic acid, CaP: calcium phosphate, PEGDA: polyethylene glycol diacrylate, GelMA: gelatin methacrylate, BFP-1: bone formation peptide-1, BMP-2: bone morphogenetic protein-2, CTGF: connective tissue growth factor, TGF-β: transforming growth factor-β, FGF-2: fibroblast growth factor-2, VEGF: vascular endothelial growth factor, hADSCs: human adipose-derived stem cell, MSCs: mesenchymal stem cells, HUVECs: human umbilical vein endothelial cells, hBMSCs: human bone mesenchymal stem cells, DPSCs: dental pulp stem cells, CDHA: calcium-deficient hydroxyapatite, P-CPC: pasty calcium phosphate cement, CPC: calcium phosphate cement