Table 1.
Recent in vitro and in vivo studies using 3D bioprinting for bone tissue engineering applications.
| Biomaterials and GFs | Cells | Main results | References |
|---|---|---|---|
| Extrusion-based bioprinting | |||
| Alginate/gelatin/bioglass | Osteoblasts | Increased cell proliferation and mineralisation by adding bioglass to the hydrogel. | Wang [76] |
| Alginate/gelatin/HA | ASCs | Structure integrity maintained for 28 days in culture with increased storage moduli. Intense matrix formation and upregulation of osteogenic markers. |
Wenz [77] |
| Alginate/GelMA/HA | BMSCs | Long-term structural integrity and high cell viability after 3 days of in vitro culture. | Wüst [74] |
| Alginate/gelatine/polyP-Ca2+ complex | Osteoblasts | Improved cell proliferation, Young's modulus and significant matrix deposition due to the calcium salt from polyP- Ca2+ complex. | Neufurth. [75] |
| LAP/alginate/methylcellulose + VEGF or BMP-2 | BMSCs, HUVECs | Viable and functional constructs in vitro (BMSCs) and ex vivo (HUVECs + VEGF). Extensive mineralisation produced by BMP-2 absorbed scaffolds compared to alginate controls and BMSC-laden scaffolds after 4 weeks, supporting bone tissue formation. |
Cidonio [31] |
| Alginate/PCL | Pre-osteoblasts, Chondrocytes | Maintained their cell viability and proliferation in culture of encapsulated cells dispensed into the pores of a pre-formed PCL framework. | Shim [55] |
| Bioglass/gliadin/PCL | Pre-osteoblasts | Scaffold with controllable architecture, high compressive strength, proper degradability and biocompatible. Osteogenesis in vivo after implantation in rabbit femoral bone defect. | Zhang [69] |
| Chitosan, Chitosan/HA, Alginate, Alginate/HA | Osteoblasts | The combination of Chitosan/HA showed viscoelastic properties, improved cell viability, proliferation and differentiation. | Dermitaş [78] |
| Collagen/PCL-HA/TCP + BMP-2 or PRP | Osteoblasts | The addition of PRP showed higher cellular activities and mineralisation for bone tissue regeneration in Collagen/PCL-HA/TCP biocomposites, compared to the addition of BMP-2. | Kim [66] |
| Gelatin/silicate nanoparticles + VEGF supplementation | HUVECs and BMSCs | Constructs with high structural stability, cell survival and proliferation during maturation in vitro. | Byambaa [68] |
| GelMA/Pluronic F-127 | BMSCs | Total bone formation, increased vascularization and implant remodelling observed after implantation in rat femoral bone defect. | Daly [41] |
| Matrigel | ECs and BMSCs | Changing fiber spacing or angle of fiber deposition yielded to scaffolds of different porosity and elastic modulus. Bone and vessel formation in printed grafts after subcutaneous implantation in immunodeficient mice. |
Fedorovich [80] |
| PCL/β-TCP | Fibroblasts, Pre-osteoblasts |
Excellent cell affinity and mechanical properties of the membrane. Enhancement of bone formation after implantation in alveolar bone defect in beagles. | Shim [67] |
| PCL/CB(6)/DAH-HA + TGFβ/Atelocollagen + BMP-2 | hTMSCs | Cytocompatible multi-layered 3D construct capable of inducing cell differentiation in vitro. In vitro and in vivo osteochondral tissue formation. | Shim [73] |
| PCL/TCP/Pluronic F-127 | hAFMSCs | Formation of new vascularized bone tissue with no necrosis, after 5 months of calvarian bone reconstruction in vivo. | Kang [25] |
| Stereolithography | |||
| GelMa/OCP | HUVECs and BMSCs | Bone-like tissue and capillary-like structure formation after 1 day of in vitro culture. | Anada [70] |
| Laser Bioprinting | |||
| HA-collagen | BMSCs | Different cell printing geometries impact on bone tissue regeneration. Proliferation of printed MSCs and improved bone regeneration 42 days post-implantation in the calvarian bone defect mouse model. |
Keriquel [47] |
Abbreviations: [HA] hydroxyapatite, [ASCs] adipose derived mesenchymal stem cells, [GelMa] gelatin methacrylamide, [BMSCs] bone marrow-derived mesenchymal stem cells, [polyP-Ca2+ complex] calcium salt of polyphosphate-calcium complex, [VEGF] vascular endothelial growth factor, [HUVECs] Human umbilical vein endothelial cells, [BMP-2] bone morphogenetic protein-2, [PCL] poly(caprolactone), [PRP] platelet rich plasma, [TCP] tricalcium phosphates, [ECs] endothelial cells, [CB(6)] Cucurbit [6]uril, [DAH-HA] 1,6-diaminohexane-conjugated hyaluronic acid, [hTMSCs] human nasal inferior turbinate tissue-derived mesenchymal stromal cells, [TGFβ] transforming growth factor, [hAFMSCs] human Amniotic fluid-derived mesenchymal stem cells, [OCP] peripheral octacalcium phosphate.