3D Bioprinting for Next-Generation Personalized Medicine
Abstract
:1. Introduction
2. Bioprinting: Methods and Materials
2.1. Bioprinting Technology
2.1.1. Inkjet Printing
2.1.2. Extrusion Printing
2.1.3. Laser-Assisted Printing
2.1.4. Stereolithography
Bioprinting Method | Key Aspects | Advantages | Disadvantages | References |
---|---|---|---|---|
Inkjet | First bioprinting technology that has a bio-ink cartridge. Minimum droplet volume of 20 nL |
|
| [13,14,15,16] |
Extrusion | A modification of inkjet-based bioprinting that prints a cylindrical stream onto a printing surface in a continuous line |
|
| [22,23,32] |
Laser-assisted | Propels bio-ink onto the printing surface |
|
| [11,20,21,33] |
Stereolithography | Uses UV light to solidify bio-ink layer-by-layer |
|
| [24,25,27,34] |
2.2. Cell Source and Bio-Inks
3. Applications in the Discovery of Personalized Medicine
3.1. Printing of Stem-Cell Differentiated Organs for Tissue Regeneration
3.1.1. Bone
3.1.2. Kidney
Target Tissue | Bioprinting Method | Cell Type | Biomaterial | Cellular Response | References |
---|---|---|---|---|---|
Bone | Commercial fused-filament fabrication 3D printer (DeltaWASP 2040; CSP srl, Massa Lombarda, Italy) | Human gingival mesenchymal stem cells (hGMSCs) | Poly(lactide) (PLA), extracellular vesicles (EVs), polyethyleneimine (PEI)-engineered EVs (PEI-EVs) | (1) Both 3D-PLA + EVs + hGMSCs and 3D-PLA + PEI-EVs + hGMSCs showed no cytotoxicity (2) Better osteogenic properties were observed in 3D-PLA + PEI-EVs + hGMSCs. New bone nodules and blood vessels were observed in calvariae after in vivo implantation in rats subjected to cortical calvaria bone tissue damage. | [62] |
3D Cloning FDM printer (Microbras, Brazil), PLA white commercial filament (1.75 mm in diameter, produced by E-Sun, China) | Porcine bone marrow stem cells (MSCs) | Poly(lactic acid) (PLA), polydopamine (PDA), type-I colla-gen (COL I) | PDA combined with COL coating increased cell adhesion and the metabolic activity of MSCs in the early stage (<7 days) of cell culture and facilitated the deposition of extracellular matrix by day 14, and produced much higher amounts of alkaline phosphatase than un-coated PLA by day 21. | ||
Kidney and Liver | Extrusion bioprinting (Cellink INKREDIBLE + 3D bioprinter) | iPS-derived parenchymal (hepatocyte-like) cells, iPS-derived hepato-cyte-like cells spheroids | Matrigel | Liver constructs from 3D printing with hepatic spheroids showed prolonged survival, reduced cell death, increased urea production, and prolonged secretion of albumin and A1AT, as compared to printed constructs using single-cell dispersion. | [66] |
Extrusion bioprinting (Novogen 3D bio-printer) | iPSC | STEMdiff APEL and TESR-E6 medium | Bioprinted line conformation increased nephron numbers, as measured by an increase in MAFB+ glomerular area, as compared to manual organoids. | [68] | |
Heart | Spheroid bioprinting with microfluidic-chip-based 3D cell-culturing system (Regenova, Cyfuse Bio-medical K.K., Tokyo, Japan) | Human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs), human adult ventricular cardiac fibroblasts (FBs), and human umbilical vein endothelial cells (ECs) | Free of biomaterials | In vivo implantation of the 3D-bioprinted cardiac patches onto nude rat hearts showed viable cells in the patch along with erythrocytes (evidence of vascularization), and the presence of human nucleic acid (HNA)-positive cells in rat myocardium (evidence of engraftment). | [69] |
Spheroid bioprinting with microfluidic-chip-based 3D cell-culturing system (Regenova, Cyfuse Biomedical K.K., Tokyo, Japan) | Human IPSC-derived cardiomyocytes, fibroblasts, and endothelial cells | Free of biomaterials | In vivo implantation of the bioprinted cardiac patches onto rat myocardial infarction model showed lower scar area, higher vessel count, and higher cardiac output than the control group without the implantation. The survival rates were 100% and 83% in the experimental and the control groups, respectively, after 4 weeks of surgery | [70] | |
Nerve | Micro-extrusion bioprinting | Frontal cortical human neural stem cells (hNSCs) | Polysaccharides alginate (Al), carboxymethyl-chitosan (CMC), and agarose (Ag) | Co-printing of cells with bio-ink allowed the formation of a porous 3D-scaffold encapsulation of stem cells for in situ expansion and differentiation. Differentiated neurons formed synaptic contacts and showed spontaneous calcium spikes and bicuculline-induced bursting activity. | [71] |
Extrusion bioprinting | Cortical neurons and glial cells de-rived from human iPSCs | Matrigel and alginate | Long-term survival of neurons, up to 70 days post-printing, was observed. Functional analysis showed calcium activity and a small degree of synchronous activity. | [49] | |
Lab-on-a-printer (LOP) technology (Aspect Biosystems’ RX1 printer) | hiPSC-derived neural progenitor cells | Fibrinogen base with alginate, cross-linked with a mixture of chitosan, calcium chloride, thrombin, and genipin | Cell viability was 91.65 ± 6.85% by day 6 of the culture period, and 64.12 ± 21.27% by day 15. The printed neural tissues showed neurite extension and the expression of neuronal marker TUJ1 and nucleated cell marker | [72,73] | |
Extrusion bioprinting | Induced pluripotent stem cell (iPSC)-derived spinal neuronal progenitor cells (sNPCs) and oligodendrocyte progenitor cells (OPCs) | Matrigel | Cell viability was >75% for both iPSC-derived sNPCs and OPCs printed in 50% Matrigel after 4 days in culture. The bioprinted sNPCs differentiated and showed progressive axon propagation in the micro-scale scaffold channels. Functionality was verified by cellular response signaling molecules, potassium and glutamate. | [54] | |
Pancreas | Micro-extrusion bioprinting | Human umbilical vein endothelial cells | Pancreatic tissue-derived dECM (pdECM) | PdECM increased the insulin secretion over the conventionally applied biomaterials, alginate and collagen. Co-culturing with human umbilical vein-derived endothelial cells decreased the central necrosis of islets. Culturing in both 3D gels (without printing) and the printed construct showed similar viability on days 1 and 5. | [74] |
Cornea | Laser-assisted bioprinting (LaBP) | Human embryonic stem-cell-derived limbal epithelial stem cells (hESC-LESC), human adipose-tissue-derived stem cells (hASCs) | Recombinant human laminin and human sourced collagen I | The printed hESC-LESCs retained an epithelium-like structure and showed apical expression of CK3 and basal expression of the progenitor markers. After 7 days in vivo transplantation in the porcine organ, the 3D-bioprinted stromal structures showed interaction and attachment to the host tissue. | [75] |
3.1.3. Heart
3.1.4. Neurons and Central Nervous System
3.1.5. Others Approaches for Pancreatic and Corneal Applications
3.2. Printing of In Vitro Models for Drug Development
3.2.1. Cardiovascular Models for Drug Development
3.2.2. Liver Models for Drug Development
3.2.3. Kidney Models for Drug Development
3.2.4. Brain Models for Drug Development
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Bio-ink Material | Description | Advantages | Disadvantages | References |
---|---|---|---|---|
Alginate | Natural negatively charged polysaccharides from brown algae |
|
| [14,35,36,37] |
Agarose | Polysaccharide obtained from seaweed | High cell viability | Poor support and limited cell growth | [35,38] |
Collagen | Structural protein in the extracellular matrix | Easily obtainable from skin and connective tissues of organisms Relatively strong 3D structures |
| [39,40] |
Nanocellulose | Cellulose that can be derived from biomass, bacteria, and marine sources |
| May not be an accurate model for human cells as we do not produce cellulase to be biodegraded | [41] |
PEGDA | Synthetic polymer used for hydrogel fabrication and UV curing |
| Material can be brittle and rigid | [42] |
Pluronic® | Synthetic polymer-poloxamer |
| Biocompatibility is not sufficient for long-term cell survival | [43,44] |
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Lam, E.H.Y.; Yu, F.; Zhu, S.; Wang, Z. 3D Bioprinting for Next-Generation Personalized Medicine. Int. J. Mol. Sci. 2023, 24, 6357. https://doi.org/10.3390/ijms24076357
Lam EHY, Yu F, Zhu S, Wang Z. 3D Bioprinting for Next-Generation Personalized Medicine. International Journal of Molecular Sciences. 2023; 24(7):6357. https://doi.org/10.3390/ijms24076357
Chicago/Turabian StyleLam, Ethan Hau Yin, Fengqing Yu, Sabrina Zhu, and Zongjie Wang. 2023. "3D Bioprinting for Next-Generation Personalized Medicine" International Journal of Molecular Sciences 24, no. 7: 6357. https://doi.org/10.3390/ijms24076357
APA StyleLam, E. H. Y., Yu, F., Zhu, S., & Wang, Z. (2023). 3D Bioprinting for Next-Generation Personalized Medicine. International Journal of Molecular Sciences, 24(7), 6357. https://doi.org/10.3390/ijms24076357