4D Printing of Hydrogels: Innovation in Material Design and Emerging Smart Systems for Drug Delivery
Abstract
:1. Introduction
2. Material Design: Development of Smart Hydrogels for Drug Delivery
2.1. Thermo-Responsive Hydrogels
2.2. Magnetic Responsive Hydrogels
2.3. Electrical Responsive Hydrogels
2.4. Photo-Responsive Hydrogels
2.5. pH Responsive Hydrogels
2.6. Water Responsive Hydrogels
3. Technical Approaches toward 4D Printing of Hydrogels
3.1. Printing Techniques for Smart Hydrogels
3.2. Crosslinking Strategies for the Fabricated 4D Printed Hydrogels
3.3. Design Considerations for 4D Printing
3.4. Multi-Materials Extrusion 4D Printing
4. Emerging 4D Printed Hydrogels for Drug Delivery
5. Conclusions and Future Perspective
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Tissue/Cellular Compartment | pH |
---|---|
Stomach | 1.0–3.0 |
Vagina | 3.8–4.5 |
Late endosome | 4.5–5.0 |
Upper small intestine | 4.8–8.2 |
Inflamed tissue/wound | 5.4–7.4 |
Early endosome | 6.0–6.5 |
Tumor, extracellular | 6.5–7.2 |
Colon | 7.0–7.5 |
Blood | 7.3–7.5 |
Materials | Printing Parameters | Crosslinking | Printed Shape Transformation | Drug & Loading Method | External Stimulus | Drug Release Profile | Ref. |
---|---|---|---|---|---|---|---|
Pluronic diacrylate macromer, and alginate | DIW: Nozzle diameter—400 µm; nozzle temperature—25 °C; print speed—15 mm/s; pressure—0.04 kPa; bed temperature—60 °C | UV curing | Square mesh to folded mesh | Methotrexate—Co-mixing | Ion (Calcium chloride) | Fast release up to 6 h followed by steady release up to 12 h | [148] |
Gelatin methacryloyl | DIW: Nozzle diameter—210 µm; nozzle temperature—26 °C; print speed—20 mm/s | UV curing | Sheet to tubular | Heparin—Co-mixing | Solvent (Water) | Fast release up to 8 h followed by steady release up to 28 h | [149] |
Poly(N-isopropylacrylamide) | DIW: Nozzle diameter—340 µm | UV curing | Expanding core–shell capsules | Brilliant blue and lemon yellow—Injection | Temperature (22 °C) | Fast release up to 15 h followed by medium release up to 48 h | [150] |
Poly(vinyl alcohol) | FDM: Nozzle diameter—400 µm; nozzle temperature—180 °C; print speed—23 mm/s | - | I to U, U to I, and helix to extended conformation | Caffeine—Co-mixing | Solvent (Water) | Fast release up to 2 h followed by steady release up to 6 h | [151] |
Methacrylamide Chitosan | 2PP: Sub-micron resolution | - | Expandable microswimmers | Doxorubicin—Immersion | Light (UV 365 nm) | Fast release up to 1 min (light ON) followed by steady release up to 6 min (light OFF) | [152] |
Gelatin methacryloyl | 2PP: Sub-micron resolution | - | Expandable microswimmers | Fluorescein isothiocyanate—Immersion | Enzyme (Metallo-proteinase 2) | Fast release up to 2 h followed by medium release up to 48 h | [153] |
Poly(ethylene glycol) diacrylate | µSLA: Layer thicknesss—50 µm | UV curing | Straight to backward-facing curved barbs in microneedle array | Rhodamine B—Immersion | Ion (Phosphate buffered saline) | Fast release in 1 min followed by medium release up to 2.5 h, and slow releases up to 3 h | [154] |
4-hydroxybutyl acrylate, and urethanepolyethylene glycol-polypropylene glycol | DLP: Layer thicknesss—100 µm | UV curing | Stretchable nerve guide tubing | Doxorubicin, and ovalbumin—Immersion | Magnetic field (1 MHz) | Fast release in 4 h (doxorubicin) or 30 min (ovalbumin) followed by medium release up to 50 h, and steady releases up to 75 h | [155] |
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Tran, T.S.; Balu, R.; Mettu, S.; Roy Choudhury, N.; Dutta, N.K. 4D Printing of Hydrogels: Innovation in Material Design and Emerging Smart Systems for Drug Delivery. Pharmaceuticals 2022, 15, 1282. https://doi.org/10.3390/ph15101282
Tran TS, Balu R, Mettu S, Roy Choudhury N, Dutta NK. 4D Printing of Hydrogels: Innovation in Material Design and Emerging Smart Systems for Drug Delivery. Pharmaceuticals. 2022; 15(10):1282. https://doi.org/10.3390/ph15101282
Chicago/Turabian StyleTran, Tuan Sang, Rajkamal Balu, Srinivas Mettu, Namita Roy Choudhury, and Naba Kumar Dutta. 2022. "4D Printing of Hydrogels: Innovation in Material Design and Emerging Smart Systems for Drug Delivery" Pharmaceuticals 15, no. 10: 1282. https://doi.org/10.3390/ph15101282