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Multiresponsive 4D Printable Hydrogels with Anti-Inflammatory Properties
Maria Regato-Herbella1,2, Daniele Mantione1,3, Agustín Blachman4
1POLYMAT University of the Basque Country UPV/EHU, Joxe Mari Korta Center. Avda. Tolosa 72, 20018, Donostia-San Sebastián, Spain.
ACS Macro Letters
|August 14, 2024
Summary
Researchers developed triple-responsive hydrogels using 4D printing. These smart biomaterials exhibit inherent anti-inflammatory properties, reducing nitric oxide by 70% without added drugs, paving the way for novel inflammatory disease treatments.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Regenerative Medicine
Background:
- Multiresponsive hydrogels are crucial for biomaterials, responding to physiological stimuli like temperature, pH, and reactive oxygen species (ROS).
- This study introduces triple-responsive hydrogels synthesized via UV photopolymerization, incorporating thermoresponsive N-isopropylacrylamide (NIPAM), pH-responsive methacrylic acid (MAA), and a ROS-responsive thioether monomer (EG3SA).
- These P[NIPAM-co-MAA-co-(EG3SA)] hydrogels are manufactured using digital light processing (DLP) for 4D printing applications.
Discussion:
- The hydrogels' thermo-, pH-, and ROS-responsiveness were validated through swelling tests and rheological measurements under varying conditions (temperature, pH, H2O2 presence).
- Ketoprofen (KET) encapsulation demonstrated tunable drug release profiles, influenced by hydrogel composition and applied stimuli.
- In vitro cytotoxicity assays using NIH 3T3 and RAW 264.7 cells confirmed the hydrogels' biocompatibility.
Key Insights:
- The P[NIPAM80-co-MAA15-co-(EG3SA)5] hydrogels exhibit significant intrinsic anti-inflammatory capacity, reducing nitric oxide production in pro-inflammatory RAW cells by approximately 70% without any encapsulated drug.
- This inherent bioactivity highlights the potential of the hydrogel material itself for therapeutic applications.
- The study successfully demonstrates the creation of customizable, 4D-printable scaffolds with potential for treating inflammatory conditions.
Outlook:
- Further research can explore optimizing hydrogel composition for enhanced drug delivery and tailored inflammatory response modulation.
- The development of these intrinsically bioactive, 4D-printable materials opens new avenues for creating advanced scaffolds for tissue engineering and regenerative medicine.
- Future work may involve in vivo studies to evaluate the efficacy and safety of these hydrogels in treating inflammatory pathologies.

