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Dendritic Hydrogels Induce Immune Modulation in Human Keratinocytes and Effectively Eradicate Bacterial Pathogens
Yanmiao Fan1, Soumitra Mohanty2,3, Yuning Zhang1
1School of Chemical Science and Engineering, Fiber and Polymer Technology, KTH Royal Institute of Technology, Teknikringen 56-58, SE-100 44 Stockholm, Sweden.
Journal of the American Chemical Society
|October 12, 2021
Summary
New cationic hydrogels combat antibiotic-resistant bacteria without antibiotics. These biomaterials show potent antimicrobial activity and reduce inflammation by stimulating host defenses, offering a novel strategy against dangerous infections.
Area of Science:
- Biomaterials Science
- Infectious Diseases
- Polymer Chemistry
Background:
- Antibiotic-resistant bacterial infections pose a significant global health threat, demanding novel therapeutic approaches.
- Biomaterials with inherent antimicrobial properties offer a promising alternative to conventional antibiotics.
Purpose of the Study:
- To investigate the antimicrobial efficacy of novel cationic hydrogels based on amino-functional hyperbranched dendritic-linear-dendritic copolymers (HBDLDs).
- To evaluate the host-mediated immune response and anti-inflammatory effects of these hydrogels in bacterial infection models.
Main Methods:
- Synthesis and characterization of HBDLD-based cationic hydrogels.
- Assessment of antimicrobial activity against Gram-positive and Gram-negative bacteria, including drug-resistant strains.
- Evaluation of host-mediated bacterial killing via antimicrobial peptide induction (RNase 7, psoriasin) in human keratinocytes (HaCaT).
- Measurement of inflammatory markers (IL-1β, NO, ROS) in infected HaCaT cells.
Main Results:
- HBDLD hydrogels demonstrated broad-spectrum antimicrobial activity against diverse bacterial strains, including resistant isolates.
- The hydrogels successfully induced RNase 7 and psoriasin expression in HaCaT cells, enhancing host-mediated bacterial clearance.
- Treatment with HBDLD hydrogels significantly reduced levels of IL-1β, NO, and mitochondrial ROS in Staphylococcus aureus-infected HaCaT cells, mitigating inflammation.
Conclusions:
- Amino-functional HBDLD copolymers form effective cationic hydrogels with potent antimicrobial properties.
- These hydrogels offer a dual mechanism of action: direct bacterial killing and modulation of the host immune response to reduce inflammation.
- This novel class of biomaterials presents a promising antibiotic-free strategy for managing infections caused by antibiotic-resistant bacteria.
