Abstract
Infections caused by antibiotic-resistant bacteria are globally a major threat, leading to high mortality rates and increased economic burden. Novel treatment strategies are therefore urgently needed by healthcare providers to protect people. Biomaterials that have inherent antibacterial properties and do not require the use of antibiotics present an attractive and feasible avenue to achieve this goal. Herein, we demonstrate the effect of a new class of cationic hydrogels based on amino-functional hyperbranched dendritic–linear–dendritic copolymers (HBDLDs) exhibiting excellent antimicrobial activity toward a wide range of clinical Gram-positive and Gram-negative bacteria, including drug-resistant strains isolated from wounds. Intriguingly, the hydrogels can induce the expression of the antimicrobial peptides RNase 7 and psoriasin, promoting host-mediated bacterial killing in human keratinocytes (HaCaT). Moreover, treatment with the hydrogels decreased the proinflammatory cytokine IL-1β, reactive nitrogen species (NO), and mitochondrial reactive oxygen species (ROS) in S. aureus-infected HaCaT cells, conjunctively resulting in reduced inflammation.
Highlights
The overuse and misuse of conventional antibiotics,[1,2] together with the accumulation of nondegradable antibiotics, contribute to the alarming evolution of resistant bacteria.[3]
Hydroxy-terminated hyperbranched dendritic−linear−dendritic copolymers (HBDLDs) were modified with boc-protected β-alanine by using fluoride-promoted esterification (FPE) chemistry,[35] followed by the removal of boc groups by using trifluoroacetic acid (TFA)
Because of the rapid reaction rate of the NHS-mediated amidation reaction, the hydrogels can be formed in aqueous solution by simple mixing of the amino-terminated HBDLDs and the cross-linkers (Figure 1c)
Summary
The overuse and misuse of conventional antibiotics,[1,2] together with the accumulation of nondegradable antibiotics, contribute to the alarming evolution of resistant bacteria.[3]. Other types of bacterial strains such as E. coli, P. aeruginosa, and GAS were tested, and a significant decrease in the bacterial numbers after treatment with the H10K-G5 hydrogel (Figure S6) was found These results serve to validate the ingenuity of these materials and their capacity to treat skin infections caused by various kinds of bacteria. The total ROS level (Figure S9) increased after treatment with H10K-G5, likely due to the increased expression of antimicrobial peptide psoriasin in keratinocytes.[52,53] The decreased IL-1β indicates that the cationic dendritic hydrogels could likely prevent inflammatory responses, while the decreased free radical species suggests that the cationic materials could probably prevent oxidative stress in S. aureus-infected HaCaT cells
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