Aug 2026· Biochemical and Biophysical Research Communications - BBRC· Vol 834, pp.
154475
· 0 citations· 29 references
Medicine
TL;DR
An enzyme-responsive supramolecular peptide hydrogel is established as a localized delivery platform to improve the therapeutic application of natural antimicrobial compounds against drug-resistant wound infections.
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) remains a major clinical challenge, particularly in wound infections where biofilm formation severely compromises antimicrobial efficacy. Here, Plumbagin (PLB), a naphthoquinone natural product, was selected as a lead anti-MRSA candidate from a high-throughput screening of 3720 natural compounds and further developed using a localized delivery strategy. PLB exhibited concentration-dependent bactericidal activity against MRSA with limited cytotoxicity toward human dermal fibroblasts. To overcome the challenges associated with poor local retention and limited sustained exposure of free PLB, PLB was incorporated into an enzyme-instructed self-assembling (EISA) peptide hydrogel. The resulting EISA-PLB hydrogel exhibited rapid gelation, favorable viscoelastic properties, and sustained PLB release under simulated wound conditions. Compared with free PLB, EISA-PLB demonstrated enhanced antibiofilm activity under physiological conditions. In a murine full-thickness MRSA-infected wound model, EISA-PLB hydrogel reduced bacterial burden and accelerated wound closure more effectively than free PLB. This study establishes an enzyme-responsive supramolecular peptide hydrogel as a localized delivery platform to improve the therapeutic application of natural antimicrobial compounds against drug-resistant wound infections.
Gel-P@Z exhibited a slow and sustained release of Gly-POX and achieved >99% antibacterial efficacy against drug-resistant bacteria without toxicity, and RNA-seq analysis revealed that Gel-P@Z accelerated healing via upregulation of the TGF-β signaling pathway, driving fibroblast-to-myofibroblast transition and promoting tissue fibrosis.
Chuanliang Fu, Wenjing Zhang, Renyuan Wang et al.· Materials Today Bio· 0 citations
Bacterial infection severely impairs wound healing, and current therapeutic strategies are limited due to their poor antibacterial efficacy and potential bio-toxicity. Herein, a novel multifunctional hydrogel (CGBAgel) was fabricated with glutathione-modified carboxymethyl cellulose (CMC-GSH) and bovine serum albumin (BSA) as matrixes. Levofloxacin (LEV) was selected as an anti-bacterial agent and encapsulated in CGBAgel to fabricated LEV@CGBAgel. Studies found that LEV@CGBAgel exhibited favorable physicochemical properties, robust broad-spectrum antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) strains, excellent biocompatibility, negligible cytotoxicity, and potent hemostatic and adhesive performance. In a mouse model of S. aureus-infected full-thickness skin wounds, LEV@CGBAgel achieved almost complete bacterial clearance, significantly accelerated wound closure with a closure rate of 99.9 ± 0.1% at 14 d, and promoted skin tissue regeneration. At the mechanistic level, LEV@CGBAgel mitigated local inflammation by inhibiting pro-inflammatory cytokines (TNF-α, IL-6), accelerated angiogenesis via upregulating VEGF and CD31, and promoted extracellular matrix remodeling by boosting collagen deposition. The in vivo safety evaluations confirmed that LEV@CGBAgel did not induce systemic, hematological, hepatic, or renal toxicity. Collectively, LEV@CGBAgel integrates multiple wound-healing functions with superior biosafety, holding great clinical translation potential for bacteria-infected wound management.
Tian-bao Wang, Ya-Qian Yang, Y. Zhuo et al.· International journal of pha...· 0 citations
Results suggest that integrating IR780SS into a hydrogen-bonded hydrogel not only enables effective antibacterial phototherapy but also facilitates functional wound reconstruction, providing valuable insight into the clinical development of regenerative dressings for MRSA-infected wounds.
A multifunctional peptide-based antibacterial hydrogel (PAHG) for treating infected wounds, constructed through the incorporation of Cys-Arg-NH2 (CR)-Ag nanoassemblies into a bioactive matrix with excellent antibacterial activity against Escherichia coli and methicillin-resistant Staphylococcus aureus.
Heng Ge, Wen Yuan, Yulin Sun et al.· Journal of materials chemist...· 0 citations
This work demonstrates a safe and effective strategy for combating MDR infections through the combined action of photothermal therapy and nanozyme catalysis, offering promising potential for clinical wound management.
Weiwei Zhang, Lixiang Fan, Xuanjun Zhang et al.· ACS Applied Materials and In...· 0 citations
A pioneering near-infrared activated antibacterial EPLGA/OHADA@HMCuS hydrogel was formulated by doping hollow mesoporous copper sulfide (HMCuS) into the three-dimensional spatial network structure formed between gallic acid-modified ε-polylysine (EPL-GA) and dopamine-engineered and oxidized hyaluronic acid (OHADA) and showcased favorable biocompatibility, sustaining cellular viability.
N. Wang, Wei Jiang, Feiyu Lu et al.· Biomaterials Advances· 0 citations
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