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An ionic gel incorporating copper nanodots with antibacterial and antioxidant dual functions for deep tissue penetration treatment of periodontitis in rats. Biomaterials science The local treatment of periodontitis has recently received extensive attention due to the advantages of mild systemic side effects and a high local drug concentration. But the local drug delivery systems are not widely used in clinical practice, and a major obstacle is the poor tissue permeability. In the present study, we report a copper nanodot based ionic gel (Cu-NDs/IL gel) with favorable tissue penetration capability, and it concurrently exhibits antibacterial and anti-inflammatory functions. A Cu-NDs/IL gel was prepared by loading copper nanodots (Cu-NDs) with triple enzyme-like activities into a multifunctional gel. The derived Cu-NDs/IL gel possesses remarkable antibacterial properties attributed to the peroxidase-like activity of Cu-NDs. In addition, Cu-NDs mimic superoxide dismutase and catalase activities, which endow the gel with excellent free radical scavenging capability in a neutral environment to relieve periodontal inflammation. More importantly, the IL moiety in the Cu-NDs/IL gel promotes the penetration of Cu-NDs into the gingival tissue, wherein the triple enzymatic activity of Cu-NDs may function. In short, the Cu-NDs/IL gel has promising potential to serve as a topical drug for periodontitis by promoting penetration, killing bacteria, and scavenging ROS. 10.1039/d3bm00309d
Microsphere-Gel Composite System with Mesenchymal Stem Cell Recruitment, Antibacterial, and Immunomodulatory Properties Promote Bone Regeneration via Sequential Release of LL37 and W9 Peptides. ACS applied materials & interfaces Various types of biomaterials have been widely used to treat complex bone defects. However, potential infection risks and inappropriate host immune responses induced by biomaterials can adversely affect the final bone repair outcome. Therefore, the development of novel bone biomaterials with antibacterial and immunomodulatory capabilities is conducive to achieving a good interaction between the host and material, thereby creating a local microenvironment favorable for osteogenesis and ultimately accelerating bone regeneration. In this study, we fabricated a porcine small intestinal submucosa (SIS) hydrogel containing LL37 peptides and polylactic-glycolic acid (PLGA) microspheres encapsulated with WP9QY(W9) peptide (LL37-W9/PLGA-SIS), which can fill irregular bone defects and exhibits excellent mechanical properties. In vitro experiments showed that the microsphere-gel composite system had sequential drug release characteristics. The LL37 peptide released first had good antibacterial performance and BMSC recruitment ability, which could prevent infection at an early stage and increase the number of BMSCs at the injured site. In addition, it also has immunomodulatory properties, showing both pro-inflammatory and anti-inflammatory activities, but its early pro-inflammatory properties are more inclined to activate the M1 phenotype of macrophages. Moreover, the subsequently released W9 peptide not only reduced the expression of pro-inflammatory genes to alleviate inflammation and induced more macrophages to convert to M2 phenotypes but also promoted the osteogenic differentiation of BMSCs. This finely regulated immune response is considered to be more closely related to the physiological bone healing process. When studying the interaction between macrophages and BMSCs mediated by the material, it was found that the immunomodulatory and osteogenic effects were enhanced. In vivo experiments, we constructed rat skull defect models, which further proved that LL37-W9/PLGA-SIS gel can properly regulate the immune response, and has a good ability to promote osteogenesis in situ. In conclusion, the LL37-W9/PLGA-SIS hydrogel has great application prospects in immune regulation and bone therapy. 10.1021/acsami.2c10242
Antibacterial Gel Coatings Inspired by the Cryptic Function of a Mussel Byssal Peptide. Advanced materials (Deerfield Beach, Fla.) Although the adhesive and cohesive nature of mussel byssal proteins have long served to inspire the design of materials embodying these properties, their characteristic amino acid compositions suggest that they might also serve to inspire an unrelated material function not yet associated with this class of protein. Herein, it is demonstrated that a peptide derived from mussel foot protein-5, a key protein in mussel adhesion, displays antibacterial properties, a yet unreported activity. This cryptic function serves as inspiration for the design of a new class of peptide-based antibacterial adhesive hydrogels prepared via self-assembly, which are active against drug-resistant Gram-positive bacteria. The gels exert two mechanisms of action, surface-contact membrane disruption and oxidative killing affected by material-produced H O . Detailed studies relating amino acid composition and sequence to material mechanical adhesion/cohesion and antibacterial activity affords the MIKA2 adhesive gel, a material with a superior activity that is shown to inhibit colonization of titanium implants in mice. 10.1002/adma.202103677