Plant-Derived Polyphenol and LL-37 Peptide-Modified Nanofibrous Scaffolds for Promotion of Antibacterial Activity, Anti-Inflammation, and Type-H Vascularized Bone Regeneration

Abstract

The regeneration of oral tissues is a challenging clinical problem because of the complex microbial and biological stress environments. Electrospun fibrous scaffolds have attracted significant interest as effective barrier membranes for guided bone regeneration (GBR); however, no mature strategy yet exists for the surface modification of fibers to provide versatility to satisfy clinical requirements. This study demonstrated a practical biosafety strategy: the combined use of plant polyphenols and LL-37 peptides to modify the fiber surface to endow the fibrous scaffold with antimicrobial activity, immunoregulation, and vascularized bone regeneration. We confirmed that the LL-37 peptides interacted with tannic acid (TA) through noncovalent bonds through experiments and molecular docking simulation analysis. In vitro experiments showed that the TA coating imparted strong antibacterial properties to the fibrous scaffold, but it also caused cytotoxicity. The grafting of LL-37 peptide promoted the spreading, migration, and osteogenic differentiation of mesenchymal stem cells and was also conducive to the M2 polarization of RAW264.7 cells. In vivo experiments further verified that the LL-37 peptide-grafted fibrous scaffold significantly enhanced angiogenesis, antiinflammatory effects, and type-H vascularized bone regeneration. Overall, the fibrous scaffold modified by the LL-37 peptide through TA grafting has significant potential for GBR applications.

Tannic Acid-Modified Decellularized Tendon Scaffold with Antioxidant and Anti-Inflammatory Activities for Tendon Regeneration

“…These results further confirmed that DTS modified with TA exhibited anti-inflammatory effects by modulating macrophage polarization. 36,62 Overall, the results of the in vivo and in vitro experiments were consistent and confirmed the tendency of TAmodified DTS to modulate macrophage polarization toward the M2-type.…”

“…The results of macrophages' cytoskeleton were consistent with those obtained from brightfield microscopy (Figure 5B), demonstrating that DTS and DTS-TA 0.1 enhanced the phenotype of M2 macrophages and that DTS-TA 0.1 had a more pronounced effect. 36 As depicted in Figure 5C, macrophages exhibited an upregulation of CD86 expression in the presence of LPS and an induction of Arginase-1 (Arg-1) expression when exposed to IL-4. The DTS-TA 0.1 group showed a higher level of Arg-1 expression than that of the DTS group, while the trend of CD86 expression was the opposite.…”

“…It is hypothesized that the rich phenolic hydroxyl groups in TA could induce apoptotic cell death, chromosome condensation, and DNA fragmentation in human cell lines 47 and destroy the structure and biological functions of the cell membrane. 36 Moreover, as a weak acid, TA can disrupt the electron transport chain, leading to a subsequent reduction in NADPH levels and impairing the activity of the mitochondrial dehydrogenase enzyme. 47 Therefore, a high concentration of TA suppresses cell proliferation and results in cytotoxic effects, as demonstrated in our study.…”

Recent Progress in Protein-Polyphenol Assemblies for Biomedical Applications

“…Compared with LbL multilayer films obtained by dipping, brushed films showed oriented collagen fibers along the brushing direction, which was favorable for the alignment and differentiation of human myoblasts. Jin et al 58 modified the electrospun fibrous scaffold with TA first and then with LL-37 peptides, and in vitro experiments showed that the modified fibrous scaffold had strong antibacterial, enhanced angiogenesis, anti-inflammatory, and type-H vascularized bone regeneration, indicating that the modified fibrous scaffold had great potential application in guiding bone regeneration.…”

“AMP plus”: Immunostimulant-Inspired Design Based on Chemotactic Motif-(PhHAhPH)n

“…Natural AMPs, however, possess various drawbacks, such as toxicity to the host, and loss of effectiveness in physical concentrations of salt and serums . Peptides that are rationally designed may be able to diminish these drawbacks in natural peptides to some extent. − …”