Materials Today Bio (Apr 2025)

Multi-active phlorotannins boost antimicrobial peptide LL-37 to promote periodontal tissue regeneration in diabetic periodontitis

  • Cancan Li,
  • Luowen Du,
  • Yingying Xiao,
  • Lei Fan,
  • Quanli Li,
  • Chris Ying Cao

Journal volume & issue
Vol. 31
p. 101535

Abstract

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The bidirectional correlation between diabetes and periodontitis positions the latter as the most prevalent complication of the former. Rehabilitation of the periodontal tissues damaged by diabetic periodontitis presents a significant clinical challenge. The multifaceted nature of the pathogenesis of diabetic periodontitis necessitates a comprehensive approach in its treatment to mitigate its adverse effects. To address this, a temperature-sensitive hydrogel containing phlorotannins (PL) and antimicrobial peptide LL-37 was developed to shift the microenvironment of diabetic periodontitis from an exacerbated high-glycemic inflammatory state to a regenerative one. The addition of PL significantly enhanced the antimicrobial properties, stability, and safety of LL-37. Vitro experiments confirmed that PL/LL-37 had good biocompatibility and promoted osteogenic differentiation of bone. PL/LL-37 demonstrated antioxidant properties by scavenging DPPH free radicals and inhibiting NO production. Furthermore, PL/LL-37 effectively modulated macrophage polarization from a M1 phenotype to an M2 phenotype through NF-κB P-p65 inflammatory pathway, thereby reducing the release of pro-inflammatory cytokines and promoting the secretion of anti-inflammatory cytokines. Interestingly, it could downregulate the AGE-RAGE signaling pathway, exerting a protective effect against diabetes. In addition, PL/LL-37 could attenuate inflammation levels, inhibit osteoclast production, promote bone regeneration, inhibit apoptosis and decrease RAGE levels in a rat model of diabetic periodontitis. These combined features synergistically accelerate diabetic periodontal bone regeneration. Consequently, PL/LL-37 emerges as a promising candidate for clinical treatment of diabetic periodontitis.

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