Bioinspired hydrogel for sustained minocycline release: A superior periodontitis solution

Area of Science:

• Biomaterials Science
• Periodontal Medicine
• Drug Delivery Systems

Background:

• Periodontitis treatment faces challenges due to conventional therapies' limitations, including cytotoxicity, poor drug retention, immune imbalance, and epithelial barrier damage.
• Existing treatments often fail to provide sustained drug delivery and a conducive microenvironment for tissue repair.

Purpose of the Study:

• To develop a dual-network hydrogel drug delivery system (M@PP) for localized periodontitis treatment.
• To investigate the M@PP hydrogel's efficacy in drug retention, antibacterial activity, anti-inflammatory properties, and bone regeneration.
• To elucidate the therapeutic mechanisms of M@PP through in vivo studies and RNA sequencing.

Main Methods:

• Development of a bioisosterism-inspired dual-network hydrogel (M@PP) for minocycline delivery.
• Evaluation of hydrogel properties: mechanical strength, bioadhesion, and sustained drug release.
• In vitro assessment of antibacterial activity against *P. gingivalis* and anti-inflammatory effects.
• In vivo studies involving macrophage polarization, cytokine expression, bone density analysis (micro-CT), and RNA sequencing.

Main Results:

• M@PP hydrogel demonstrated optimal mechanical strength and bioadhesion for sustained minocycline release.
• Achieved 98.1% antibacterial activity against *P. gingivalis* and significant anti-inflammatory effects.
• In vivo studies showed M@PP regulated macrophage polarization, promoted epithelial barrier restoration, and enhanced alveolar bone regeneration (increased bone density and thickness).
• RNA sequencing revealed therapeutic mechanisms involving bacterial defense, immune modulation, and pro-regenerative signaling.

Conclusions:

• The M@PP hydrogel system offers a promising localized therapeutic strategy for periodontitis by overcoming limitations of conventional treatments.
• M@PP facilitates a favorable immune microenvironment, promotes epithelial barrier restoration, and stimulates alveolar bone regeneration.
• This innovative approach demonstrates superior therapeutic outcomes compared to commercial products, addressing biofilm-associated disorders effectively.