Localized in-situ heating and self-regulated delivery of antioxidant nanoparticles in dynamic hydrogels for treating periodontitis

Abstract

Periodontitis is a long-term inflammatory condition triggered by the buildup of harmful microorganisms within dental biofilms, resulting in progressive damage to periodontal tissues and potentially culminating in tooth loss if left unmanaged. It has also been linked to systemic diseases like diabetes and cardiovascular disorders, highlighting the close relationship between oral health and overall systemic well-being. The development of periodontitis is largely attributed to dysregulated immune responses, in which the overgeneration of reactive oxygen species (ROS) intensifies inflammatory processes and accelerates tissue destruction. ROS, generated by immune cells like macrophages, contribute to oxidative stress, which worsens tissue degradation and perpetuates chronic inflammation.

Macrophages are important in controlling the inflammatory response during periodontitis. They secrete pro- and anti-inflammatory cytokines to regulate inflammation, promote tissue repair, and restore balance. However, if macrophages do not properly shift from the pro-inflammatory M1 type to the repair-associated M2 type, chronic inflammation persists, leading to further tissue damage.

In response to these challenges, a new multifunctional hydrogel was created, integrating dopamine-modified Prussian Blue nanoparticles (PB NPs), aimed at eliminating reactive oxygen species (ROS) and guiding macrophage transition from the M1 inflammatory state to the M2 healing state. The hyaluronic acid-based hydrogel, formed by host-guest interactions, provides a biocompatible platform for encapsulation and controlled release of the PP NPs, supporting the alleviation of oxidative damage and inflammatory responses, and enhancing tissue repair.

One distinct characteristic of the PP hydrogel is its capacity to utilize near-infrared (NIR) light to trigger the controlled release of PP NPs. Upon NIR exposure, the hydrogel captures energy and transforms it into heat, resulting in a localized temperature rise. This temperature rise weakens the supramolecular interactions within the hydrogel, leading to the dissociation of the supramolecular interactions formed between β-cyclodextrin (CD) and adamantane (Ad). As a result, the controlled release of PP NPs is initiated, providing a self-regulated and adaptive mechanism for drug delivery. This NIR-triggered release ensures that the drugs are released at the right time and location, enhancing therapeutic outcomes while reducing unwanted side effects.

Our in vitro experiments demonstrated that the PP hydrogel effectively modulated immune responses, reduced ROS levels, and promoted macrophage polarization. This resulted in reduced inflammation and enhanced tissue regeneration in periodontal tissues. Using NIR light to control the release of PP NPs from hydrogels provides a promising and less invasive strategy for treating periodontitis. This novel strategy not only addresses the underlying oxidative stress and inflammation but also supports tissue repair, presenting a potential breakthrough in the treatment of periodontal diseases.