Periodontitis medical-occupational cross-bifunctional mesoporous HMUiO-66-NH2 nanoparticles for bone remodeling and ROS clearance in the treatment of periodontitis

This article is selected:Periodontal bone defect is an irreversible consequence of periodontitis associated with reactive oxygen species (ROS). However, the indiscriminate removal of ROS has proved to be counterproductive to tissue repair and insufficient to solve the existing bone defects. In the treatment of periodontitis, it is very important to relieve local ROS and promote bone regeneration. In this study, Zr-based macroporous layered mesoporous organometallic framework (MOF) nanoparticles (NPs) HMUiO-66-NH2 have been successfully proposed as a bifunctional nanomaterial for bone regeneration and ROS removal in the treatment of periodontitis. HMUiO-66-NH2 NPs showed excellent biocompatibility in vitro and in vivo. Notably, these NPs enhanced the osteogenic differentiation of bone mesenchymal stem cells (BMSC), up-regulated the expression of osteogenic genes and reduced oxidative stress under normal and high ROS conditions. In addition, in vivo imaging showed that HMUiO-66-NH2 NPs was gradually degraded in periodontal tissue. Local injection of HMUiO-66-NH2 can effectively reduce the bone defect and ROS level in C57BL/6 mice induced by periodontitis. RNA sequencing emphasized that differentially expressed genes (DEG) were mainly involved in bone tissue development, and Wnt and TGF-β signaling pathways were significantly up-regulated. In a word, HMUiO-66-NH2 has dual functions in relieving oxidative stress and promoting bone repair, which makes it an effective strategy to resist bone resorption in periodontitis related to oxidative stress.

Innovations: 1. Developed HMUiO-66-NH2 nanoparticles with dual functions for the first time, and realized ROS clearance and bone remodeling at the same time; 2. Innovative use of the macroporous layered structure of MOF materials to achieve controllable degradation and continuous treatment effects; 3. Systematically proved that this material can promote the osteogenic differentiation of bone mesenchymal stem cells under normal and high ROS conditions; 4. The molecular mechanism of materials promoting bone regeneration was revealed by RNA sequencing, especially the role of Wnt and TGF-β signaling pathway. 

Scientific research inspiration: 1. Demonstrate the multifunctional application value of nano-materials in the treatment of complex diseases; 2. Revealed the key role of oxidative stress regulation in tissue regeneration; 3. Provide a new idea of precise treatment based on MOF materials; 4. The importance of multi-group analysis in elucidating the therapeutic mechanism was proved.

 Extension of ideas: 1. Explore the application of similar bifunctional nanomaterials in other inflammatory bone diseases; 2. To study the influence mechanism of MOF material structure on the therapeutic effect; 3. Develop more functional nano-therapeutic material systems; 4. Explore the potential of synergistic therapy of nano-materials and stem cells; 5. Thoroughly analyze the temporal relationship between ROS clearance and bone regeneration; 6. Design intelligent and responsive tissue repair materials; 7. Study the biological safety evaluation of long-term use of nanomaterials.

DOI : 10.1016/j.biomaterials.2024.122872