As the incidence of osteomyelitis increases and the overuse of antibiotics leads to the emergence of drug-resistant bacteria, traditional treatments face huge challenges. Bacterial proliferation and intracellular infection lead to recurrent and prolonged infections through the formation of biofilms. At the same time, the immune response triggered by bacterial infection disrupts the metabolic balance of bones, leading to inflammatory bone resorption. Herein, a cerium-alendronate supramolecular hydrogel (CAG) with multiple antimicrobial capabilities and bone metabolism modulating effects was developed to address the multifaceted challenges of osteomyelitis. CAG hydrogel is injectable and self-healing, exhibits significant antibacterial activity against Staphylococcus aureus (S.A) and Escherichia coli (EcN) in a reactive oxygen species (ROS) microenvironment, and effectively destroys biofilms and eliminate intracellular infection. Ce ions in CAG inhibit bacterial energy production by destroying bacterial membranes and interfering with bacterial membrane potential. Furthermore, CAG successfully reversed endotoxin-induced apoptosis and abnormal osteoblast differentiation. RNA sequencing results showed that CAG promoted osteogenic differentiation by promoting the influx of calcium ions, regulating the calcium signaling pathway and TGFβ pathway, and upregulating the expression of proteins related to the Bmp2/Smad5 pathway. In in vivo experiments, CAG successfully treated osteomyelitis caused by Staphylococcus aureus and improved bone tissue production in 7- and 28-day osteomyelitis mouse models. Overall, this study proposes a comprehensive therapy aimed at targeting the entire stage of bacterial infection and restoring bone metabolic balance, providing an innovative treatment for bone infection.

Innovation points:
1. This study developed a cerium-alendronate supramolecular hydrogel (CAG), which not only has antibacterial function, but also enhances its antibacterial effect through the reactive oxygen species (ROS) microenvironment , and effectively fight against common pathogenic bacteria such as Staphylococcus aureus and Escherichia coli.
2. CAG hydrogel effectively destroys bacterial biofilms in bacterial infection areas and clears intracellular bacteria by enhancing the ROS microenvironment, thereby improving the anti-infection effect.
3. CAG is not only antibacterial, but also regulates bone metabolism by promoting osteogenic differentiation.
4. CAG has self-healing and injectable properties, and can form an effective local treatment at the infected bone site, improving its convenience and effectiveness in clinical application.
5. This study proposes a comprehensive treatment strategy that not only targets the entire process of bone infection, but also provides a new treatment idea for osteomyelitis and other bone infections by restoring bone metabolic balance.

 Inspiration for scientific research work:
1. This study highlights the potential of hydrogels to exert enhanced effects in specific microenvironments (such as ROS microenvironments).
2. The development of hydrogels with multiple functions, especially the comprehensive effects of antibacterial, promoting bone metabolism, and anti-inflammation, can provide a more effective strategy for the treatment of bone infections and other chronic diseases.
3. Through RNA sequencing analysis, the molecular mechanism of hydrogel in promoting osteogenic differentiation was revealed.
4. This study proposes a dual mechanism for the treatment of osteomyelitis by combining bacterial biofilm destruction and endotoxin reversal, providing a reference for the treatment of other types of infections.

Extension of ideas:
1. More biomaterials can be combined to design new hydrogels, which not only target bone infections, but can also be used to treat soft tissue infections or other pathological conditions, and explore their wide application in clinical practice.
2. In the future, hydrogels can be combined with drug delivery systems, such as loading antibiotics or osteogenesis-promoting factors into the hydrogel to further improve its therapeutic effect and enhance the dual effects of anti-infection and promoting bone healing.
3. The hydrogel proposed in this study can further verify its effect through animal experiments or clinical trials, and explore its feasibility in clinical treatment, especially its potential in dealing with drug-resistant bacteria and chronic bone infections.

4. Based on different pathological types (such as infection type, immune status, etc.), design personalized hydrogel treatment plans to achieve the best therapeutic effect and adapt to the needs of different patients.

Mater. Today
Pub Date  : 2024-11-28
DOI : 10.1016/j.mattod.2024.11.007

Zhihui Han, Shunyi Lu, Jie Cao, Shumin Sun, Nailin Yang, Shuning Cheng, Xuan Huang, Jie Wu, Jingrui Li, Liang Cheng