Periodontitis-Polyphenol-mediated redox active hydrogel coupled with H2S gas bioelectricity for diabetic periodontal bone healing

Excessive oxidation reaction, unbalanced immune regulation and impaired function of mesenchymal stem cells in diabetic periodontitis make it a great challenge to realize comprehensive regeneration of periodontal tissue. Here, a kind of polyphenol-mediated redox active seaweed gel/gelatin hydrogel was developed, which encapsulated a poly-dopamine-mediated silk microfiber network assembled by conductive poly (3,4- ethylenedioxythio) and a hydrogen sulfide slow-release system using bovine serum albumin nanoparticles. It is found that this hydrogel can reverse the hyperglycemic inflammatory microenvironment of diabetic periodontitis patients and enhance functional tissue regeneration. Polydopamine endows hydrogel with antioxidant and anti-inflammatory activities. Hydrogen sulfide is released slowly and continuously from bovine serum albumin nanoparticles, which can recruit mesenchymal stem cells and promote subsequent angiogenesis and osteogenesis. In addition, polydopamine-mediated silk microfibers assembled by poly (3,4- ethylenedioxythiobenzene) endow the hydrogel with good conductivity, which enables it to transmit endogenous bioelectricity, promote cell arrangement and increase the inflow of calcium ions. In addition, the synergistic effect of hydrogen sulfide gas-induced electrical coupling promotes bone formation by amplifying autophagy in periodontal ligament stem cells and regulating macrophage polarization through lipid metabolism regulation. This study provides innovative insights for the synergistic effect of electrical conductivity, reactive oxygen species scavenging and hydrogen sulfide on periodontal tissue in hyperglycemia inflammatory microenvironment, and provides a strategy for the design of gaseous bioelectric biomaterials to promote functional tissue regeneration in immune-related diseases.

Innovations: 1. A multifunctional hydrogel system is developed, which integrates the functions of antioxidation, conductivity and biological activity release; 2. The coupling and synergy between H2S gas molecules and bioelectrical signals is realized for the first time; 3. Establish a therapeutic strategy that can simultaneously regulate oxidative stress, immune response and stem cell function; 4. Innovative use of gas-electric coupling effect to regulate autophagy and macrophage polarization. 

Scientific research inspiration: 1. The integration of multiple treatment mechanisms can solve the problem of tissue regeneration in complex disease environment more effectively; 2. The synergistic effect of gaseous signal molecules and physical signals provides a new idea for biomaterial design; 3. Microenvironment control plays a key role in tissue engineering, and its systematic influence should be paid attention to; 4. The application value of nano-carrier system in gas delivery.

 Extension of ideas: 1. We can explore other intelligent response characteristics, such as temperature sensitivity or light response, to achieve more accurate treatment regulation: temperature-controlled release is achieved by adding temperature-sensitive polymers; Integrating photosensitive materials to realize light-triggered therapy; Develop multiple stimulus response systems. 2. Nanotechnology can be introduced to enhance the function of materials: nanoparticles are used to improve the efficiency of drug delivery; Using nanostructures to enhance electrical conductivity; Optimizing cell interaction through nano-surface modification. 3. Real-time monitoring and feedback adjustment can be realized by combining new detection technology: integrating biosensor to monitor microenvironment changes; Develop a visual tracer system to track the treatment process; Establish an intelligent feedback adjustment mechanism. 4. Intelligent point of view: develop real-time monitoring system; Build an intelligent feedback control platform; Design a remote treatment control system; Research and development of biosensing integrated system; Develop AI-aided optimization algorithm; Build a digital treatment platform. 5. From the angle of material design: develop gas bioelectric hydrogel with self-repairing function; Develop gradient structure materials to realize multi-level gas release; Introducing phase change materials to regulate gas release kinetics; Design intelligent hydrogel with shape memory function; Develop a multi-stimulus responsive material system; The construction method of new conductive polymer was studied.

DOI : 10.1038/s41467-024-53290-6