An Off‐the‐Shelf Artificial Blood Clot Hydrogel Neutralizing Multiple Proinflammatory Mediators for Pro‐Regenerative Periodontitis Treatment

Abstract Periodontitis is a destructive and chronic inflammatory disease initiated and sustained by multiple proinflammatory mediators. Current therapies mainly deal with bacteria elimination, but directly addressing the over‐accumulated multiple inflammatory mediators in the periodontal microenvironment still remains a substantial challenge for regenerative periodontitis treatment. Herein, inspired by blood coagulation, an off‐the‐shelf artificial blood clot hydrogel encapsulated with platelet‐rich plasma (PRP) is reported to mitigate the deteriorative inflammatory environment in periodontitis. The hydrogel (CCS‐RSF@PRP) with a hierarchical fibers‐interwoven network structure, in which the activated platelets are enriched, is structurally similar to the native blood clot. Functionally, in addition to the function of enriching and releasing growth factors, CCS‐RSF@PRP can remarkably scavenge reactive oxygen species (ROS), neutralize endotoxin lipopolysaccharide (LPS), and proinflammatory cytokines (TNF‐α, IFN‐γ and IL‐1β), inhibit M1 macrophage polarization and induce M2 macrophage polarization, thus blocking the chronic inflammatory feedback loop in the periodontitis. In rat periodontitis model, CCS‐RSF@PRP hydrogel significantly expedits the repair of periodontium by normalizing the periodontal immune‐environment. The work highlights the importance of local immunomodulation in the treatment of periodontitis, and the engineered PRP‐derived hydrogel can mimic and expand the structure and function of native blood clot, holding great promise in treating chronic inflammatory diseases.