Microgel-integrated, high-strength in-situ formed hydrogel enables timely emergency trauma treatment.

High-strength hydrogels formed in situ through a convenient gel transition process are highly desirable for emergency treatment due to their ability to quickly respond to accidents. However, current in-situ formed hydrogels require a laborious precursor preparation process or lack sufficient mechanical strength. Herein, we reported a series of microgels that were capable of convenient in-situ transition to high-strength hydrogels from their easily portable form, thereby facilitating emergency treatment. Three kinds of microgels were derived from two types of hydrogen bonds (H-bonds; OH⋯OC, NH⋯OC) crosslinked preformed hydrogels, and all exhibited excellent stability when stored at room temperature. After mixing with water, all these microgels could undergo a quick hydration process and then transform into high-strength hydrogels in situ through H-bonds. Specifically, stronger H-bond crosslinked microgels could build hydrogels with higher mechanical strength, albeit at the cost of longer hydration and operation time. Nevertheless, the whole operation process could be finished within several minutes, and the resultant hydrogels could exhibit maximally megapascal-level compressive strength and tens of kilopascal storage modulus. In the comparison of emergency application performance with commercial chitosan hemostatic powder (CHP), we found that the microgels could stop accidental bleeding almost immediately, and the whole process from taking out the stored microgels to hemostasis could be completed within 15 s, which was superior to CHP. Overall, the results indicated that the in-situ formed microgel-based hydrogels with convenient gel-transition ability and high strength showed great potential in emergency treatments.

Sequential Delivery of Different MicroRNA Nanocarriers Facilitates the M1-to-M2 Transition of Macrophages.

The early-stage repair of bone injuries dominated by the inflammatory phase is significant for successful bone healing, and the phenotypic transition of macrophages in the inflammatory phase plays indispensable roles during the bone healing process. The goal of this paper is to design a microRNA delivery nanocarrier for strictly temporal guidance of the polarization of macrophages by the sequential delivery of different microRNAs. The results showed that microRNA nanocarriers, synthesized through free radical polymerization, could be internalized by macrophages with about a cellular uptake efficiency of 80%, and the sequential delivery of microRNA-155 nanocarriers and microRNA-21 nanocarriers proved, for the first time, that it could promote an efficient and timely switch from the M1 to the M2 phenotype along the time point of bone tissue repair. The strategy proposed in this paper holds potential for controlling sequential M1-to-M2 polarization of macrophages, which provides another perspective for the treatment of bone tissue regeneration.