Circadian clock disorder during tissue degeneration has been considered the potential pathogenesis for various chronic diseases, such as intervertebral disc degeneration (IVDD). In this study, circadian clock‐regulating biomaterials (ClockMPs) that can effectively activate the intrinsic circadian clock of nucleus pulposus cells (NPCs) in IVDD and improve the physiological function of NPCs for disc regeneration are fabricated via air‐microfluidic technique and the chemical cross‐linking between polyvinyl alcohol and modified‐phenylboronic acid. In vitro experiments verified that ClockMPs can scavenge reactive oxygen species to maintain a stable microenvironment for the circadian clock by promoting the binding of BMAL1 and CLOCK proteins. ClockMPs can regulate the expression of core circadian clock genes by activating the PI3K‐AKT pathway in NPCs to remodel the intrinsic circadian clock and promote extracellular matrix synthesis. Furthermore, in vivo experiments of IVDD treated with ClockMPs proved that ClockMPs can promote disc regeneration by regulating the circadian clock of NPCs. In conclusion, ClockMPs provided a novel and promising strategy for circadian clock regulation during tissue regeneration.
Nebulization is the most widely used respiratory delivery technique with non‐invasive properties. However, nebulized drugs often fail to function due to the excretion and immune clearance of the respiratory system. In this work, inspired by pollen in nature, novel shell–core aerosol particles (APs) capable of Brownian motion are constructed for respiratory delivery. Drugs‐loaded poly(lactic‐co‐glycolic acid) nanoparticles are prepared by emulsification to form the inner core, and the membranes of macrophages are extracted to form the outer shell. The optimized size and the shell–core structure endow APs with Brownian motion and atomization stability, thus enabling the APs to reach the bronchi and alveoli deeply for effective deposition. Camouflaging the macrophage membranes equips the APs with immune evasion. In vitro experiments prove that deferoxamine (DFO)‐loaded APs (DFO@APs) can promote the angiogenesis of human umbilical vein endothelial cells. A hyperoxia‐induced bronchopulmonary dysplasia (BPD) model is constructed to validate the efficiency of DFO@APs. In BPD mice, DFO@APs can release DFO in the alveolar interstitium, thus promoting the reconstruction of microvasculature, ultimately inducing lung development for treating BPD. In conclusion, this study develops “pollen”‐inspired shell–core aerosol particles capable of Brownian motion, which provides a novel idea and theoretical basis for respiratory administration.
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