Spatiotemporalized Hydrogel Microspheres Promote Vascularized Osteogenesis via Ultrasound Oxygen Delivery

Abstract

Disturbance of spatiotemporal oxygen balance is the main cause of delayed healing or nonhealing of large bone defects. The accurate administration of oxygen to regulate disruptions in the spatiotemporal oxygen equilibrium during 9 h of hypoxia is imperative for bone tissue regeneration. Herein, oxygen‐loaded nanobubbles prepared by double emulsification are successfully embedded in GelMA/HepMA microsphere macromolecular meshwork by microfluidic techniques, and a spatiotemporalized hydrogel microsphere is constructed by noncovalently binding bone morphogenetic protein 2 (BMP‐2). The spatiotemporalized hydrogel microspheres precisely “remote control” oxygen release by ultrasound in vitro 9 h after bone injury to regulate spatiotemporal oxygen homeostasis disorder, maintain a high level of vascular endothelial growth factor (VEGF) expression, and accelerate bone repair. The spatiotemporalized hydrogel microspheres possess good oxygen‐carrying capacity and ultrasonic responsiveness, and the oxygen concentration increases to 1.63, 1.95, 2.11, and 2.29 times under the ultrasound action at different intensities of 1, 2, 3, and 4 W, respectively, providing the conditions for the precise regulation of spatiotemporal oxygen balance disorder by ultrasound. In the in vitro hypoxia model and in vivo rat femoral defect model, the spatiotemporal hydrogel microspheres show good vascularization and osteogenesis capabilities, which provide a new strategy for the clinical treatment of large bone defects.

Degradation-Dependent Self-Release Hydrogel with over Three Months of Antioxidation and Anti-inflammation for Osteoporotic Bone Repair

“…Hydrogels possess a three-dimensional (3D) network similar to the bone extracellular matrix (ECM) as well as high loading capacity − and thus have been widely used for loading drugs to treat osteoporotic bone defects. , Unfortunately, since the mesh size of hydrogels is huge for the drug molecules, the loaded drugs are released easily, with the release cycles lasting as little as a few hours or days. − To overcome the diffusion-caused quick release, a size-assisted release strategy has recently been proposed, in which the drugs are encapsulated first in micro/nanoparticles after which the drug-containing micro/nanoparticles are loaded into the degradable hydrogels. , Owing to the “increased” size, the drug release can be controlled not mainly by the diffusion but by the degradation of hydrogels, thus prolonging the release cycle . For example, Li et al formed TPCD nanoparticles by self-assembly of the β-cyclodextrin conjugated with both antioxidative phenylboronic acid pinacol ester and anti-inflammatory Tempol and loaded them in the Poloxamer 407 hydrogel.…”

Selenol-ene chemistry-based one pot reaction for unsymmetric selenides synthesis and rate regulation of selenide oxidative elimination

“…The novel ROS-responsive PEG lipid strategy presents a promising avenue for the development of next-generation intelligent lipid nanoparticles (LNPs) with spatiotemporally controlled drug delivery capabilities. 16,17…”